Separation of phytochemicals from Helichrysum italicum: An analysis of different isolation techniques and biological activity of prepared extracts.

PubMed

Maksimovic, Svetolik; Tadic, Vanja; Skala, Dejan; Zizovic, Irena

2017-06-01

Helichrysum italicum presents a valuable source of natural bioactive compounds. In this work, a literature review of terpenes, phenolic compounds, and other less common phytochemicals from H. italicum with regard to application of different separation methods is presented. Data including extraction/separation methods and experimental conditions applied, obtained yields, number of identified compounds, content of different compound groups, and analytical techniques applied are shown as corresponding tables. Numerous biological activities of both isolates and individual compounds are emphasized. In addition, the data reported are discussed, and the directions for further investigations are proposed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigating biological activity spectrum for novel styrylquinazoline analogues.

PubMed

Jampilek, Josef; Musiol, Robert; Finster, Jacek; Pesko, Matus; Carroll, James; Kralova, Katarina; Vejsova, Marcela; O'Mahony, Jim; Coffey, Aidan; Dohnal, Jiri; Polanski, Jaroslaw

2009-10-23

In this study, series of ring-substituted 2-styrylquinazolin-4(3H)-one and 4-chloro-2-styrylquinazoline derivatives were prepared. The syntheses of the discussed compounds are presented. The compounds were analyzed by RP-HPLC to determine lipophilicity. They were tested for their inhibitory activity on photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Primary in vitro screening of the synthesized compounds was also performed against four mycobacterial strains and against eight fungal strains. Several compounds showed biological activity comparable with or higher than that of the standard isoniazid. It was found that the electronic properties of the R substituent, and not the total lipophilicity of the compound, were decisive for the photosynthesis-inhibiting activity of tested compounds.

Benzoxazine derivatives of phytophenols show anti-plasmodial activity via sodium homeostasis disruption.

PubMed

Sharma, Vijeta; Amarnath, Nagarjuna; Shukla, Swapnil; Ayana, R; Kumar, Naveen; Yadav, Nisha; Kannan, Deepika; Sehrawat, Seema; Pati, Soumya; Lochab, Bimlesh; Singh, Shailja

2018-05-15

Development of new class of anti-malarial drugs is an essential requirement for the elimination of malaria. Bioactive components present in medicinal plants and their chemically modified derivatives could be a way forward towards the discovery of effective anti-malarial drugs. Herein, we describe a new class of compounds, 1,3-benzoxazine derivatives of pharmacologically active phytophenols eugenol (compound 3) and isoeugenol (compound 4) synthesised on the principles of green chemistry, as anti-malarials. Compound 4, showed highest anti-malarial activity with no cytotoxicity towards mammalian cells. Compound 4 induced alterations in the intracellular Na + levels and mitochondrial depolarisation in intraerythrocytic Plasmodium falciparum leading to cell death. Knowing P-type cation ATPase PfATP4 is a regulator for sodium homeostasis, binding of compound 3, compound 4 and eugenol to PfATP4 was analysed by molecular docking studies. Compounds showed binding to the catalytic pocket of PfATP4, however compound 4 showed stronger binding due to the presence of propylene functionality, which corroborates its higher anti-malarial activity. Furthermore, anti-malarial half maximal effective concentration of compound 4 was reduced to 490 nM from 17.54 µM with nanomaterial graphene oxide. Altogether, this study presents anti-plasmodial potential of benzoxazine derivatives of phytophenols and establishes disruption of parasite sodium homeostasis as their mechanism of action. Copyright © 2018 Elsevier Ltd. All rights reserved.

Case study: Comparison of biological active compounds in milk from organic and conventional dairy herds

USDA-ARS?s Scientific Manuscript database

Conflicting reports of the quantities of biologically active compounds present in milk from organic grass-fed and conventional herds show that more research is required, especially as these compounds are linked to human health benefits and can improve the health value consumers place on dairy produc...

The Involvement of Morphological Information in the Memorization of Chinese Compound Words: Evidence from Memory Errors.

PubMed

Liu, Duo

2016-02-01

The processing of morphological information during Chinese word memorization was investigated in the present study. Participants were asked to study words presented to them on a computer screen in the studying phase and then judge whether presented words were old or new in the test phase. In addition to parent words (i.e. the words studied in the study phase), the test phase also included conjunction lures (constructed out of morphemes in the parent words) and new words (constructed out of entirely new morphemes). Three kinds of words (i.e. subordinate compounds, coordinative compounds, and single-morpheme words) were involved. In both two experiments, performance on lures worsened when both parent words and lures were coordinative compounds, compared to the condition when both were subordinate compounds. The different performance between compounds with different compounding structures in the test phase suggests the involvement of morphological information in the memorization of Chinese compound words. The spreading activation theory for memory and the interactive activation model for the processing of morphologically complex words were referred to for interpreting the results.

Antiarrhythmic and antioxidant activity of novel pyrrolidin-2-one derivatives with adrenolytic properties

PubMed Central

Nowaczyk, Alicja; Kulig, Katarzyna

2010-01-01

A series of novel pyrrolidin-2-one derivatives (17 compounds) with adrenolytic properties was evaluated for antiarrhythmic, electrocardiographic and antioxidant activity. Some of them displayed antiarrhythmic activity in barium chloride-induced arrhythmia and in the rat coronary artery ligation-reperfusion model, and slightly decreased the heart rate, prolonged P–Q, Q–T intervals and QRS complex. Among them, compound EP-40 (1-[2-hydroxy-3-[4-[(2-hydroxyphenyl)piperazin-1-yl]propyl]pyrrolidin-2-one showed excellent antiarrhythmic activity. This compound had significantly antioxidant effect, too. The present results suggest that the antiarrhythmic effect of compound EP-40 is related to their adrenolytic and antioxidant properties. A biological activity prediction using the PASS software shows that compound EP-35 and EP-40 can be characterized by antiischemic activity; whereas, compound EP-68, EP-70, EP-71 could be good tachycardia agents. PMID:20949258

Antiarrhythmic and antioxidant activity of novel pyrrolidin-2-one derivatives with adrenolytic properties.

PubMed

Sapa, Jacek; Nowaczyk, Alicja; Kulig, Katarzyna

2011-01-01

A series of novel pyrrolidin-2-one derivatives (17 compounds) with adrenolytic properties was evaluated for antiarrhythmic, electrocardiographic and antioxidant activity. Some of them displayed antiarrhythmic activity in barium chloride-induced arrhythmia and in the rat coronary artery ligation-reperfusion model, and slightly decreased the heart rate, prolonged P-Q, Q-T intervals and QRS complex. Among them, compound EP-40 (1-[2-hydroxy-3-[4-[(2-hydroxyphenyl)piperazin-1-yl]propyl]pyrrolidin-2-one showed excellent antiarrhythmic activity. This compound had significantly antioxidant effect, too. The present results suggest that the antiarrhythmic effect of compound EP-40 is related to their adrenolytic and antioxidant properties. A biological activity prediction using the PASS software shows that compound EP-35 and EP-40 can be characterized by antiischemic activity; whereas, compound EP-68, EP-70, EP-71 could be good tachycardia agents.

Isolation, Separation, and Preconcentration of Biologically Active Compounds from Plant Matrices by Extraction Techniques.

PubMed

Raks, Victoria; Al-Suod, Hossam; Buszewski, Bogusław

2018-01-01

Development of efficient methods for isolation and separation of biologically active compounds remains an important challenge for researchers. Designing systems such as organomineral composite materials that allow extraction of a wide range of biologically active compounds, acting as broad-utility solid-phase extraction agents, remains an important and necessary task. Selective sorbents can be easily used for highly selective and reliable extraction of specific components present in complex matrices. Herein, state-of-the-art approaches for selective isolation, preconcentration, and separation of biologically active compounds from a range of matrices are discussed. Primary focus is given to novel extraction methods for some biologically active compounds including cyclic polyols, flavonoids, and oligosaccharides from plants. In addition, application of silica-, carbon-, and polymer-based solid-phase extraction adsorbents and membrane extraction for selective separation of these compounds is discussed. Potential separation process interactions are recommended; their understanding is of utmost importance for the creation of optimal conditions to extract biologically active compounds including those with estrogenic properties.

Selection of quantum chemical descriptors by chemometric methods in the study of antioxidant activity of flavonoid compounds

NASA Astrophysics Data System (ADS)

Weber, K. C.; Honório, K. M.; da Silva, S. L.; Mercadante, R.; da Silva, A. B. F.

In the present study, the aim was to select electronic properties responsible for free radical scavenging ability of a set of 25 flavonoid compounds employing chemometric methods. Electronic parameters were calculated using the AM1 semiempirical method, and chemometric methods (principal component analysis, hierarchical cluster analysis, and k-nearest neighbor) were used with the aim to build models able to find relationships between electronic features and the antioxidant activity presented by the compounds studied. According to these models, four electronic variables can be considered important to discriminate more and less antioxidant flavonoid compounds: polarizability (α), charge at carbon 3 (QC3), total charge at substituent 5 (QS5), and total charge at substituent 3' (QS3'). The features found as being responsible for the antioxidant activity of the flavonoid compounds studied are consistent with previous results found in the literature. The results obtained can also bring improvements in the search for better antioxidant flavonoid compounds.

Therapeutic Potential of Pterocarpus santalinus L.: An Update

PubMed Central

Bulle, Saradamma; Reddyvari, Hymavathi; Nallanchakravarthula, Varadacharyulu; Vaddi, Damodara Reddy

2016-01-01

Recently there has been increasing interest in plants and plant-derived compounds as raw food and medicinal agents. In Ayurveda, an Indian system of traditional medicine, a wide spectrum of medicinal properties of Pterocarpus santalinus is described. Many important bioactive phytocompounds have been extracted and identified from the heartwood of P. santalinus. Bioactive compounds typically occur in small amounts and have more subtle effects than nutrients. These bioactive compounds influence cellular activities that modify the risk of disease rather than prevent deficiency diseases. A wide array of biological activities and potential health benefits of P. santalinus have been reported, including antioxidative, antidiabetic, antimicrobial, anticancer, and anti-inflammatory properties, and protective effects on the liver, gastric mucosa, and nervous system. All these protective effects were attributed to bioactive compounds present in P. santalinus. The major bioactive compounds present in the heartwood of P. santalinus are santalin A and B, savinin, calocedrin, pterolinus K and L, and pterostilbenes. The bioactive compounds have potentially important health benefits: These compounds can act as antioxidants, enzyme inhibitors and inducers, inhibitors of receptor activities, and inducers and inhibitors of gene expression, among other actions. The present review aims to understand the pharmacological effects of P. santalinus on health and disease with “up-to-date” discussion. PMID:27041873

Therapeutic Potential of Pterocarpus santalinus L.: An Update.

PubMed

Bulle, Saradamma; Reddyvari, Hymavathi; Nallanchakravarthula, Varadacharyulu; Vaddi, Damodara Reddy

2016-01-01

Recently there has been increasing interest in plants and plant-derived compounds as raw food and medicinal agents. In Ayurveda, an Indian system of traditional medicine, a wide spectrum of medicinal properties of Pterocarpus santalinus is described. Many important bioactive phytocompounds have been extracted and identified from the heartwood of P. santalinus. Bioactive compounds typically occur in small amounts and have more subtle effects than nutrients. These bioactive compounds influence cellular activities that modify the risk of disease rather than prevent deficiency diseases. A wide array of biological activities and potential health benefits of P. santalinus have been reported, including antioxidative, antidiabetic, antimicrobial, anticancer, and anti-inflammatory properties, and protective effects on the liver, gastric mucosa, and nervous system. All these protective effects were attributed to bioactive compounds present in P. santalinus. The major bioactive compounds present in the heartwood of P. santalinus are santalin A and B, savinin, calocedrin, pterolinus K and L, and pterostilbenes. The bioactive compounds have potentially important health benefits: These compounds can act as antioxidants, enzyme inhibitors and inducers, inhibitors of receptor activities, and inducers and inhibitors of gene expression, among other actions. The present review aims to understand the pharmacological effects of P. santalinus on health and disease with "up-to-date" discussion.

In vitro evaluation of cytotoxicity and leishmanicidal activity of phthalimido-thiazole derivatives.

PubMed

Aliança, Amanda Silva Dos Santos; Oliveira, Arsênio Rodrigues; Feitosa, Ana Paula Sampaio; Ribeiro, Karla Raíza Cardoso; de Castro, Maria Carolina Accioly Brelaz; Leite, Ana Cristina Lima; Alves, Luiz Carlos; Brayner, Fábio André

2017-07-15

It is estimated that the worldwide prevalence of leishmaniasis is around 12 million individuals in 80 countries, with 400,000new cases per year. In the search for new leishmanicidal agents, the hybrid phthalimido-thiazoles have been identified as an important scaffold for drug design and discovery. The present study thus reports the in vitro activity of a series of phthalimido-thiazole derivatives. Cytotoxicity against a strain of L. infantum, Vero cells, J774 macrophages and peritoneal macrophages was evaluated, as well as nitric oxide (NO) production. Activity against amastigote and promastigote forms of L. infantum and microscopic changes in the parasite and intracellular targets of the parasite were achieved. The results show that the compounds arising from hybridization of phthalimide and 1,3-thiazole exhibit promising leishmanicidal activity. Compounds 2j and 2m were the most potent of the series tested and the parasites treated with these compounds exhibited ultrastructural changes, such as cell body shrinkage, loss of cellular membrane integrity, vacuolization of cytoplasm, membrane profiles surrounding organelles and swelling of mitochondria. The data showed that these compounds reduced the survival of intracellular amastigotes and presented low toxicity for mammalian cells. The compounds produced increased NO production compared to untreated cells in non-infected macrophages. Treated promastigote forms showed an increase in the number of cells stained with propidium iodide. The compounds brought about significant changes in mitochondrial membrane potential. According to the present study, phthalimido-thiazole compounds exhibit leishmanicidal activity and could be used to develop novel antileishmaniasis drugs and explore potential molecular targets. Copyright © 2017 Elsevier B.V. All rights reserved.

Design, synthesis, antiviral activity and mode of action of phenanthrene-containing N-heterocyclic compounds inspired by the phenanthroindolizidine alkaloid antofine.

PubMed

Yu, Xiuling; Wei, Peng; Wang, Ziwen; Liu, Yuxiu; Wang, Lizhong; Wang, Qingmin

2016-02-01

The phenanthroindolizidine alkaloid antofine and its analogues have excellent antiviral activity against tobacco mosaic virus (TMV). To simplify the structure and the synthesis of the phenanthroindolizidine alkaloid, a series of phenanthrene-containing N-heterocyclic compounds (compounds 1 to 33) were designed and synthesised, based on the intermolecular interaction of antofine and TMV RNA, and systematically evaluated for their anti-TMV activity. Most of these compounds exhibited good to reasonable anti-TMV activity. The optimum compounds 5, 12 and 21 displayed higher activity than the lead compound antofine and commercial ribavirin. Compound 12 was chosen for field trials of antiviral efficacy against TMV, and was found to exhibit better activity than control plant virus inhibitors. Compounds 5 and 12 were chosen for mode of action studies. The changes in fluorescence intensity of compounds 5 and 12 on separated TMV RNA showed that these small molecules can also bind to TMV RNA, but the mode is very different from that of antofine. The compounds combining phenanthrene and an N-heterocyclic ring could maintain the anti-TMV activity of phenanthroindolizidines, but their modes of action are different from that of antofine. The present study lays a good foundation for us to find more efficient anti-plant virus reagents. © 2015 Society of Chemical Industry.

Comparative Inhibition Study of Compounds Identified in the Methanolic Extract of Apamarga Kshara Against Trichomonas vaginalis Carbamate Kinase (TvCK): An Enzoinformatics Approach.

PubMed

Shaikh, Sibhghatulla; Aaqil, Hamida; Rizvi, Syed Mohd Danish; Shakil, Shazi; Abuzenadah, Adel M; Gupta, Pragya; Saxena, Soumya; Tiwari, Rohit Kr; Kumar, Ajai

2016-12-01

In the present study, we have identified ten compounds, namely dodecanol acid, myristic acid, neophytadiene, palmitic acid, heptadecanoic acid, linoleic acid, elaidic acid, 3-7-dimethyl acid, stearic acid and methyl eicos acid, of the methanolic extract of Apamarga Kshara by GC-MS analysis. Apamarga Kshara has been reported to be active against cervical erosion. Major causal organism for cervical erosion is Trichomonas vaginalis. However, there is a paucity of information about the mechanism of action and inhibitory effect of the biologically active natural compounds presented in A. Kshara against this organism (T. vaginalis). Therefore, present investigation was conducted to observe possible interactions of these compounds on T. vaginalis carbamate kinase using molecular docking software 'AutoDock 4.2.' Identification of the amino acid residues crucial for the interaction between T. vaginalis carbamate kinase and these natural compounds is of due scientific interest. The study will aid in efficacious and safe clinical use of the above-mentioned compounds.

Antioxidative activities and phenolic compounds of pumpkin (Cucurbita pepo) seeds and amaranth (Amaranthus caudatus) grain extracts.

PubMed

Peiretti, Pier Giorgio; Meineri, Giorgia; Gai, Francesco; Longato, Erica; Amarowicz, Ryszard

2017-09-01

Phenolic compounds were extracted from pumpkin (Cucurbita pepo) seed and amaranth (Amaranthus caudatus) grain into 80% (v/v) methanol. The extracts obtained were characterised by the contents of total phenolic compounds (TPC), trolox equivalent antioxidant capacity (TEAC), ferric-reducing antioxidant power (FRAP) and antiradical activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH · ) radical. The content of individual phenolic compounds was determined by HPLC-DAD method. Pumpkin seeds showed the higher content of TPC than that from amaranth. The TEAC values of both extracts were similar each other. The lower value of FRAP was observed for pumpkin seed. Phenolic compound present in amaranth grain exhibited strongest antiradical properties against DPPH radical. Several peaks were present on the HPLC chromatograms of two extracts. The UV-DAD spectra confirmed the presence of vanillic acid derivatives in the amaranth grain. The three main phenolic compound present in pumpkin seed were characterised by UV-DAD spectra with maximum at 258, 266 and 278 nm.

Effect of compounds with antibacterial activities in human milk on respiratory syncytial virus and cytomegalovirus in vitro.

PubMed

Portelli, J; Gordon, A; May, J T

1998-11-01

The effect of some antibacterial compounds present in human milk were tested for antiviral activity against respiratory syncytial virus, Semliki Forest virus and cytomegalovirus. These included the gangliosides GM1, GM2 and GM3, sialyl-lactose, lactoferrin and chondroitin sulphate A, B and C, which were all tested for their ability to inhibit the viruses in cell culture. Of the compounds tested, only the ganglioside GM2, chondroitin sulphate B and lactoferrin inhibited the absorption and growth of respiratory syncytial virus in cell culture, and none inhibited the growth of Semliki Forest virus, indicating that lipid antiviral activity was not associated with any of the gangliosides. While the concentrations of these two compounds required to inhibit respiratory syncytial virus were in excess of those present in human milk, sialyl-lactose concentrations similar to those present in human milk increased the growth of cytomegalovirus. Lactoferrin was confirmed as inhibiting both respiratory syncytial virus and cytomegalovirus growth in culture even when used at lower concentrations than those present in human milk. The antiviral activities of GM2, chondroitin sulphate B and lactoferrin were tested when added to an infant formula. Lactoferrin continued to have antiviral activity against cytomegalovirus, but a lower activity against respiratory syncytial virus; ganglioside GM2 and chondroitin sulphate B still maintained antiviral activity against respiratory syncytial virus.

A review of QSAR studies to discover new drug-like compounds actives against leishmaniasis and trypanosomiasis.

PubMed

Castillo-Garit, Juan Alberto; Abad, Concepción; Rodríguez-Borges, J Enrique; Marrero-Ponce, Yovani; Torrens, Francisco

2012-01-01

The neglected tropical diseases (NTDs) affect more than one billion people (one-sixth of the world's population) and occur primarily in undeveloped countries in sub-Saharan Africa, Asia, and Latin America. Available drugs for these diseases are decades old and present an important number of limitations, especially high toxicity and, more recently, the emergence of drug resistance. In the last decade several Quantitative Structure-Activity Relationship (QSAR) studies have been developed in order to identify new organic compounds with activity against the parasites responsible for these diseases, which are reviewed in this paper. The topics summarized in this work are: 1) QSAR studies to identify new organic compounds actives against Chaga's disease; 2) Development of QSAR studies to discover new antileishmanial drusg; 3) Computational studies to identify new drug-like compounds against human African trypanosomiasis. Each topic include the general characteristics, epidemiology and chemotherapy of the disease as well as the main QSAR approaches to discovery/identification of new actives compounds for the corresponding neglected disease. The last section is devoted to a new approach know as multi-target QSAR models developed for antiparasitic drugs specifically those actives against trypanosomatid parasites. At present, as a result of these QSAR studies several promising compounds, active against these parasites, are been indentify. However, more efforts will be required in the future to develop more selective (specific) useful drugs.

Phytotoxicity of vulpia residues: III. Biological activity of identified allelochemicals from Vulpia myuros.

PubMed

An, M; Pratley, J E; Haig, T

2001-02-01

Twenty compounds identified in vulpia (Vulpia myuros) residues as allelochemicals were individually and collectively tested for biological activity. Each exhibited characteristic allelochemical behavior toward the test plant, i.e., inhibition at high concentrations and stimulation or no effect at low concentrations, but individual activities varied. Allelopathins present in large quantities, such as syringic, vanillic, and succinic acids, possessed low activity, while those present in small quantities, such as catechol and hydrocinnamic acid, possessed strong inhibitory activity. The concept of a phytotoxic strength index was developed for quantifying the biological properties of each individual allelopathin in a concise, comprehensive, and meaningful format. The individual contribution of each allelopathin, assessed by comparing the phytotoxic strength index to the overall toxicity of vulpia residues, was variable according to structure and was influenced by its relative proportion in the residue. The majority of compounds possessed low or medium biological activity and contributed most of the vulpia phytotoxicity, while compounds with high biological activity were in the minority and only present at low concentration. Artificial mixtures of these pure allelochemicals also produced phytotoxicity. There were additive/synergistic effects evident in the properties of these mixtures. One such mixture, formulated from allelochemicals found in the same proportions as occur in vulpia extract, produced stronger activity than another formulated from the same set of compounds but in equal proportions. These results suggest that the exploration of the relative composition of a cluster of allelopathins may be more important than simply focusing on the identification of one or two compounds with strong biological activity and that synergism is fundamental to the understanding of allelopathy.

Semiconducting compounds and devices incorporating same

DOEpatents

Marks, Tobin J; Facchetti, Antonio; Boudreault, Pierre-Luc; Miyauchi, Hiroyuki

2014-06-17

Disclosed are molecular and polymeric compounds having desirable properties as semiconducting materials. Such compounds can exhibit desirable electronic properties and possess processing advantages including solution-processability and/or good stability. Organic transistor and photovoltaic devices incorporating the present compounds as the active layer exhibit good device performance.

Semiconducting compounds and devices incorporating same

DOEpatents

Marks, Tobin J.; Facchetti, Antonio; Boudreault, Pierre-Luc; Miyauchi, Hiroyuki

2016-01-19

Disclosed are molecular and polymeric compounds having desirable properties as semiconducting materials. Such compounds can exhibit desirable electronic properties and possess processing advantages including solution-processability and/or good stability. Organic transistor and photovoltaic devices incorporating the present compounds as the active layer exhibit good device performance.

Compositions for enhancing hydroysis of cellulosic material by cellulolytic enzyme compositions

DOEpatents

Quinlan, Jason; Xu, Feng; Sweeney, Matthew; Johansen, Katja Salomon

2014-09-30

The present invention relates to compositions comprising a GH61 polypeptide having cellulolytic enhancing activity and an organic compound comprising a carboxylic acid moiety, a lactone moiety, a phenolic moiety, a flavonoid moiety, or a combination thereof, wherein the combination of the GH61 polypeptide having cellulolytic enhancing activity and the organic compound enhances hydrolysis of a cellulosic material by a cellulolytic enzyme compared to the GH61 polypeptide alone or the organic compound alone. The present invention also relates to methods of using the compositions.

Pharmacological effects of primaquine ureas and semicarbazides on the central nervous system in mice and antimalarial activity in vitro.

PubMed

Kedzierska, Ewa; Orzelska, Jolanta; Perković, Ivana; Knežević, Danijel; Fidecka, Sylwia; Kaiser, Marcel; Zorc, Branka

2016-02-01

New primaquine (PQ) urea and semicarbazide derivatives 1-4 were screened for the first time for central nervous system (CNS) and antimalarial activity. Behavioural tests were performed on mice. In vitro cytotoxicity on L-6 cells and activity against erythrocytic stages of Plasmodium falciparum was determined. Compound 4 inhibited 'head-twitch' responses and decreased body temperature of mice, which suggests some involvement of the serotonergic system. Compound 4 protected mice against clonic seizures and was superior in the antimalarial test. A hybrid of two PQ urea 2 showed a strong antimalarial activity, confirming the previous findings of the high activity of bis(8-aminoquinolines) and other bisantimalarial drugs. All the compounds decreased the locomotor activity of mice, what suggests their weak depressive effects on the CNS, while PQ derivatives 1 and 2 increased amphetamine-induced hyperactivity. None of the compounds impaired coordination, what suggests a lack of their neurotoxicity. All the tested compounds presented an antinociceptive activity in the 'writhing' test. Compounds 3 and 4 were active in nociceptive tests, and those effects were reversed by naloxone. Compound 4 could be a useful lead compound in the development of CNS active agents and antimalarials, whereas compound 3 may be considered as the most promising lead for new antinociceptive agents. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Antimicrobial Action of Compounds from Marine Seaweed

PubMed Central

Pérez, María José; Falqué, Elena; Domínguez, Herminia

2016-01-01

Seaweed produces metabolites aiding in the protection against different environmental stresses. These compounds show antiviral, antiprotozoal, antifungal, and antibacterial properties. Macroalgae can be cultured in high volumes and would represent an attractive source of potential compounds useful for unconventional drugs able to control new diseases or multiresistant strains of pathogenic microorganisms. The substances isolated from green, brown and red algae showing potent antimicrobial activity belong to polysaccharides, fatty acids, phlorotannins, pigments, lectins, alkaloids, terpenoids and halogenated compounds. This review presents the major compounds found in macroalga showing antimicrobial activities and their most promising applications. PMID:27005637

Structure-property studies on the antioxidant activity of flavonoids present in diet.

PubMed

Teixeira, Susana; Siquet, Christophe; Alves, Carla; Boal, Isabel; Marques, M Paula; Borges, Fernanda; Lima, José L F C; Reis, Salette

2005-10-15

The screening of natural flavonoids for their bioactivity as antioxidants is usually carried out by determinination of their profile as chain-breaking antioxidants, by the evaluation of their direct free radical-scavenging activity as hydrogen- or electron-donating compounds. Since this may not be the only mechanism underlying the antioxidant activity it is important to check the ability of these compounds to act as chelators of transition metal ions. Accordingly, in the present study the acidity constants of catechin and taxifolin, as well as the formation constants of the corresponding copper (II) complexes, were investigated by potentiometry and/or spectrophotometry. Moreover, a detailed quantitative examination of the coordination species formed is presented. In addition, the partition coefficients of both catechin and taxifolin in a biomimetic system (micelles) were determined, since these properties may also contribute to the antioxidant behavior of this type of compound. The log P values determined depend on the electrostatic interactions of the compounds with the differently charged micelles (the highest values were obtained for zwitterionic and cationic micelles). The prooxidant behavior of the compounds was assessed through the oxidation of 2'-deoxyguanosine, induced by a Fenton reaction, catalyzed by copper. The data obtained reveal that the flavonoids under study did not present prooxidant activity, in this particular system. The results obtained are evidence of a clear difference among the pKa, the complexation properties, and the lipophilicity of the flavonoids studied, which can partially explain their distinct antioxidant activity. The most stable geometries of the free compounds were determined by theoretical (ab initio) methods, in order to properly account for the electron correlation effects which occur in these systems, thus allowing a better interpretation of the experimental data.

Positive modulator of bone morphogenic protein-2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua

Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

Positive modulator of bone morphogenic protein-2

DOEpatents

Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

2009-01-27

Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

In Vitro Antifungal Activities of a Series of Dication-Substituted Carbazoles, Furans, and Benzimidazoles

PubMed Central

Del Poeta, Maurizio; Schell, Wiley A.; Dykstra, Christine C.; Jones, Susan K.; Tidwell, Richard R.; Kumar, Arvind; Boykin, David W.; Perfect, John R.

1998-01-01

Aromatic dicationic compounds possess antimicrobial activity against a wide range of eucaryotic pathogens, and in the present study an examination of the structures-functions of a series of compounds against fungi was performed. Sixty-seven dicationic molecules were screened for their inhibitory and fungicidal activities against Candida albicans and Cryptococcus neoformans. The MICs of a large number of compounds were comparable to those of the standard antifungal drugs amphotericin B and fluconazole. Unlike fluconazole, potent inhibitory compounds in this series were found to have excellent fungicidal activities. The MIC of one of the most potent compounds against C. albicans was 0.39 μg/ml, and it was the most potent compound against C. neoformans (MIC, ≤0.09 μg/ml). Selected compounds were also found to be active against Aspergillus fumigatus, Fusarium solani, Candida species other than C. albicans, and fluconazole-resistant strains of C. albicans and C. neoformans. Since some of these compounds have been safely given to animals, these classes of molecules have the potential to be developed as antifungal agents. PMID:9756748

Dual evaluation of some novel 2-amino-substituted coumarinylthiazoles as anti-inflammatory-antimicrobial agents and their docking studies with COX-1/COX-2 active sites.

PubMed

Chandak, Navneet; Kumar, Pawan; Kaushik, Pawan; Varshney, Parul; Sharma, Chetan; Kaushik, Dhirender; Jain, Sudha; Aneja, Kamal R; Sharma, Pawan K

2014-08-01

Synthesis of total eighteen 2-amino-substituted 4-coumarinylthiazoles including sixteen new compounds (3a-o and 5b) bearing the benzenesulfonamide moiety is described in the present report. All the synthesized target compounds were examined for their in vivo anti-inflammatory (AI) activity and in vitro antimicrobial activity. Results revealed that six compounds (3 d, 3 f, 3 g, 3 h, 3 j and 3 n) exhibited pronounced anti-inflammatory activity comparable to the standard drug indomethacin. AI results were further confirmed by the docking studies of the most active (3n) and the least active compound (3a) with COX-1 and COX-2 active sites. In addition, most of the compounds exhibited moderate antimicrobial activity against Gram-positive bacteria as well as fungal yeast, S. cervisiae. Comparison between 3 and 5 indicated that incorporation of additional substituted pyrazole nucleus into the scaffold significantly enhanced AI activity.

In view of an optimal gut antifungal therapeutic strategy: an in vitro susceptibility and toxicity study testing a novel phyto-compound.

PubMed

Metugriachuk, Yussef; Kuroi, Olivia; Pavasuthipaisit, Kanok; Tsuchiya, Junji; Minelli, Emilio; Okura, Ruichi; Fesce, Edoardo; Marotta, F

2005-01-01

In view of the raising concern for gut fungal infection, the aim of the present research was to carry out a systematic in vitro study testing the antifungal activity and possible toxicity of a polygodyal-anethole compound (Kolorex) in several strains of Candida albicans and in other fungal pathogens. The in vitro susceptibility tests were carried out on 4 strains of C. albicans (C. krusei, C. lipolytica, C. tropicalis, C. utilis), Aspergillus flavus and A. fumigatus. Cultures were also analyzed by varying medium, pH and inoculum size, and a time-course killing test was carried out. In the present study the polygodyal-anethole compound showed remarkable in vitro activity against the most common fungi, which was significantly better than polygodyal alone. Moreover, such mixture compound was shown to exert its activity against a wide spectrum of fungi, including C. lipolytica and C. tropicalis, which required significantly higher MIC of polygodyal to be unfeasible in clinical application. The activity of the polygodyal-anethole compound was significantly better than polygodyal alone with high inoculum size and low pH. Moreover, it proved to exert a significantly faster biological activity against low inoculum. This study suggests that the mixture compound Kolorex has a very good profile of antifungal activity in terms of effectiveness and spectrum of action while being devoid of any significant toxicity.

Synthesis and pharmacological evaluation of pyrazolo[4,3-c]cinnoline derivatives as potential anti-inflammatory and antibacterial agents.

PubMed

Tonk, Rajiv Kumar; Bawa, Sandhya; Chawla, Gita; Deora, Girdhar Singh; Kumar, Suresh; Rathore, Vandana; Mulakayala, Naveen; Rajaram, Azad; Kalle, Arunasree M; Afzal, Obaid

2012-11-01

A series of pyrazolo[4,3-c]cinnoline derivatives was synthesized, characterized and evaluated for anti-inflammatory and antibacterial activity. Test compounds that exhibited good anti-inflammatory activity were further screened for their ulcerogenic and lipid peroxidation activity. Compounds 4d and 4l showed promising anti-inflammatory activity with reduced ulcerogenic and lipid peroxidation activity when compared to naproxen. Docking results of these two compounds with COX-2 (PDB ID: 1CX2) also exhibited a strong binding profile. Among the test derivatives, compound 4i displayed significant antibacterial property against gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria. However, compound 4b emerged as the best dual anti-inflammatory-antibacterial agent in the present study. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Phenolic compounds, organic acids and antioxidant activity of grape juices produced in industrial scale by different processes of maceration.

PubMed

Lima, Marcos dos Santos; da Conceição Prudêncio Dutra, Maria; Toaldo, Isabela Maia; Corrêa, Luiz Claudio; Pereira, Giuliano Elias; de Oliveira, Débora; Bordignon-Luiz, Marilde Terezinha; Ninow, Jorge Luiz

2015-12-01

The effect of maceration process on the profile of phenolic compounds, organic acids composition and antioxidant activity of grape juices from new varieties of Vitis labrusca L. obtained in industrial scale was investigated. The extraction process presented a high yield without pressing the grapes. The use of a commercial pectinase resulted in an increase on extraction yield and procyanidins B1 and B2 concentrations and a decrease on turbidity and concentration of catechins. The combination of 60 °C and 3.0 mL 100 kg(-1) of enzyme resulted in the highest extraction of phenolic compounds, reducing the content of acetic acid. The juices presented high antioxidant activity, related to the great concentration of malvidin, cyanidin, catechin and caffeic, cinnamic and gallic acids. Among the bioactive compounds, the juices presented high concentration of procyanidin B1, caffeic acid and trans-resveratrol, with higher levels compared to those reported in the literature. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antiprotozoal activity of quinonemethide triterpenes from Maytenus ilicifolia (Celastraceae).

PubMed

Dos Santos, Vania A F F M; Leite, Karoline M; da Costa Siqueira, Mariana; Regasini, Luis O; Martinez, Isabel; Nogueira, Camila T; Galuppo, Mariana Kolos; Stolf, Beatriz S; Pereira, Ana Maria Soares; Cicarelli, Regina M B; Furlan, Maysa; Graminha, Marcia A S

2013-01-15

The present study describes the leishmanicidal and trypanocidal activities of two quinonemethide triterpenes, maytenin (1) and pristimerin (2), isolated from Maytenus ilicifolia root barks (Celastraceae). The compounds were effective against the Trypanosomatidae Leishmania amazonensis and Leishmania chagasi and Trypanosoma cruzi, etiologic agents of leishmaniasis and Chagas' disease, respectively. The quinonemethide triterpenes 1 and 2 exhibited a marked in vitro leishmanicidal activity against promastigotes and amastigotes with 50% inhibitory concentration (IC(50)) values of less than 0.88 nM. Both compounds showed IC(50) lower than 0.3 nM against Trypanosoma cruzi epimastigotes. The selectivity indexes (SI) based on BALB/c macrophages for L. amazonensis and L. chagasi were 243.65 and 46.61 for (1) and 193.63 and 23.85 for (2) indicating that both compounds presented high selectivity for Leishmania sp. The data here presented suggests that these compounds should be considered in the development of new and more potent drugs for the treatment of leishmaniasis and Chagas' disease.

[ANTIOXIDANT POTENTIAL OF MELIPONA BEECHEII HONEY AND ITS RELATIONSHIP TO HEALTH: A REVIEW].

PubMed

Cauich Kumul, Roger; Ruiz Ruiz, Jorge Carlos; Ortíz Vázquez, Elizabeth; Segura Campos, Maira Rubi

2015-10-01

The present article provides a literature review about the biological potential of Melipona beecheii. The objective is to project some tendecies in research about nutraceutical aspects related to the bioactive compounds presents in the honey of this stingless bee species, known for its medicinal properties traditional, in the Yucatan Peninsula. Currently, there is strong evidence that M. beecheii honey has bioactive compounds such as proteins, flavonoids and polyphenols with high antioxidant activity. The scientific evidence allows to propose to the honey of stingless bee species as a potential alternative for the obtention of bioactive compounds with antioxidant activity in the Yucatan Peninsula and natural food being proposed to reduce some diseases associated with stress oxidative physiological human cells. However, there is still information that explains such antioxidant activity, therefore, according to the literature reviewed, sees the need to address nutraceuticals and functional aspects correlated with the bioactive compounds present in this honey bee. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Characterization of the major aroma-active compounds in mango (Mangifera indica L.) cultivars Haden, White Alfonso, Praya Sowoy, Royal Special, and Malindi by application of a comparative aroma extract dilution analysis.

PubMed

Munafo, John P; Didzbalis, John; Schnell, Raymond J; Schieberle, Peter; Steinhaus, Martin

2014-05-21

The aroma-active compounds present in tree-ripened fruits of the five mango (Mangifera indica L.) cultivars Haden, White Alfonso, Praya Sowoy, Royal Special, and Malindi were isolated by solvent extraction followed by solvent-assisted flavor evaporation (SAFE) and analyzed by gas chromatography-olfactometery (GC-O). Application of a comparative aroma extract dilution analysis (cAEDA) afforded 54 aroma-active compounds in the flavor dilution (FD) factor range from 4 to ≥2048, 16 of which are reported for the first time in mango. The results of the identification experiments in combination with the FD factors revealed 4-hydroxy-2,5-dimethyl-3(2H)-furanone as an important aroma compound in all cultivars analyzed. Twenty-seven aroma-active compounds were present in at least one mango cultivar at an FD factor ≥128. Clear differences in the FD factors of these odorants between each of the mango cultivars suggested that they contributed to the unique sensory profiles of the individual cultivars.

Lipid encapsulated phenolic compounds by fluidization

USDA-ARS?s Scientific Manuscript database

Phenolic compounds exhibit antioxidant and antimicrobial activities with applications as functional food and feed additives. Ferulic acid, a phenolic compound present in grain crops and lignocellulose biomass, was encapsulated with saturated triglycerides using a laboratory fluidizer. Stability of t...

Effect of nitrogen species supply and mycorrhizal colonization on organosulfur and phenolic compounds in onions.

PubMed

Perner, Henrike; Rohn, Sascha; Driemel, Gregor; Batt, Natalie; Schwarz, Dietmar; Kroh, Lothar W; George, Eckhard

2008-05-28

The aim of the present study was to test whether variations in the root environment affect the content of health-related organosulfur compounds, total phenolic compounds, and flavonol glycoside concentrations in onions. For this purpose, greenhouse-grown onions ( Allium cepa L.) were either inoculated with a commercial arbuscular mycorrhizal inoculum or a sterile inoculum and were provided with two NH(4)(+):NO(3)(-) ratios as a nitrogen source. Onion growth, arbuscular mycorrhizal colonization rate, sugars, and nutrient element concentrations were also quantified. The plant antioxidant activity and quercetin monoglucoside and organosulfur compound concentrations increased with dominant nitrate supply. Furthermore, mycorrhizal colonization increased the antioxidant activity and also concentrations of the major quercetin glucosides. The present study provides clear evidence that antioxidant activity, quercetin glycosides, and organosulfur compounds can be increased in sufficiently supplied onion plants by dominant nitrate supply or application of arbuscular mycorrhizal fungi. This was probably due to increased precursor production and induced defense mechanisms.

Antimicrobial and enhancement of the antibiotic activity by phenolic compounds: Gallic acid, caffeic acid and pyrogallol.

PubMed

Lima, Valéria N; Oliveira-Tintino, Cícera D M; Santos, Enaide S; Morais, Luís P; Tintino, Saulo R; Freitas, Thiago S; Geraldo, Yuri S; Pereira, Raimundo L S; Cruz, Rafael P; Menezes, Irwin R A; Coutinho, Henrique D M

2016-10-01

The indiscriminate use of antimicrobial drugs has increased the spectrum of exposure of these organisms. In our studies, these phenolic compounds were evaluated: gallic acid, caffeic acid and pyrogallol. The antibacterial, antifungal and modulatory of antibiotic activities of these compounds were assayed using microdilution method of Minimum Inhibitory Concentration (MIC) to bacteria and Minimum Fungicide Concentration (MFC) to fungi. The modulation was made by comparisons of the MIC and MFC of the compounds alone and combined with drugs against bacteria and fungi respectively, using a sub-inhibitory concentration of 128 μg/mL of substances (MIC/8). All substances not demonstrated clinically relevant antibacterial activity with a MIC above ≥1024 μg/mL. As a result, we observed that the caffeic acid presented a potentiating antibacterial effect over the 3 groups of bacteria studied. Pyrogallol showed a synergistic effect with two of the antibiotics tested, but only against Staphylococcus aureus. In general, caffeic acid was the substance that presented with the greatest number of antibiotics and with the greatest number of bacteria. In relation to the antifungal activity of all the compounds, the verified results were ≥1024 μg/mL, not demonstrating significant activity. Regarding potentiation of the effect of fluconazole, was observed synergistic effect only when assayed against Candida tropicalis, with all substances. Therefore, as can be seen, the compounds presented as substances that can be promising potentiating agents of antimicrobial drugs, even though they do not have direct antibacterial and antifungal action. Copyright © 2016 Elsevier Ltd. All rights reserved.

Phenolic compounds can delay the oxidation of polyunsaturated fatty acids and the growth of Listeria monocytogenes: structure-activity relationships.

PubMed

Pernin, Aurélia; Dubois-Brissonnet, Florence; Roux, Stéphanie; Masson, Marine; Bosc, Véronique; Maillard, Marie-Noëlle

2018-04-20

Phenolic compounds present a potential solution to ensuring food quality and safety. Indeed, they can limit oxidation reactions and bacterial growth in food products. Although their antioxidant mechanisms of action are well known, their antibacterial ones are less well understood, especially in light of their chemical structures. The aim of this study was to first quantify both aspects of a series of natural phenolic compounds and then link these activities to their chemical structure. We evaluated antioxidant activity by measuring the capacity of phenolic compounds to delay free linoleic acid oxidation caused by the action of a hydrophilic azo-radical initiator (AAPH). We evaluated antibacterial activity by measuring the growth inhibition of Listeria monocytogenes and determining the non-inhibitory and minimum inhibitory concentrations for each compound. Compounds with ortho-diphenolic structures were the best antioxidants, whereas those belonging to the simple phenol category were the best antibacterial compounds. The physico-chemical properties of the compounds influenced both activities, but not in the same way. The chemical environment of the phenolic group and the presence of delocalization structures are the most important parameters for antioxidant activity, whereas the partition coefficient logP is one of the most important factors involved in antibacterial activity. This article is protected by copyright. All rights reserved.

Synthesis, biological evaluation and molecular modeling of novel series of pyridine derivatives as anticancer, anti-inflammatory and analgesic agents

NASA Astrophysics Data System (ADS)

Helal, M. H.; El-Awdan, S. A.; Salem, M. A.; Abd-elaziz, T. A.; Moahamed, Y. A.; El-Sherif, A. A.; Mohamed, G. A. M.

2015-01-01

This paper presents a combined synthesis; characterization, computational and biological activity studies of novel series of pyridines heterocyclic compounds. The compounds have been characterized by elemental analyses and spectral like IR, 1H NMR, 13C NMR and MS studies. Michael addition of substituted-2-methoxycarbonylacetanilide 2a,b on the α-substituted cinnamonitriles 3a-d gave the corresponding 2-pyridone derivatives 5-10. Structures of the titled compounds cited in this article were elucidated by spectrometric data (IR, 1H NMR, 13C NMR and MS). The molecular modeling of the synthesized compounds has been drawn and their molecular parameters were calculated. Also, valuable information is obtained from the calculation of molecular parameters including electronegativity, net dipole moment of the compounds, total energy, electronic energy, binding energy, HOMO and LUMO energy. Various in vitro antitumor as well as in vivo anti-inflammatory and analgesic activities of the synthesized compounds were investigated. Evaluation of anti-inflammatory activity of test compounds was performed using carrageenan induced paw edema in rats. All the tested compounds showed moderate to good activity. The SAR results indicate that all compounds showed moderate to good activity, among these 7 and 10 compounds having -N(CH3)2 group are most effective.

Synthesis and in vitro antiproliferative and antibacterial activity of new thiazolidine-2,4-dione derivatives.

PubMed

Trotsko, Nazar; Przekora, Agata; Zalewska, Justyna; Ginalska, Grażyna; Paneth, Agata; Wujec, Monika

2018-12-01

In our present research, we synthesised new thiazolidine-2,4-diones (12-28). All the newly synthesised compounds were evaluated for antiproliferative and antibacterial activity. Antiproliferative evaluation was carried out using normal human skin fibroblasts and tumour cell lines: A549, HepG2, and MCF-7. The IC 50 values were determined for tested compounds revealing antiproliferative activity. Moreover, safety index (SI) was calculated. Among all tested derivatives, the compound 18 revealed the highest antiproliferative activity against human lung, breast, and liver cancer cells. More importantly, the derivative 18 showed meaningfully lower IC 50 values when compared to the reference substance, irinotecan, and relatively high SI values. Moreover, newly synthesised compounds were screened for the bacteria growth inhibition in vitro. According to our screening results, most active compound was the derivative 18 against Gram-positive bacteria. Therefore, it may be implied that the novel compound 18 appears to be a very promising agent for anticancer treatment.

Adsorption of aromatic compounds from the biodegradation of azo dyes on activated carbon

NASA Astrophysics Data System (ADS)

Faria, P. C. C.; Órfão, J. J. M.; Figueiredo, J. L.; Pereira, M. F. R.

2008-03-01

The adsorption of three selected aromatic compounds (aniline, sulfanilic acid and benzenesulfonic acid) on activated carbons with different surface chemical properties was investigated at different solution pH. A fairly basic commercial activated carbon was modified by means of chemical treatment with HNO 3, yielding an acid activated carbon. The textural properties of this sample were not significantly changed after the oxidation treatment. Equilibrium isotherms of the selected compounds on the mentioned samples were obtained and the results were discussed in relation to their surface chemistry. The influence of electrostatic and dispersive interactions involved in the uptake of the compounds studied was evaluated. The Freundlich model was used to fit the experimental data. Higher uptakes are attained when the compounds are present in their molecular form. In general, adsorption was disfavoured by the introduction of oxygen-containing groups on the surface of the activated carbon.

Synthesis and evaluation of (Z)-2,3-diphenylacrylonitrile analogs as anti-cancer and anti-microbial agents.

PubMed

Alam, Mohammad Sayed; Nam, Young-Joo; Lee, Dong-Ung

2013-11-01

In the present study, a series of (Z)-2,3-diphenylacrylonitrile analogs were synthesized and then evaluated in terms of their cytotoxic activities against four human cancer cell lines, e.g. lung cancer (A549), ovarian cancer (SK-OV-3), skin cancer (SK-MEL-2), and colon cancer (HCT15), as well as anti-microbial activities against three microbes, e.g. Staphylococcus aureus, Salmonella typhi, and Aspergillus niger. The title compounds were synthesized by Knoevenagel condensation reaction of benzyl cyanide or p-nitrobenzyl cyanide with substituted benzaldehydes in good yields. Most of the compounds exhibited significant suppressive activities against the growth of all cancer cell lines. Compound 3c was most active in inhibiting the growth of A549, SK-OV-3, SK-MEL-2, and HCT15 cells lines with IC50 values of 0.57, 0.14, 0.65, and 0.34 mg/mL, respectively, followed by compounds 3f, 3i, and 3h. Compound 3c exhibited 2.4 times greater cytotoxic activity against HCT15 cells, whereas it showed similar potency against SK-OV-3 cells to that of the standard anti-cancer agent doxorubicin. Structure-activity relationship study revealed that electron-donating groups at the para-position of phenyl ring B were more favorable for improved cytotoxic activity, whereas the presence of electron-withdrawing groups was unfavorable compare to unsubstituted acrylonitrile. An optimal electron density on phenyl ring A of (Z)-2,3-diphenylacrylonitrile analogs was crucial for their cytotoxic activities against human cancer cell lines used in the present study. Qualitative structure-cytotoxic activity relationships were studied using physicochemical parameters; a good correlation between calculated polar surface area (PSA), a lipophobic parameter, and cytotoxic activity was found. Moreover, all compounds showed significant anti-bacterial activities against S. typhi, whereas compound 3k showed potent inhibition against both S. aureus and S. typhi bacterial strains. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

A new alkaloid from Portulaca oleracea L. and its antiacetylcholinesterase activity.

PubMed

Xiu, Fen; Li, Xuetao; Zhang, Wenjie; He, Fan; Ying, Xixiang; Stien, Didier

2018-04-18

A new alkaloid, (10E, 12E)-9-ureidooctadeca-10, 12-dienoic acid, named oleraurea (1) and 10 known compounds, p-hydroxybenzaldehyde (2), p-hydroxybenzoic acid (3), p-hydroxyacetophenone (4), benzamide (5), (E)-p-coumaramide (6), (E)-ferulamide (7), soyalkaloid A (8), β-carboline-3-carboxylic acid (9), 2, 3, 4, 9-tetrahydro-1H-pyrido [3, 4-b] indole-3-carboxylic acid (10), (1S, 3S)-1-methyl-1, 2, 3, 4-tetrahydro-β-carboline-3-carboxylic acid (11) were obtained from Portulaca oleracea L., in which, compounds 4, 5, 8-11 were isolated from the plant for the first time. The structure of the compound 1 was identified using spectroscopic methods including 1D and 2D NMR, HR-ESI-TOF-MS. The compounds 1, 5-11 presented anticholinesterase activities, but the P. oleracea extract (POE) presented very low anticholinesterase activity.

Identification and quantification of antifungal compounds produced by lactic acid bacteria and propionibacteria.

PubMed

Le Lay, Céline; Coton, Emmanuel; Le Blay, Gwenaëlle; Chobert, Jean-Marc; Haertlé, Thomas; Choiset, Yvan; Van Long, Nicolas Nguyen; Meslet-Cladière, Laurence; Mounier, Jérôme

2016-12-19

Fungal growth in bakery products represents the most frequent cause of spoilage and leads to economic losses for industrials and consumers. Bacteria, such as lactic acid bacteria and propionibacteria, are commonly known to play an active role in preservation of fermented food, producing a large range of antifungal metabolites. In a previous study (Le Lay et al., 2016), an extensive screening performed both in vitro and in situ allowed for the selection of bacteria exhibiting an antifungal activity. In the present study, active supernatants against Penicillium corylophilum and Aspergillus niger were analyzed to identify and quantify the antifungal compounds associated with the observed activity. Supernatant treatments (pH neutralization, heating and addition of proteinase K) suggested that organic acids played the most important role in the antifungal activity of each tested supernatant. Different methods (HPLC, mass spectrometry, colorimetric and enzymatic assays) were then applied to analyze the supernatants and it was shown that the main antifungal compounds corresponded to lactic, acetic and propionic acids, ethanol and hydrogen peroxide, as well as other compounds present at low levels such as phenyllactic, hydroxyphenyllactic, azelaic and caproic acids. Based on these results, various combinations of the identified compounds were used to evaluate their effect on conidial germination and fungal growth of P. corylophilum and Eurotium repens. Some combinations presented the same activity than the bacterial culture supernatant thus confirming the involvement of the identified molecules in the antifungal activity. The obtained results suggested that acetic acid was mainly responsible for the antifungal activity against P. corylophilum and played an important role in E. repens inhibition. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthesis and blood pressure lowering activity of benzylic ethers of 2-diethylaminoethanol and a related diamine.

PubMed

El-Antably, S M; Soine, T O; Shaath, N A; Gupta, P K

1975-08-01

Based upon the unpublished finding that 3'-hydroxy-4'-(beta-diethylaminoethoxy)-3',4'-dihydroseselin possessed a potent blood pressure lowering effect in the cat at a dose of 1 mg/kg, the present study examined the activities of several related compounds. These compounds were derived by dissection of the parent compound to give four benzylic ethers of 2-diethylaminoethanol and a diamine, derived by replacing the ether oxygen of the parent compound with an N--CH3 function. The simplest compounds were the benzyl and 2,6-dimethoxybenzyl ethers of the aminoalcohol. Closely related to the benzyl compound was a congener with a hydroxymethyl group on the benzylic carbon. The beta-diethylaminoethyl ether of 4-chromanol was the most complex of the ethers. The blood pressure measurements were carried out on male cats and compared to papaverine hydrochloride as a standard. In all cases, the most potent blood pressure lowering activity resided in the parent compound, which was not greatly superior to the diamine but substantially more active than the other compounds.

New compounds from acid hydrolyzed products of the fruits of Momordica charantia L. and their inhibitory activity against protein tyrosine phosphatas 1B.

PubMed

Zeng, Ke; He, Yan-Ni; Yang, Di; Cao, Jia-Qing; Xia, Xi-Chun; Zhang, Shi-Jun; Bi, Xiu-Li; Zhao, Yu-Qing

2014-06-23

Four new cucurbitane-type triterpene sapogenins, compounds 1-4, together with other eight known compounds were isolated from the acid-hydrolyzed fruits extract of Momordica charantia L. Their chemical structures were established by NMR, mass spectrometry and X-ray crystallography. Compounds 1-7 and 9-12 were evaluated for their inhibitory activities toward protein tyrosine phosphatase 1B (PTP1B), a tyrosine phosphatase that has been implicated as a key target for therapy against type II diabetes. Compounds 1, 2, 4, 7 and 9 were shown inhibitory activities of 77%, 62%, 62% 60% and 68% against PTP1B, respectively. All of these tested compounds were exhibited higher PTP1B inhibition activities than that of the Na3VO4, a known PTP1B inhibitor used as positive control in present study. Structure activity relationship (SAR) analysis indicated that the inhibition activity of PTP1B was associated with the presence and number of -OH groups. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Pharmacodynamics of selective androgen receptor modulators.

PubMed

Yin, Donghua; Gao, Wenqing; Kearbey, Jeffrey D; Xu, Huiping; Chung, Kiwon; He, Yali; Marhefka, Craig A; Veverka, Karen A; Miller, Duane D; Dalton, James T

2003-03-01

The present study aimed to identify selective androgen receptor modulators (SARMs) with in vivo pharmacological activity. We examined the in vitro and in vivo pharmacological activity of four chiral, nonsteroidal SARMs synthesized in our laboratories. In the in vitro assays, these compounds demonstrated moderate to high androgen receptor (AR) binding affinity, with K(i) values ranging from 4 to 37 nM, and three of the compounds efficaciously stimulated AR-mediated reporter gene expression. The compounds were then administered subcutaneously to castrated rats to appraise their in vivo pharmacological activity. Androgenic activity was evaluated by the ability of these compounds to maintain the weights of prostate and seminal vesicle, whereas levator ani muscle weight was used as a measure of anabolic activity. The maximal response (E(max)) and dose for half-maximal effect (ED(50)) were determined for each compound and compared with that observed for testosterone propionate (TP). Compounds S-1 and S-4 demonstrated in vivo androgenic and anabolic activity, whereas compounds S-2 and S-3 did not. The activities of S-1 and S-4 were tissue-selective in that both compounds stimulated the anabolic organs more than the androgenic organs. These two compounds were less potent and efficacious than TP in androgenic activity, but their anabolic activity was similar to or greater than that of TP. Neither S-1 nor S-4 caused significant luteinizing hormone or follicle stimulating hormone suppression at doses near the ED(50) value. Thus, compounds S-1 and S-4 were identified as SARMs with potent and tissue-selective in vivo pharmacological activity, and represent the first members of a new class of SARMs with selective anabolic effects.

Profiling polyphenol composition by HPLC-DAD-ESI/MSn and the antibacterial activity of infusion preparations obtained from four medicinal plants.

PubMed

Ziani, Borhane E C; Barros, Lillian; Boumehira, Ali Z; Bachari, Khaldoun; Heleno, Sandrina A; Alves, Maria Jose; Ferreira, Isabel C F R

2018-01-24

The infusions of Thymus pallescens Noë, Saccocalyx satureioides Coss. et Dur., Ptychotis verticillata Briq. and Limoniastrum guyonianum Boiss. have been used as medicinal remedies for many diseases in Algerian folk medicine. These species have also been well documented as rich sources of phytochemicals, such as phenolic compounds with wide diversified chemical structures, which exhibit far-ranging biological activities. Thus, the phenolic compound profile of the aqueous extracts, obtained by infusing, of the mentioned species was obtained by HPLC-DAD-ESI/MS, and their antibacterial activity was evaluated against clinical isolates. Several phenolic acids were identified and quantified, particularly caffeic acid derivatives along with glycosylated flavonoids. T. pallescens and S. satureioides contain 13 phenolic compounds, where rosmarinic acid was the most abundant phenolic acid present, while L. guyonianum presented myricetin-3-O-glucoside and myricetin-O-rhamnoside as the main compounds among the eight detected molecules. P. verticillata presented a profile of ten phenolic compounds, where 5-O-caffeoylquinic acid was the most abundant phenolic acid, followed by the flavone luteolin-3-O-glucoside. The antibacterial activity of the infusions ranged between 2.5 and 20 mg mL -1 (MIC values), and L. guyonianum showed the highest activity against all of the tested bacteria, Staphylococcus aureus and Pseudomonas aeruginosa being the most sensitive and resistant strains, respectively. Thus, the studied plant species are sources of natural antibacterial substances that can be used to fight against pathogenic microorganisms.

Different phenolic compounds activate distinct human bitter taste receptors.

PubMed

Soares, Susana; Kohl, Susann; Thalmann, Sophie; Mateus, Nuno; Meyerhof, Wolfgang; De Freitas, Victor

2013-02-20

Bitterness is a major sensory attribute of several common foods and beverages rich in polyphenol compounds. These compounds are reported as very important for health as chemopreventive compounds, but they are also known to taste bitter. In this work, the activation of the human bitter taste receptors, TAS2Rs, by six polyphenol compounds was analyzed. The compounds chosen are present in a wide range of plant-derived foods and beverages, namely, red wine, beer, tea, and chocolate. Pentagalloylglucose (PGG) is a hydrolyzable tannin, (-)-epicatechin is a precursor of condensed tannins, procyanidin dimer B3 and trimer C2 belong to the condensed tannins, and malvidin-3-glucoside and cyanidin-3-glucoside are anthocyanins. The results show that the different compounds activate different combinations of the ~25 TAS2Rs. (-)-Epicatechin activated three receptors, TAS2R4, TAS2R5, and TAS2R39, whereas only two receptors, TAS2R5 and TAS2R39, responded to PGG. In contrast, malvidin-3-glucoside and procyanidin trimer stimulated only one receptor, TAS2R7 and TAS2R5, respectively. Notably, tannins are the first natural agonists found for TAS2R5 that display high potency only toward this receptor. The catechol and/or galloyl groups appear to be important structural determinants that mediate the interaction of these polyphenolic compounds with TAS2R5. Overall, the EC(50) values obtained for the different compounds vary 100-fold, with the lowest values for PGG and malvidin-3-glucoside compounds, suggesting that they could be significant polyphenols responsible for the bitterness of fruits, vegetables, and derived products even if they are present in very low concentrations.

Pharmacological Potential of Sea Cucumbers

PubMed Central

Khotimchenko, Yuri

2018-01-01

This review presents a detailed analysis of published research data focused on the pharmacological activity exerted by biologically active compounds isolated from sea cucumbers belonging to the class of Holothuroidea, phylum Echinodermata. The review contains descriptions of the structure, physico-chemical properties and pharmacological effects of these active substances. Particular attention is given to compounds with anticoagulant, antithrombotic, antioxidant, anticancer, anti-infectious, immune-stimulating and anti-ACE (angiotensin converting enzyme) activities as well as to the substances exerting a regulating influence on lipid and carbohydrate metabolism. All these compounds may be considered as prototypes for development of new pharmaceutical substances and medicines. PMID:29724051

Microscopic Analysis of Activated Sludge. Training Manual.

ERIC Educational Resources Information Center

Office of Water Program Operations (EPA), Cincinnati, OH. National Training and Operational Technology Center.

This training manual presents material on the use of a compound microscope to analyze microscope communities, present in wastewater treatment processes, for operational control. Course topics include: sampling techniques, sample handling, laboratory analysis, identification of organisms, data interpretation, and use of the compound microscope.…

Drugs as habitable planets in the space of dark chemical matter.

PubMed

Siramshetty, Vishal B; Preissner, Robert

2018-03-01

A recent study demonstrated antifungal activity of dark chemical matter (DCM) compounds that were otherwise inactive in more than 100 HTS assays. These compounds were proposed to possess unique activity and 'clean' safety profiles. Here, we present an outlook of the promiscuity and safety of these compounds by retrospectively comparing their chemical and biological spaces with those of drugs. Significant amounts of marketed drugs (16%), withdrawn drugs (16.5%) and natural compounds (3.5%) share structural identity with DCM. Compound promiscuity assessment indicates that dark matter compounds could potentially interact with multiple biological targets. Further, thousands of DCM compounds showed presence of frequent-hitting pan-assay interference compound (PAINS) substructures. In light of these observations, filtering these compounds from screening libraries can be an irrevocable loss. Copyright © 2017 Elsevier Ltd. All rights reserved.

Organic Compounds Complexify Transport in the Amargosa Desert—The Case for Phytotritiation

NASA Astrophysics Data System (ADS)

Stonestrom, D. A.; Luo, W.; Andraski, B. J.; Baker, R. J.; Maples, S.; Mayers, C. J.; Young, M. B.

2014-12-01

Civilian low-level radioactive waste containing organic compounds was disposed in 2- to 15-m deep unlined trenches in a 110-m deep unsaturated zone at the present-day USGS Amargosa Desert Research Site. Tritium represents the plurality of disposed activity. A plume of gas-phase contaminants surrounds the disposal area, with 60 distinct volatile organic compounds (VOCs) identified to date. The distribution of tritiated water in the unsaturated zone surrounding the disposal area is highly enigmatic, with orders of magnitude separating observed levels from those predicted by multiphase models of mass and energy transport. Peaks of tritium and VOCs are coincidently located in sediments tens of meters below the root zone, suggesting abiotic stratigraphic control on lateral transport at depth. Surprisingly, the highest observed levels of tritium occur at a depth of about 1.5 m, the base of the creosote-bush plant-community root zone, where levels of waste-derived VOCs are low (approaching atmospheric levels). Bulk water-vapor samples from shallow and deep unsaturated-zone profile hot spots were trapped as water ice in cold fingers immersed in dry ice-isopropyl alcohol filled Dewar flasks, then melted and sequentially extracted by purge-and-trap VOC degassing followed by elution through activated carbon solid-phase extraction (SPE) cartridges. Analysis of tritium activities and mass spectrometer results indicate that over 98% of tritium activity at depth is present as water, whereas about 15% of basal root zone tritium activity is present as organic compounds trapped with the water. Of these, the less-volatile compound group removed by SPE accounted for about 85% of the organic tritium activity, with mass spectrometry identifying 2-ethyl-1-hexanol as the principal compound removed. This plant-produced fatty alcohol is ubiquitous in the root zone of creosote-bush communities and represents a family of hydroxyl-containing plant produced compounds that give the plants their pungency. These findings suggest that tritiated hydroxyl groups on plant-produced organic compounds provide an important reservoir and pathway for tritium transport.

Dark and Photoinduced Cytotoxic Activity of the New Chlorophyll-a Derivatives with Oligoethylene Glycol Substituents on the Periphery of Their Macrocycles.

PubMed

Pylina, Yana I; Shadrin, Dmitry M; Shevchenko, Oksana G; Startseva, Olga M; Velegzhaninov, Igor O; Belykh, Dmitry V; Velegzhaninov, Ilya O

2017-01-05

In the present work, we investigated the dark and photoinduced cytotoxic activity of the new chlorophyll-a derivatives which contain the substituents of oligoethylene glycol on the periphery of their macrocycles. These compounds were tested using human cell lines to estimate their potential as photosensitizers for photodynamic therapy of cancer. It was shown that all the tested compounds have expressed photoinduced cytotoxic activity in vitro. Detailed study of the biological activity of one of the most perspective compound in this series-pyropheophorbide-a 17-diethylene glycol ester (Compound 21 ) was performed. This new compound is characterized by lower dark cytotoxicity and higher photoinduced cytotoxicity than previously described in a similar compound (DH-I-180-3) and clinically used Photolon TM . Using fluorescent microscopy, it was shown that Compound 21 quickly penetrates the cells. Analysis of caspase-3 activity indicated an apoptosis induction 40 min after exposure to red light (λ = 660 nm). The induction of DNA damages and apoptosis was shown using Comet assay. The results of expression analysis of the stress-response genes indicate an activation of the genes which control the cell cycle and detoxification of the free radicals after an exposure of HeLa cells to Compound 21 and to red light. High photodynamic activity of this compound and the ability to oxidize biomolecules was demonstrated on nuclear-free mice erythrocytes. In addition, it was shown that Compound 21 is effectively activated with low energy 700 nm light, which can penetrate deep into the tissue. Thus, Compound 21 is a prospective substance for development of the new drugs for photodynamic therapy of cancer.

In vitro inhibition of Plasmodium falciparum by substances isolated from Amazonian antimalarial plants.

PubMed

de Andrade-Neto, Valter F; Pohlit, Adrian M; Pinto, Ana Cristina S; Silva, Ellen Cristina C; Nogueira, Karla L; Melo, Márcia R S; Henrique, Marycleuma C; Amorim, Rodrigo C N; Silva, Luis Francisco R; Costa, Mônica R F; Nunomura, Rita C S; Nunomura, Sergio M; Alecrim, Wilson D; Alecrim, M das Graças C; Chaves, F Célio M; Vieira, Pedro Paulo R

2007-06-01

In the present study, a quassinoid, neosergeolide, isolated from the roots and stems of Picrolemma sprucei (Simaroubaceae), the indole alkaloids ellipticine and aspidocarpine, isolated from the bark of Aspidosperma vargasii and A. desmanthum (Apocynaceae), respectively, and 4-nerolidylcatechol, isolated from the roots of Pothomorphe peltata (Piperaceae), all presented significant in vitro inhibition (more active than quinine and chloroquine) of the multi-drug resistant K1 strain of Plasmodium falciparum. Neosergeolide presented activity in the nanomolar range. This is the first report on the antimalarial activity of these known, natural compounds. This is also the first report on the isolation of aspidocarpine from A. desmanthum. These compounds are good candidates for pre-clinical tests as novel lead structures with the aim of finding new antimalarial prototypes and lend support to the traditional use of the plants from which these compounds are derived.

Synthesis, structure-activity relationship and molecular docking of cyclohexenone based analogous as potent non-nucleoside reverse-transcriptase inhibitors

NASA Astrophysics Data System (ADS)

Nazar, Muhammad Faizan; Abdullah, Muhammad Imran; Badshah, Amir; Mahmood, Asif; Rana, Usman Ali; Khan, Salah Ud-Din

2015-04-01

The chalcones core in compounds is advantageously chosen effective synthons, which offer exciting perspectives in biological and pharmacological research. The present study reports the successful development of eight new cyclohexenone based anti-reverse transcriptase analogous using rational drug design synthesis principles. These new cyclohexenone derivatives (CDs) were synthesized by following a convenient route of Robinson annulation, and the molecular structure of these CDs were later confirmed by various analytical techniques such as 1H NMR, 13C NMR, FT-IR, UV-Vis spectroscopy and mass spectrometry. All the synthesized compounds were screened theoretically and experimentally against reverse transcriptase (RT) and found potentially active reverse transcriptase (RT) inhibitors. Of the compounds studied, the compound 2FC4 showed high interaction with RT at non-nucleoside binding site, contributing high free binding energy (ΔG -8.01 Kcal) and IC50 (0.207 μg/ml), respectively. Further results revealed that the compounds bearing more halogen groups, with additional hydrophobic character, offered superior anti-reverse transcriptase activity as compared to rest of compounds. It is anticipate that the present study would be very useful for the selection of potential reverse transcriptase inhibitors featuring inclusive pharmacological profiles.

Flavor characteristics of seven grades of black tea produced in Turkey.

PubMed

Alasalvar, Cesarettin; Topal, Bahar; Serpen, Arda; Bahar, Banu; Pelvan, Ebru; Gökmen, Vural

2012-06-27

Seven grades of black tea [high-quality black tea (grades 1-3) and low-quality black tea (grades 4-7)], processed by ÇAYKUR Tea Processing Plant (Rize, Turkey), were compared for their differences in descriptive sensory analysis (DSA), aroma-active compounds (volatile compounds), and taste-active compounds (sugar, organic acid, and free amino acid compositions). Ten flavor attributes such as 'after taste', 'astringency', 'bitter', 'caramel-like', 'floral/sweet', 'green/grassy', 'hay-like', 'malty', 'roasty', and 'seaweed' were identified. Intensities for a number of flavor attributes ('after taste', 'caramel-like', 'malty', and 'seaweed') were not significantly different (p > 0.05) among seven grades of black tea. A total of 57 compounds in seven grades of black tea (14 aldehydes, eight alcohols, eight ketones, two esters, four aromatic hydrocarbons, five aliphatic hydrocarbons, nine terpenes, two pyrazines, one furan, two acids, and two miscellaneous compounds) were tentatively identified. Of these, aldeyhdes comprised more than 50% to the total volatile compounds identified. In general, high-grade quality tea had more volatiles than low-grade quality tea. With respect to taste-active compounds, five sugars, six organic acids, and 18 free amino acids were positively identified in seven grades of black tea, of which fructose, tannic acid, and theanine predominated, respectively. Some variations (p < 0.05), albeit to different extents, were observed among volatile compounds, sugars, organic acids, and free amino acids in seven grades of black tea. The present study suggests that a certain flavor attributes correlate well with taste- and aroma-active compounds. High- and low-quality black teas should not be distinguished solely on the basis of their DSA and taste- and aroma-active compounds. The combination of taste-active compounds together with aroma-active compounds renders combination effects that provide the characteristic flavor of each grade of black tea.

Cytotoxic, Cytostatic and HIV-1 PR Inhibitory Activities of the Soft Coral Litophyton arboreum

PubMed Central

Ellithey, Mona S.; Lall, Namrita; Hussein, Ahmed A.; Meyer, Debra

2013-01-01

Bioassay-guided fractionation using different chromatographic and spectroscopic techniques in the analysis of the Red Sea soft coral Litophyton arboreum led to the isolation of nine compounds; sarcophytol M (1), alismol (2), 24-methylcholesta-5,24(28)-diene-3β-ol (3), 10-O-methyl alismoxide (4), alismoxide (5), (S)-chimyl alcohol (6), 7β-acetoxy-24-methylcholesta-5-24(28)-diene-3,19-diol (7), erythro-N-dodecanoyl-docosasphinga-(4E,8E)-dienine (8), and 24-methylcholesta-5,24(28)-diene-3β,7β,19-triol (9). Some of the isolated compounds demonstrated potent cytotoxic- and/or cytostatic activity against HeLa and U937 cancer cell lines and inhibitory activity against HIV-1 protease (PR). Compound 7 was strongly cytotoxic against HeLa cells (CC50 4.3 ± 0.75 µM), with selectivity index of SI 8.1, which was confirmed by real time cell electronic sensing (RT-CES). Compounds 2, 7, and 8 showed strong inhibitory activity against HIV-1 PR at IC50s of 7.20 ± 0.7, 4.85 ± 0.18, and 4.80 ± 0.92 µM respectively. In silico docking of most compounds presented comparable scores to that of acetyl pepstatin, a known HIV-1 PR inhibitor. Interestingly, compound 8 showed potent HIV-1 PR inhibitory activity in the absence of cytotoxicity against the cell lines used. In addition, compounds 2 and 5 demonstrated cytostatic action in HeLa cells, revealing potential use in virostatic cocktails. Taken together, data presented here suggest Litophyton arboreum to contain promising compounds for further investigation against the diseases mentioned. PMID:24336129

[Stability of physical state on compound hawthorn dropping pills].

PubMed

Zhang, Wei; Chen, Hong-Yan; Jiang, Jian-Lan

2008-11-01

To evaluate the stability of physical state with accelerate test and dropping in process before and after on compound hawthorn dropping pills. Scanning electron microscope, TG-DTA, FT-IR and XRD were used. The active components presented amorphous, tiny crystal and molecular state in dropping pills, and it had no obvious reaction between PEG 4000 and active components. With time prolonging, a little of active components changed from amorphous state to tiny crystal or molecular state. Solid dispersion improved the stability and dissolution of compound hawthorn dropping pills.

Comparative study on the larvicidal activity of drimane sesquiterpenes and nordrimane compounds against Drosophila melanogaster til-til.

PubMed

Montenegro, Ivan; Pino, Luis; Werner, Enrique; Madrid, Alejandro; Espinoza, Luis; Moreno, Luis; Villena, Joan; Cuellar, Mauricio

2013-04-10

Natural compounds from Drimys winteri Forst and derivatives exhibited larvicidal effects against Drosophila melanogaster til-til. The most active compound was isodrimenin (4). The highest lethal concentration to the larvae of D. melanogaster was 4.5 ± 0.8 mg/L. At very low concentrations drimenol (1), confertifolin (3), and drimanol (5) displayed antifeedant and larvae growth regulatory activity. The antifeedant results of nordrimanic and drimanic compounds were better in first instar larvae. The EC₅₀ value of polygodial (2) was 60.0 ± 4.2 mg/L; of diol 15 45.0 ± 2.8 mg/L, and of diol 17 36.9 ± 3.7 mg/L, while the new nordrimane compound 12 presented a value of 83.2 ± 3.5 mg/L.

Antibacterial Potential of Northeastern Portugal Wild Plant Extracts and Respective Phenolic Compounds

PubMed Central

Ferreira, Isabel C. F. R.; Barros, Lillian; Carvalho, Ana Maria; Soares, Graça; Henriques, Mariana

2014-01-01

The present work aims to assess the antibacterial potential of phenolic extracts, recovered from plants obtained on the North East of Portugal, and of their phenolic compounds (ellagic, caffeic, and gallic acids, quercetin, kaempferol, and rutin), against bacteria commonly found on skin infections. The disk diffusion and the susceptibility assays were used to identify the most active extracts and phenolic compounds. The effect of selected phenolic compounds on animal cells was assessed by determination of cellular metabolic activity. Gallic acid had a higher activity, against gram-positive (S. epidermidis and S. aureus) and gram-negative bacteria (K. pneumoniae) at lower concentrations, than the other compounds. The caffeic acid, also, showed good antibacterial activity against the 3 bacteria used. The gallic acid was effective against the 3 bacteria without causing harm to the animal cells. Gallic and caffeic acid showed a promising applicability as antibacterial agents for the treatment of infected wounds. PMID:24804249

Bilingual Reading of Compound Words

ERIC Educational Resources Information Center

Ko, In Yeong; Wang, Min; Kim, Say Young

2011-01-01

The present study investigated whether bilingual readers activate constituents of compound words in one language while processing compound words in the other language via decomposition. Two experiments using a lexical decision task were conducted with adult Korean-English bilingual readers. In Experiment 1, the lexical decision of real English…

Antitrypanosomal and antioxidant properties of 4-hydroxycoumarins derivatives.

PubMed

Pérez-Cruz, Fernanda; Serra, Silvia; Delogu, Giovanna; Lapier, Michel; Maya, Juan Diego; Olea-Azar, Claudio; Santana, Lourdes; Uriarte, Eugenio

2012-09-01

In the present communication we prepared a series of six 4-hydroxycoumarin derivatives, isosters of quercetin, recognized as an antioxidant natural compound, with the aim of evaluating the antitrypanosomal activity against Trypanosoma cruzi, the parasite responsible for Chagas disease, and the antioxidant properties. We have used the 4-hydroxycoumarin moiety (compound 1) as the molecular template for the synthesis of compounds 2-7. These derivates have shown moderate trypanocidal activity. However they have been proved to be good antioxidants. In particular compound 7 is the most active antioxidant and it is, therefore, a potential candidate for a successful employment in conditions characterized by free radicals overproduction. Copyright © 2012 Elsevier Ltd. All rights reserved.

Compound annotation with real time cellular activity profiles to improve drug discovery.

PubMed

Fang, Ye

2016-01-01

In the past decade, a range of innovative strategies have been developed to improve the productivity of pharmaceutical research and development. In particular, compound annotation, combined with informatics, has provided unprecedented opportunities for drug discovery. In this review, a literature search from 2000 to 2015 was conducted to provide an overview of the compound annotation approaches currently used in drug discovery. Based on this, a framework related to a compound annotation approach using real-time cellular activity profiles for probe, drug, and biology discovery is proposed. Compound annotation with chemical structure, drug-like properties, bioactivities, genome-wide effects, clinical phenotypes, and textural abstracts has received significant attention in early drug discovery. However, these annotations are mostly associated with endpoint results. Advances in assay techniques have made it possible to obtain real-time cellular activity profiles of drug molecules under different phenotypes, so it is possible to generate compound annotation with real-time cellular activity profiles. Combining compound annotation with informatics, such as similarity analysis, presents a good opportunity to improve the rate of discovery of novel drugs and probes, and enhance our understanding of the underlying biology.

Structure-In Vitro Activity Relationships of Pentamidine Analogues and Dication-Substituted Bis-Benzimidazoles as New Antifungal Agents

PubMed Central

Del Poeta, Maurizio; Schell, Wiley A.; Dykstra, Christine C.; Jones, Susan; Tidwell, Richard R.; Czarny, Agnieszka; Bajic, Miroslav; Bajic, Marina; Kumar, Arvind; Boykin, David; Perfect, John R.

1998-01-01

Twenty analogues of pentamidine, 7 primary metabolites of pentamidine, and 30 dicationic substituted bis-benzimidazoles were screened for their inhibitory and fungicidal activities against Candida albicans and Cryptococcus neoformans. A majority of the compounds had MICs at which 80% of the strains were inhibited (MIC80s) comparable to those of amphotericin B and fluconazole. Unlike fluconazole, many of these compounds were found to have potent fungicidal activity. The most potent compound against C. albicans had an MIC80 of ≤0.09 μg/ml, and the most potent compound against C. neoformans had an MIC80 of 0.19 μg/ml. Selected compounds were also found to be active against Aspergillus fumigatus, Fusarium solani, Candida species other than C. albicans, and fluconazole-resistant strains of C. albicans and C. neoformans. It is clear from the data presented here that further studies on the structure-activity relationships, mechanisms of action and toxicities, and in vivo efficacies of these compounds are warranted to determine their clinical potential. PMID:9756747

Isolation and Identification of Algicidal Compound from Streptomyces and Algicidal Mechanism to Microcystis aeruginosa

PubMed Central

Luo, Jianfei; Wang, Yuan; Tang, Shuishui; Liang, Jianwen; Lin, Weitie; Luo, Lixin

2013-01-01

The biological control of cyanobacterial harmful algal blooms (cyanoHABs) is important to promote human health, environmental protection, and economic growth. Active algicidal compounds and algicidal mechanisms should be identified and investigated to control cyanoHABs. In this study, the algicidal actinobacterium Streptomyces sp. L74 was isolated from the soil of a nearby pond which located in the center lake of Guanghzou Higher Education Mega Center. Results showed that the algicidal activities of cyanoHABs are mainly achieved via an indirect attack by producing algicidal compounds. All active algicidal compounds are hydrophilic substances that are heat and pH stable. In the present study, an active compound (B3) was isolated and purified by high-performance liquid chromatography and identified as a type of triterpenoid saponin (2-hydroxy-12-oleanene-3, 28-O-D-glucopyranosyl) with a molecular formula of C42H70O13 as determined by infrared spectrometry, electrospray ionization mass spectrometry, and nuclear magnetic resonance. Active algicidal compounds from Streptomyces sp. L74 were shown to disrupt the antioxidant systems of Microcystis aeruginosa cells. PMID:24098501

Isolation and identification of algicidal compound from Streptomyces and algicidal mechanism to Microcystis aeruginosa.

PubMed

Luo, Jianfei; Wang, Yuan; Tang, Shuishui; Liang, Jianwen; Lin, Weitie; Luo, Lixin

2013-01-01

The biological control of cyanobacterial harmful algal blooms (cyanoHABs) is important to promote human health, environmental protection, and economic growth. Active algicidal compounds and algicidal mechanisms should be identified and investigated to control cyanoHABs. In this study, the algicidal actinobacterium Streptomyces sp. L74 was isolated from the soil of a nearby pond which located in the center lake of Guanghzou Higher Education Mega Center. Results showed that the algicidal activities of cyanoHABs are mainly achieved via an indirect attack by producing algicidal compounds. All active algicidal compounds are hydrophilic substances that are heat and pH stable. In the present study, an active compound (B3) was isolated and purified by high-performance liquid chromatography and identified as a type of triterpenoid saponin (2-hydroxy-12-oleanene-3, 28-O-D-glucopyranosyl) with a molecular formula of C42H70O13 as determined by infrared spectrometry, electrospray ionization mass spectrometry, and nuclear magnetic resonance. Active algicidal compounds from Streptomyces sp. L74 were shown to disrupt the antioxidant systems of Microcystis aeruginosa cells.

Target Fishing for Chemical Compounds using Target-Ligand Activity data and Ranking based Methods

PubMed Central

Wale, Nikil; Karypis, George

2009-01-01

In recent years the development of computational techniques that identify all the likely targets for a given chemical compound, also termed as the problem of Target Fishing, has been an active area of research. Identification of likely targets of a chemical compound helps to understand problems such as toxicity, lack of efficacy in humans, and poor physical properties associated with that compound in the early stages of drug discovery. In this paper we present a set of techniques whose goal is to rank or prioritize targets in the context of a given chemical compound such that most targets that this compound may show activity against appear higher in the ranked list. These methods are based on our extensions to the SVM and Ranking Perceptron algorithms for this problem. Our extensive experimental study shows that the methods developed in this work outperform previous approaches by 2% to 60% under different evaluation criterions. PMID:19764745

Bilingual reading of compound words.

PubMed

Ko, In Yeong; Wang, Min; Kim, Say Young

2011-02-01

The present study investigated whether bilingual readers activate constituents of compound words in one language while processing compound words in the other language via decomposition. Two experiments using a lexical decision task were conducted with adult Korean-English bilingual readers. In Experiment 1, the lexical decision of real English compound words was more accurate when the translated compounds (the combination of the translation equivalents of the constituents) in Korean (the nontarget language) were real words than when they were nonwords. In Experiment 2, when the frequency of the second constituents of compound words in English (the target language) was manipulated, the effect of lexical status of the translated compounds was greater on the compounds with high-frequency second constituents than on those with low-frequency second constituents in the target language. Together, these results provided evidence for morphological decomposition and cross-language activation in bilingual reading of compound words.

Key structural features of nonsteroidal ligands for binding and activation of the androgen receptor.

PubMed

Yin, Donghua; He, Yali; Perera, Minoli A; Hong, Seoung Soo; Marhefka, Craig; Stourman, Nina; Kirkovsky, Leonid; Miller, Duane D; Dalton, James T

2003-01-01

The purposes of the present studies were to examine the androgen receptor (AR) binding ability and in vitro functional activity of multiple series of nonsteroidal compounds derived from known antiandrogen pharmacophores and to investigate the structure-activity relationships (SARs) of these nonsteroidal compounds. The AR binding properties of sixty-five nonsteroidal compounds were assessed by a radioligand competitive binding assay with the use of cytosolic AR prepared from rat prostates. The AR agonist and antagonist activities of high-affinity ligands were determined by the ability of the ligand to regulate AR-mediated transcriptional activation in cultured CV-1 cells, using a cotransfection assay. Nonsteroidal compounds with diverse structural features demonstrated a wide range of binding affinity for the AR. Ten compounds, mainly from the bicalutamide-related series, showed a binding affinity superior to the structural pharmacophore from which they were derived. Several SARs regarding nonsteroidal AR binding were revealed from the binding data, including stereoisomeric conformation, steric effect, and electronic effect. The functional activity of high-affinity ligands ranged from antagonist to full agonist for the AR. Several structural features were found to be determinative of agonist and antagonist activities. The nonsteroidal AR agonists identified from the present studies provided a pool of candidates for further development of selective androgen receptor modulators (SARMs) for androgen therapy. Also, these studies uncovered or confirmed numerous important SARs governing AR binding and functional properties by nonsteroidal molecules, which would be valuable in the future structural optimization of SARMs.

Exploring reserve lots of Cymbopogon citratus, Aloysia citrodora and Thymus × citriodorus as improved sources of phenolic compounds.

PubMed

Rita, Ingride; Pereira, Carla; Barros, Lillian; Ferreira, Isabel C F R

2018-08-15

Given the increasing consumers demand for novelty, tea companies have been presenting new added value products such as reserve lots of aromatic plants. Herein, infusions from different lots of three aromatic plants were assessed in terms of phenolic composition (HPLC-DAD-ESI/MS) and antioxidant properties (reducing power, free radical scavenging and lipid peroxidation inhibition capacity). Cymbopogon citratus (C. citratus; main compound 5-O-caffeoylquinic acid) and Aloysia citrodora (A. citrodora; prevalence of verbascoside) reserve lots revealed higher phenolic compounds concentration than the respective standard lots. Thymus × citriodorus (T. citriodorus; main compound rosmarinic acid) standard lot presented higher amounts of phenolic acids than the reserve lot, nonetheless, total flavonoids and phenolic compounds were not significantly different. The differences between both lots antioxidant activity were more noticeable in C. citratus, with the reserve lot presenting the highest activity. This study provides evidence of the differences between these plants chemical composition and bioactivity depending on the harvesting conditions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Synthesis, spectroscopic characterization, DFT study and antimicrobial activity of novel alkylaminopyrazole derivatives

NASA Astrophysics Data System (ADS)

Zalaru, Christina; Dumitrascu, Florea; Draghici, Constantin; Tarcomnicu, Isabela; Tatia, Rodica; Moldovan, Lucia; Chifiriuc, Mariana-Carmen; Lazar, Veronica; Marinescu, Maria; Nitulescu, Mihai George; Ferbinteanu, Marilena

2018-03-01

A new series of substituted N,N-bis-[(1H-pyrazol-1-yl)methyl]-aminohexadecane Mannich bases were synthesized, characterized by IR, 1H NMR 13C NMR, UV-Vis, MS and elemental analysis, and tested for their biological activity. All the synthesized compounds were tested for in vitro antimicrobial activity against a panel of selected bacterial and fungal strains using erythromycin and clotrimazole as standards. Most of the synthesized compounds demonstrated very good activity at minimum inhibitory concentrations (MICs). Compound 3b with an halogen atom into the pharmacophore structure exhibited the most significant activity against Bacillus subtilis (MIC = 0.007 μgmLL-1) versus erythromycin as standard. In vitro cytotoxicity of the new compounds was studied using MTT assay. The analysis of the test cells showed that the newly synthesized alkylaminopyrazoles derivatives were biocompatible until a concentration of 5 μgmL-1; two compounds presented a high degree of biocompatibility on the studied concentration range.

Antiosteoporotic compounds from seeds of Cuscuta chinensis.

PubMed

Yang, Lijuan; Chen, Qianfeng; Wang, Fei; Zhang, Guolin

2011-05-17

The seeds of Cuscuta chinensis (Tu-Si-Zi, TSZ) have long been used for the treatment of osteoporosis in China and some Asian countries. The compounds in TSZ responsible for the antiosteoporotic activity are still poorly understood. The present study was designed to investigate the osteogenic compounds in TSZ, and to evaluate their antiosteoporotic effects in osteoblastic cells. Osteoblast-like UMR-106 cells were used for bioactivity-guided isolation of the active compounds. The activity of alkaline phosphatase (ALP) in UMR-106 cells was measured by p-nitrophenyl sodium phosphate assay. The proliferation of UMR-106 cells was assayed by Alamar-Blue method. Estrogenic activity of the extracts and isolated compounds was evaluated by activation of estrogen response element (ERE) luciferase reporter expression in HeLa cells co-transfected with human estrogen receptor subtypes (ERα or ERβ) expression vectors and 5×ERE luciferase reporter plasmid. Antiestrogenic activity of the extracts and isolated compounds were evaluated by activation of activator protein-1 (AP-1) luciferase reporter expression in HeLa cells co-transfected with human estrogen receptor subtypes (ERα or ERβ) expression vectors and 6×AP-1 luciferase reporter plasmid. ALP-guided fractionation led to the isolation of five known flavonoids, quercetin, kaempferol, isorhamnetin, hyperoside and astragalin from the crude ethanolic extract of TSZ. Further study showed that kaempferol and hyperoside significantly increased the ALP activity in UMR-106 cells. Astragalin promoted the proliferation of UMR-106 cells whereas other compounds had no such effect. The isolated compounds showed estrogenic activity but quercetin, kaempferol and isorhamnetin showed more potent ERβ agonist activity. However, compared with their ER agonist activity, only quercetin and kaempferol showed potent ER antagonist activity by activating ERα/β-mediated AP-1 reporter expression. Our findings validated the clinical use of TSZ in the treatment of osteoporosis, and demonstrated that kaempferol and hyperoside are the active compounds in TSZ for the osteogenic effect. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Effects of dietary lead acetate on hepatic detoxication enzyme activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wagstaff, D.J.

1979-12-01

Lead-containing compounds usually inhibit enzymic and metabolic processes. This inhibition is presumed to be the mechanism of intoxication by these compounds. Inhibition of detoxication activities of liver microsomal enzymes could be particularly detrimental because the toxicity of many different substances would be increased. Exposure of experimental animals to lead compounds in several studies has been associated with depressed activity of hepatic microsomal enzymes, reduced levels of hepatic cytochrome P-450, reduced levels of hepatic microsomal protein, and prolonged hexobarbital sleep times. The present report contains observations that under certain experimental conditions there is stimulated hepatic meicrosomal enzyme activity in rats fedmore » lead acetate.« less

Synthesis and pharmacological evaluation of polyfunctional benzimidazole-NSAID chimeric molecules combining anti-inflammatory, immunomodulatory and antioxidant activities.

PubMed

Bansal, Yogita; Silakari, Om

2014-11-01

Polyfunctional compounds comprise a novel class of therapeutic agents for treatment of multifactorial diseases. The present study reports a series of benzimidazole-non-steroidal anti-inflammatory drugs (NSAIDs) conjugates (1-10) as novel polyfunctional compounds synthesized in the presence of orthophosphoric acid. The compounds were evaluated for anti-inflammatory (carageenan-induced paw edema model), immunomodulatory (direct haemagglutination test and carbon clearance index models), antioxidant (in vitro and in vivo) and for ulcerogenic effects. Each of the compound has retained the anti-inflammatory activity of the corresponding parent NSAID while exhibiting significantly reduced gastric ulcers. Additionally, the compounds are found to possess potent immunostimulatory and antioxidant activities. The compound 8 was maximally potent (antibody titre value 358.4 ± 140.21, carbon clearance index 0.053 ± 0.002 and antioxidant EC50 value 0.03 ± 0.006). These compounds, exhibiting such multiple pharmacological activities, can be taken as lead for the development of potent drugs for the treatment of chronic multifactorial diseases involving inflammation, immune system modulation and oxidative stress such as cancers. The Lipinski's parameters suggested the compounds to be bear drug like properties.

In vitro assessment of the growth and plasma membrane H+ -ATPase inhibitory activity of ebselen and structurally related selenium- and sulfur-containing compounds in Candida albicans.

PubMed

Orie, Natalie N; Warren, Andrew R; Basaric, Jovana; Lau-Cam, Cesar; Piętka-Ottlik, Magdalena; Młochowski, Jacek; Billack, Blase

2017-06-01

Ebselen (EB, compound 1) is an investigational organoselenium compound that reduces fungal growth, in part, through inhibition of the fungal plasma membrane H + -ATPase (Pma1p). In the present study, the growth inhibitory activity of EB and of five structural analogs was assessed in a fluconazole (FLU)-resistant strain of Candida albicans (S2). While none of the compounds were more effective than EB at inhibiting fungal growth (IC 50  ∼ 18 μM), two compounds, compounds 5 and 6, were similar in potency. Medium acidification assays performed with S2 yeast cells revealed that compounds 4 and 6, but not compounds 2, 3, or 5, exerted an inhibitory activity comparable to EB (IC 50  ∼ 14 μM). Using a partially purified Pma1p preparation obtained from S2 yeast cells, EB and all the analogs demonstrated a similar inhibitory activity. Taken together, these results indicate that EB analogs are worth exploring further for use as growth inhibitors of FLU-resistant fungi. © 2017 Wiley Periodicals, Inc.

Synthesis, SAR and molecular docking studies of benzo[d]thiazole-hydrazones as potential antibacterial and antifungal agents.

PubMed

Zha, Gao-Feng; Leng, Jing; Darshini, N; Shubhavathi, T; Vivek, H K; Asiri, Abdullah M; Marwani, Hadi M; Rakesh, K P; Mallesha, N; Qin, Hua-Li

2017-07-15

A series of new benzo[d]thiazole-hydrazones analogues were synthesized and screened for their in vitro antibacterial and antifungal activities. The results revealed that compounds 13, 14, 15, 19, 20, 28 and 30 exhibited superior antibacterial potency compared to the reference drug chloramphenicol and rifampicin. Compounds 5, 9, 10, 11, 12, 28 and 30 were found to be good antifungal activity compared to the standard drug ketoconazole. A preliminary study of the structure-activity relationship (SAR) revealed that the antimicrobial activity depended on the effect of different substituents on the phenyl ring. The electron donating (OH and OCH 3 ) groups presented in the analogues, increase the antibacterial activity (except compound 12), interestingly, while the electron withdrawing (Cl, NO 2 , F and Br) groups increase the antifungal activity (except compound 19 and 20). In addition, analogues containing thiophene (28) and indole (30) showed good antimicrobial activities. Whereas, aliphatic analogues (24-26) shown no activities in both bacterial and fungal stains even in high concentrations (100µg/mL). Molecular docking studies were performed for all the synthesized compounds of which compounds 11, 19 and 20 showed the highest glide G-score. Copyright © 2017 Elsevier Ltd. All rights reserved.

PASS assisted prediction and pharmacological evaluation of novel nicotinic analogs for nootropic activity in mice.

PubMed

Khurana, Navneet; Ishar, Mohan Pal Singh; Gajbhiye, Asmita; Goel, Rajesh Kumar

2011-07-15

The aim of present study is to predict the probable nootropic activity of novel nicotine analogues with the help of computer program, PASS (prediction of activity spectra for substances) and evaluate the same. Two compounds from differently substituted pyridines were selected for synthesis and evaluation of nootropic activity based on their high probable activity (Pa) value predicted by PASS computer program. Evaluation of nootropic activity of compounds after acute and chronic treatment was done with transfer latency (TL) and step down latency (SDL) methods which showed significant nootropic activity. The effect on scopolamine induced amnesia was also observed along with their acetylcholine esterase inhibitory activity which also showed positive results which strengthened their efficacy as nootropic agents through involvement of cholinergic system. This nootropic effect was similar to the effect of nicotine and donepezil used as standard drugs. Muscle coordination and locomotor activity along with their addiction liability, safety and tolerability studies were also evaluated. These studies showed that these compounds are well tolerable and safe over a wide range of doses tested along with the absence of withdrawal effect which is present in nicotine due to its addiction liability. The study showed that these compounds are true nicotine analogs with desirable efficacy and safety profile for their use as effective nootropic agents. Copyright © 2011 Elsevier B.V. All rights reserved.

Isolation of cholinesterase and β-secretase 1 inhibiting compounds from Lycopodiella cernua.

PubMed

Nguyen, Van Thu; To, Dao Cuong; Tran, Manh Hung; Oh, Sang Ho; Kim, Jeong Ah; Ali, Md Yousof; Woo, Mi-Hee; Choi, Jae Sue; Min, Byung Sun

2015-07-01

Three new serratene-type triterpenoids (1-3) and a new hydroxy unsaturated fatty acid (13) together with nine known compounds (4-12) were isolated from Lycopodiella cernua. The chemical structures were established using NMR, MS, and Mosher's method. Compound 13 showed the most potent inhibitory activity against acetylcholinesterase (AChE) with an IC50 value of 0.22μM. For butyrylcholinesterase (BChE) inhibitory activity, 5 showed the most potent activity with an IC50 value of 0.42μM. Compound 2 showed the most potent activity with an IC50 of 0.23μM for BACE-1 inhibitory activity. The kinetic activities were investigated to determine the type of enzyme inhibition involved. The types of AChE inhibition shown by compounds 4, 5, and 13 were mixed; BChE inhibition by 5 was competitive, while 2 and 6 showed mixed-types. In addition, molecular docking studies were performed to investigate the interaction of these compounds with the pocket sites of AChE. The docking results revealed that the tested inhibitors 3, 4, and 13 were stably present in several pocket domains of the AChE residue. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antioxidant activity of oils extracted from orange (Citrus sinensis) seeds.

PubMed

Jorge, Neuza; Silva, Ana Carolina da; Aranha, Caroline P M

2016-05-31

Due to the increasing production of food in the world with consequent increase of the production of waste, the importance of developing researches for its use is noticed. Thus, the interest in vegetable oils with bioactive compounds, such as the ones extracted from fruit seeds, is growing. Therefore, the present study aims to characterize the oils extracted from seeds of Hamlin, Natal, Pera-rio and Valencia orange varieties (Citrus sinensis), as to the levels of total carotenoids, total phenolic compounds, tocopherols and phytosterols, as well as to determine their antioxidant activity. The orange seed oils presented important content of total carotenoids (19.01 mg/kg), total phenolic compounds (4.43 g/kg), α-tocopherol (135.65 mg/kg) and phytosterols (1304.2 mg/kg). The antioxidant activity ranged from 56.0% (Natal) to 70.2% (Pera-rio). According to the results it is possible to conclude that the orange seed oils can be used as specialty oils in diet, since they contain considerable amounts of bioactive compounds and antioxidants.

Anti-inflammatory activity effect of 2-substituted-1,4,5,6-tetrahydrocyclopenta[b]pyrrole on TPA-induced skin inflammation in mice.

PubMed

Xu, Xue-Tao; Mou, Xue-Qing; Xi, Qin-Mei; Liu, Wei-Ting; Liu, Wen-Feng; Sheng, Zhao-Jun; Zheng, Xi; Zhang, Kun; Du, Zhi-Yun; Zhao, Su-Qing; Wang, Shao-Hua

2016-11-01

2-Substituted-1,4,5,6-tetrahydrocyclopenta[b]pyrrole, a key structural moiety exiting in many bioactive molecules, has been shown to have excellent selective activity on COX-2. In the present study, the anti-inflammatory activity and the underlying molecular mechanism of 2-substituted-1,4,5,6-tetrahydrocyclopenta[b]pyrrole on skin inflammation were assessed by 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mice. Most of the compounds showed anti-inflammatory activity on TPA-induced skin inflammation. The anti-inflammatory activity of compound 4 showed higher anti-inflammatory activity than celecoxib (3.2-fold). Compound 4 pretreatment resulted in markedly suppression of TPA-induced IL-1β, IL-6, TNF-α, and COX-2, respectively. Furthermore, the mechanical study indicated that the anti-inflammatory activity of compound 4 was associated with its ability to inhibit activation of factor kappa-κB (NF-κB) by blocking IκB kinase (IKK) activities. Accordingly, compound 4 could be used as a potential anti-inflammatory agent for skin inflammation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antimalarial Activity of Small-Molecule Benzothiazole Hydrazones

PubMed Central

Sarkar, Souvik; Siddiqui, Asim A.; Saha, Shubhra J.; De, Rudranil; Mazumder, Somnath; Banerjee, Chinmoy; Iqbal, Mohd S.; Nag, Shiladitya; Adhikari, Susanta

2016-01-01

We synthesized a new series of conjugated hydrazones that were found to be active against malaria parasite in vitro, as well as in vivo in a murine model. These hydrazones concentration-dependently chelated free iron and offered antimalarial activity. Upon screening of the synthesized hydrazones, compound 5f was found to be the most active iron chelator, as well as antiplasmodial. Compound 5f also interacted with free heme (KD [equilibrium dissociation constant] = 1.17 ± 0.8 μM), an iron-containing tetrapyrrole released after hemoglobin digestion by the parasite, and inhibited heme polymerization by parasite lysate. Structure-activity relationship studies indicated that a nitrogen- and sulfur-substituted five-membered aromatic ring present within the benzothiazole hydrazones might be responsible for their antimalarial activity. The dose-dependent antimalarial and heme polymerization inhibitory activities of the lead compound 5f were further validated by following [3H]hypoxanthine incorporation and hemozoin formation in parasite, respectively. It is worth mentioning that compound 5f exhibited antiplasmodial activity in vitro against a chloroquine/pyrimethamine-resistant strain of Plasmodium falciparum (K1). We also evaluated in vivo antimalarial activity of compound 5f in a murine model where a lethal multiple-drug-resistant strain of Plasmodium yoelii was used to infect Swiss albino mice. Compound 5f significantly suppressed the growth of parasite, and the infected mice experienced longer life spans upon treatment with this compound. During in vitro and in vivo toxicity assays, compound 5f showed minimal alteration in biochemical and hematological parameters compared to control. In conclusion, we identified a new class of hydrazone with therapeutic potential against malaria. PMID:27139466

Phenolic composition and antioxidant potential of grain legume seeds: A review.

PubMed

Singh, Balwinder; Singh, Jatinder Pal; Kaur, Amritpal; Singh, Narpinder

2017-11-01

Legumes are a good source of bioactive phenolic compounds which play significant roles in many physiological as well as metabolic processes. Phenolic acids, flavonoids and condensed tannins are the primary phenolic compounds that are present in legume seeds. Majority of the phenolic compounds are present in the legume seed coats. The seed coat of legume seeds primarily contains phenolic acids and flavonoids (mainly catechins and procyanidins). Gallic and protocatechuic acids are common in kidney bean and mung bean. Catechins and procyanidins represent almost 70% of total phenolic compounds in lentils and cranberry beans (seed coat). The antioxidant activity of phenolic compounds is in direct relation with their chemical structures such as number as well as position of the hydroxyl groups. Processing mostly leads to the reduction of phenolic compounds in legumes owing to chemical rearrangements. Phenolic content also decreases due to leaching of water-soluble phenolic compounds into the cooking water. The health benefits of phenolic compounds include acting as anticarcinogenic, anti-thrombotic, anti-ulcer, anti-artherogenic, anti-allergenic, anti-inflammatory, antioxidant, immunemodulating, anti-microbial, cardioprotective and analgesic agents. This review provides comprehensive information of phenolic compounds identified in grain legume seeds along with discussing their antioxidant and health promoting activities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis, structural characterization and density functional studies of ethyl 4-(biphenyl-4-yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate A non-merohedral twinned structure

NASA Astrophysics Data System (ADS)

Yıdırım, Sema Öztürk; Büyükmumcu, Zeki; Butcher, Ray J.; Çetin, Gökalp; Şimşek, Rahime; Şafak, Cihat

2018-07-01

1,4-Dihydropyridine (1,4-DHP) derivatives have the reducing effect of extracellular Ca2+ ions influx on the L-type calcium channel. Because of this effect many 1,4-DHP derivatives are potent calcium channel blockers and antihypertensive agents. The biphenyl group is present in the structures of the most biologically active compounds and thus is an important group. By introducing this moiety into the structure of various compounds, active compounds are obtained. Thus, pharmacologically active structures can be condensed with the biphenyl structure to achieve novel biologically active compounds or compounds with increased activity. In this study, to achieve an active calcium channel blocker compound, the biphenyl group was introduced into the 1,4-DHP structure. The structure of the compound is proved by IR, 1H NMR, Mass spectroscopy, X-ray crystallography and elemental analysis. The cytotoxic activity assays have continued and positive results have been obtained. The phenyl rings [C16-C21 and C22-C27] make dihedral angles of 84.4 (1) and 87.5 (1)°, respectively, with the 1,4-dihydropyridine ring [N1/C1/C4-C9]. In the crystal, adjacent molecules are linked by Nsbnd H … O and Csbnd H … O hydrogen bonds into chains parallel to [010].

A new parameter to simultaneously assess antioxidant activity for multiple phenolic compounds present in food products.

PubMed

Yang, Hong; Xue, Xuejia; Li, Huan; Tay-Chan, Su Chin; Ong, Seng Poon; Tian, Edmund Feng

2017-08-15

In this work, we established a new methodology to simultaneously assess the relative reaction rates of multiple antioxidant compounds in one experimental set-up. This new methodology hypothesizes that the competition among antioxidant compounds towards limiting amount of free radical (in this article, DPPH) would reflect their relative reaction rates. In contrast with the conventional detection of DPPH decrease at 515nm on a spectrophotometer, depletion of antioxidant compounds treated by a series of DPPH concentrations was monitored instead using liquid chromatography coupled with quadrupole time-of-flight (LC-QTOF). A new parameter, namely relative antioxidant activity (RAA), has been proposed to rank these antioxidants according to their reaction rate constants. We have investigated the applicability of RAA using pre-mixed standard phenolic compounds, and also extended this application to two food products, i.e. red wine and green tea. It has been found that RAA correlates well with the reported k values. This new parameter, RAA, provides a new perspective in evaluating antioxidant compounds present in food and herbal matrices. It not only realistically reflects the antioxidant activity of compounds when co-existing with competitive constituents; and it could also quicken up the discovery process in the search for potent yet rare antioxidants from many herbs of food/medicinal origins. Copyright © 2017 Elsevier Ltd. All rights reserved.

Arbidol: a quarter-century after. Past, present and future of the original Russian antiviral

NASA Astrophysics Data System (ADS)

Balakin, K. V.; Filosa, R.; Lavrenov, S. N.; Mkrtchayn, A. S.; Nawrozkij, M. B.; Novakov, I. A.

2018-06-01

The present review is concerned with the synthesis and structure–activity relationship studies of Arbidol and its structural analogues. The latter are roughly divided into several unequal parts: indole- and benzofuran-based compounds, benzimidazole and imidazopyridine bioisosteres and ring-expanded quinoline derivatives. Much attention is focused on various types of antiviral activity of the above-mentioned Arbidol congeners, as well as of the parent compound itself. Features of Arbidol synthesis and metabolic changes are also discussed. The bibliography includes 166 references.

Potential Pharmacological Resources: Natural Bioactive Compounds from Marine-Derived Fungi

PubMed Central

Jin, Liming; Quan, Chunshan; Hou, Xiyan; Fan, Shengdi

2016-01-01

In recent years, a considerable number of structurally unique metabolites with biological and pharmacological activities have been isolated from the marine-derived fungi, such as polyketides, alkaloids, peptides, lactones, terpenoids and steroids. Some of these compounds have anticancer, antibacterial, antifungal, antiviral, anti-inflammatory, antioxidant, antibiotic and cytotoxic properties. This review partially summarizes the new bioactive compounds from marine-derived fungi with classification according to the sources of fungi and their biological activities. Those fungi found from 2014 to the present are discussed. PMID:27110799

Steroidal hormones and other endocrine active compounds in shallow groundwater in nonagricultural areas of Minnesota—Study design, methods, and data, 2009–10

USGS Publications Warehouse

Erickson, Melinda L.

2012-01-01

The U.S. Geological Survey, in cooperation with the Minnesota Pollution Control Agency, completed a study on the occurrence of steroidal hormones and other endocrine active compounds in shallow groundwater in nonagricultural areas of Minnesota during 2009–10. This report describes the study design and methods, and presents the data collected on steroidal hormones and other related compounds. Environmental and quality-control samples were collected from 40 wells as part of this study. Samples were analyzed by the U.S. Geological Survey National Water Quality Laboratory for 16 steroidal hormones and 4 other related compounds, of which all but 2 compounds are endocrine active compounds. Most of the water samples did not contain detectable concentrations of any of the 20 compounds analyzed. Water samples from three wells had detectable concentrations of one or more compounds. Bisphenol A was detected in samples from three wells, and trans-diethylstilbestrol was detected in one of the samples in which bisphenol A also was detected.

Synthesis of New Hydrazone Derivatives for MAO Enzymes Inhibitory Activity.

PubMed

Can, Nafiz Öncü; Osmaniye, Derya; Levent, Serkan; Sağlık, Begüm Nurpelin; İnci, Beril; Ilgın, Sinem; Özkay, Yusuf; Kaplancıklı, Zafer Asım

2017-08-20

In the present work, 14 new 1-substituted-2-phenylhydrazone derivatives were synthesized to evaluate their inhibitory activity against hMAO enzymes. The structures of the newly synthesized hydrazones 2a-2n were characterized by IR, 1H-NMR, 13C-NMR, HR-MS spectroscopic methods. The inhibitory activity of compounds 2a-2n against hMAO-A and hMAO-B enzymes was elucidated by using an in-vitro Amplex Red® reagent assay based on fluorometric methods. According to the activity studies, 2a and 2b were found to be the most active compounds against hMAO-A enzyme, with IC50 values of 0.342 µM and 0.028 µM, respectively. The most active compounds 2a-2b were evaluated by means of enzyme kinetics and docking studies. Moreover, these compounds were subjected to cytotoxicity and genotoxicity tests to establish their preliminary toxicological profiles and were found to be non-cytotoxic and non-genotoxic. Consequently, the findings of this study display the biological importance of compounds 2a, 2b as selective, irreversible and competitive inhibitors of hMAO-A. Docking studies revealed that there is a strong interaction between hMAO-A and the most active compound 2b.

Synthesis and antimycobacterial screening of new thiazolyl-oxazole derivatives.

PubMed

Abhale, Yogita K; Sasane, Amit V; Chavan, Abhijit P; Shekh, Saddam Husen; Deshmukh, Keshav K; Bhansali, Sujit; Nawale, Laxman; Sarkar, Dhiman; Mhaske, Pravin C

2017-05-26

In the present study a series of 4-methyl-2-aryl-5-(2-aryl/benzyl thiazol-4-yl) oxazole (4a-v) have been synthesized and evaluated for their preliminary antitubercular, antimicrobial and cytotoxicity activity. Among all the synthesized compounds, 4v reported comparable activity against dormant M. tuberculosis H 37 Ra and M. bovis BCG strains with respect to standard drug rifampicin. The active compounds from the antitubercular study were further tested for anti-proliferative activity against HeLa, A549 and PANC-1 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Further, the synthesized compounds were found to have potential antibacterial activities with MIC range of 2.1-26.8 μg/mL. High potency, lower cytotoxicity and promising antimycobacterial activity suggested that these compounds could serve as good leads for further optimisation and development. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Neural activity in the hippocampus during conflict resolution.

PubMed

Sakimoto, Yuya; Okada, Kana; Hattori, Minoru; Takeda, Kozue; Sakata, Shogo

2013-01-15

This study examined configural association theory and conflict resolution models in relation to hippocampal neural activity during positive patterning tasks. According to configural association theory, the hippocampus is important for responses to compound stimuli in positive patterning tasks. In contrast, according to the conflict resolution model, the hippocampus is important for responses to single stimuli in positive patterning tasks. We hypothesized that if configural association theory is applicable, and not the conflict resolution model, the hippocampal theta power should be increased when compound stimuli are presented. If, on the other hand, the conflict resolution model is applicable, but not configural association theory, then the hippocampal theta power should be increased when single stimuli are presented. If both models are valid and applicable in the positive patterning task, we predict that the hippocampal theta power should be increased by presentation of both compound and single stimuli during the positive patterning task. To examine our hypotheses, we measured hippocampal theta power in rats during a positive patterning task. The results showed that hippocampal theta power increased during the presentation of a single stimulus, but did not increase during the presentation of a compound stimulus. This finding suggests that the conflict resolution model is more applicable than the configural association theory for describing neural activity during positive patterning tasks. Copyright © 2012 Elsevier B.V. All rights reserved.

Anti-plasmodial activity of Dicoma tomentosa (Asteraceae) and identification of urospermal A-15-O-acetate as the main active compound

PubMed Central

2012-01-01

Background Natural products could play an important role in the challenge to discover new anti-malarial drugs. In a previous study, Dicoma tomentosa (Asteraceae) was selected for its promising anti-plasmodial activity after a preliminary screening of several plants traditionally used in Burkina Faso to treat malaria. The aim of the present study was to further investigate the anti-plasmodial properties of this plant and to isolate the active anti-plasmodial compounds. Methods Eight crude extracts obtained from D. tomentosa whole plant were tested in vitro against two Plasmodium falciparum strains (3D7 and W2) using the p-LDH assay (colorimetric method). The Peters’ four-days suppressive test model (Plasmodium berghei-infected mice) was used to evaluate the in vivo anti-plasmodial activity. An in vitro bioguided fractionation was undertaken on a dichloromethane extract, using preparative HPLC and TLC techniques. The identity of the pure compound was assessed using UV, MS and NMR spectroscopic analysis. In vitro cytotoxicity against WI38 human fibroblasts (WST-1 assay) and haemolytic activity were also evaluated for extracts and pure compounds in order to check selectivity. Results The best in vitro anti-plasmodial results were obtained with the dichloromethane, diethylether, ethylacetate and methanol extracts, which exhibited a high activity (IC50 ≤ 5 μg/ml). Hot water and hydroethanolic extracts also showed a good activity (IC50 ≤ 15 μg/ml), which confirmed the traditional use and the promising anti-malarial potential of the plant. The activity was also confirmed in vivo for all tested extracts. However, most of the active extracts also exhibited cytotoxic activity, but no extract was found to display any haemolytic activity. The bioguided fractionation process allowed to isolate and identify a sesquiterpene lactone (urospermal A-15-O-acetate) as the major anti-plasmodial compound of the plant (IC50 < 1 μg/ml against both 3D7 and W2 strains). This was also found to be the main cytotoxic compound (SI = 3.3). While this melampolide has already been described in the plant, this paper is the first report on the biological properties of this compound. Conclusions The present study highlighted the very promising anti-plasmodial activity of D. tomentosa and enabled to identify its main active compound, urospermal A-15-O-acetate. The high anti-plasmodial activity of this compound merits further study about its anti-plasmodial mechanism of action. The active extracts of D. tomentosa, as well as urospermal A 15-O-acetate, displayed only a moderate selectivity, and further studies are needed to assess the safety of the use of the plant by the local population. PMID:22909422

Development of Prophylactic Anti-Fungal Preparations.

DTIC Science & Technology

1980-10-01

activity of griseofulvin relative to clotriinazole, miconazole , and thiabendazole (3). This present report will direct its attention primarily to...number of drugs against T. Menta intections. These included griseofulvin, clotrimazole, miconazole and thiabendazole. Each of these compounds were...T. Menta under the test procedure than was observed miconazole or clotrimazole {4). Therefore, these compounds are not sufficiently active to be

Cholesterol esterase inhibitory activity of bioactives from leaves of Mangifera indica L

PubMed Central

Gururaja, G. M.; Mundkinajeddu, Deepak; Dethe, Shekhar M.; Sangli, Gopala K.; Abhilash, K.; Agarwal, Amit

2015-01-01

Background: In the earlier studies, methanolic extract of Mangifera indica L leaf was exhibited hypocholesterol activity. However, the bioactive compounds responsible for the same are not reported so far. Objective: To isolate the bioactive compounds with hypocholesterol activity from the leaf extract using cholesterol esterase inhibition assay which can be used for the standardization of extract. Materials and Methods: The leaf methanolic extract of M. indica (Sindoora variety) was partitioned with ethyl acetate and chromatographed on silica gel to yield twelve fractions and the activity was monitored by using cholesterol esterase inhibition assay. Active fractions were re-chromatographed to yield individual compounds. Results and Discussion: A major compound mangiferin present in the extract was screened along with other varieties of mango leaves for cholesterol esterase inhibition assay. However, the result indicates that compounds other than mangiferin may be active in the extract. Invitro pancreatic cholesterol esterase inhibition assay was used for bioactivity guided fractionation (BAGF) to yield bioactive compound for standardization of extract. Bioactivity guided fractionation afford the active fraction containing 3b-taraxerol with an IC50 value of 0.86μg/ml. Conclusion: This study demonstrates that M. indica methanol extract of leaf have significant hypocholesterol activity which is standardized with 3b-taraxerol, a standardized extract for hypocholesterol activity resulted in development of dietary supplement from leaves of Mangifera indica. PMID:26692750

Lignans, bacteriocides and organochlorine compounds activate the human pregnane X receptor (PXR)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacobs, Miriam N.; Nolan, Gail T.; Hood, Steven R.

2005-12-01

The pregnane X receptor (PXR) mediates the induction of enzymes involved in steroid metabolism and xenobiotic detoxification. The receptor is expressed in liver and intestinal tissues and is activated by a wide range of compounds. The ability of a diverse range of dietary compounds to activate PXR-mediated transcription was assayed in HuH7 cells following transient transfection with human PXR (hPXR). The compounds investigated included phytochemicals such as lignans and phytoestrogens, organochlorine dietary contaminants such as polychlorinated biphenyls (PCBs) and triclosan and selected steroid, drug and herbal compounds. The hPXR activation at the top concentrations tested (10 {mu}M) relative to themore » positive control 10 {mu}M rifampicin ranged from 1.3% (trans-resveratrol) to 152% (ICI 182780). Hydroxylated compounds were marginally more potent than the parent compounds (tamoxifen activation was 74.6% whereas 4 hydroxytamoxifen activation was 84.2%) or significantly greater (vitamin D{sub 3} activation was 1.6%, while hydroxylated vitamin D{sub 3} activation was 55.6%). Enterolactone, the metabolite of common dietary lignans, was a medium activator of PXR (35.6%), compared to the lower activation of a parent lignan, secoisolariciresinol (20%). Two non-hydroxylated PCB congeners (PCB 118 and 153), which present a larger fraction of the PCB contamination of fatty foods, activated hPXR by 26.6% and 17%, respectively. The pesticide trans-nonachlor activation was 53.8%, while the widely used bacteriocide triclosan was a medium activator of hPXR at 46.2%. The responsiveness of PXR to activation by lignan metabolites suggests that dietary intake of these compounds may affect the metabolism of drugs that are CYP3A substrates. Additionally, the evidence that organochlorine chemicals, particularly the ubiquitous triclosan, activate hPXR suggests that these environmental chemicals may, in part, exhibit their endocrine disruptor activities by altering PXR-regulated steroid hormone metabolism with potential adverse health effects in exposed individuals.« less

Benzimidazobenzothiazole-based highly-efficient thermally activated delayed fluorescence emitters for organic light-emitting diodes: A quantum-chemical TD-DFT study

NASA Astrophysics Data System (ADS)

Zhu, Qiuling; Wen, Keke; Feng, Songyan; Guo, Xugeng; Zhang, Jinglai

2018-03-01

Based upon two thermally activated delayed fluorescence (TADF) emitters 1 and 2, compounds 3-6 have been designed by replacing the carbazol group with the bis(4-biphenyl)amine one (3 and 4) and introducing the electron-withdrawing CF3 group into the acceptor unit of 3 and 4 (5 and 6). It is found that the present calculations predict comparable but relatively large energy differences (approximate 0.5 eV) between the lowest singlet S1 and triplet T1 states (Δ EST) for the six targeted compounds. In order to explain the highly-efficient TADF behavior observed in compounds 1 and 2, the"triplet reservoir" mechanism has been proposed. In addition, the fluorescence rates of all six compounds are very large, in 107-108 orders of magnitude. According to the present calculations, it is a reasonable assumption that the newly designed compounds 3-6 could be considered as the potential TADF emitters, which needs to be further verified by experimental techniques.

Anti-malarial property of steroidal alkaloid conessine isolated from the bark of Holarrhena antidysenterica.

PubMed

Dua, Virendra K; Verma, Gaurav; Singh, Bikram; Rajan, Aswathy; Bagai, Upma; Agarwal, Dau Dayal; Gupta, N C; Kumar, Sandeep; Rastogi, Ayushi

2013-06-10

In the face of chronic and emerging resistance of parasites to currently available drugs and constant need for new anti-malarials, natural plant products have been the bastion of anti-malarials for thousands of years. Moreover natural plant products and their derivatives have traditionally been a common source of drugs, and represent more than 30% of the current pharmaceutical market. The present study shows evaluation of anti-malarial effects of compound conessine isolated from plant Holarrhena antidysenterica frequently used against malaria in the Garhwal region of north-west Himalaya. In vitro anti-plasmodial activity of compound was assessed using schizont maturation and parasite lactate dehydrogenase (pLDH) assay. Cytotoxic activities of the examined compound were determined on L-6 cells of rat skeletal muscle myoblast. The four-day test for anti-malarial activity against a chloroquine-sensitive Plasmodium berghei NK65 strain in BALB/c mice was used for monitoring in vivo activity of compound. In liver and kidney function test, the activity of alkaline phosphatase (ALP) was examined by p-NPP method, bilirubin by Jendrassik and Grof method. The urea percentage was determined by modified Berthelot method and creatinine by alkaline picrate method in serum of mice using ENZOPAK/CHEMPAK reagent kits. Compound conessine showed in vitro anti-plasmodial activity with its IC₅₀ value 1.9 μg/ml and 1.3 μg/ml using schizont maturation and pLDH assay respectively. The compound showed cytotoxity IC₅₀= 14 μg/ml against L6 cells of rat skeletal muscle myoblast. The isolated compound from plant H. antidysenterica significantly reduced parasitaemia (at 10 mg/kg exhibited 88.95% parasite inhibition) in P. berghei-infected mice. Due to slightly toxic nature (cytotoxicity = 14), biochemical analysis (liver and kidney function test) of the serum from mice after administration of conessine were also observed. The present investigation demonstrates that the compound conessine exhibited substantial anti-malarial property. The isolated compound could be chemically modified to obtain a more potent chemical entity with improved characteristics against malaria.

Antileishmanial, antimalarial and antimicrobial activities of the extract and isolated compounds from Austroplenckia populnea (Celastraceae).

PubMed

Andrade, Sérgio F; da Silva Filho, Ademar A; de O Resende, Dimas; Silva, Márcio L A; Cunha, Wilson R; Nanayakkara, N P Dhammika; Bastos, Jairo Kenupp

2008-01-01

Austroplenckia populnea (Celastraceae), known as "marmelinho do campo", is used in Brazilian folk medicine as antimicrobial, anti-inflammatory, and antitumoural agent. The aim of the present work was to evaluate the antimicrobial, antileishmanial and antimalarial activities of the crude hydroalcoholic extract of A. populnea (CHE) and some of its isolated compounds. The phytochemical study of the CHE was carried out affording the isolation of methyl populnoate (1), populnoic acid (2), and stigmast-5-en-3-O-beta-(D-glucopyranoside) (3). This is the first time that the presence of compound 3 in A. populnea is reported. The results showed that the CHE presents antifungal and antibacterial activities, especially against Candida glabrata and Candida albicans, for which the CHE showed IC50 values of 0.7 microg mL(-1) and 5.5 microg mL(-1), respectively, while amphotericin B showed an IC50 value of 0.1 microg mL(-1) against both microorganisms. Compounds 1-3 were inactive against all tested microorganisms. In the antileishmanial activity test against Leishmania donovani, the CHE showed an IC50 value of 52 microg mL(-1), while compounds 2 and 3 displayed an IC50 value of 18 microg mL(-1) In the antimalarial assay against Plasmodium falciparum (D6 and W2 clones), it was observed that all evaluated samples were inactive. In order to compare the effect on the parasites with the toxicity to mammalian cells, the cytotoxicity activity of the isolated compounds was evaluated against Vero cells, showing that all evaluated samples exhibited no cytotoxicity at the maximum dose tested.

Effects of copper on the antioxidant activity of olive polyphenols in bulk oil and oil-in-water emulsions.

PubMed

Paiva-Martins, Fátima; Santos, Vera; Mangericão, Hugo; Gordon, Michael H

2006-05-17

The antioxidant activity and interactions with copper of four olive oil phenolic compounds, namely oleuropein, hydroxytyrosol, 3,4-dihydroxyphenylethanol-elenolic acid (1), and 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde (2), in olive oil and oil-in-water emulsions stored at 60 degrees C were studied. All four phenolic compounds significantly extended the induction time of lipid oxidation in olive oil with the order of activity being hydroxytyrosol > compound 1 > compound 2 > oleuropein > alpha-tocopherol; but in the presence of Cu(ll), the stability of oil samples containing phenolic compounds decreased by at least 90%, and the antioxidant activity of hydroxytyrosol and compounds 1 and 2 became similar. In oil-in-water emulsions prepared from olive oil stripped of tocopherols, hydroxytyrosol enhanced the prooxidant effect of copper at pH 5.5 but not at pH 7.4. The stability of samples containing copper at pH 5.5 was not significantly different if oleuropein was present from that of the control. Oleuropein at pH 7.4, and compounds 1 and 2 at both pH values tested, reduced the prooxidant effect of copper. The lower stability and the higher reducing capacity of all compounds at pH 7.4 could not explain the higher stability of emulsions containing phenolic compounds at this pH value. However, mixtures containing hydroxytyrosol or oleuropein with copper showed higher 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity at pH 7.4 than at pH 5.5. Moreover, the compound 2-copper complex showed higher radical scavenging activity then the uncomplexed compound at pH 5.5. It can be concluded that the formation of a copper complex with radical scavenging activity is a key step in the antioxidant action of the olive oil phenolic compounds in an emulsion containing copper ions.

Wightianines A-E, dihydro-β-agarofuran sesquiterpenes from Parnassia wightiana, and their antifungal and insecticidal activities.

PubMed

Wang, Dong-Mei; Zhang, Cheng-Chen; Zhang, Qiang; Shafiq, Nusrat; Pescitelli, Gennaro; Li, Deng-Wu; Gao, Jin-Ming

2014-07-16

Five new sesquiterpene polyol esters with a dihydro-β-agarofuran skeleton, designated as wightianines A-E (1-5), besides two known compounds, were isolated from the methanolic extract of the whole plant of the traditional herbal medicine Parnassia wightiana Wall. The structures of the isolated compounds were elucidated on the basis of spectroscopic analyses, including two-dimensional nuclear magnetic resonance techniques (correlation spectroscopy, heteronuclear multiple-quantum coherence, nuclear Overhauser effect spectrometry, and heteronuclear multiple-bond correlation) and electronic circular dichroism studies. The antifungal and insecticidal activities of five compounds were evaluated against several plant pathogenic fungi and armyworm larvae (Mythimna separata Walker). Among the test metabolites, compounds 2 and 7 both exhibited potent antifungal activity against the phytopathogenic fungus Cytospora sp. with minimum inhibitory concentration values of 0.78 μg/mL, which are equal to the two positive controls, hymexazol and carbendazim. However, no insecticidal activity of the test compounds was observed in the present study. Compounds 2 and 7 could be promising leads for developing new fungicides against agriculturally important fungus Cytospora sp.

Floral volatiles in a sapromyiophilous plant and their importance in attracting house fly pollinators.

PubMed

Zito, Pietro; Dötterl, Stefan; Sajeva, Maurizio

2015-04-01

Floral scent in sapromyiophilous plants often consists of complex blends with not only fetid (e.g., sulfides) but also sweet (e.g., terpenoids) volatile organic compounds, and a recent study suggests that both groups of compounds are involved in pollinator attraction. However, little is known about the number and identity of compounds involved in pollinator attraction in these deceptive plants that mimic breeding sites of fly pollinators. In the present paper, we studied flower volatiles of sapromyiophilous Periploca laevigata and their capability to elicit biological responses in one of the pollinator species, Musca domestica. Floral volatiles were collected by dynamic headspace and analyzed by gas chromatography/mass spectrometry (GC/MS), and electrophysiological (GC/EAD) and behavioral assays (two choice olfactometer) were conducted. In the floral scent of P. laevigata, we detected 44 compounds, of which indole, β-caryophyllene, and germacrene D, as well as dimethyl trisulfide, which was present in trace amounts, were electrophysiologically active in the antennae of M. domestica. However, when we evaluated in behavioral experiments the attractiveness of the electrophysiologically active compounds (complete mixture against partial mixtures or against single compounds), we found that indole was the only attractive compound for the flies.

A Rational Design, Synthesis, Biological Evaluation and Structure--Activity Relationship Study of Novel Inhibitors against Cyanobacterial Fructose-1,6-bisphosphate Aldolase.

PubMed

Han, Xinya; Zhu, Xiuyun; Zhu, Shuaihua; Wei, Lin; Hong, Zongqin; Guo, Li; Chen, Haifeng; Chi, Bo; Liu, Yan; Feng, Lingling; Ren, Yanliang; Wan, Jian

2016-01-25

In the present study, a series of novel maleimide derivatives were rationally designed and optimized, and their inhibitory activities against cyanobacteria class-II fructose-1,6-bisphosphate aldolase (Cy-FBA-II) and Synechocystis sp. PCC 6803 were further evaluated. The experimental results showed that the introduction of a bigger group (Br, Cl, CH3, or C6H3-o-F) on the pyrrole-2',5'-dione ring resulted in a decrease in the Cy-FBA-II inhibitory activity of the hit compounds. Generally, most of the hit compounds with high Cy-FBA-II inhibitory activities could also exhibit high in vivo activities against Synechocystis sp. PCC 6803. Especially, compound 10 not only shows a high Cy-FBA-II activity (IC50 = 1.7 μM) but also has the highest in vivo activity against Synechocystis sp. PCC 6803 (EC50 = 0.6 ppm). Thus, compound 10 was selected as a representative molecule, and its probable interactions with the surrounding important residues in the active site of Cy-FBA-II were elucidated by the joint use of molecular docking, molecular dynamics simulations, ONIOM calculations, and enzymatic assays to provide new insight into the binding mode of the inhibitors and Cy-FBA-II. The positive results indicate that the design strategy used in the present study is very likely to be a promising way to find novel lead compounds with high inhibitory activities against Cy-FBA-II in the future. The enzymatic and algal inhibition assays suggest that Cy-FBA-II is very likely to be a promising target for the design, synthesis, and development of novel specific algicides to solve cyanobacterial harmful algal blooms.

Mesoionic compounds with antifungal activity against Fusarium verticillioides.

PubMed

Paiva, Rojane de Oliveira; Kneipp, Lucimar Ferreira; dos Reis, Camilla Moretto; Echevarria, Aurea

2015-02-04

Fungi contaminate the food of humans and animals, are a risk to health, and can cause financial losses. In this work, the antifungal activities of 16 mesoionic compounds (MI 1-16) were evaluated against mycotoxigenic fungi, including Aspergillus spp., Fusarium verticillioides and Penicillium citrinum. Furthermore, the decreased ergosterol in the total lipid content of Fusarium verticillioides was investigated. F. verticillioides was the most sensitive fungus to the mesoionic compounds. Among the evaluated compounds, MI-11 and MI-16 presented higher antifungal effects against F. verticillioides, with MIC values of 7.8 μg/ml, and MI-2 and MI-3 followed, with MICs of 15.6 μg/ml. The most active compounds were those with heterocyclic ring phenyl groups substituted by electron donor moieties (MI-11 and MI-16). Among some compounds with higher activity (MI-2, MI-11 and MI-16), decreased ergosterol content in the total lipid fraction of F. verticillioides was demonstrated. MI-2 reduced the ergosterol content approximately 40% and 80% at concentrations of 7.8 μg/ml and 15.6 μg/ml, respectively, and MI-11 and MI-16 decreased the content by 30% and 50%, respectively, when at a concentration of 7.8 μg/ml. These findings indicate that mesoionic compounds have significant antifungal activity against F. verticillioides.

Antifungal activity of schinol and a new biphenyl compound isolated from Schinus terebinthifolius against the pathogenic fungus Paracoccidioides brasiliensis.

PubMed

Johann, Susana; Sá, Nívea P; Lima, Luciana A R S; Cisalpino, Patricia S; Cota, Betania B; Alves, Tânia M A; Siqueira, Ezequias P; Zani, Carlos L

2010-10-12

The aim of this study was to isolate and identify the antifungal compounds from the extracts of Schinus terebinthifolius (Anacardiaceae) against clinical isolates of the pathogenic fungus Paracoccidioides brasiliensis. The hexane and dichlomethane fractions from leaves and stems of S. terebinthifolius were fractionated using several chromatography techniques to afford four compounds. The compounds isolated from S. terebinthifolius were identified as schinol (1), a new biphenyl compound, namely, 4'-ethyl-4-methyl-2,2',6,6'-tetrahydroxy[1,1'-biphenyl]-4,4'-dicarboxylate (2), quercetin (3), and kaempferol (4). Compounds 1 and 2 were active against different strains of P. brasiliensis, showing a minimal inhibitory concentration value against the isolate Pb B339 of 15.6 μg/ml. The isolate Pb 1578 was more sensitive to compound 1 with a MIC value of 7.5 μg/ml. Schinol presented synergistic effect only when combined with itraconazole. The compounds isolated from S. terebinthifolius were not able to inhibit cell wall synthesis or assembly using the sorbitol assay. This work reveals for the first time the occurrence of compound 2 and discloses activity of compounds 1 and 2 against several clinical isolates of P. brasiliensis. These results justify further studies to clarify the mechanisms of action of these compounds.

Synthesis, cytotoxicity and haemolytic activity of Pulsatilla saponin A, D derivatives.

PubMed

Chen, Zhong; Duan, Huaqing; Wang, Minglei; Han, Li; Liu, Yanli; Zhu, Yongming; Yang, Shilin

2015-06-15

The strong haemolytic activity of Pulsatilla saponin A (PSA), D (PSD) hampered their clinical development of antitumor agents. In order to solve this problem, C-28 position modification derivatives of PSA/PSD were synthesized. The cytotoxicity and haemolytic activity of these compounds were evaluated. Structure-activity relationship and structure-toxicity relationship had been observed. The mice acute toxicity of compound 11 was reduced greatly than that of PSA. This study indicates that compound 11 may represent an interesting class of potent antitumor agents from triterpenoid saponins avoiding the haemolysis problem. The present study has important significance for the development of antitumor saponins. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis of some new 3-coumaranone and coumarin derivatives as dual inhibitors of acetyl- and butyrylcholinesterase.

PubMed

Alipour, Masoumeh; Khoobi, Mehdi; Nadri, Hamid; Sakhteman, Amirhossein; Moradi, Alireza; Ghandi, Mehdi; Foroumadi, Alireza; Shafiee, Abbas

2013-08-01

A novel series of coumarin and 3-coumaranone derivatives encompassing the phenacyl pyridinium moiety were synthesized and evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity using Ellman's method. All compounds presented inhibitory activity against both AChE and BuChE in the micromolar range. The molecular docking simulations revealed that all compounds were dual binding site inhibitors of AChE. A kinetic study was performed and the mechanism of enzyme inhibition was proved to be of mixed type. All compounds were tested for their antioxidant activity and no significant activity was observed. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antimycobacterial and antimalarial activities of endophytic fungi associated with the ancient and narrowly endemic neotropical plant Vellozia gigantea from Brazil.

PubMed

Ferreira, Mariana C; Cantrell, Charles L; Wedge, David E; Gonçalves, Vívian N; Jacob, Melissa R; Khan, Shabana; Rosa, Carlos A; Rosa, Luiz H

2017-10-01

Endophytic fungi, present mainly in the Ascomycota and Basidiomycota phyla, are associated with different plants and represent important producers of bioactive natural products. Brazil has a rich biodiversity of plant species, including those reported as being endemic. Among the endemic Brazilian plant species, Vellozia gigantea (Velloziaceae) is threatened by extinction and is a promising target to recover endophytic fungi. The present study focused on bioprospecting of bioactive compounds of the endophytic fungi associated with V. gigantea, an endemic, ancient, and endangered plant species that occurs only in the rupestrian grasslands of Brazil. The capability of 285 fungal isolates to produce antimicrobial and antimalarial activities was examined. Fungi were grown at solid-state fermentation to recover their crude extracts in dichloromethane. Bioactive extracts were analysed by chromatographic fractionation and NMR and displayed compounds with antimicrobial, antimycobacterial, and antimalarial activities. Five fungi produced antimicrobial and antimalarial compounds. Extracts of Diaporthe miriciae showed antifungal, antibacterial, and antimalarial activities; Trichoderma effusum displayed selective antibacterial activity against methicillin-resistant Staphylococcus aureus and Mycobacterium intracellulare; and three Penicillium species showed antibacterial activity. D. miriciae extract contained highly functionalised secondary metabolites, yielding the compound epoxycytochalasin H with high antimalarial activity against the chloroquine-resistant strain of Plasmodium falciparum, with an IC50 approximately 3.5-fold lower than that with chloroquine. Our results indicate that V. gigantea may represent a microhabitat repository hotspot of potential fungi producers of bioactive compounds and suggest that endophytic fungal communities might be an important biological component contributing to the fitness of the plants living in the rupestrian grassland.

A ranking method for the concurrent learning of compounds with various activity profiles.

PubMed

Dörr, Alexander; Rosenbaum, Lars; Zell, Andreas

2015-01-01

In this study, we present a SVM-based ranking algorithm for the concurrent learning of compounds with different activity profiles and their varying prioritization. To this end, a specific labeling of each compound was elaborated in order to infer virtual screening models against multiple targets. We compared the method with several state-of-the-art SVM classification techniques that are capable of inferring multi-target screening models on three chemical data sets (cytochrome P450s, dehydrogenases, and a trypsin-like protease data set) containing three different biological targets each. The experiments show that ranking-based algorithms show an increased performance for single- and multi-target virtual screening. Moreover, compounds that do not completely fulfill the desired activity profile are still ranked higher than decoys or compounds with an entirely undesired profile, compared to other multi-target SVM methods. SVM-based ranking methods constitute a valuable approach for virtual screening in multi-target drug design. The utilization of such methods is most helpful when dealing with compounds with various activity profiles and the finding of many ligands with an already perfectly matching activity profile is not to be expected.

Synthesis of new Schiff bases bearing 1,2,4-triazole, thiazolidine and chloroazetidine moieties and their pharmacological evaluation.

PubMed

Kandile, Nadia G; Mohamed, Mansoura I; Ismaeel, Hind M

2017-12-01

New compounds based on oxindole moiety were synthesized via the reaction of 5-substitued isatins 1a-e with different nucleophiles such as benzidine, 3,3'-dimethoxybenzidine 2a,b and 2,6-diaminopyridine 3 to afford three different classes of bis-Schiff bases 4a-e, 5a-e and 6a-e, respectively. The structures of the new compounds were elucidated on the basis of their FTIR, 1 H NMR, 13 C NMR, GC/MS spectral data and elemental analysis. The in vitro antimicrobial activity of the new compounds was evaluated using a broth dilution technique in terms of minimal inhibitory concentration (MIC) against four bacterial and two fungal pathogens and anticancer activities against HELA cervix. The revealed data showed that compound 9d has excellent activity against Gram + ve and Gram -ve bacteria, and compounds 11b presented promising anticancer activity against HELA cervix. [Formula: see text].

Identification of the active compounds and significant pathways of yinchenhao decoction based on network pharmacology

PubMed Central

Huang, Jihan; Cheung, Fan; Tan, Hor-Yue; Hong, Ming; Wang, Ning; Yang, Juan; Feng, Yibin; Zheng, Qingshan

2017-01-01

Yinchenhao decoction (YCHD) is a traditional Chinese medicine formulation, which has been widely used for the treatment of jaundice for 2,000 years. Currently, YCHD is used to treat various liver disorders and metabolic diseases, however its chemical/pharmacologic profiles remain to be elucidated. The present study identified the active compounds and significant pathways of YCHD based on network pharmacology. All of the chemical ingredients of YCHD were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. Absorption, distribution, metabolism and excretion screening with oral bioavailability (OB) screening, drug-likeness (DL) and intestinal epithelial permeability (Caco-2) evaluation were applied to discover the bioactive compounds in YCHD. Following this, target prediction, pathway identification and network construction were employed to clarify the mechanism of action of YCHD. Following OB screening, and evaluation of DL and Caco-2, 34 compounds in YCHD were identified as potential active ingredients, of which 30 compounds were associated with 217 protein targets. A total of 31 significant pathways were obtained by performing enrichment analyses of 217 proteins using the JEPETTO 3.x plugin, and 16 classes of gene-associated diseases were revealed by performing enrichment analyses using Database for Annotation, Visualization and Integrated Discovery v6.7. The present study identified potential active compounds and significant pathways in YCHD. In addition, the mechanism of action of YCHD in the treatment of various diseases through multiple pathways was clarified. PMID:28791364

Disubstituted thiourea derivatives and their activity on CNS: synthesis and biological evaluation.

PubMed

Stefanska, Joanna; Szulczyk, Daniel; Koziol, Anna E; Miroslaw, Barbara; Kedzierska, Ewa; Fidecka, Sylwia; Busonera, Bernardetta; Sanna, Giuseppina; Giliberti, Gabriele; La Colla, Paolo; Struga, Marta

2012-09-01

A series of new thiourea derivatives of 1,2,4-triazole have been synthesized. The difference in structures of obtained compounds are directly connected with the kind of isothiocyanate (aryl/alkyl). The (1)H NMR, (13)C NMR, MS methods were used to confirm structures of obtained thiourea derivatives. The molecular structure of (1, 17) was determined by an X-ray analysis. Two of the new compounds (8 and 14) were tested for their pharmacological activity on animal central nervous system (CNS) in behavioural animal tests. The results presented in this work indicate the possible involvement of the serotonergic system in the activity of 8 and 14. In the case of 14 is also a possible link between its activity and the endogenous opioid system. All obtained compounds were tested for antibacterial activity against gram-positive cocci, gram-negative rods and antifungal activity. Compounds (1, 2, 5, 7, 9) showed significant inhibition against gram-positive cocci. Microbiological evaluation was carried out over 20 standard strains and 30 hospital strains. Selected compounds (1-13) were examined for cytotoxicity, antitumor, and anti-HIV activity. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Characterization of ToxCast Phase II compounds disruption of ...

EPA Pesticide Factsheets

The development of multi-well microelectrode array (mwMEA) systems has increased in vitro screening throughput making them an effective method to screen and prioritize large sets of compounds for potential neurotoxicity. In the present experiments, a multiplexed approach was used to determine compound effects on both neural function and cell health in primary cortical networks grown on mwMEA plates following exposure to ~1100 compounds from EPA’s Phase II ToxCast libraries. On DIV 13, baseline activity (40 min) was recorded prior to exposure to each compound at 40 µM. DMSO and the GABAA antagonist bicuculline (BIC) were included as controls on each mwMEA plate. Changes in spontaneous network activity (mean firing rate; MFR) and cell viability (lactate dehydrogenase; LDH and CellTiter Blue; CTB) were assessed within the same well following compound exposure. Activity calls (“hits”) were established using the 90th and 20th percentiles of the compound-induced change in MFR (medians of triplicates) across all tested compounds; compounds above (top 10% of compounds increasing MFR), and below (bottom 20% of compounds decreasing MFR) these thresholds, respectively were considered hits. MFR was altered beyond one of these thresholds by 322 compounds. Four compound categories accounted for 66% of the hits, including: insecticides (e.g. abamectin, lindane, prallethrin), pharmaceuticals (e.g. haloperidol, reserpine), fungicides (e.g. hexaconazole, fenamidone), and h

Antimalarial Activity of Small-Molecule Benzothiazole Hydrazones.

PubMed

Sarkar, Souvik; Siddiqui, Asim A; Saha, Shubhra J; De, Rudranil; Mazumder, Somnath; Banerjee, Chinmoy; Iqbal, Mohd S; Nag, Shiladitya; Adhikari, Susanta; Bandyopadhyay, Uday

2016-07-01

We synthesized a new series of conjugated hydrazones that were found to be active against malaria parasite in vitro, as well as in vivo in a murine model. These hydrazones concentration-dependently chelated free iron and offered antimalarial activity. Upon screening of the synthesized hydrazones, compound 5f was found to be the most active iron chelator, as well as antiplasmodial. Compound 5f also interacted with free heme (KD [equilibrium dissociation constant] = 1.17 ± 0.8 μM), an iron-containing tetrapyrrole released after hemoglobin digestion by the parasite, and inhibited heme polymerization by parasite lysate. Structure-activity relationship studies indicated that a nitrogen- and sulfur-substituted five-membered aromatic ring present within the benzothiazole hydrazones might be responsible for their antimalarial activity. The dose-dependent antimalarial and heme polymerization inhibitory activities of the lead compound 5f were further validated by following [(3)H]hypoxanthine incorporation and hemozoin formation in parasite, respectively. It is worth mentioning that compound 5f exhibited antiplasmodial activity in vitro against a chloroquine/pyrimethamine-resistant strain of Plasmodium falciparum (K1). We also evaluated in vivo antimalarial activity of compound 5f in a murine model where a lethal multiple-drug-resistant strain of Plasmodium yoelii was used to infect Swiss albino mice. Compound 5f significantly suppressed the growth of parasite, and the infected mice experienced longer life spans upon treatment with this compound. During in vitro and in vivo toxicity assays, compound 5f showed minimal alteration in biochemical and hematological parameters compared to control. In conclusion, we identified a new class of hydrazone with therapeutic potential against malaria. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

In vitro activity of new N-benzyl-1H-benzimidazol-2-amine derivatives against cutaneous, mucocutaneous and visceral Leishmania species.

PubMed

Nieto-Meneses, Rocío; Castillo, Rafael; Hernández-Campos, Alicia; Maldonado-Rangel, Armando; Matius-Ruiz, Jeferson B; Trejo-Soto, Pedro Josué; Nogueda-Torres, Benjamín; Dea-Ayuela, Ma Auxiliadora; Bolás-Fernández, Francisco; Méndez-Cuesta, Carlos; Yépez-Mulia, Lilián

2018-01-01

The identification of specific therapeutic targets and the development of new drugs against leishmaniasis are urgently needed, since chemotherapy currently available for its treatment has several problems including many adverse side effects. In an effort to develop new antileishmanial drugs, in the present study a series of 28 N-benzyl-1H-benzimidazol-2-amine derivatives was synthesized and evaluated in vitro against Leishmania mexicana promastigotes. Compounds 7 and 8 with the highest antileishmanial activity (micromolar) and lower cytotoxicity than miltefosine and amphotericin B were selected to evaluate their activity against L. braziliensis 9and L. donovani, species causative of mucocutaneous and visceral leishmaniasis, respectively. Compound 7 showed significantly higher activity against L. braziliensis promastigotes than compound 8 and slightly lower than miltefosine. Compounds 7 and 8 had IC 50 values in the micromolar range against the amastigote of L. mexicana and L. braziliensis. However, both compounds did not show better activity against L. donovani than miltefosine. Compound 8 showed the highest SI against both parasite stages of L. mexicana. In addition, compound 8 inhibited 68.27% the activity of recombinant L. mexicana arginase (LmARG), a therapeutic target for the treatment of leishmaniasis. Docking studies were also performed in order to establish the possible mechanism of action by which this compound exerts its inhibitory effect. Compound 8 shows promising potential for the development of more potent antileishmanial benzimidazole derivatives. Copyright © 2017 Elsevier Inc. All rights reserved.

The antibacterial activity of compounds isolated from oakmoss against Legionella pneumophila and other Legionella spp.

PubMed

Nomura, Harue; Isshiki, Yasunori; Sakuda, Keisuke; Sakuma, Katsuya; Kondo, Seiichi

2012-01-01

Oakmoss is a natural fragrance ingredient exhibiting highly specific, potent antibacterial activity against Legionella pneumophila, a causative agent of severe water-bone pneumonia. In the present study, the antibacterial activity of individual compounds isolated from oakmoss was investigated against L. pneumophila and other Legionella spp. A total of 18 known compounds and two minor novel compounds (i.e., 3-methoxy-5-methylphenyl-2,4-dihydroxy-6-methylbenzoate (compound 9) and 8-(2,4-dihydroxy-6-(2-oxoheptyl)-phenoxy)-6-hydroxy-3-pentyl-1H-isochromen-1-one (compound 20)) were purified from oakmoss. The minimum inhibitory concentrations (MICs) against clinical and environmental isolates of L. pneumophila, L. bozemanii, L. micdadei, L. longbeachae, and L. dumoffii for 11 of the 20 compounds were less than 100 µg/mL (range 0.8-64.0 µg/mL). Novel compounds 9 and 20 exhibited potent antibacterial activity against L. pneumophila strains (MIC ranges of 1.3-8.0 µg/mL and 3.3-13.3 µg/mL, respectively) and also against four other Legionella species (MIC ranges of 0.8-8.0 µg/mL and 3.3-21.3 µg/mL, respectively). Time-kill assays indicated that compounds 9 and 20 kill bacteria at a concentration equivalent to 2×MIC after 1 h and 6 h co-incubations, respectively. While oakmoss and the purified components exhibited antibacterial activity against Legionella spp., they were not active against other Gram-negative and -positive bacteria such as Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus.

Formation, characterization, aggregation, fluorescence and antioxidant properties of novel tetrasubstituted metal-free and metallophthalocyanines bearing (4-(methylthio)phenoxy) moieties

NASA Astrophysics Data System (ADS)

Yıldırım, Nurdan; Bilgiçli, Ahmet T.; Alici, Esma Hande; Arabacı, Gulnur; Yarasir, M. Nilüfer

2017-09-01

The synthesis and characterization of peripherally tetra 4-(methylthio)phenoxy substituted metal-free(2), Zn(II) (3) and Co(II) (4) phthalocyanine derivatives were reported. These newly synthesized phthalocyanine derivatives showed the enhanced solubility in organic solvents and they were characterized by a combination of elemental analysis, FTIR, 1H NMR, 13C NMR, UV-vis and MALDI-TOF/MS spectral data. Their aggregation properties were investigated in THF by UV-vis and fluorescence. These metal-free and metallophthalocyanine compounds were also evaluated for their total antioxidant abilities by using three different antioxidant methods such as 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging, ferrous ion chelating and reducing power activity. All tested compounds showed radical scavenging activity. The highest radical scavenging activity was found from cobalt phthalocyanine (4) compound respectively. IC50 values of the compounds and standards (BHT and Trolox) were also determined. The results showed that the compound 4 had the highest antioxidant activity among all tested compounds including standards. The tested phthalocyanine compounds had ferrous ion chelating activity. In addition, they showed very high reducing power. All tested compounds had higher reducing power than the standards such as ascorbic acid and BHT. The present study shows that the synthesized tetra phthalocyanine [M: 2H(2), Zn(II)(3), Co(II)(4)] with four peripheral 4-(methylthio) phenoxy compounds have the effective antioxidant properties that can be used as antioxidant agents.

Selenitetriglicerydes affect CYP1A1 and QR activity by involvement of reactive oxygen species and Nrf2 transcription factor.

PubMed

Suchocki, Piotr; Misiewicz-Krzemińska, Irena; Skupińska, Katarzyna; Niedźwiecka, Katarzyna; Lubelska, Katarzyna; Fijałek, Zbigniew; Kasprzycka-Guttman, Teresa

2010-01-01

Selenitetriglycerides are a group of compounds that contain selenium (Se) (IV). In this paper, we present the results of examinations of three structurally-related selenitetriglicerydes that contain various Se concentrations: 2%, 5% and 7% Selol. The present study concentrates on the effect of Selol on phase 1 and 2 enzyme activity and the implications of free radicals and the nuclear erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway in the activity of this compound. The cytotoxic and cytostatic activities of the three kinds of Selol were evaluated; however, the cytotoxic effect was observed only for 7% Selol. Our results show that 2% Selol acts as a monofunctional inducer of phase 2 enzyme activity, and the induction is mediated by the Nrf2 transcription factor. Selol 7% acts in an opposite manner and induces phase 1 with simultaneous inhibition of phase 2 enzyme activity. The differential effect can be associated with the increase in Se content, leading to a change in the structure of the compound.

Potential Antiviral Agents from Marine Fungi: An Overview

PubMed Central

Zorofchian Moghadamtousi, Soheil; Nikzad, Sonia; Abdul Kadir, Habsah; Abubakar, Sazaly; Zandi, Keivan

2015-01-01

Biodiversity of the marine world is only partially subjected to detailed scientific scrutiny in comparison to terrestrial life. Life in the marine world depends heavily on marine fungi scavenging the oceans of lifeless plants and animals and entering them into the nutrient cycle by. Approximately 150 to 200 new compounds, including alkaloids, sesquiterpenes, polyketides, and aromatic compounds, are identified from marine fungi annually. In recent years, numerous investigations demonstrated the tremendous potential of marine fungi as a promising source to develop new antivirals against different important viruses, including herpes simplex viruses, the human immunodeficiency virus, and the influenza virus. Various genera of marine fungi such as Aspergillus, Penicillium, Cladosporium, and Fusarium were subjected to compound isolation and antiviral studies, which led to an illustration of the strong antiviral activity of a variety of marine fungi-derived compounds. The present review strives to summarize all available knowledge on active compounds isolated from marine fungi with antiviral activity. PMID:26204947

One-pot microwave assisted synthesis and structural elucidation of novel ethyl 3-substituted-7-methylindolizine-1-carboxylates with larvicidal activity against Anopheles arabiensis

NASA Astrophysics Data System (ADS)

Chandrashekharappa, Sandeep; Venugopala, Katharigatta N.; Nayak, Susanta K.; Gleiser, Raquel M.; García, Daniel A.; Kumalo, Hezekiel M.; Kulkarni, Rashmi S.; Mahomoodally, Fawzi M.; Venugopala, Rashmi; Mohan, Mahendra K.; Odhav, Bharti

2018-03-01

In the present investigation a series of novel ethyl 3-substituted-7-methylindolizine-1-carboxylates was achieved by microwave assisted one-pot method. The purity of the compounds was ascertained by HPLC and structural elucidation of the title compounds was achieved by FT-IR, NMR (1H and 13C), LC-MS and elemental analysis. One randomly selected compound from the series was further studied by single crystal X-ray method for intra and intermolecular interactions. Larvicidal properties of the characterized compounds were evaluated against Anopheles arabiensis and it was found that indolizine pharmacophore influences larvicidal activity as we can see larvicidal activity for all the analogues. The synthesized analogues (2j, 2m and 2f) were the most potent compounds based on the functional groups on the indolizine pharmacophore for larvicidal assay.

Synthesis, antiproliferative and apoptotic activities of N-(6(4)-indazolyl)-benzenesulfonamide derivatives as potential anticancer agents.

PubMed

Abbassi, Najat; Chicha, Hakima; Rakib, El Mostapha; Hannioui, Abdellah; Alaoui, Mdaghri; Hajjaji, Abdelouahed; Geffken, Detlef; Aiello, Cinzia; Gangemi, Rosaria; Rosano, Camillo; Viale, Maurizio

2012-11-01

Recently, it has been reported that compounds bearing a sulfonamide moiety possess many types of biological activities, including anticancer activity. The present work reports the synthesis and antiproliferative evaluation of some N-(6(4)-indazolyl)benzenesulfonamides and 7-ethoxy-N-(6(4)-indazolyl)benzenesulfonamides. All compounds were evaluated for their in vitro antiproliferative activity against three tumor cell lines: A2780 (human ovarian carcinoma) A549 (human lung adenocarcinoma) and P388 (murine leukemia). The results indicated that sulfonamides 2c, 3c, 6d, 8, 13, 3b and 16 were endowed with a pharmacologically interesting antiproliferative activity with compounds 2c and 3c showing the lower IC(50) (from 0.50 ± 0.09 to 1.83 ± 0.52 μM and from 0.58 ± 0.17 to 5.83 ± 1.83 μM, respectively). Moreover, these indazoles were able to trigger apoptosis through the upregulation of the typical apoptosis markers p53 and bax. As regard to the hypothetic targets of these compounds, a preliminary docking analysis showed that all compounds seemed to interact with β-tubulin, in particular compound 3b that showed the lower Ki. The cytofluorimetric analysis of the cell cycle phases indicates that all compounds, when administered at their IC(75), caused a block in the G2/M phase of the cell cycle with the generation of subpopulations of cells with a number of chromosome >4n. When the IC(50)s were applied we observed a prevalent block in the G0/G1 phase except for compounds 16 and 8 where a partial G2/M block was present with a concomitant decrease of cells in the G0/G1 and S phases of the cell cycle. Altogether these results suggest a possible, but not exclusive, interaction with microtubules. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Dimers of coumarin-1,2,3-triazole hybrids bearing alkyl spacer: Design, microwave-assisted synthesis, molecular docking and evaluation as antimycobacterial and antimicrobial agents

NASA Astrophysics Data System (ADS)

Ashok, Dongamanti; Gundu, Srinivas; Aamate, Vikas Kumar; Devulapally, Mohan Gandhi; Bathini, Raju; Manga, Vijjulatha

2018-04-01

The present study demonstrated the synthesis of new series of coumarin-1,2,3-triazole hybrids under microwave irradiation method. Several dimers of coumarin based 1,2,3-triazole derivatives were synthesized and their antimycobacterial and antimicrobial activities were investigated. The antimycobacterial activity screening results revealed that compounds 6i and 6j were the most active against Mycobacterium tuberculosis H37Rv strain. The active compounds were further evaluated for cytotoxicity with HEK cell lines and exhibited less % of inhibition. The same synthetic hybrids were evaluated for their antimicrobial activity against various bacterial strains and fungal strains and compounds 6e, 6h, 6i and 6j were found to be the most promising antimicrobial potent molecules. Furthermore, the active compounds against Mycobacterium tuberculosis were evaluated for their molecular docking studies against pantothenate synthetase (PS) enzyme of MTB and the docking results are in well agreement with the antitubercular evaluation results.

Hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives and evaluation of their anticancer and antimycobacterial activity.

PubMed

Mantu, Dorina; Antoci, Vasilichia; Moldoveanu, Costel; Zbancioc, Gheorghita; Mangalagiu, Ionel I

2016-01-01

The design, synthesis, structure, and in vitro anticancer and antimycobacterial activity of new hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives are described. The strategy adopted for synthesis is straight and efficient, involving a three-step setup procedure: N-acylation, N-alkylation, and quaternization of nitrogen heterocycle. The solubility in microbiological medium and anticancer and antimycobacterial activity of a selection of new synthesized compounds were evaluated. The hybrid derivatives have an excellent solubility in microbiological medium, which make them promising from the pharmacological properties point of view. One of the hybrid compounds, 9 (with a benzimidazole and 8-aminoquinoline skeleton), exhibits a very good and selective antitumor activity against Renal Cancer A498 and Breast Cancer MDA-MB-468. Moreover, the anticancer assay suggests that the hybrid Imz (Bimz)/2-AP (8-AQ) compounds present a specific affinity to Renal Cancer A498. Concerning the antimycobacterial activity, only the hybrid compound, 9, has a significant activity. SAR correlations have been performed.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Medyantseva, E.P.; Budnikov, G.K.; Balakaeva, T.A.

The interest in the analytical chemistry of ruthenium and its compounds has recently been increasing. Ruthenium compounds can be used an antitumor agents and in the treatment of tuberculosis and fungal infections. It has been suggested that there is a specific relationship between the reduction potentials of the compounds and their biological activity. Of greatest interest among the biologically active compounds are the compounds with nitrogen-containing heterocycles. In order to obtain information on the degree of oxidation of the central atom in the complexes and to select the optimum conditions for the determination of the mono- and bi-nuclear complexes ofmore » ruthenium compounds with biologically active ligands such as imidazole (Im), histidine (His), benzimidazole (BIm) and its methyl derivative [1,2(CH{sub 3}){sub 2} - BIm], benzohyroxamic acid (Bha), and 1-phenyl-2-methylamino-1-propanol or ephedrine (Eph) in the present work, the authors studied their electrochemical behavior at dropping mercury (dme) and a platinum electrodes. 6 refs., 1 fig., 2 tabs.« less

Gas Chromatography-Mass Spectrometry-Olfactometry To Control the Aroma Fingerprint of Extra Virgin Olive Oil from Three Tunisian Cultivars at Three Harvest Times.

PubMed

Ben Brahim, Samia; Amanpour, Asghar; Chtourou, Fatma; Kelebek, Hasim; Selli, Serkan; Bouaziz, Mohamed

2018-03-21

Gas chromatography-mass spectrometry-olfactometry was used for the analysis of volatile compounds and key odorants of three less studied Tunisian olive oil cultivars for the first time. A total of 42 aroma compounds were identified and quantified in extra virgin olive oils. The present study revealed that the most dominant volatiles in olive oil samples qualitatively and quantitatively were aldehydes and alcohols, followed by terpenes and esters. Indeed, chemometric analysis has shown a correlation between chemical compounds and sensory properties. The determination of aroma-active compounds of olive oil samples was carried out using aroma extract dilution analysis. A total of 15 aroma-active compounds were detected in the aromatic extract of extra virgin olive oil, of which 14 were identified. On the basis of the flavor dilution (FD) factor, the most potent aromatic active compound was hexanal (FD = 512) in Fakhari olive oil, (FD = 256) in Touffehi oils, and (FD = 128) in Jemri olive oil.

Compound cycle engine program

NASA Technical Reports Server (NTRS)

Bobula, G. A.; Wintucky, W. T.; Castor, J. G.

1987-01-01

The Compound Cycle Engine (CCE) is a highly turbocharged, power compounded power plant which combines the lightweight pressure rise capability of a gas turbine with the high efficiency of a diesel. When optimized for a rotorcraft, the CCE will reduce fuel burn for a typical 2 hr (plus 30 min reserve) mission by 30 to 40 percent when compared to a conventional advanced technology gas turbine. The CCE can provide a 50 percent increase in range-payload product on this mission. A program to establish the technology base for a Compound Cycle Engine is presented. The goal of this program is to research and develop those technologies which are barriers to demonstrating a multicylinder diesel core in the early 1990's. The major activity underway is a three-phased contract with the Garrett Turbine Engine Company to perform: (1) a light helicopter feasibility study, (2) component technology development, and (3) lubricant and material research and development. Other related activities are also presented.

Compound cycle engine program

NASA Technical Reports Server (NTRS)

Bobula, G. A.; Wintucky, W. T.; Castor, J. G.

1986-01-01

The Compound Cycle Engine (CCE) is a highly turbocharged, power compounded power plant which combines the lightweight pressure rise capability of a gas turbine with the high efficiency of a diesel. When optimized for a rotorcraft, the CCE will reduce fuel burned for a typical 2 hr (plus 30 min reserve) mission by 30 to 40 percent when compared to a conventional advanced technology gas turbine. The CCE can provide a 50 percent increase in range-payload product on this mission. A program to establish the technology base for a Compound Cycle Engine is presented. The goal of this program is to research and develop those technologies which are barriers to demonstrating a multicylinder diesel core in the early 1990's. The major activity underway is a three-phased contract with the Garrett Turbine Engine Company to perform: (1) a light helicopter feasibility study, (2) component technology development, and (3) lubricant and material research and development. Other related activities are also presented.

Anti-leptospiral activities of an endemic plant Glyptopetalum calocarpum (Kurz.) Prain used as a medicinal plant by Nicobarese of Andaman and Nicobar Islands.

PubMed

Chander, M Punnam; Kumar, K Vinod; Shriram, A N; Vijayachari, P

2015-01-01

Leaves of an endemic plant Glyptopetalum calocarpum are used by Nicobarese tribes of Andaman and Nicobar Islands, India, to prepare traditional medicine for treating fever. In the present investigation, pharmacologically active compounds were isolated from this plant and their antimicrobial efficacy was evaluated against the leptospiral strains. The anti-leptospiral activity of six plant-derived compounds was determined by both microdilution and macrodilution methods. Two out of six compounds, namely lupenone and stigmasterol, showed anti-leptospiral activity. The minimum inhibitory concentrations of the two compounds tested against pathogenic leptospiral strains belonging to 10 serovars were in the range of 100-200 μg/mL. The range of minimum bactericidal concentrations was 400-800 μg/mL. Compounds lupenone, stigmasterol, lupeol, β-amyrin and β-amyrin acetate had negligible or no haemolytic activity, exhibiting IC50 values of greater than 5 mg/mL. Further in vivo studies are needed to investigate the pharmacological and toxicological properties of G. calocarpum before it can be considered as a new anti-leptospiral agent.

The active and passive sampling of benzene, toluene, ethyl benzene and xylenes compounds using the inside needle capillary adsorption trap device.

PubMed

Shojania, S; Oleschuk, R D; McComb, M E; Gesser, H D; Chow, A

1999-08-23

A new and simple method of solventless extraction of volatile organic compounds (VOCs) from air is presented. The sampling device has an adsorbing carbon coating on the interior surface of a hollow needle, and is called the inside needle capillary adsorption trap (INCAT). This paper describes a study of the reproducibility in the preparation and sampling of the INCAT device. In addition, this paper examines the effects of sample volume in active sampling and exposure time in passive sampling on the analyte adsorption. Analysis was achieved by sampling the air from an environmental chamber doped with benzene, toluene, ethyl benzene and xylenes (BTEX) compounds. Initial rates of adsorption were found to vary among the different compounds, but ranged from 0.0099 to 0.016 nmol h(-1) for passive sampling and from 2.2 to 10 nmol h(-1) for active sampling. Analysis was done by thermal desorption of the adsorbed compounds directly into a gas chromatograph injection port. Quantification of the analysis was done by comparison to actively sampled activated carbon solid phase extraction (SPE) measurements.

Antioxidant and Anticholinesterase Activities of Some Dialkylamino Substituted 3-Hydroxyflavone Derivatives.

PubMed

Culhaoglu, Burcu; Capan, Asli; Boga, Mehmet; Ozturk, Mehmet; Ozturk, Turan; Topcu, Gulacti

2017-01-01

Flavones, are a class of naturally occuring polyphenolic compounds which have 2-phenylchromen-4-one structure. Various studies showed that flavones have several pharmacological activities such as antioxidant, anti-inflammatory, antimicrobial, cytotoxic, antitumour and antiallergic. In the present study, 3-hydroxyflavones also called flavonols, posessing 4'-dialkylamino moiety were synthesized, and their antioxidant and anticholinesterase activities were investigated by comparison with unmodified 3-hydroxflavone. For investigation of antioxidant potential, radical scavenging assays (DPPH•, ABTS+_, O2.-) were used along with CUPRAC and lipid peroxidation inhibitory assays, as well as anticholinesterase activity by Ellman method. The best results were obtained for 4'-N,N-dimethyl flavonol (1) in both antioxidant and anticholinesterase activity tests, possibly due to its least steric hinderance effect. It exhibited remarkable DPPH free radical scavenging activity (2.43±0,09 μg/mL) competing with a standard compound quercetin (2.10±0,10 μg/mL). Moreover, the other tested flavonols also showed high antioxidant activities. Compounds 5 and 6 exhibited close IC50 values to those of compound 1. Antioxidant activity test results were found to be well correlated with anticholinesterase activity test results indicating possible role of antioxidant compounds in the treatment of Alzheimer's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Insecticidal activity against Aedes aegypti of m-pentadecadienyl-phenol isolated from Myracrodruon urundeuva seeds.

PubMed

Souza, Terezinha M; Cunha, Arcelina P; Farias, Davi F; Machado, Lyeghyna K; Morais, Selene M; Ricardo, Nágila Mps; Carvalho, Ana Fu

2012-10-01

Myracrodruon urundeuva Fr. Allemao is a common tree in the Caatinga that has been widely used for various medical purposes. Previous studies showed that the ethanol seed extract of M. urundeuva has potent activity against the larval stage of the dengue vector Aedes aegypti. Given this potential insecticidal activity, bioguided separation steps were performed in order to isolate the active compound(s). The isolation process resulted in only one active chemical compound, identified by infrared spectroscopy and mass spectrometry as m-pentadecadienyl-phenol. This compound presented potent larvicidal and pupicidal activity (LC50 10.16 and 99.06 µg mL(-1) respectively) and great egg hatching inhibitory activity (IC50 49.79 µg mL(-1)). The mode of action was investigated through observations of behavioural and morphological changes performed in third-instar larvae treated with m-pentadecadienyl-phenol solution after 1, 6, 12, 16 and 20 h of exposure. Some changes were observed as flooding of the tracheal system, alterations in siphonal valves and anal gills and lethargy, probably caused by the strong anticholinesterasic activity reported previously. The compound isolated from M. urundeuva seeds, m-pentadecadienyl-phenol, showed potent activity against immature stages of dengue vector, Ae. aegypti, being considered the main larvicidal principle. Copyright © 2012 Society of Chemical Industry.

Identification of geranic acid, a tyrosinase inhibitor in lemongrass (Cymbopogon citratus).

PubMed

Masuda, Toshiya; Odaka, Yuka; Ogawa, Natsuko; Nakamoto, Katsuo; Kuninaga, Hideki

2008-01-23

Lemongrass is a popular Asian herb having a lemon-like flavor. Very recently, potent tyrosinase inhibitory activity has been found in lemongrass in addition to various biological activities reported in the literature. The aim of the present study is to identify the active compounds in the lemongrass. An assay-guided purification revealed that one of the active substances was geranic acid. Geranic acid has two stereoisomers, which are responsible for the trans and cis geometry on the conjugated double bond. Both isomers are present in the active ethyl acetate-soluble extract of the lemongrass, and their IC50 values were calculated to be 0.14 and 2.3 mM, respectively. The structure requirement of geranic acid for the potent tyrosinase inhibitory activity was investigated using geranic acid-related compounds.

Identification and quantification of phenolic compounds of selected fruits from Madeira Island by HPLC-DAD-ESI-MS(n) and screening for their antioxidant activity.

PubMed

Spínola, Vítor; Pinto, Joana; Castilho, Paula C

2015-04-15

Five fruits species commonly cultivated and consumed in Madeira Island (Portugal) were investigated for their phenolic profile by means of reversed phase high-performance liquid chromatography coupled to diode array detection and electrospray ionisation mass spectrometry (HPLC-DAD-ESI/MS(n)) and antioxidant potential. A large number of compounds were characterised, flavonoids and phenolic acids being the major components found in target samples, 39 compounds (flavonoids, phenolic acids, terpenoids, cyanogenic glycosides and organic acids) were identified in cherimoyas, lemons, papayas, passion-fruits and strawberries for the first time. Furthermore, all samples were systematically analysed for their total phenolic and flavonoid contents along with two radical scavenging methods (ABTS and ORAC) for antioxidant activity measurement. Target fruits presented high phenolic contents which is responsible for most of the antioxidant activity against radical reactive species (R(2)>0.80). Quantitative data showed that anthocyanins, in particular pelargonidin-3-O-hexoside (>300 mg/100 mL), present only in strawberries were the compounds in largest amounts but are the ones which contribute less to the antioxidant activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ecotoxicological assessment of soils polluted with chemical waste from lindane production: Use of bacterial communities and earthworms as bioremediation tools.

PubMed

Muñiz, Selene; Gonzalvo, Pilar; Valdehita, Ana; Molina-Molina, José Manuel; Navas, José María; Olea, Nicolás; Fernández-Cascán, Jesús; Navarro, Enrique

2017-11-01

An ecotoxicological survey of soils that were polluted with wastes from lindane (γ-HCH) production assessed the effects of organochlorine compounds on the metabolism of microbial communities and the toxicity of these compounds to a native earthworm (Allolobophora chlorotica). Furthermore, the bioremediation role of earthworms as facilitators of soil washing and the microbial degradation of these organic pollutants were also studied. Soil samples that presented the highest concentrations of ε-HCH, 2,4,6-trichlorophenol, pentachlorobenzene and γ-HCH were extremely toxic to earthworms in the short term, causing the death of almost half of the population. In addition, these soils inhibited the heterotrophic metabolic activity of the microbial community. These highly polluted samples also presented substances that were able to activate cellular detoxification mechanisms (measured as EROD and BFCOD activities), as well as compounds that were able to cause endocrine disruption. A few days of earthworm activity increased the extractability of HCH isomers (e.g., γ-HCH), facilitating the biodegradation of organochlorine compounds and reducing the intensity of endocrine disruption in soils that had low or medium contamination levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Inhibitors of 7-Dehydrocholesterol Reductase: Screening of a Collection of Pharmacologically Active Compounds in Neuro2a Cells.

PubMed

Kim, Hye-Young H; Korade, Zeljka; Tallman, Keri A; Liu, Wei; Weaver, C David; Mirnics, Karoly; Porter, Ned A

2016-05-16

A small library of pharmacologically active compounds (the NIH Clinical Collection) was assayed in Neuro2a cells to determine their effect on the last step in the biosynthesis of cholesterol, the transformation of 7-dehydrocholesterol (7-DHC) to cholesterol promoted by 7-dehydrocholesterol reductase, DHCR7. Of some 727 compounds in the NIH Clinical Collection, over 30 compounds significantly increased 7-DHC in Neuro2a cells when assayed at 1 μM. Active compounds that increased 7-DHC with a Z-score of +3 or greater generally gave rise to modest decreases in desmosterol and increases in lanosterol levels. Among the most active compounds identified in the library were the antipsychotic, antidepressant, and anxiolytic compounds that included perospirone, nefazodone, haloperidol, aripiprazole, trazodone, and buspirone. Fluoxetine and risperidone were also active at 1 μM, and another 10 compounds in this class of pharmaceuticals were identified in the screen at concentrations of 10 μM. Increased levels of 7-DHC are associated with Smith-Lemli-Opitz syndrome (SLOS), a human condition that results from a mutation in the gene that encodes DHCR7. The SLOS phenotype includes neurological deficits and congenital malformations, and it is linked to a higher incidence of autism spectrum disorder. The significance of the current study is that it identifies common pharmacological compounds that may induce a biochemical presentation similar to SLOS. Little is known about the side effects of elevated 7-DHC postdevelopmentally, and the elevated 7-DHC that results from exposure to these compounds may also be a confounder in the diagnosis of SLOS.

Imidazopyridine-fused [1,3]-diazepinones: synthesis and antiproliferative activity.

PubMed

Gallud, Audrey; Vaillant, Ophélie; Maillard, Ludovic T; Arama, Dominique P; Dubois, Joëlle; Maynadier, Marie; Lisowski, Vincent; Garcia, Marcel; Martinez, Jean; Masurier, Nicolas

2014-03-21

A series of 15 pyrido-imidazo-1,3-diazepin-5-ones and pyrido-1,3-diazepine-2,5-diones were synthesized and their anticancer activities were evaluated. Among tested compounds on a cell lines panel, compound 6a presents the best growth inhibition activity on 21 cell lines with a cytotoxic effect on MDA-MB-435 melanoma cells. This compound led to deep cell morphological changes and revealed to be an inhibitor of the Hepatocyte progenitor kinase-like kinase (HGK), which is known to be implicated in the migration, adhesion and invasion of various tumor cells. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Critical review of controlled release packaging to improve food safety and quality.

PubMed

Chen, Xi; Chen, Mo; Xu, Chenyi; Yam, Kit L

2018-03-19

Controlled release packaging (CRP) is an innovative technology that uses the package to release active compounds in a controlled manner to improve safety and quality for a wide range of food products during storage. This paper provides a critical review of the uniqueness, design considerations, and research gaps of CRP, with a focus on the kinetics and mechanism of active compounds releasing from the package. Literature data and practical examples are presented to illustrate how CRP controls what active compounds to release, when and how to release, how much and how fast to release, in order to improve food safety and quality.

Cannabinoid-like anti-inflammatory compounds from flax fiber.

PubMed

Styrczewska, Monika; Kulma, Anna; Ratajczak, Katarzyna; Amarowicz, Ryszard; Szopa, Jan

2012-09-01

Flax is a valuable source of fibers, linseed and oil. The compounds of the latter two products have already been widely examined and have been proven to possess many health-beneficial properties. In the course of analysis of fibers extract from previously generated transgenic plants overproducing phenylpropanoids a new terpenoid compound was discovered.The UV spectra and the retention time in UPLC analysis of this new compound reveal similarity to a cannabinoid-like compound, probably cannabidiol (CBD). This was confirmed by finding two ions at m/z 174.1 and 231.2 in mass spectra analysis. Further confirmation of the nature of the compound was based on a biological activity assay. It was found that the compound affects the expression of genes involved in inflammatory processes in mouse and human fibroblasts and likely the CBD from Cannabis sativa activates the specific peripheral cannabinoid receptor 2 (CB2) gene expression. Besides fibers, the compound was also found in all other flax tissues. It should be pointed out that the industrial process of fabric production does not affect CBD activity.The presented data suggest for the first time that flax products can be a source of biologically active cannabinoid-like compounds that are able to influence the cell immunological response. These findings might open up many new applications for medical flax products, especially for the fabric as a material for wound dressing with anti-inflammatory properties.

Cyclobutane-Containing Alkaloids: Origin, Synthesis, and Biological Activities

PubMed Central

Sergeiko, Anastasia; Poroikov, Vladimir V; Hanuš, Lumir O; Dembitsky, Valery M

2008-01-01

Present review describes research on novel natural cyclobutane-containing alkaloids isolated from terrestrial and marine species. More than 60 biological active compounds have been confirmed to have antimicrobial, antibacterial, antitumor, and other activities. The structures, synthesis, origins, and biological activities of a selection of cyclobutane-containing alkaloids are reviewed. With the computer program PASS some additional biological activities are also predicted, which point toward new possible applications of these compounds. This review emphasizes the role of cyclobutane-containing alkaloids as an important source of leads for drug discovery. PMID:19696873

Synthesis, antimicrobial activity and advances in structure-activity relationships (SARs) of novel tri-substituted thiazole derivatives.

PubMed

Reddy, Guda Mallikarjuna; Garcia, Jarem Raul; Reddy, Vemulapati Hanuman; de Andrade, Ageo Meier; Camilo, Alexandre; Pontes Ribeiro, Renan Augusto; de Lazaro, Sergio Ricardo

2016-11-10

Trisubstituted thiazoles were synthesized and studied for their antimicrobial activity and supported by theoretical calculations. In addition, MIC, MBC and MFC were also tested. Moreover, the present study was analyzed to scrutinize comprehensive structure-activity relationships. In fact, LUMO orbital energy and orbital orientation was reliable to explain their antibacterial and antifungal assay. Amongst the tested compounds, tri-methyl-substituted thiazole compound showed higher antimicrobial activity and low MIC value due to highest LUMO energy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Anticancer effects of different seaweeds on human colon and breast cancers.

PubMed

Moussavou, Ghislain; Kwak, Dong Hoon; Obiang-Obonou, Brice Wilfried; Maranguy, Cyr Abel Ogandaga; Dinzouna-Boutamba, Sylvatrie-Danne; Lee, Dae Hoon; Pissibanganga, Ordelia Gwenaelle Manvoudou; Ko, Kisung; Seo, Jae In; Choo, Young Kug

2014-09-24

Seafoods and seaweeds represent some of the most important reservoirs of new therapeutic compounds for humans. Seaweed has been shown to have several biological activities, including anticancer activity. This review focuses on colorectal and breast cancers, which are major causes of cancer-related mortality in men and women. It also describes various compounds extracted from a range of seaweeds that have been shown to eradicate or slow the progression of cancer. Fucoidan extracted from the brown algae Fucus spp. has shown activity against both colorectal and breast cancers. Furthermore, we review the mechanisms through which these compounds can induce apoptosis in vitro and in vivo. By considering the ability of compounds present in seaweeds to act against colorectal and breast cancers, this review highlights the potential use of seaweeds as anticancer agents.

Synthesis and leishmanicidal activity of eugenol derivatives bearing 1,2,3-triazole functionalities.

PubMed

Teixeira, Róbson Ricardo; Gazolla, Poliana Aparecida Rodrigues; da Silva, Adalberto Manoel; Borsodi, Maria Paula Gonçalves; Bergmann, Bartira Rossi; Ferreira, Rafaela Salgado; Vaz, Boniek Gontijo; Vasconcelos, Géssica Adriana; Lima, Wallace Pacienza

2018-02-25

In this paper, it is described the synthesis and the evaluation of the leishmanicidal activity of twenty-six eugenol derivatives bearing 1,2,3-triazole functionalities. The evaluation of the compounds on promastigotes of Leishmania amazonensis (WHOM/BR/75/Josefa) showed that eugenol derivatives present leishmanicidal activities with varying degrees of effectiveness. The most active compound, namely 4-(3-(4-allyl-2-methoxyphenoxy)propyl)-1-(4-methylbenzyl)-1H-1,2,3-triazole (7k) (IC 50  = 7.4 ± 0.8 μmol L -1 ), also targeted Leishmania parasites inside peritoneal macrophages (IC 50  = 1.6 μmol L -1 ) without interfering with cell viability. The cytotoxicity of 7k against macrophage cells presented IC 50 of 211.9 μmol L -1 and the selective index was equal to 132.5. Under similar conditions, compound 7k was more effective than glucantime and pentamidine, two drugs currently in the clinic. In addition, theoretical calculations showed that this compound also presents most physicochemical and pharmacokinetic properties within the ranges expected for orally available drugs. It is believed that eugenol bearing 1,2,3-triazole functionalities may represent a scaffold to be explored toward the development of new agents to treat leishmaniasis. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Antioxidant and antimicrobial activity of natural phenolic extract from defatted soybean flour by-product for stone fruit postharvest application.

PubMed

Villalobos, María del Carmen; Serradilla, Manuel Joaquín; Martín, Alberto; Ordiales, Elena; Ruiz-Moyano, Santiago; Córdoba, María de Guía

2016-04-01

Fresh fruit is highly perishable during storage and transport, so there has been growing interest in finding safe and natural antimicrobial compounds as a control tool. Phenolic compounds are secondary metabolites naturally present in vegetable material and have been associated with antimicrobial and antioxidant properties. Therefore, the aim of this study was to investigate the antioxidant capacity and potential antimicrobial effect of phenolic extract obtained from defatted soybean flour against selected pathogenic bacteria and microorganisms responsible of fruit decay. Analysis of phenolic composition by HPLC-MS showed the presence of a wide range of compounds, with isoflavones and phenolic acids the main polyphenols identified. Furthermore, the phenolic extract had important antioxidant activity by two different assays. Related to antimicrobial activity, in vitro experiments demonstrated that phenolic extract displayed a high activity against the main foodborne pathogens, while a moderate inhibition was found against five spoilage yeasts and Monilia laxa and a scarce effect for Penicillium glabrum, Cladosporium uredinicola and Botrytis cinerea. Interestingly these compounds considerably inhibited the mycelial growth of Monilia laxa, in both in vitro and in vivo experiments. The results of the present study revealed that defatted soybean flour is an important source of phenolic compounds with remarkable antimicrobial and antioxidant activity, suggesting the possibility of using them as natural additives in postharvest treatments to extend the shelf life of fruit. © 2015 Society of Chemical Industry.

Endocrine disruptor activity of multiple environmental food chain contaminants.

PubMed

Wielogórska, E; Elliott, C T; Danaher, M; Connolly, L

2015-02-01

Industrial chemicals, antimicrobials, drugs and personal care products have been reported as global pollutants which enter the food chain. Some of them have also been classified as endocrine disruptors based on results of various studies employing a number of in vitro/vivo tests. The present study employed a mammalian reporter gene assay to assess the effects of known and emerging contaminants on estrogen nuclear receptor transactivation. Out of fifty-nine compounds assessed, estrogen receptor agonistic activity was observed for parabens( n = 3), UV filters (n = 6), phthalates (n = 4) and a metabolite, pyrethroids (n = 9) and their metabolites (n = 3). Two compounds were estrogen receptor antagonists while some of the agonists enhanced 17b-estradiol mediated response.This study reports five new compounds (pyrethroids and their metabolites) possessing estrogen agonist activity and highlights for the first time that pyrethroid metabolites are of particular concern showing much greater estrogenic activity than their parent compounds.

Antimicrobial Activity of Oleanolic and Ursolic Acids: An Update

PubMed Central

Jesus, Jéssica A.; Lago, João Henrique G.; Laurenti, Márcia D.; Yamamoto, Eduardo S.; Passero, Luiz Felipe D.

2015-01-01

Triterpenoids are the most representative group of phytochemicals, as they comprise more than 20,000 recognized molecules. These compounds are biosynthesized in plants via squalene cyclization, a C30 hydrocarbon that is considered to be the precursor of all steroids. Due to their low hydrophilicity, triterpenes were considered to be inactive for a long period of time; however, evidence regarding their wide range of pharmacological activities is emerging, and elegant studies have highlighted these activities. Several triterpenic skeletons have been described, including some that have presented with pentacyclic features, such as oleanolic and ursolic acids. These compounds have displayed incontestable biological activity, such as antibacterial, antiviral, and antiprotozoal effects, which were not included in a single review until now. Thus, the present review investigates the potential use of these triterpenes against human pathogens, including their mechanisms of action, via in vivo studies, and the future perspectives about the use of compounds for human or even animal health are also discussed. PMID:25793002

TREATMENT STUDIES OF CCL CONTAMINANTS

EPA Science Inventory

Bench-scale screening-level treatment data are presented for compounds listed in the Contaminant Candidate List (CCL). All of the CCl compounds are predicted to be economically removed by either activated carbon or air stripping technologies. To complete the screening-level treat...

Pharmacophore Modelling and Synthesis of Quinoline-3-Carbohydrazide as Antioxidants

PubMed Central

El Bakkali, Mustapha; Ismaili, Lhassane; Tomassoli, Isabelle; Nicod, Laurence; Pudlo, Marc; Refouvelet, Bernard

2011-01-01

From well-known antioxidants agents, we developed a first pharmacophore model containing four common chemical features: one aromatic ring and three hydrogen bond acceptors. This model served as a template in virtual screening of Maybridge and NCI databases that resulted in selection of sixteen compounds. The selected compounds showed a good antioxidant activity measured by three chemical tests: DPPH radical, OH° radical, and superoxide radical scavenging. New synthetic compounds with a good correlation with the model were prepared, and some of them presented a good antioxidant activity. PMID:25954520

Rapid identification of microorganisms for biodegradation of alkylphenols and alkylphenol ethercarboxylates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hemming, B.; Williams, J.B.

1995-12-31

Alkylphenols, especially nonylphenol and octylphenol, are used in a wide variety of applications. These compounds, and alkylphenol ethercarboxylates, are also believed to be formed during the biodegradation of alkylphenol ethoxylates in activated sludge wastewater treatment systems. Microbe Inotech Laboratories has developed a rapid assay to identify the microorganisms present in activated sludge wastewater treatment systems (GC-FAME) and a screening assay to measure the biodegradation of compounds. These assays were used to show that alkylphenols and their corresponding ethercarboxylates were degraded aerobically even when these compounds were the sole carbon source.

Chemical constituents of Aspergillus sp EJC08 isolated as endophyte from Bauhinia guianensis and their antimicrobial activity.

PubMed

Pinheiro, Eduardo A A; Carvalho, Josiwander M; Santos, Diellem C P dos; Feitosa, André O; Marinho, Patrícia S B; Guilhon, Giselle Maria S P; Santos, Lourivaldo S; Souza, Afonso L D de; Marinho, Andrey M R

2013-01-01

The present work reports the isolation of five compounds from Aspergillus sp EJC08 isolated as endophytic from Bauhinia guianensis, a tipical plant of the Amazon. The compounds ergosterol (1), ergosterol peroxide (2), mevalolactone (3), monomethylsulochrin (4) and trypacidin A (5) were isolated by chromatographic procedures and identified by spectral methods of 1D and 2D NMR and MS. Compounds 3, 4 and 5 were tested against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus and showed good activity.

Synthesis and evaluation of curcumin-related compounds for anticancer activity.

PubMed

Wei, Xingchuan; Du, Zhi-Yun; Zheng, Xi; Cui, Xiao-Xing; Conney, Allan H; Zhang, Kun

2012-07-01

Sixty-one curcumin-related compounds were synthesized and evaluated for their anticancer activity toward cultured prostate cancer PC-3 cells, pancreas cancer Panc-1 cells and colon cancer HT-29 cells. Inhibitory effects of these compounds on the growth of PC-3, Panc-1 and HT-29 cells were determined by the MTT assay. Compounds E10, F10, FN1 and FN2 exhibited exceptionally potent inhibitory effects on the growth of cultured PC-3, Panc-1 and HT-29 cells. The IC(50) for these compounds was lower than 1 μM in all three cell lines. E10 was 72-, 46- and 117-fold more active than curcumin for inhibiting the growth of PC-3, Panc-1 and HT-29 cells, respectively. F10 was 69-, 34- and 72-fold more active than curcumin for inhibiting the growth of PC-3, Panc-1 and HT-29 cells, respectively. FN1 and FN2 had about the same inhibitory effect as E10 and F10 toward Panc-1 cells but were less active than E10 and F10 toward PC-3 and HT-29 cells. The active compounds were potent stimulators of apoptosis. The present study indicates that E10, F10, FN1 and FN2 may have useful anticancer activity. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Cholinesterase Inhibitory Activity of Some semi-Rigid Spiro Heterocycles: POM Analyses and Crystalline Structure of Pharmacophore Site.

PubMed

Hadda, Taibi Ben; Talhi, Oualid; Silva, Artur S M; Senol, Fatma Sezer; Orhan, Ilkay Erdogan; Rauf, Abdur; Mabkhot, Yahia N; Bachari, Khaldoun; Warad, Ismail; Farghaly, Thoraya A; Althagafi, Ismail I; Mubarak, Mohammad S

2018-01-01

Cholinesterase family consists of two sister enzymes; acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) which hydrolyze acetylcholine. Since deficit of acetylcholine has been evidenced in patients of Alzheimer's disease (AD), cholinesterase inhibitors are currently the most prescribed drugs for the treatment of AD. our aim in this article was to investigate the inhibitory potential of five known compounds (2-6) with spiro skeleton against AChE and BChE using ELISA microplate assays. In addition to their ChE inhibitory effect, their physico-chemical properties were also calculated. Moreover, the present work aims at investigating the charge/geometrical effect of a hypothetical pharmacophore or bidentate site in a bioactive group, on the inhibition efficiency of spiro compounds 2-6 by using Petra/Osiris/ molinspiration (POM) and X-ray analyses. In the present study, five compounds (2-6) with spiro skeleton have been synthesized and tested in vitro for their inhibitory potential against AChE and BChE using ELISA microtiter plate assays at 25 µg/mL. Results revealed that three of the spiro compounds tested exert more than 50% inhibition against one of cholinesterases. Compound 5 displayed 68.73 ± 4.73% of inhibition toward AChE, whereas compound 6 showed 56.17 ± 0.83% of inhibition toward BChE; these two previously synthesized compounds have been the most active hits. Our data obtained from screening of compounds 2-6 against the two cholinesterases indicate that three of these show good potential to selectively inhibit AChE or BChE. Spiro compounds 2, 5, and 6 exhibited the most potent activity of the series against AChE or BChE with inhibition values in the range 55-70%. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The underlying mechanism of action for various medicinal properties of Piper betle (betel).

PubMed

Haslan, H; Suhaimi, F H; Thent, Zar Chi; Das, S

2015-01-01

Piper betle (betel) plant belongs to the Piperaceae family. Piper. betle is widely known for its potent medicinal properties. Various active compounds are present in Piper. betle such as allylpyrocatechol, hydroxychavicol, piperbetol, ethylpiperbetol, piperol A, piperol B, chavibetol, and alkaloids which account for these beneficial medicinal properties. In the present narrative review, we looked into the various active compounds present in the Piper betle and attempted to understand their underlying mechanism of action. Proper understanding of the molecular biology involving the mechanism of action may help in better drug formulation and provide better therapeutic actions in the field of alternative and complementary medicine.

Alkaloids in Marine Algae

PubMed Central

Güven, Kasım Cemal; Percot, Aline; Sezik, Ekrem

2010-01-01

This paper presents the alkaloids found in green, brown and red marine algae. Algal chemistry has interested many researchers in order to develop new drugs, as algae include compounds with functional groups which are characteristic from this particular source. Among these compounds, alkaloids present special interest because of their pharmacological activities. Alkaloid chemistry has been widely studied in terrestrial plants, but the number of studies in algae is insignificant. In this review, a detailed account of macro algae alkaloids with their structure and pharmacological activities is presented. The alkaloids found in marine algae may be divided into three groups: 1. Phenylethylamine alkaloids, 2. Indole and halogenated indole alkaloids, 3. Other alkaloids. PMID:20390105

Taraxacum officinale and Urtica dioica extracts inhibit dengue virus serotype 2 replication in vitro.

PubMed

Flores-Ocelotl, María R; Rosas-Murrieta, Nora H; Moreno, Diego A; Vallejo-Ruiz, Verónica; Reyes-Leyva, Julio; Domínguez, Fabiola; Santos-López, Gerardo

2018-03-16

Urtica dioica, Taraxacum officinale, Calea integrifolia and Caesalpinia pulcherrima are widely used all over the world for treatment of different illnesses. In Mexico, these plants are traditionally used to alleviate or counteract rheumatism and inflammatory muscle diseases. In the present study we evaluated the activity of aqueous and methanolic extracts of these four plants, on the replication of dengue virus serotype 2 (DENV2). Extraction process was carried out in a Soxtherm® system at 60, 85 and 120 °C; a chemical fractionation in silica gel chromatography was performed and compounds present in the active fractions were identified by HPLC-DAD-ESI/MSn. The cytotoxic concentration and the inhibitory effect of extracts or fractions on the DENV2 replication were analyzed in the BHK-21 cell line (plaque forming assay). The half maximal inhibitory concentration (IC 50 ) and the selectivity index (SI) were calculated for the extracts and fractions. The methanolic extracts at 60 °C of T. officinale and U. dioica showed the higher inhibitory effects on DENV2 replication. After the chemical fractionation, the higher activity fraction was found for U. dioica and T. officinale, presenting IC 50 values of 165.7 ± 3.85 and 126.1 ± 2.80 μg/ml, respectively; SI values were 5.59 and 6.01 for each fraction. The compounds present in T. officinale, were luteolin and caffeoylquinic acids derivatives and quercertin diclycosides. The compounds in the active fraction of U. dioica, were, chlorogenic acid, quercertin derivatives and flavonol glycosides (quercetin and kaempferol). Two fractions from U. dioica and T. officinale methanolic extracts with anti-dengue activity were found. The compounds present in both fractions were identified, several recognized molecules have demonstrated activity against other viral species. Subsequent biological analysis of the molecules, alone or in combination, contained in the extracts will be carried out to develop therapeutics against DENV2.

Synthesis and antibacterial activity of sulfonamides. SAR and DFT studies

NASA Astrophysics Data System (ADS)

Boufas, Wahida; Dupont, Nathalie; Berredjem, Malika; Berrezag, Kamel; Becheker, Imène; Berredjem, Hajira; Aouf, Nour-Eddine

2014-09-01

A series of substituted sulfonamide derivatives were synthesized from chlorosulfonyl isocyanate (CSI) in tree steps (carbamoylation, sulfamoylation and deprotection). Antibacterial activity in vitro of some newly formed compounds investigated against clinical strains Gram-positive and Gram-negative: Escherichia coli and Staphylococcus aureus applying the method of dilution and minimal inhibition concentration (MIC) methods. These compounds have significant bacteriostatic activity with totalities of bacterial strains used. DFT calculations with B3LYP/6-31G(d) level have been used to analyze the electronic and geometric characteristics deduced for the stable structure of three compounds presenting conjugation between a nitrogen atom N through its lone pair and an aromatic ring next to it. The principal quantum chemical descriptors have been correlated with the antibacterial activity.

Antidyslipidemic effect and antioxidant activity of anthraquinone derivatives from Rheum emodi rhizomes in dyslipidemic rats.

PubMed

Mishra, Sunil K; Tiwari, Shashi; Shrivastava, Atul; Srivastava, Shishir; Boudh, Goutam K; Chourasia, Shivendra K; Chaturvedi, Upma; Mir, Snober S; Saxena, Anil K; Bhatia, Gitika; Lakshmi, Vijai

2014-04-01

The aim of the present study was to evaluate the antidyslipidemic effect of ethanolic extract of Rheum emodi rhizomes and its constituents in Triton-WR-1339 and high-fat diet (HFD)-induced dyslipidemic rats. In preliminary screening, the ethanolic extract showed significant activity in Triton-treated rats. Bioassay-guided fractionation of the ethanolic extract resulted in the identification of four anthraquinone derivatives, viz. chrysophanol, emodin, chrysophanol 8-O-β-D-glucopyranoside and emodin 8-O-β-D-glucopyranoside as active constituents. All these compounds significantly reduced plasma lipid levels. The most active compound emodin showed significant lipid-lowering activity in the HFD-fed model. In addition, these compounds showed significant antioxidant activity. The effect of emodin on enzymes modulating lipid metabolism confirms and supports the efficiency of emodin as a potent antidyslipidemic agent.

Identification of Three Classes of Heteroaromatic Compounds with Activity against Intracellular Trypanosoma cruzi by Chemical Library Screening

PubMed Central

Bettiol, Esther; Samanovic, Marie; Murkin, Andrew S.; Raper, Jayne; Buckner, Frederick; Rodriguez, Ana

2009-01-01

The development of new drugs against Chagas disease is a priority since the currently available medicines have toxic effects, partial efficacy and are targeted against the acute phase of disease. At present, there is no drug to treat the chronic stage. In this study, we have optimized a whole cell-based assay for high throughput screening of compounds that inhibit infection of mammalian cells by Trypanosoma cruzi trypomastigotes. A 2000-compound chemical library was screened using a recombinant T. cruzi (Tulahuen strain) expressing β-galactosidase. Three hits were selected for their high activity against T. cruzi and low toxicity to host cells in vitro: PCH1, NT1 and CX1 (IC50: 54, 190 and 23 nM, respectively). Each of these three compounds presents a different mechanism of action on intracellular proliferation of T. cruzi amastigotes. CX1 shows strong trypanocidal activity, an essential characteristic for the development of drugs against the chronic stage of Chagas disease where parasites are found intracellular in a quiescent stage. NT1 has a trypanostatic effect, while PCH1 affects parasite division. The three compounds also show high activity against intracellular T. cruzi from the Y strain and against the related kinetoplastid species Leishmania major and L. amazonensis. Characterization of the anti–T. cruzi activity of molecules chemically related to the three library hits allowed the selection of two compounds with IC50 values of 2 nM (PCH6 and CX2). These values are approximately 100 times lower than those of the medicines used in patients against T. cruzi. These results provide new candidate molecules for the development of treatments against Chagas disease and leishmaniasis. PMID:19238193

Identification of three classes of heteroaromatic compounds with activity against intracellular Trypanosoma cruzi by chemical library screening.

PubMed

Bettiol, Esther; Samanovic, Marie; Murkin, Andrew S; Raper, Jayne; Buckner, Frederick; Rodriguez, Ana

2009-01-01

The development of new drugs against Chagas disease is a priority since the currently available medicines have toxic effects, partial efficacy and are targeted against the acute phase of disease. At present, there is no drug to treat the chronic stage. In this study, we have optimized a whole cell-based assay for high throughput screening of compounds that inhibit infection of mammalian cells by Trypanosoma cruzi trypomastigotes. A 2000-compound chemical library was screened using a recombinant T. cruzi (Tulahuen strain) expressing beta-galactosidase. Three hits were selected for their high activity against T. cruzi and low toxicity to host cells in vitro: PCH1, NT1 and CX1 (IC(50): 54, 190 and 23 nM, respectively). Each of these three compounds presents a different mechanism of action on intracellular proliferation of T. cruzi amastigotes. CX1 shows strong trypanocidal activity, an essential characteristic for the development of drugs against the chronic stage of Chagas disease where parasites are found intracellular in a quiescent stage. NT1 has a trypanostatic effect, while PCH1 affects parasite division. The three compounds also show high activity against intracellular T. cruzi from the Y strain and against the related kinetoplastid species Leishmania major and L. amazonensis. Characterization of the anti-T. cruzi activity of molecules chemically related to the three library hits allowed the selection of two compounds with IC(50) values of 2 nM (PCH6 and CX2). These values are approximately 100 times lower than those of the medicines used in patients against T. cruzi. These results provide new candidate molecules for the development of treatments against Chagas disease and leishmaniasis.

Induction of apoptosis in human cervical carcinoma HeLa cells by active compounds from Hypericum ascyron L.

PubMed

Li, Xiu-Mei; Luo, Xue-Gang; He, Jun-Fang; Wang, Nan; Zhou, Hao; Yang, Pei-Long; Zhang, Tong-Cun

2018-03-01

Hypericum ascyron L. (Great St. Johnswort), which belongs to the Hypericaceae family, has been used for the treatment of hematemesis, metrorrhagia, rheumatism, swelling, stomach ache, abscesses, dysentery and irregular menstruation for >2,000 years in China. The aim of the present study was to clarify the anticancer activity compounds from H. ascyron L. and the underlying molecular mechanism. Anticancer activity of H. ascyron L. extract was evaluated using an MTT assay. To confirm the anticancer mechanism of activity compounds, Hoechst 33258, Annexin V-fluorescein isothiocyanate/propidium iodide, 2',7'-dichlorodihydrofluorescein diacetate, rhodamine 123 staining and caspase-3 activity analysis were performed. The results demonstrated that the anti-proliferative action of the mixture of kaempferol 3-O-β-(2″-acetyl) galactopyranoside (K) and quercetin (Q) (molar ratio, 1:1) was significantly increased compared with either of these two compounds separately, and the active fraction of the H. ascyron L. extract |(HALE). HALE, indicating that the anti-proliferative function of H. ascyron L. may be a synergic effect of K and Q. Furthermore, the inhibitory effect of KQ on the growth of HeLa cells was mediated by the induction of apoptosis. To the best of our knowledge, the present study is the first to identify that KQ exhibits significant anti-proliferation activity on HeLa cells via the apoptotic pathway, and is also the first to evaluate the anticancer potential of H. ascyron L. The results of the present study may provide a rational base for the use of H. ascyron L. in the clinic, and shed light on the development of novel anticancer drugs.

Experimental and theoretical studies of a pyrazole-thiazolidin-2,4-di-one hybrid

NASA Astrophysics Data System (ADS)

Mushtaque, Md.; Avecilla, Fernando; Haque, Ashanul; Perwez, Ahmad; Khan, Md. Shahzad; Rizvi, M. Moshahid Alam

2017-08-01

The present work describes synthesis, characterization and biological evaluations of a hybrid compound 10 composed of two intriguing scaffolds pyrazole and thiazolidin-2,4-di-one. The title compound was obtained via multi-step reaction and characterized by a number of techniques (viz. IR, UV-Visible, 1H-NMR, 13C-NMR and MS) including X-ray crystallography. The structural and photophysical data of compound 10 were well supported by theoretical calculations performed at density functional (DFT) level. In-vitro anticancer studies on different human cancer cell lines indicated moderate to low activity of the compounds. The molecular target of the compound was predicted through in-silico studies. Finding of the studies are presented herein.

Phytochemical profile and free radical nitric oxide (NO) scavenging activity of Averrhoa bilimbi L. fruit extract.

PubMed

Suluvoy, Jagadish Kumar; Berlin Grace, V M

2017-05-01

Averrhoa bilimbi L. belongs to family Oxalidaceae. Traditionally, people use this plant (root, bark, leaves and fruits) for treating several illnesses include itches, boils, syphilis, whooping cough, hypertension, fever and inflammation. The aim of the study was to evaluate the nitric oxide (NO) scavenging activity and GC-MS analysis of A. bilimbi L. fruit extract. Averrhoa bilimbi L. fruits were collected for the preliminary phytochemical analysis, antioxidant scavenging activity and biologically important compounds were identified by GC-MS analysis. The preliminary phytochemicals, GC-MS, total phenolic content and NO scavenging activity of the plant were analysed. In the present investigation, the A. bilimbi L. fruit extract has major phytochemicals. Among the 151 compounds identified in GC-MS, 15 compounds are found to have diverse biological activity. We also observed that the A. bilimbi L. fruit extract has high level of total phenolic compounds at a concentration of 209.25 GAE mg/g. Presence of phenolic compound apparently explains the antioxidant activity of the plant. Antioxidant activity of A. bilimbi L. fruit extract is proven from its high level of NO scavenging activity of potent IC50 value of 108.10. From the above study, it is apparent that the A. bilimbi L. fruit extract is a rich source of phytochemicals (natural products) with biological activity. The GC-MS report on this fruit proves that natural products have pharmacologically and biologically active compounds. A high phenolic content is observed in our study. A. bilimbi L. fruit extract is also found to have NO scavenging activity in our study.

Inhibitors of calling behavior of Plodia interpunctella.

PubMed

Hirashima, Akinori; Shigeta, Yoko; Eiraku, Tomohiko; Kuwano, Eiichi

2003-01-01

Some octopamine agonists were found to suppress the calling behavior of the stored product Indian meal moth, Plodia interpunctella. Compounds were screened using a calling behavior bioassay using female P. interpunctella. Four active derivatives, with inhibitory activity at the nanomolar range, were identified in order of decreasing activity: 2-(1-phenylethylamino)-2-oxazoline > 2-(2-ethyl,6-methylanilino)oxazolidine > 2-(2-methyl benzylamino)-2-thiazoline > 2-(2,6-diethylanilino)thiazolidine. Three-dimensional pharmacophore hypotheses were built from a set of 15 compounds. Among the ten common-featured models generated by the program Catalyst/HipHop, a hypothesis including a hydrogen-bond acceptor lipid, a hydrophobic aromatic and two hydrophobic aliphatic features was considered to be essential for inhibitory activity in the calling behavior. Active compounds mapped well onto all the hydrogen-bond acceptor lipid, hydrophobic aromatic and hydrophobic aliphatic features of the hypothesis. On the other hand, less active compounds were shown not to achieve the energetically favorable conformation that is found in the active molecules in order to fit the 3D common-feature pharmacophore models. The present studies demonstrate that inhibition of calling behavior is via an octopamine receptor.

Efficient Electrochemical Synthesis, Antimicrobial and Antiinflammatory Activity of 2–amino-5-substituted- 1,3,4-oxadiazole Derivatives

PubMed Central

Kumar, S.; Srivastava, D. P.

2010-01-01

An efficient electrochemical method for the preparation of 2-amino-5-substituted-1,3,4-oxadiazoles (4a-k) at platinum anode through the electrooxidation of semicarbazone (3a-k) at controlled potential electrolysis has been reported in the present study. The electrolysis was carried out in the acetic acid solvent and lithium perchlorate was used as supporting electrolyte. The products were characterized by IR,1H-NMR,13C-NMR, mass spectra and elemental analysis. The synthesized compounds were screened for their in vitro growth inhibiting activity against different strains of bacteria viz., Klebsilla penumoniae, Escherichia coli, Bassilus subtilis and Streptococcus aureus and antifungal activity against Aspergillus niger and Crysosporium pannical and results have been compared with the standard antibacterial streptomycin and antifungal griseofulvin. Compounds exhibits significant antibacterial activity and antifungal activity. Compounds 4a and g exhibited equal while 4c, d, i and j slightly less antibacterial activity than standard streptomycin. Compounds 4a and g exhibited equal while 4b, c, d, f and i displayed slightly less antifungal activity than standard griseofulvins. PMID:21218056

Antifungal activity of schinol and a new biphenyl compound isolated from Schinus terebinthifolius against the pathogenic fungus Paracoccidioides brasiliensis

PubMed Central

2010-01-01

Background The aim of this study was to isolate and identify the antifungal compounds from the extracts of Schinus terebinthifolius (Anacardiaceae) against clinical isolates of the pathogenic fungus Paracoccidioides brasiliensis. Methods The hexane and dichlomethane fractions from leaves and stems of S. terebinthifolius were fractionated using several chromatography techniques to afford four compounds. Results The compounds isolated from S. terebinthifolius were identified as schinol (1), a new biphenyl compound, namely, 4'-ethyl-4-methyl-2,2',6,6'-tetrahydroxy[1,1'-biphenyl]-4,4'-dicarboxylate (2), quercetin (3), and kaempferol (4). Compounds 1 and 2 were active against different strains of P. brasiliensis, showing a minimal inhibitory concentration value against the isolate Pb B339 of 15.6 μg/ml. The isolate Pb 1578 was more sensitive to compound 1 with a MIC value of 7.5 μg/ml. Schinol presented synergistic effect only when combined with itraconazole. The compounds isolated from S. terebinthifolius were not able to inhibit cell wall synthesis or assembly using the sorbitol assay. Conclusion This work reveals for the first time the occurrence of compound 2 and discloses activity of compounds 1 and 2 against several clinical isolates of P. brasiliensis. These results justify further studies to clarify the mechanisms of action of these compounds. PMID:20939907

Synthesis of new substituted azetidinoyl and thiazolidinoyl-1,3,4-thiadiazino (6,5-b) indoles as promising anti-inflammatory agents.

PubMed

Bhati, Sudhir Kumar; Kumar, Ashok

2008-11-01

Various N-({5-[(arylmethylene)amino]-1,3,4-thiadiazol-2-yl}methyl) [1,3,4] thiadiazino[6,5-b]indol-3-amine (6a-6h), 2-aryl-3-{5-[([1,3,4] thiadiazino[6,5-b]indol-3-ylamino)methyl]-1,3,4-thiadiazol-2-yl}-1,3-thiazolidin-4-one (7a-7h), and 3-chloro-4-aryl-1-{5-[{[1,3,4]thiadiazino[6,5-b]indol-3-ylamino]methyl]-1,3,4-thiadiazol-2-yl}azetidin-2-one (8a-8h) have been synthesized in the present study. The structure of these newly synthesized compounds were confirmed by their analytical and spectral data. These compounds were also evaluated for their anti-inflammatory, ulcerogenic and analgesic activities. Compound 8g has shown most active anti-inflammatory and analgesic activities with better ulcerogenic activity than phenylbutazone, while this compound was found to be associated with lesser degree of anti-inflammatory and analgesic activities as compared to indomethacin.

Secondary metabolites of Eichhornia crassipes (Waterhyacinth): a review (1949 to 2011).

PubMed

Lalitha, Pottail; Sripathi, Shubashini K; Jayanthi, Ponnusamy

2012-09-01

Eichhornia crassipes (Mart.) Solms (Waterhyacinth), an aquatic perennial herb present throughout the world, has a myriad of metabolites. Phenalenone compounds and sterols have been isolated from this plant. Extracts, as well as pure compounds isolated from this plant, have been demonstrated to possess pharmacological activities. An account of the phytochemistry, pharmacological activities and several applications ofwaterhyacinth are included in this review.

Linear and branched alkyl-esters and amides of gallic acid and other (mono-, di- and tri-) hydroxy benzoyl derivatives as promising anti-HCV inhibitors.

PubMed

Rivero-Buceta, Eva; Carrero, Paula; Doyagüez, Elisa G; Madrona, Andrés; Quesada, Ernesto; Camarasa, María José; Peréz-Pérez, María Jesús; Leyssen, Pieter; Paeshuyse, Jan; Balzarini, Jan; Neyts, Johan; San-Félix, Ana

2015-03-06

Linear and branched compounds that contain two, three or five units of galloyl (3,4,5-trihydroxybenzoyl) or its isomer 2,3,4-trihydroxybenzoyl, as well as other mono- or dihydroxybenzoyl moieties have been synthesized. These molecules have been evaluated for their in vitro inhibitory effects against a wide panel of viruses showing preferential activity against HIV and HCV. Our structure-activity relationship studies demonstrated that the 2,3,4-trihydroxybenzoyl moiety provides better antiviral activities than the galloyl (3,4,5-trihydroxybenzoyl) moiety that is present in natural green tea catechins. This observation can be of interest for the further rational exploration of compounds with anti-HCV/HIV properties. The most notable finding with respect to HIV is that the tripodal compounds 43 and 45, with three 2,3,4-trihydroxybenzoyl moieties, showed higher activities than linear compounds with only one or two. With respect to HCV, the linear compounds, 52 and 41, containing a 12 polymethylene chain and two 2,3 di- or 2,3,4 tri-hydroxybenzoyl groups respectively at the ends of the molecule showed good antiviral efficiency. Furthermore, the anti-HCV activity of both compounds was observed at concentrations well below the cytotoxicity threshold. A representative member of these compounds, 41, showed that the anti-HCV activity was largely independent of the genetic make-up of the HCV subgenomic replicon and cell lines used. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Design and Synthesis of Curcumin-Like Diarylpentanoid Analogues as Potential Anticancer Agents.

PubMed

Qudjani, Elahe; Iman, Maryam; Davood, Asghar; Ramandi, Mahdi F; Shafiee, Abbas

2016-01-01

Curcumin is a polyphenolic natural compound with multiple targets that used for the prophylaxis and treatment of some type of cancers like cervical and pancreatic cancers. Some recent patent for curcumin for cancer has also been reviewed. In this study, ten new curcumin derivatives were designed and synthesized and their cytostatic activity evaluated against the Hela and Panc cell lines that some of them showed more activity than curcumin. In the present study, a series of mono-carbonyl derivatives of curcumin were designed and prepared. The details of the synthesis and chemical characterization of the synthesized compounds are described. The cytostatic activities of the designed compounds are assessed in two different tumor cell lines using MTT test. In vitro screening for human cervix carcinoma cell lines (Hela) and pancreatic cell lines (Panc-1) at 24 and 48 hour showed that all the analogs possessed good activity against these tumor cell lines and compounds 5a, 5c and 6 with high potency can be used as a new lead compounds for the designing and finding new and potent cytostatic agents. Docking studies indicated that compound 5c readily binds the active site of human glyoxalase I protein via two strong hydrogen bonds engaging residues of Glu-99 and Lys-156. Our results are useful in guiding a design of optimized ligands with improved pharmacokinetic properties and increased of anti-cancer activity vs. the prototype curcumin compound.

The QSAR and docking calculations of fullerene derivatives as HIV-1 protease inhibitors

NASA Astrophysics Data System (ADS)

Saleh, Noha A.

2015-02-01

The inhibition of HIV-1 protease is considered as one of the most important targets for drug design and the deactivation of HIV-1. In the present work, the fullerene surface (C60) is modified by adding oxygen atoms as well as hydroxymethylcarbonyl (HMC) groups to form 6 investigated fullerene derivative compounds. These compounds have one, two, three, four or five O atoms + HMC groups at different positions on phenyl ring. The effect of the repeating of these groups on the ability of suggested compounds to inhibit the HIV protease is studied by calculating both Quantitative Structure Activity Relationship (QSAR) properties and docking simulation. Based on the QSAR descriptors, the solubility and the hydrophilicity of studied fullerene derivatives increased with increasing the number of oxygen atoms + HMC groups in the compound. While docking calculations indicate that, the compound with two oxygen atoms + HMC groups could interact and binds with HIV-1 protease active site. This is could be attributed to the active site residues of HIV-1 protease are hydrophobic except the two aspartic acids. So that, the increase in the hydrophilicity and polarity of the compound is preventing and/or decreasing the hydrophobic interaction between the compound and HIV-1 protease active site.

Molecular interaction of novel benzothiazolyl triazolium analogues with calf thymus DNA and HSA-their biological investigation as potent antimicrobial agents.

PubMed

Maddili, Swetha K; Katla, Ramesh; Kannekanti, Vijaya Kumar; Bejjanki, Naveen Kumar; Tuniki, Balaraju; Zhou, Cheng-He; Gandham, Himabindu

2018-04-25

The binding behaviour between calf thymus DNA and synthesized benzothiazolyl triazolium derivatives as potent antimicrobial agents was explored by means of spectroscopic applications together with molecular docking study at the sub-domain IIA, binding site I of human serum albumin (HSA). Most of the synthesized derivatives presented significant antimicrobial inhibition when compared with the clinical Norfloxacin, Chloromycin, and Fluconazole. In particular, compound 5q presented efficient anti-Bacillus subtilis, anti-Escherichia coli, anti-Salmonella typhi, and anti-Psuedomonas aeruginosa activity with low MIC values of 2-8 μg/mL which were relatively superior to the reference drugs. The preliminarily investigation of interaction studies with calf thymus DNA demonstrated that the most active compound 5q could effectively intercalate into DNA to form 5q-DNA complex. Further investigations revealed that human serum albumin could effectively transport compound 5q while molecular modelling studies with good docking score showed that hydrophobic interactions as well as hydrogen bonds played a significant role in the interaction of compound 5q with HSA. In addition, the cytotoxic investigation carried out on four different cancerous cell lines (3 human cell lines and 1 murine cell lines) by MTT assay presented that compound 5n is active against MDA cell lines with IC 50 values less than 100 μg/mL. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemical composition and antioxidant activity of dried powder formulations of Agaricus blazei and Lentinus edodes.

PubMed

Carneiro, Andreia A J; Ferreira, Isabel C F R; Dueñas, Montserrat; Barros, Lillian; da Silva, Roberto; Gomes, Eleni; Santos-Buelga, Celestino

2013-06-15

Several mushroom species have been pointed out as sources of antioxidant compounds, in addition to their important nutritional value. Agaricus blazei and Lentinus edodes are among the most studied species all over the world, but those studies focused on their fruiting bodies instead of other presentations, such as powdered preparations, used as supplements. In the present work the chemical composition (nutrients and bioactive compounds) and antioxidant activity (free radical scavenging activity, reducing power and lipid peroxidation inhibition) of dried powder formulations of the mentioned mushroom species (APF and LPF, respectively) were evaluated. Powder formulations of both species revealed the presence of essential nutrients, such as proteins, carbohydrates and unsaturated fatty acids. Furthermore, they present a low fat content (<2g/100g) and can be used in low-calorie diets, just like the mushrooms fruiting bodies. APF showed higher antioxidant activity and higher content of tocopherols and phenolic compounds (124 and 770 μg/100g, respectively) than LPF (32 and 690 μg/100g). Both formulations could be used as antioxidant sources to prevent diseases related to oxidative stress. Copyright © 2012 Elsevier Ltd. All rights reserved.

PON1 and Mediterranean Diet

PubMed Central

Lou-Bonafonte, José M.; Gabás-Rivera, Clara; Navarro, María A.; Osada, Jesús

2015-01-01

The Mediterranean diet has been proven to be highly effective in the prevention of cardiovascular diseases. Paraoxonase 1 (PON1) has been implicated in the development of those conditions, especially atherosclerosis. The present work describes a systematic review of current evidence supporting the influence of Mediterranean diet and its constituents on this enzyme. Despite the differential response of some genetic polymorphisms, the Mediterranean diet has been shown to exert a protective action on this enzyme. Extra virgin olive oil, the main source of fat, has been particularly effective in increasing PON1 activity, an action that could be due to low saturated fatty acid intake, oleic acid enrichment of phospholipids present in high-density lipoproteins that favor the activity, and increasing hepatic PON1 mRNA and protein expressions induced by minor components present in this oil. Other Mediterranean diet constituents, such as nuts, fruits and vegetables, have been effective in modulating the activity of the enzyme, pomegranate and its compounds being the best characterized items. Ongoing research on compounds isolated from all these natural products, mainly phenolic compounds and carotenoids, indicates that some of them are particularly effective, and this may enhance the use of nutraceuticals and functional foods capable of potentiating PON1 activity. PMID:26024295

PON1 and Mediterranean Diet.

PubMed

Lou-Bonafonte, José M; Gabás-Rivera, Clara; Navarro, María A; Osada, Jesús

2015-05-27

The Mediterranean diet has been proven to be highly effective in the prevention of cardiovascular diseases. Paraoxonase 1 (PON1) has been implicated in the development of those conditions, especially atherosclerosis. The present work describes a systematic review of current evidence supporting the influence of Mediterranean diet and its constituents on this enzyme. Despite the differential response of some genetic polymorphisms, the Mediterranean diet has been shown to exert a protective action on this enzyme. Extra virgin olive oil, the main source of fat, has been particularly effective in increasing PON1 activity, an action that could be due to low saturated fatty acid intake, oleic acid enrichment of phospholipids present in high-density lipoproteins that favor the activity, and increasing hepatic PON1 mRNA and protein expressions induced by minor components present in this oil. Other Mediterranean diet constituents, such as nuts, fruits and vegetables, have been effective in modulating the activity of the enzyme, pomegranate and its compounds being the best characterized items. Ongoing research on compounds isolated from all these natural products, mainly phenolic compounds and carotenoids, indicates that some of them are particularly effective, and this may enhance the use of nutraceuticals and functional foods capable of potentiating PON1 activity.

Marine Invertebrate Xenobiotic-Activated Nuclear Receptors: Their Application as Sensor Elements in High-Throughput Bioassays for Marine Bioactive Compounds

PubMed Central

Richter, Ingrid; Fidler, Andrew E.

2014-01-01

Developing high-throughput assays to screen marine extracts for bioactive compounds presents both conceptual and technical challenges. One major challenge is to develop assays that have well-grounded ecological and evolutionary rationales. In this review we propose that a specific group of ligand-activated transcription factors are particularly well-suited to act as sensors in such bioassays. More specifically, xenobiotic-activated nuclear receptors (XANRs) regulate transcription of genes involved in xenobiotic detoxification. XANR ligand-binding domains (LBDs) may adaptively evolve to bind those bioactive, and potentially toxic, compounds to which organisms are normally exposed to through their specific diets. A brief overview of the function and taxonomic distribution of both vertebrate and invertebrate XANRs is first provided. Proof-of-concept experiments are then described which confirm that a filter-feeding marine invertebrate XANR LBD is activated by marine bioactive compounds. We speculate that increasing access to marine invertebrate genome sequence data, in combination with the expression of functional recombinant marine invertebrate XANR LBDs, will facilitate the generation of high-throughput bioassays/biosensors of widely differing specificities, but all based on activation of XANR LBDs. Such assays may find application in screening marine extracts for bioactive compounds that could act as drug lead compounds. PMID:25421319

Antioxidant Activity of Phenolic Compounds from Fava Bean Sprouts.

PubMed

Okumura, Koharu; Hosoya, Takahiro; Kawarazaki, Kai; Izawa, Norihiko; Kumazawa, Shigenori

2016-06-01

Fava beans are eaten all over the world and recently, marketing for their sprouts began in Japan. Fava bean sprouts contain more polyphenols and l-3,4-dihydroxyphenylalanine (l-DOPA) than the bean itself. Our antioxidant screening program has shown that fava bean sprouts also possess a higher antioxidant activity than other commercially available sprouts and mature beans. However, the individual constituents of fava bean sprouts are not entirely known. In the present study, we investigated the phenolic compounds of fava bean sprouts and their antioxidant activity. Air-dried fava bean sprouts were treated with 80% methanol and the extract was partitioned in water with chloroform and ethyl acetate. HPLC analysis had shown that the ethyl acetate-soluble parts contained phenolic compounds, separated by preparative HPLC to yield 5 compounds (1-5). Structural analysis using NMR and MS revealed that the compounds isolated were kaempferol glycosides. All isolated compounds had an α-rhamnose at the C-7 position with different sugars attached at the C-3 position. Compounds 1-5 had β-galactose, β-glucose, α-rhamnose, 6-acetyl-β-galactose and 6-acetyl-β-glucose, respectively, at the C-3 position. The amount of l-DOPA in fava bean sprouts was determined by the quantitative (1) H NMR technique. The l-DOPA content was 550.45 mg ± 11.34 /100 g of the raw sprouts. The antioxidant activities of compounds 2-5 and l-DOPA were evaluated using the 2,2-diphenyl-1-picrylhydrazyl scavenging assay. l-DOPA showed high antioxidant activity, but the isolated kaempferol glycosides showed weak activity. Therefore, it can be suggested that l-DOPA contributed to the antioxidant activity of fava bean sprouts. © 2016 Institute of Food Technologists®

New Whitening Constituents from Taiwan-Native Pyracantha koidzumii: Structures and Tyrosinase Inhibitory Analysis in Human Epidermal Melanocytes.

PubMed

Lin, Rong-Dih; Chen, Mei-Chuan; Liu, Yan-Ling; Lin, Yi-Tzu; Lu, Mei-Kuang; Hsu, Feng-Lin; Lee, Mei-Hsien

2015-12-02

Nontoxic natural products useful in skin care cosmetics are of considerable interest. Tyrosinase is a rate-limiting enzyme for which its inhibitor is useful in developing whitening cosmetics. Pyracantha koidzumii (Hayata) Rehder is an endemic species in Taiwan that exhibits tyrosinase-inhibitory activity. To find new active natural compounds from P. koidzumii, we performed bioguided isolation and studied the related activity in human epidermal melanocytes. In total, 13 compounds were identified from P. koidzumii in the present study, including two new compounds, 3,6-dihydroxy-2,4-dimethoxy-dibenzofuran (9) and 3,4-dihydroxy-5-methoxybiphenyl-2'-O-β-d-glucopyranoside (13), as well as 11 known compounds. The new compound 13 exhibited maximum potency in inhibiting cellular tyrosinase activity, the protein expression of cellular tyrosinase and tyrosinase-related protein-2, as well as the mRNA expression of Paired box 3 and microphthalmia-associated transcription factor in a concentration-dependent manner. In the enzyme kinetic assay, the new compound 13 acted as an uncompetitive mixed-type inhibitor against the substrate l-3,4-dihydroxyphenylalanine and had a Km value against this substrate of 0.262 mM, as calculated using the Lineweaver-Burk plots. Taken together, our findings show compound 13 exhibits tyrosinase inhibition in human melanocytes and compound 13 may be a potential candidate for use in cosmetics.

New Whitening Constituents from Taiwan-Native Pyracantha koidzumii: Structures and Tyrosinase Inhibitory Analysis in Human Epidermal Melanocytes

PubMed Central

Lin, Rong-Dih; Chen, Mei-Chuan; Liu, Yan-Ling; Lin, Yi-Tzu; Lu, Mei-Kuang; Hsu, Feng-Lin; Lee, Mei-Hsien

2015-01-01

Nontoxic natural products useful in skin care cosmetics are of considerable interest. Tyrosinase is a rate-limiting enzyme for which its inhibitor is useful in developing whitening cosmetics. Pyracantha koidzumii (Hayata) Rehder is an endemic species in Taiwan that exhibits tyrosinase-inhibitory activity. To find new active natural compounds from P. koidzumii, we performed bioguided isolation and studied the related activity in human epidermal melanocytes. In total, 13 compounds were identified from P. koidzumii in the present study, including two new compounds, 3,6-dihydroxy-2,4-dimethoxy-dibenzofuran (9) and 3,4-dihydroxy-5-methoxybiphenyl-2ʹ-O-β-d-glucopyranoside (13), as well as 11 known compounds. The new compound 13 exhibited maximum potency in inhibiting cellular tyrosinase activity, the protein expression of cellular tyrosinase and tyrosinase-related protein-2, as well as the mRNA expression of Paired box 3 and microphthalmia-associated transcription factor in a concentration-dependent manner. In the enzyme kinetic assay, the new compound 13 acted as an uncompetitive mixed-type inhibitor against the substrate l-3,4-dihydroxyphenylalanine and had a Km value against this substrate of 0.262 mM, as calculated using the Lineweaver–Burk plots. Taken together, our findings show compound 13 exhibits tyrosinase inhibition in human melanocytes and compound 13 may be a potential candidate for use in cosmetics. PMID:26633381

Classification of auxin plant hormones by interaction property similarity indices

NASA Astrophysics Data System (ADS)

Tomić, Sanja; Gabdoulline, Razif R.; Kojić-Prodić, Biserka; Wade, Rebecca C.

1998-01-01

Although auxins were the first type of plant hormone to be identified, little is known about the molecular mechanism of this important class of plant hormones. We present a classification of a set of about 50 compounds with measured auxin activities, according to their interaction properties. Four classes of compounds were defined: strongly active, weakly active with weak antiauxin behaviour, inactive and inhibitory. All compounds were modeled in two low-energy conformations, `P' and `T', so as to obtain the best match to the `planar' and `tilted' conformations, respectively, of indole 3-acetic acid. Each set of conformers was superimposed separately using several different alignment schemes. Molecular interaction energy fields were computed for each molecule with five different chemical probes and then compared by computing similarity indices. Similarity analysis showed that the classes are on average distinguishable, with better differentiation achieved for the T conformers than the P conformers. This indicates that the T conformation might be the active one. Further, a screening was developed which could distinguish compounds with auxin activity from inactive compounds and most antiauxins using the T conformers. The classifications rationalize ambiguities in activity data found in the literature and should be of value in predicting the activities of new plant growth substances and herbicides.

Purine derivatives with antituberculosis activity

NASA Astrophysics Data System (ADS)

Gruzdev, D. A.; Musiyak, V. V.; Levit, G. L.; Krasnov, V. P.; Charushin, V. N.

2018-06-01

The review summarizes the data published over the last 10–15 years concerning the key groups of purine derivatives with antituberculosis activity. The structures of purines containing heteroatoms (S, O, N), fragments of heterocycles, amino acids and peptides, in the 6-position, as well as of purine nucleosides are presented. The possible targets for the action of such compounds and structure–activity relationship are discussed. Particular attention is paid to the most active compounds, which are of considerable interest as a basis for the development of efficient antituberculosis drugs. The bibliography includes 99 references.

Bioactive Compounds of Blueberries: Post-Harvest Factors Influencing the Nutritional Value of Products

PubMed Central

Michalska, Anna; Łysiak, Grzegorz

2015-01-01

Blueberries, besides having commonly-recognized taste properties, are also a valuable source of health-promoting bioactive compounds. For several decades, blueberries have gained in popularity all over the world, and recent years have seen not only an increase in fresh consumption, but also in the importance of blueberries for the processing industry. Blueberry processing mostly consists of freezing and juicing. Recently, more attention has been drawn to dewatering and drying, which are promising areas for developing novel blueberry products. Processing affects each biologically-active compound in a different way, and it is still unknown what changes those compounds undergo at the molecular level after the application of different processing technologies. This work presents the most recent state of knowledge about the pre-treatment and processing methods applied to blueberries and their influence on the content of biologically-active compounds. The presentation of methods is preceded by a brief overview of the characteristics of the blueberry species, a description of the chemical composition of the fruit and a short note about the main growing areas, production volumes and the management of fruit crops. PMID:26266408

Bioactive Compounds of Blueberries: Post-Harvest Factors Influencing the Nutritional Value of Products.

PubMed

Michalska, Anna; Łysiak, Grzegorz

2015-08-10

Blueberries, besides having commonly-recognized taste properties, are also a valuable source of health-promoting bioactive compounds. For several decades, blueberries have gained in popularity all over the world, and recent years have seen not only an increase in fresh consumption, but also in the importance of blueberries for the processing industry. Blueberry processing mostly consists of freezing and juicing. Recently, more attention has been drawn to dewatering and drying, which are promising areas for developing novel blueberry products. Processing affects each biologically-active compound in a different way, and it is still unknown what changes those compounds undergo at the molecular level after the application of different processing technologies. This work presents the most recent state of knowledge about the pre-treatment and processing methods applied to blueberries and their influence on the content of biologically-active compounds. The presentation of methods is preceded by a brief overview of the characteristics of the blueberry species, a description of the chemical composition of the fruit and a short note about the main growing areas, production volumes and the management of fruit crops.

Conventional and microwave assisted synthesis of pyrazolone Mannich bases possessing anti-inflammatory, analgesic, ulcerogenic effect and antimicrobial properties.

PubMed

Sivakumar, Kullampalayam Krishnasamy; Rajasekaran, Aiyalu; Senthilkumar, Palaniappan; Wattamwar, Prasad P

2014-07-01

In the present study, an efficient synthesis of some Mannich base of 5-methyl-2-[(2-oxo-2H-chromen-3-yl)carbonyl]-2,4-dihydro-3H-pyrazol-3-one (4a-j) have been described by using conventional and non-conventional (microwave) techniques. Microwave assisted reactions showed that require shorter reaction time and good yield. The newly synthesized compounds were screened for their anti-inflammatory, analgesic activity, antioxidant, and antibacterial effects were compared with standard drug. Among the compounds studied, compound (4f) showing nearly equipotent anti-inflammatory and analgesic activity than the standard drug (indomethacin), along with minimum ulcerogenic index. Compounds (4b and 4i) showing 1.06 times more active than ciprofloxacin against tested Gram-negative bacteria. Copyright © 2014 Elsevier Ltd. All rights reserved.

An elemental model of retrospective revaluation without within-compound associations.

PubMed

Connor, Patrick C; Lolordo, Vincent M; Trappenberg, Thomas P

2014-03-01

When retrospective revaluation phenomena (e.g., unovershadowing: AB+, then A-, then test B) were discovered, simple elemental models were at a disadvantage because they could not explain such phenomena. Extensions of these models and novel models appealed to within-compound associations to accommodate these new data. Here, we present an elemental, neural network model of conditioning that explains retrospective revaluation apart from within-compound associations. In the model, previously paired stimuli (say, A and B, after AB+) come to activate similar ensembles of neurons, so that revaluation of one stimulus (A-) has the opposite effect on the other stimulus (B) through changes (decreases) in the strength of the inhibitory connections between neurons activated by B. The ventral striatum is discussed as a possible home for the structure and function of the present model.

Analysis of phytochemical profile of Terminalia arjuna bark extract with antioxidative and antimicrobial properties

PubMed Central

Mandal, Shreya; Patra, Arpita; Samanta, Animesh; Roy, Suchismita; Mandal, Arpita; Mahapatra, Tapasi Das; Pradhan, Shrabani; Das, Koushik; Nandi, Dilip Kumar

2013-01-01

Objective To investigate phytochemical screening, antimicrobial activity and qualitative thin layer chromatographic separation of flavonoid components, antioxidant activity and total flavonoid compound of Terminalia arjuna. Methods For phytochemical screening, some common and available standard tests were done. Antimicrobial bioassay was done through agar well diffusion method. Detection of antioxidant activity and flavonoid compounds were done through thin layer chromatography. Total antioxidant activity was measured by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) in colorimetric method. Aluminum chloride colorimetric method was used for total flavonoid determination. Results Phytochemical screening showed the active compounds presence in high concentration, such as phytosterol, lactones, flavonoids, phenolic compounds and tannins and glycosides. The antimicrobial activity of extract showed that greater inhibition zone against Gram negative bacteria than Gram positive bacteria. This methanolic extract showed a promising antioxidant activity, as absorption of DPPH redicles decreased in DPPH free radical scavenging assay. Flavonoids components having antioxidant property present in the methanol extract at a level of 199.00 mg quercetin equivalent/g of dried methanol extract in colorimetric method. Conclusions The Terminalia arjuna bark extract revealed the presence of bio-active constituents which are known to exhibit medicinal as well as physiological activities. PMID:24093787

Benzimidazole--ibuprofen/mesalamine conjugates: potential candidates for multifactorial diseases.

PubMed

Bansal, Yogita; Kaur, Maninder; Silakari, Om

2015-01-07

Ibuprofen (IB) and mesalamine (MES) are commonly used NSAIDs whereas benzimidazole (BZ) and 2-aminobenzimidazole (ABZ) are important pharmacophore for immunomodulatory activities. In the present study, IB and MES were coupled with variedly substituted BZ or ABZ nucleus to synthesize IB-BZ (2a-2e), IB-ABZ (3a-3e), MES-BZ (4a-4e) and MES-ABZ (5a-5e) chimeric conjugates as novel compounds that could elicit both anti-inflammatory and immunomodulatory activities. Each compound retained the anti-inflammatory activity of the parent NSAID. The BZ conjugates (2 and 4) were found immunostimulatory whereas the ABZ conjugates (3 and 5) were immunosuppressive. Each compound also exhibited good antioxidant activity, which is attributed to the electron rich BZ and ABZ nuclei. Compound 2a, 2e, 3a, 3e and 5b exhibited the most significant anti-inflammatory and immunomodulatory activities. Hence, these were evaluated for in vivo acute gastric ulcerogenicity. The compounds were safe to gastric mucosa, probably due to masking of the free -COOH group of IB and MES, and/or to the BZ nucleus itself. A benzoyl group at 5-position of BZ and ABZ incurred maximum immunostimulatory activity. In contrast, a -NO2 group incurred the maximum immunosuppressive action. Docking analysis revealed the compounds to be more selective towards COX-2 enzyme, which support the gastroprotective activity. These results suggest that the compounds can be taken as lead for development of new drugs for the treatment of immune related inflammatory disorders, such as cancer and rheumatoid arthritis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Co-evaluation of plant extracts as petrochemical substitutes and for biologically active compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

McChesney, J.D.; Adams, R.P.

Recent efforts to discover phytochemicals that could substitute for petroleum-derived fuels and industrial feedstocks have not given much attention to the potential of these same phytochemicals to provide sources of biologically active compounds. The suitability of extraction products made to assess specific plants as potential botanochemical sources has been evaluated for use in screening procedures for evidence of biologically active compounds. Screening procedures for antibacterial, antifungal and toxic properties are discussed. Screening results are presented for extracts of nearly 80 species of plants from the southeastern United States and southern Great Plains that had previously been evaluated as sources ofmore » botanochemicals.« less

Ontology-based content analysis of US patent applications from 2001-2010.

PubMed

Weber, Lutz; Böhme, Timo; Irmer, Matthias

2013-01-01

Ontology-based semantic text analysis methods allow to automatically extract knowledge relationships and data from text documents. In this review, we have applied these technologies for the systematic analysis of pharmaceutical patents. Hierarchical concepts from the knowledge domains of chemical compounds, diseases and proteins were used to annotate full-text US patent applications that deal with pharmacological activities of chemical compounds and filed in the years 2001-2010. Compounds claimed in these applications have been classified into their respective compound classes to review the distribution of scaffold types or general compound classes such as natural products in a time-dependent manner. Similarly, the target proteins and claimed utility of the compounds have been classified and the most relevant were extracted. The method presented allows the discovery of the main areas of innovation as well as emerging fields of patenting activities - providing a broad statistical basis for competitor analysis and decision-making efforts.

Synthesis, spectroscopic characterization, and antibacterial evaluation of new Schiff bases bearing benzimidazole moiety

NASA Astrophysics Data System (ADS)

Redayan, Muayed Ahmed; Salih Hussein, Maha; Tark lafta, Ashraf

2018-05-01

The present work comprise synthesis of new derivatives for Schiff bases bearing benzimidazole ring. Compounds 1(a-d) were prepared by reaction of o-pheneylenediamine with a various of amino acids (glycine, alanine, phenyl alanine and tyrosine) in the presence 6N HCl to yielded derivatives of benzimidazole compounds containing free –NH2 group. Then these compounds used to prepare different Schiff bases through reaction with various of aromatic aldehydes. The chemical structure of synthesized compounds were confirmed by FTIR,1H,13C-NMR, and 13C-NMR dept135 spectroscopy. Some selected compounds were evaluated in vitro for their antibacterial activity against two types of Gram-positive bacteria namely (Staphylococcous aureus, Bacillus subtilis) and Gram-negative bacteria namely (Pseudomonas aeruginosa, Escherichia coli). Most of the results of the antibacterial activity of these compounds were good when compared with the standard antibiotic ampicillin and ciprofloxacin.

Carvacrol derivatives as mushroom tyrosinase inhibitors; synthesis, kinetics mechanism and molecular docking studies.

PubMed

Ashraf, Zaman; Rafiq, Muhammad; Nadeem, Humaira; Hassan, Mubashir; Afzal, Samina; Waseem, Muhammad; Afzal, Khurram; Latip, Jalifah

2017-01-01

The present work describesthe development of highly potent mushroom tyrosinase inhibitor better than the standard kojic acid. Carvacrol derivatives 4a-f and 6a-d having substituted benzoic acid and cinnamic acidresidues were synthesized with the aim to possess potent tyrosinase inhibitory activity.The structures of the synthesized compounds were ascertained by their spectroscopic data (FTIR, 1HNMR, 13CNMR and Mass Spectroscopy).Mushroom tyrosinase inhibitory activity of synthesized compounds was determined and it was found that one of the derivative 6c possess higher activity (IC50 0.0167μM) than standard kojic acid (IC50 16.69μM). The derivatives 4c and 6b also showed good tyrosinase inhibitory activity with (IC50 16.69μM) and (IC50 16.69μM) respectively.Lineweaver-Burk and Dixon plots were used for the determination of kinetic mechanism of the compounds 4c and 6b and 6c. The kinetic analysis revealed that compounds 4c and 6b showed mixed-type inhibition while 6c is a non-competitive inhibitor having Ki values19 μM, 10 μM, and 0.05 μMrespectively. The enzyme inhibitory kinetics further showed thatcompounds 6b and 6c formed irreversible enzyme inhibitor complex while 4c bind reversibly with mushroom tyrosinase.The docking studies showed that compound 6c have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (-7.90 kcal/mol) as compared to others.The 2-hydroxy group in compound 6c interacts with amino acid HIS85 which is present in active binding site. The wet lab results are in good agreement with the dry lab findings.Based upon our investigation we may propose that the compound 6c is promising candidate for the development of safe cosmetic agent.

Rapid, convenient method for screening imidazole-containing compounds for heme oxygenase inhibition.

PubMed

Vlahakis, Jason Z; Rahman, Mona N; Roman, Gheorghe; Jia, Zongchao; Nakatsu, Kanji; Szarek, Walter A

2011-01-01

Sensitive assays for measuring heme oxygenase activity have been based on the gas-chromatographic detection of carbon monoxide using elaborate, expensive equipment. The present study describes a rapid and convenient method for screening imidazole-containing candidates for inhibitory activity against heme oxygenase using a plate reader, based on the spectroscopic evaluation of heme degradation. A PowerWave XS plate reader was used to monitor the absorbance (as a function of time) of heme bound to purified truncated human heme oxygenase-1 (hHO-1) in the individual wells of a standard 96-well plate (with or without the addition of a test compound). The degradation of heme by heme oxygenase-1 was initiated using l-ascorbic acid, and the collected relevant absorbance data were analyzed by three different methods to calculate the percent control activity occurring in wells containing test compounds relative to that occurring in control wells with no test compound present. In the cases of wells containing inhibitory compounds, significant shifts in λ(max) from 404 to near 412 nm were observed as well as a decrease in the rate of heme degradation relative to that of the control. Each of the three methods of data processing (overall percent drop in absorbance over 1.5h, initial rate of reaction determined over the first 5 min, and estimated pseudo first-order reaction rate constant determined over 1.5h) gave similar and reproducible results for percent control activity. The fastest and easiest method of data analysis was determined to be that using initial rates, involving data acquisition for only 5 min once reactions have been initiated using l-ascorbic acid. The results of the study demonstrate that this simple assay based on the spectroscopic detection of heme represents a rapid, convenient method to determine the relative inhibitory activity of candidate compounds, and is useful in quickly screening a series or library of compounds for heme oxygenase inhibition. Copyright © 2010 Elsevier Inc. All rights reserved.

Three-dimensional common-feature hypotheses of inhibitors of calling behaviour and in vitro [14C]acetate incorporation by pheromone glands of Plodia interpunctella.

PubMed

Hirashima, Akinori; Eiraku, Tomohiko; Shigeta, Yoko; Kuwano, Eiichi; Taniguchi, Eiji; Eto, Morifusa

2002-11-01

Some octopamine (OA) agonists were found to suppress the calling behaviour and pheromone biosynthesis in vitro of the Indian meal moth, Plodia interpunctella (Hübner), a stored-product pest. Compounds were screened using a calling behaviour bioassay of female P interpunctella. Three active derivatives, with activity at the nanomolar level, were identified. In order of decreasing pheromonostatic activity these were: 2-(2-ethyl-6-methylanilino)oxazolidine > 2-(2,6-diethylanilino)thiazolidine > 2-(2,6-diethylanilino)oxazolidine. These compounds showed also in vitro inhibitory activities in de novo pheromone biosynthesis. Three-dimensional pharmacophore hypotheses were built from a set of 19 compounds. Among the ten common-featured models generated by the program Catalyst/HipHop, a hypothesis including a ring aromatic group (RA), a positive ionizable group (PI) and two hydrophobic aliphatic (HpA1) features was considered to be essential for inhibitory activity in the calling behaviour and pheromone biosynthesis in vitro. Active compounds mapped well onto all the RA, PI and HpA1 features of the hypothesis. Less-active compounds were shown not to achieve the energetically favourable conformation which was found in the active molecules in order to fit the 3-D common-feature pharmacophore models. The present studies demonstrate that inhibition of calling behaviour and PBAN-stimulated incorporation of radioactivity is by OA-agonistic activity.

Oleuropein in Olive and its Pharmacological Effects

PubMed Central

Omar, Syed Haris

2010-01-01

Olive from Olea europaea is native to the Mediterranean region and, both the oil and the fruit are some of the main components of the Mediterranean diet. The main active constituents of olive oil include oleic acid, phenolic constituents, and squalene. The main phenolic compounds, hydroxytyrosol and oleuropein, give extra-virgin olive oil its bitter, pungent taste. The present review focuses on recent works that have analyzed the relationship between the major phenolic compound oleuropein and its pharmacological activities including antioxidant, anti-inflammatory, anti-atherogenic, anti-cancer activities, antimicrobial activity, antiviral activity, hypolipidemic and hypoglycemic effect. PMID:21179340

Simple amides of oleanolic acid as effective penetration enhancers.

PubMed

Bednarczyk-Cwynar, Barbara; Partyka, Danuta; Zaprutko, Lucjusz

2015-01-01

Transdermal transport is now becoming one of the most convenient and safe pathways for drug delivery. In some cases it is necessary to use skin penetration enhancers in order to allow for the transdermal transport of drugs that are otherwise insufficiently skin-permeable. A series of oleanolic acid amides as potential transdermal penetration enhancers was formed by multistep synthesis and the synthesis of all newly prepared compounds is presented. The synthetized amides of oleanolic acid were tested for their in vitro penetration promoter activity. The above activity was evaluated by means of using the Fürst method. The relationships between the chemical structure of the studied compounds and penetration activity are presented.

Simple Amides of Oleanolic Acid as Effective Penetration Enhancers

PubMed Central

Bednarczyk-Cwynar, Barbara; Partyka, Danuta; Zaprutko, Lucjusz

2015-01-01

Transdermal transport is now becoming one of the most convenient and safe pathways for drug delivery. In some cases it is necessary to use skin penetration enhancers in order to allow for the transdermal transport of drugs that are otherwise insufficiently skin-permeable. A series of oleanolic acid amides as potential transdermal penetration enhancers was formed by multistep synthesis and the synthesis of all newly prepared compounds is presented. The synthetized amides of oleanolic acid were tested for their in vitro penetration promoter activity. The above activity was evaluated by means of using the Fürst method. The relationships between the chemical structure of the studied compounds and penetration activity are presented. PMID:26010090

Antimalarial Activity of Plant Metabolites.

PubMed

Pan, Wen-Hui; Xu, Xin-Ya; Shi, Ni; Tsang, Siu Wai; Zhang, Hong-Jie

2018-05-06

Malaria, as a major global health problem, continues to affect a large number of people each year, especially those in developing countries. Effective drug discovery is still one of the main efforts to control malaria. As natural products are still considered as a key source for discovery and development of therapeutic agents, we have evaluated more than 2000 plant extracts against Plasmodium falciparum . As a result, we discovered dozens of plant leads that displayed antimalarial activity. Our phytochemical study of some of these plant extracts led to the identification of several potent antimalarial compounds. The prior comprehensive review article entitled “Antimalarial activity of plant metabolites” by Schwikkard and Van Heerden (2002) reported structures of plant-derived compounds with antiplasmodial activity and covered literature up to the year 2000. As a continuation of this effort, the present review covers the antimalarial compounds isolated from plants, including marine plants, reported in the literature from 2001 to the end of 2017. During the span of the last 17 years, 175 antiplasmodial compounds were discovered from plants. These active compounds are organized in our review article according to their plant families. In addition, we also include ethnobotanical information of the antimalarial plants discussed.

Synthesis and antitumoral activity of novel 3-(2-substituted-1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-3-yl) beta-carboline derivatives.

PubMed

Formagio, Anelise S Nazari; Tonin, Lilian T Düsman; Foglio, Mary Ann; Madjarof, Christiana; de Carvalho, João Ernesto; da Costa, Willian Ferreira; Cardoso, Flávia P; Sarragiotto, Maria Helena

2008-11-15

Several novel 1-substituted-phenyl beta-carbolines bearing the 2-substituted-1,3,4-oxadiazol-5-yl and 5-substituted-1,2,4-triazol-3-yl groups at C-3 were synthesized and evaluated for their in vitro anticancer activity. The assay results pointed thirteen compounds with growth inhibition effect (GI(50)<100 microM) for all eight different types of human cancer cell lines tested. The beta-carbolines 7a and 7h, bearing the 3-(2-metylthio-1,3,4-oxadiazol-5-yl) group, displayed high selectivity and potent anticancer activity against ovarian cell line with GI(50) values lying in the nanomolar concentration range (GI(50)=10 nM for both compounds). The 1-(N,N-dimethylaminophenyl)-3-(5-thioxo-1,2,4-triazol-3-yl) beta-carboline (8g) was the most active compound, showing particular effectiveness on lung (GI(50)=0.06 microM), ovarian and renal cell lines. The potent anticancer activity presented for synthesized compounds 7a, 7h, and 8g, together with their easiness of synthesis, makes these compounds promising anticancer agents.

Data on changes in red wine phenolic compounds, headspace aroma compounds and sensory profile after treatment of red wines with activated carbons with different physicochemical characteristics.

PubMed

Filipe-Ribeiro, Luís; Milheiro, Juliana; Matos, Carlos C; Cosme, Fernanda; Nunes, Fernando M

2017-06-01

Data in this article presents the changes on phenolic compounds, headspace aroma composition and sensory profile of a red wine spiked with 4-ethylphenol and 4-ethylguaiacol and treated with seven activated carbons with different physicochemical characteristics, namely surface area, micropore volume and mesopore volume ("Reduction of 4-ethylphenol and 4-ethylguaiacol in red wine by activated carbons with different physicochemical characteristics: impact on wine quality" Filipe-Ribeiro et al. (2017) [1]). Data on the physicochemical characteristics of the activated carbons are shown. Statistical data on the sensory expert panel consistency by General Procrustes Analysis is shown. Statistical data is also shown, which correlates the changes in chemical composition of red wines with the physicochemical characteristics of activated carbons used.

The role of within-compound associations in learning about absent cues.

PubMed

Witnauer, James E; Miller, Ralph R

2011-05-01

When two cues are reinforced together (in compound), most associative models assume that animals learn an associative network that includes direct cue-outcome associations and a within-compound association. All models of associative learning subscribe to the importance of cue-outcome associations, but most models assume that within-compound associations are irrelevant to each cue's subsequent behavioral control. In the present article, we present an extension of Van Hamme and Wasserman's (Learning and Motivation 25:127-151, 1994) model of retrospective revaluation based on learning about absent cues that are retrieved through within-compound associations. The model was compared with a model lacking retrieval through within-compound associations. Simulations showed that within-compound associations are necessary for the model to explain higher-order retrospective revaluation and the observed greater retrospective revaluation after partial reinforcement than after continuous reinforcement alone. These simulations suggest that the associability of an absent stimulus is determined by the extent to which the stimulus is activated through the within-compound association.

The role of within-compound associations in learning about absent cues

PubMed Central

Witnauer, James E.

2011-01-01

When two cues are reinforced together (in compound), most associative models assume that animals learn an associative network that includes direct cue–outcome associations and a within-compound association. All models of associative learning subscribe to the importance of cue–outcome associations, but most models assume that within-compound associations are irrelevant to each cue's subsequent behavioral control. In the present article, we present an extension of Van Hamme and Wasserman's (Learning and Motivation 25:127–151, 1994) model of retrospective revaluation based on learning about absent cues that are retrieved through within-compound associations. The model was compared with a model lacking retrieval through within-compound associations. Simulations showed that within-compound associations are necessary for the model to explain higher-order retrospective revaluation and the observed greater retrospective revaluation after partial reinforcement than after continuous reinforcement alone. These simulations suggest that the associability of an absent stimulus is determined by the extent to which the stimulus is activated through the within-compound association. PMID:21264569

Oleamide: a member of the endocannabinoid family?

PubMed Central

Fowler, Christopher J

2003-01-01

The fatty acid amide class of compounds, which include the endocannabinoid anandamide and the sleep-inducing compound oleamide, have been shown in vitro to have a multiplicity of actions upon different neurochemical systems. In the present issue of this journal, Leggett et al present data indicating that oleamide functionally activates CB1 cannabinoid receptors in vitro. The significance of their finding is discussed in this commentary. PMID:14691053

A machine learning approach to computer-aided molecular design

NASA Astrophysics Data System (ADS)

Bolis, Giorgio; Di Pace, Luigi; Fabrocini, Filippo

1991-12-01

Preliminary results of a machine learning application concerning computer-aided molecular design applied to drug discovery are presented. The artificial intelligence techniques of machine learning use a sample of active and inactive compounds, which is viewed as a set of positive and negative examples, to allow the induction of a molecular model characterizing the interaction between the compounds and a target molecule. The algorithm is based on a twofold phase. In the first one — the specialization step — the program identifies a number of active/inactive pairs of compounds which appear to be the most useful in order to make the learning process as effective as possible and generates a dictionary of molecular fragments, deemed to be responsible for the activity of the compounds. In the second phase — the generalization step — the fragments thus generated are combined and generalized in order to select the most plausible hypothesis with respect to the sample of compounds. A knowledge base concerning physical and chemical properties is utilized during the inductive process.

Natural bioactive compounds from winery by-products as health promoters: a review.

PubMed

Teixeira, Ana; Baenas, Nieves; Dominguez-Perles, Raul; Barros, Ana; Rosa, Eduardo; Moreno, Diego A; Garcia-Viguera, Cristina

2014-09-04

The relevance of food composition for human health has increased consumers' interest in the consumption of fruits and vegetables, as well as foods enriched in bioactive compounds and nutraceuticals. This fact has led to a growing attention of suppliers on reuse of agro-industrial wastes rich in healthy plant ingredients. On this matter, grape has been pointed out as a rich source of bioactive compounds. Currently, up to 210 million tons of grapes (Vitis vinifera L.) are produced annually, being the 15% of the produced grapes addressed to the wine-making industry. This socio-economic activity generates a large amount of solid waste (up to 30%, w/w of the material used). Winery wastes include biodegradable solids namely stems, skins, and seeds. Bioactive compounds from winery by-products have disclosed interesting health promoting activities both in vitro and in vivo. This is a comprehensive review on the phytochemicals present in winery by-products, extraction techniques, industrial uses, and biological activities demonstrated by their bioactive compounds concerning potential for human health.

Plant-derived phenolic compounds prevent the DNA single-strand breakage and cytotoxicity induced by tert-butylhydroperoxide via an iron-chelating mechanism.

PubMed Central

Sestili, Piero; Diamantini, Giuseppe; Bedini, Annalida; Cerioni, Liana; Tommasini, Ilaria; Tarzia, Giorgio; Cantoni, Orazio

2002-01-01

The protective effects of selected members from a series of caffeic acid esters and flavonoids were tested in various toxicity paradigms using U937 cells, previously shown to be sensitive to either iron chelators or bona fide radical scavengers or to both classes of compounds. It was found that all the protective polyphenols were active at very low concentrations and that their effects were observed only under those conditions in which iron chelators also afforded protection. Consistently, active polyphenolic compounds, unlike the inactive ones, effectively chelated iron in an in vitro system. It follows that, at least under the experimental conditions utilized in the present study, the most prominent activity of these polyphenolic compounds resides in their ability to chelate iron. Further studies revealed that the protective effects afforded by the caffeic acid esters and flavonoids were largely mediated by the catechol moiety and that the relative biological potency of these compounds was a direct function of their lipophilicity. PMID:11988084

Anticancer Principles from Medicinal Piper (胡椒 Hú Jiāo) Plants

PubMed Central

Wang, Yue-Hu; Morris-Natschke, Susan L.; Yang, Jun; Niu, Hong-Mei; Long, Chun-Lin; Lee, Kuo-Hsiung

2014-01-01

The ethnomedical uses of Piper (胡椒 Hú Jiāo) plants as anticancer agents, in vitro cytotoxic activity of both extracts and compounds from Piper plants, and in vivo antitumor activity and mechanism of action of selected compounds are reviewed in the present paper. The genus Piper (Piperaceae) contains approximately 2000 species, of which 10 species have been used in traditional medicines to treat cancer or cancer-like symptoms. Studies have shown that 35 extracts from 24 Piper species and 32 compounds from Piper plants possess cytotoxic activity. Amide alkaloids account for 53% of the major active principles. Among them, piplartine (piperlongumine) shows the most promise, being toxic to dozens of cancer cell lines and having excellent in vivo activity. It is worthwhile to conduct further anticancer studies both in vitro and in vivo on Piper plants and their active principles. PMID:24872928

[The estimation method of compounds opiate activity based on universal three-dimensional model of the nonselective opiate pharmacophore].

PubMed

Kuz'mina, N E; Iashkir, V A; Merkulov, V A; Osipova, E S

2012-01-01

Created by means alternative strategy of structural similarity search universal three-dimensional model of the nonselective opiate pharmacophore and the estimation method of agonistic and antagonistic properties of opiate receptors ligands based on its were described. The examples of the present method use are given for opiate activity estimation of compounds essentially distinguished on the structure from opiates and traditional opioids.

Combustion Organic Aerosol as Cloud Condensation Nuclei in Ship Tracks.

NASA Astrophysics Data System (ADS)

Russell, Lynn M.; Noone, Kevin J.; Ferek, Ronald J.; Pockalny, Robert A.; Flagan, Richard C.; Seinfeld, John H.

2000-08-01

Polycyclic aromatic hydrocarbons (PAHs) have been sampled in marine stratiform clouds to identify the contribution of anthropogenic combustion emissions in activation of aerosol to cloud droplets. The Monterey Area Ship Track experiment provided an opportunity to acquire data on the role of organic compounds in ambient clouds and in ship tracks identified in satellite images. Identification of PAHs in cloud droplet residual samples indicates that several PAHs are present in cloud condensation nuclei in anthropogenically influenced air and do result in activated droplets in cloud. These results establish the presence of combustion products, such as PAHs, in submicrometer aerosols in anthropogenically influenced marine air, with enhanced concentrations in air polluted by ship effluent. The presence of PAHs in droplet residuals in anthropogenically influenced air masses indicates that some fraction of those combustion products is present in the cloud condensation nuclei that activate in cloud. Although a sufficient mass of droplet residuals was not collected to establish a similar role for organics from measurements in satellite-identified ship tracks, the available evidence from the fraction of organics present in the interstitial aerosol is consistent with part of the organic fraction partitioning to the droplet population. In addition, the probability that a compound will be found in cloud droplets rather than in the unactivated aerosol and the compound's water solubility are compared. The PAHs studied are only weakly soluble in water, but most of the sparse data collected support more soluble compounds having a higher probability of activation.

Trends and exceptions of physical properties on antibacterial activity for Gram-positive and Gram-negative pathogens.

PubMed

Brown, Dean G; May-Dracka, Tricia L; Gagnon, Moriah M; Tommasi, Ruben

2014-12-11

To better understand the difficulties surrounding the identification of novel antibacterial compounds from corporate screening collections, physical properties of ∼3200 antibacterial project compounds with whole cell activity against Gram-negative or Gram-positive pathogens were profiled and compared to actives found from high throughput (HTS) screens conducted on both biochemical and phenotypic bacterial targets. The output from 23 antibacterial HTS screens illustrated that when compared to the properties of the antibacterial project compounds, the HTS actives were significantly more hydrophobic than antibacterial project compounds (typically 2-4 log units higher), and furthermore, for 14/23 HTS screens, the average clogD was higher than the screening collection average (screening collection clogD = 2.45). It was found that the consequences of this were the following: (a) lead identification programs often further gained hydrophobic character with increased biochemical potency, making the separation even larger between the physicochemical properties of known antibacterial agents and the HTS active starting point, (b) the probability of plasma protein binding and cytotoxicity are often increased, and (c) cell-based activity in Gram-negative bacteria was severely limited or, if present, demonstrated significant efflux. Our analysis illustrated that compounds least susceptible to efflux were those which were highly polar and small in MW or very large and typically zwitterionic. Hydrophobicity was often the dominant driver for HTS actives but, more often than not, precluded whole cell antibacterial activity. However, simply designing polar compounds was not sufficient for antibacterial activity and pointed to a lack of understanding of complex and specific bacterial penetration mechanisms.

A strategy based on gas chromatography-mass spectrometry and virtual molecular docking for analysis and prediction of bioactive composition in natural product essential oil.

PubMed

Wang, Haiyang; Gu, Dongyu; Wang, Miao; Guo, Hong; Wu, Huijuan; Tian, Guangliang; Li, Qian; Yang, Yi; Tian, Jing

2017-06-09

The discovery of leads from medicinal plants is crucial to drug development. The present study presents a strategy based on GC-MS coupled with molecular docking for analysis, identification and prediction of protein tyrosine phosphatase 1B inhibitors in the essential oil from Himalayan Cedar (HC). The essential oil with IC 50 value of 120.71±0.26μg/mL exhibited potential activity against protein tyrosine phosphatase 1B (PTP1B) in vitro. After GC-MS analysis, 35 compounds were identified from this oil. The identified compounds were individually docked with PTP1B. Caryophyllene oxide with the lowest binding energy of -6.28kcal/mol was completely wrapped by the active site of PTP1B. The docking results indicated that caryophyllene oxide has potential PTP1B inhibitory activity and may be responsible for the PTP1B inhibitory activity of the essential oil. Caryophyllene oxide in the essential oil of Himalayan Cedar was isolated by HSCCC and the PTP1B inhibitory activity of this compound was then evaluated; the IC 50 value was 31.32±0.38μM. The result revealed that the present strategy can effectively discover the active composition from the complex mixture of medicinal plants. Copyright © 2017 Elsevier B.V. All rights reserved.

A new class of potential chloroquine-resistance reversal agents for Plasmodia: syntheses and biological evaluation of 1-(3'-diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines.

PubMed

Batra, S; Srivastava, P; Roy, K; Pandey, V C; Bhaduri, A P

2000-09-07

1-(3'-Diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines were synthesized and evaluated for CQ-resistant reversal activity. In general the compounds of the series elicit better biological response than their phenylmethyl analogues. The most active compound 4b has been evaluated in vivo in detail, and the results are presented. The possible mode of action of the compounds of this series is by inhibition of the enzyme heme oxygenase, thereby increasing the levels of heme and hemozoin, which are lethal to the parasite.

Interactions of polyphenols with carbohydrates, lipids and proteins.

PubMed

Jakobek, Lidija

2015-05-15

Polyphenols are secondary metabolites in plants, investigated intensively because of their potential positive effects on human health. Their bioavailability and mechanism of positive effects have been studied, in vitro and in vivo. Lately, a high number of studies takes into account the interactions of polyphenols with compounds present in foods, like carbohydrates, proteins or lipids, because these food constituents can have significant effects on the activity of phenolic compounds. This paper reviews the interactions between phenolic compounds and lipids, carbohydrates and proteins and their impact on polyphenol activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Assessment of ten density functionals through the use of local hyper-softness to get insights about the catalytic activity : Iron-based organometallic compounds for ethylene polymerization as testing molecules.

PubMed

Martínez-Araya, Jorge I; Glossman-Mitnik, Daniel

2018-01-18

Ten functionals were used to assess their capability to compute a local reactivity descriptor coming from the Conceptual Density Functional Theory on a group of iron-based organometallic compounds that have been synthesized by Zohuri, G.H. et al. in 2010; these compounds bear the following substituent groups: H-, O 2 N- and CH 3 O- at the para position of the pyridine ring and their catalytic activities were experimentally measured by these authors. The present work involved a theoretical analysis applied on the aforementioned iron-based compounds thus leading to suggest a new 2,6-bis(imino)pyridine catalyst based on iron(II) bearing a fluorine atom whose possible catalytic activity is suggested to be near the catalytic activity of the complex bearing a hydrogen atom as a substituent group by means of the so called local hyper-softness (LHS) thus opening a chance to estimate a possible value of catalytic activity for a new catalyst that has not been synthesized yet without simulating the entire process of ethylene polymerization. Since Conceptual DFT is not a predictive theory, but rather interpretative, an analysis of the used reactivity descriptor and its dependence upon the level of theory was carried in the present work, thus revealing that care should be taken when DFT calculations are used for these purposes.

Compound stimulus presentation and the norepinephrine reuptake inhibitor atomoxetine enhance long-term extinction of cocaine-seeking behavior.

PubMed

Janak, Patricia H; Bowers, M Scott; Corbit, Laura H

2012-03-01

Drug abstinence is frequently compromised when addicted individuals are re-exposed to environmental stimuli previously associated with drug use. Research with human addicts and in animal models has demonstrated that extinction learning (non-reinforced cue-exposure) can reduce the capacity of such stimuli to induce relapse, yet extinction therapies have limited long-term success under real-world conditions (Bouton, 2002; O'Brien, 2008). We hypothesized that enhancing extinction would reduce the later ability of drug-predictive cues to precipitate drug-seeking behavior. We, therefore, tested whether compound stimulus presentation and pharmacological treatments that augment noradrenergic activity (atomoxetine; norepinephrine reuptake inhibitor) during extinction training would facilitate the extinction of drug-seeking behaviors, thus reducing relapse. Rats were trained that the presentation of a discrete cue signaled that a lever press response would result in cocaine reinforcement. Rats were subsequently extinguished and spontaneous recovery of drug-seeking behavior following presentation of previously drug-predictive cues was tested 4 weeks later. We find that compound stimulus presentations or pharmacologically increasing noradrenergic activity during extinction training results in less future recovery of responding, whereas propranolol treatment reduced the benefit seen with compound stimulus presentation. These data may have important implications for understanding the biological basis of extinction learning, as well as for improving the outcome of extinction-based therapies.

Antimicrobial and Antiradical Activity of Extracts Obtained from Leaves of Five Species of the Genus Bergenia: Identification of Antimicrobial Compounds.

PubMed

Żbikowska, Beata; Franiczek, Roman; Sowa, Alina; Połukord, Grażyna; Krzyżanowska, Barbara; Sroka, Zbigniew

2017-09-01

An important focus of modern medicine is the search for new substances and strategies to combat infectious diseases, which present an increasing threat due to the growth of bacterial resistance to antibiotics. Another problem concerns free radicals, which in excess can cause several serious diseases. An alternative to chemical synthesis of antimicrobial and antiradical compounds is to find active substances in plant raw materials. We prepared extracts from leaves of five species of the genus Bergenia: B. purpurascens, B. cordifolia, B. ligulata, B. crassifolia, and B. ciliata. Antimicrobial and antiradical features of extracts and raw materials were assessed, and the quantities of phenolic compounds were determined. We also evaluated, using high-performance liquid chromatography, the amounts of arbutin and hydroquinone, compounds related to antimicrobial activity of these raw materials. The strongest antiradical properties were shown by leaves of B. crassifolia and B. cordifolia, the lowest by leaves of B. ciliata. The antiradical activity of extracts showed a strong positive correlation with the amount of phenols. All raw materials have significant antimicrobial properties. Among them, the ethyl acetate extracts were the most active. Antimicrobial activity very weakly correlated with the amount of arbutin, but correlated very strongly with the contents of both hydroquinone and phenolic compounds. Additional experiments using artificially prepared mixtures of phenolic compounds and hydroquinone allowed us to conclude that the most active antimicrobial substance is hydroquinone.

Ultrasound promoted one pot synthesis of novel fluorescent triazolyl spirocyclic oxindoles using DBU based task specific ionic liquids and their antimicrobial activity.

PubMed

Singh, Harjinder; Sindhu, Jayant; Khurana, Jitender M; Sharma, Chetan; Aneja, K R

2014-04-22

Spirocyclic oxindoles and triazolyl derivatives posses remarkable biological activities. In present work, we have described an efficient one pot four-component domino reaction of 1-(prop-2-ynyl)indoline-2,3-dione, cyclic 1,3-diketones, malononitrile and various aryl azides in DBU based ionic liquids [DBU-H]OAc and [DBU-Bu]OH under ultrasonic irradiation for the construction of heterocycles, comprising spiro-oxindole, 2-amino-4H-pyran, and 1,2,3-triazoles substructures. The antimicrobial activity of all compounds has been investigated against six microbial strains. All compounds showed good antimicrobial activity. All newly synthesized compounds exhibit fluorescence in methanol with large stoke shift. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

N-cinnamoylated chloroquine analogues as dual-stage antimalarial leads.

PubMed

Pérez, Bianca C; Teixeira, Cátia; Albuquerque, Inês S; Gut, Jiri; Rosenthal, Philip J; Gomes, José R B; Prudêncio, Miguel; Gomes, Paula

2013-01-24

The control of malaria is challenged by drug resistance, and new antimalarial drugs are needed. New drug discovery efforts include consideration of hybrid compounds as potential multitarget antimalarials. Previous work from our group has demonstrated that hybrid structures resulting from cinnamic acid conjugation with heterocyclic moieties from well-known antimalarials present improved antimalarial activity. Now, we report the synthesis and SAR analysis of an expanded series of cinnamic acid derivatives displaying remarkably high activities against both blood- and liver-stage malaria parasites. Two compounds judged most promising, based on their in vitro activity and druglikeness according to the Lipinski rules and Veber filter, were active in vivo against blood-stage rodent malaria parasites. Therefore, the compounds reported represent a new entry as promising dual-stage antimalarial leads.

Design, synthesis, and herbicidal activity of novel substituted 3-(pyridin-2-yl)benzenesulfonamide derivatives.

PubMed

Xie, Yong; Chi, Hui-Wei; Guan, Ai-Ying; Liu, Chang-Ling; Ma, Hong-Juan; Cui, Dong-Liang

2014-12-31

A series of novel substituted 3-(pyridin-2-yl)benzenesulfonamide derivatives were designed and synthesized using 2-phenylpridines as the lead compound by intermediate derivatization methods in an attempt to obtain novel compound candidates for weed control. The herbicidal activity assay in glasshouse tests showed several compounds (II6, II7, II8, II9, II10, II11, III2, III3, III4, and III5) could efficiently control velvet leaf, youth-and-old age, barnyard grass, and foxtail at the 37.5 g/ha active substance. Especially, the activities of II6, II7, III2, and III4 were proved roughly equivalent to the saflufenacil and better than 95% sulcotrione at the same concentration. The result of the herbicidal activity assay in field tests demonstrated that II7 at 60 g/ha active substance could give the same effect as bentazon at 1440 g/ha active substance to control dayflower and nightshade, meanwhile II7 showed better activity than oxyfluorfen to control arrowhead and security to rice. The present work indicates that II7 may be a novel compound candidate for potential herbicide.

Structural features, kinetics and SAR study of radical scavenging and antioxidant activities of phenolic and anilinic compounds

PubMed Central

2013-01-01

Background Phenolic compounds are widely distributed in plant kingdom and constitute one of the most important classes of natural and synthetic antioxidants. In the present study fifty one natural and synthetic structurally variant phenolic, enolic and anilinic compounds were examined as antioxidants and radical scavengers against DPPH, hydroxyl and peroxyl radicals. The structural diversity of the used phenolic compounds includes monophenols with substituents frequently present in natural phenols e.g. alkyl, alkoxy, ester and carboxyl groups, besides many other electron donating and withdrawing groups, in addition to polyphenols with 1–3 hydroxyl groups and aminophenols. Some common groups e.g. alkyl, carboxyl, amino and second OH groups were incorporated in ortho, meta and para positions. Results SAR study indicates that the most important structural feature of phenolic compounds required to possess good antiradical and antioxidant activities is the presence of a second hydroxyl or an amino group in o- or p-position because of their strong electron donating effect in these positions and the formation of a stable quinone-like products upon two hydrogen-atom transfer process; otherwise, the presence of a number of alkoxy (in o or p-position) and /or alkyl groups (in o, m or p-position) should be present to stabilize the resulted phenoxyl radical and reach good activity. Anilines showed also similar structural feature requirements as phenols to achieve good activities, except o-diamines which gave low activity because of the high energy of the resulted 1,2-dimine product upon the 2H-transfer process. Enols with ene-1,2-diol structure undergo the same process and give good activity. Good correlations were obtained between DPPH inhibition and inhibition of both OH and peroxyl radicals. In addition, good correlations were obtained between DPPH inhibition and antioxidant activities in sunflower oil and liver homogenate systems. Conclusions In conclusion, the structures of good anti radical and antioxidant phenols and anilines are defined. The obtained good correlations imply that measuring anti DPPH activity can be used as a simple predictive test for the anti hydroxyl and peroxyl radical, and antioxidant activities. Kinetic measurements showed that strong antioxidants with high activity have also high reaction rates indicating that factors stabilizing the phenoxyl radicals lower also the activation energy of the hydrogen transfer process. PMID:23497653

The red wine extract-induced activation of endothelial nitric oxide synthase is mediated by a great variety of polyphenolic compounds.

PubMed

Auger, Cyril; Chaabi, Mehdi; Anselm, Eric; Lobstein, Annelise; Schini-Kerth, Valérie B

2010-07-01

Phenolic extracts from red wine (RWPs) have been shown to induce nitric oxide (NO)-mediated vasoprotective effects, mainly by causing the PI3-kinase/Akt-dependent activation of endothelial NO synthase (eNOS). RWPs contain several hundreds of phenolic compounds. The aim of the present study was to identify red wine phenolic compounds capable of activating eNOS in endothelial cells using multi-step fractionation. The red wine phenolic extract was fractionated using Sephadex LH-20 and preparative RP-HPLC approaches. The ability of a fraction to activate eNOS was assessed by determining the phosphorylation level of Akt and eNOS by Western blot analysis, and NO formation by electron spin resonance spectroscopy. Tentative identification of phenolic compounds in fractions was performed by MALDI-TOF and HPLC-MS techniques. Separation of RWPs by Sephadex LH-20 generated nine fractions (fractions A to I), of which fractions F, G, H and I caused significant eNOS activation. Fraction F was then subjected to semi-preparative RP-HPLC to generate ten subfractions (subfraction SF1 to SF10), all of which caused eNOS activation. The active fractions and subfractions contained mainly procyanidins and anthocyanins. Isolation of phenolic compounds from SF9 by semi-preparative RP-HLPC lead to the identification of petunidin-O-coumaroyl-glucoside as a potent activator of eNOS.

Discovery of antifungal constituents from the Miao medicinal plant Isodon flavidus.

PubMed

Li, Ji-Xin; Li, Qi-Ji; Guan, Yi-Fu; Song, Xun; Liu, Ya-Hua; Zhang, Jing-Jie; Li, Wan-Fei; Du, Jiang; Zhu, Min; Banas, Jeffrey A; Li, Xiao-Nian; Pan, Lu-Tai; Zhang, Hong-Jie

2016-09-15

Leigong Mountain is an area in the Southwest of China where there is a high incidence rate of athlete's foot, but the Miao people, a Chinese minority who reside in this mountainous area have suffered less from this disease due to their use of the herbal medicine Isodon flavidus (Hand.-Mazz.) H. Hara. The present study is to identify the active chemical constituents responsible for antifungal effects of the folk medicine plant. The natural compounds were separated from the methanol extract of the twigs and leaves of I. flavidus by phytochemical study using chromatographic methods, and their chemical structures were determined by analysis of the spectroscopic data including 1D and 2D NMR spectra. The absolute configuration of fladin A (1) was further confirmed by X-ray crystallographic analysis. The compounds were evaluated for their antifungal activity against the athlete's foot fungus Trichophyton rubrum. They were further evaluated for their antimicrobial and anti-biofilm activity against the dental pathogens Streptococcus mutans, Porphyromonas gingivalis and Candida albicans. Phytochemical and biological studies of I. flavidus led to the discovery of two antifungal compounds, fladin A (1) and lophanic acid (2). Fladin A (1) is a novel diterpene with an unprecedented cyclic ether group formed between C-4 and C-9. Lophanic acid (2) displayed inhibition activity against the athlete's foot fungus Trichophyton rubrum with an MIC value of 7.8μg/mL, and fladin A (1) also showed inhibition activity against the fungus with a MIC value of 62.5μg/mL. Our identification of two antifungal compounds provided strong evidence for the Miao people to use I. flavidus as a medicinal plant for treatment of athlete's foot disease. The very different chemical structures of the active compounds from those in the market presents them as potential antifungal lead compounds for follow-up study. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hygroscopicity of organic compounds as a function of carbon chain length, carboxyl, hydroperoxy, and carbonyl functional groups

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petters, Sarah Suda; Pagonis, Demetrios; Claflin, Megan Suzanne

The albedo and microphysical properties of clouds are controlled in part by the hygroscopicity of particles serving as cloud condensation nuclei (CCN). Hygroscopicity of complex organic mixtures in the atmosphere varies widely and remains challenging to predict. Here we present new measurements characterizing the CCN activity of pure compounds in which carbon chain length and the number of hydroperoxy, carboxyl, and carbonyl functional groups were systematically varied to establish the contributions of these groups to organic aerosol apparent hygroscopicity. Apparent hygroscopicity decreased with carbon chain length and increased with polar functional groups in the order carboxyl > hydroperoxy > carbonyl.more » Activation diameters at different supersaturations deviated from the -3/2 slope in log-log space predicted by Köhler theory, suggesting that water solubility limits CCN activity of particles composed of weakly functionalized organic compounds. Results are compared to a functional group contribution model that predicts CCN activity of organic compounds. The model performed well for most compounds but under-predicted the CCN activity of hydroperoxy groups. New best-fit hydroperoxy group/water interaction parameters were derived from the available CCN data. Lastly, these results may help improve estimates of the CCN activity of ambient organic aerosols from composition data.« less

Synthesis and evaluation of 4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran] analogues against both active and dormant Mycobacterium tuberculosis.

PubMed

Alluri, Kiran Kumar; Reshma, Rudraraju Srilakshmi; Suraparaju, Raghuram; Gottapu, Suryanarayana; Sriram, Dharmarajan

2018-05-01

Need for new drugs to fight against tuberculosis (TB) is increasing day by day. In the present work we have taken a spiro compound (GSK 2200150A) reported by GSK as a lead and we modified the structure of the lead to study the antitubercular activity. For structure activity profiling twenty-one molecules have been synthesized, characterized and evaluated for their antimycobacterial potency against both active and dormant TB. Compound 06, 1-((4-methoxyphenyl)sulfonyl)-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran] was found to be the most potent compound (MIC: 8.23 µM) in active TB and was less effective than the lead but more potent than standard first line drug ethambutol. It was also found to be more efficacious than Isoniazid and Rifampicin and equipotent as Moxifloxacin against dormant Mycobacterium tuberculosis (MTB). Compound 06 also showed good inhibitory potential against over expressed latent MTB enzyme lysine ε-amino transferase with an IC 50 of 1.04 ± 0.32 µM. This compound is a good candidate for drug development owing to potential against both active and dormant stages of MTB. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hygroscopicity of organic compounds as a function of carbon chain length, carboxyl, hydroperoxy, and carbonyl functional groups

DOE PAGES

Petters, Sarah Suda; Pagonis, Demetrios; Claflin, Megan Suzanne; ...

2017-06-16

The albedo and microphysical properties of clouds are controlled in part by the hygroscopicity of particles serving as cloud condensation nuclei (CCN). Hygroscopicity of complex organic mixtures in the atmosphere varies widely and remains challenging to predict. Here we present new measurements characterizing the CCN activity of pure compounds in which carbon chain length and the number of hydroperoxy, carboxyl, and carbonyl functional groups were systematically varied to establish the contributions of these groups to organic aerosol apparent hygroscopicity. Apparent hygroscopicity decreased with carbon chain length and increased with polar functional groups in the order carboxyl > hydroperoxy > carbonyl.more » Activation diameters at different supersaturations deviated from the -3/2 slope in log-log space predicted by Köhler theory, suggesting that water solubility limits CCN activity of particles composed of weakly functionalized organic compounds. Results are compared to a functional group contribution model that predicts CCN activity of organic compounds. The model performed well for most compounds but under-predicted the CCN activity of hydroperoxy groups. New best-fit hydroperoxy group/water interaction parameters were derived from the available CCN data. Lastly, these results may help improve estimates of the CCN activity of ambient organic aerosols from composition data.« less

Thiazole-based nitrogen mustards: Design, synthesis, spectroscopic studies, DFT calculation, molecular docking, and antiproliferative activity against selected human cancer cell lines

NASA Astrophysics Data System (ADS)

Łączkowski, Krzysztof Z.; Świtalska, Marta; Baranowska-Łączkowska, Angelika; Plech, Tomasz; Paneth, Agata; Misiura, Konrad; Wietrzyk, Joanna; Czaplińska, Barbara; Mrozek-Wilczkiewicz, Anna; Malarz, Katarzyna; Musioł, Robert; Grela, Izabela

2016-09-01

Synthesis, characterization and investigation of antiproliferative activity of ten thiazole-based nitrogen mustard against human cancer cells lines (MV4-11, A549, MCF-7 and HCT116) and normal mouse fibroblast (BALB/3T3) is presented. The structures of novel compounds were determined using 1H and 13C NMR, FAB(+)-MS, and elemental analyses. Among the derivatives, 5b, 5c, 5e, 5f and 5i were found to exhibit high activity against human leukaemia MV4-11 cells with IC50 values of 2.17-4.26 μg/ml. The cytotoxic activity of compound 5c and 5f against BALB/3T3 cells is up to 20 times lower than against cancer cell lines. Our results also show that compounds 5e and 5i have very strong activity against MCF-7 and HCT116 with IC50 values of 3.02-4.13 μg/ml. Moreover, spectroscopic characterization and cellular localization for selected compound were performed. In order to identify potential drug targets we perform computer simulations with DNA-binding site of hTopoI and hTopoII and quantum chemical calculation of interaction and binding energies in complexes of the five most active compounds with guanine.

Identification and evaluation of magnolol and chrysophanol as the principle protein tyrosine phosphatase-1B inhibitory compounds in a Kampo medicine, Masiningan.

PubMed

Onoda, Toshihisa; Li, Wei; Sasaki, Tatsunori; Miyake, Megumi; Higai, Koji; Koike, Kazuo

2016-06-20

Masiningan is a traditional medicine consisting of six crude drugs that have been used for treating constipation and diabetes mellitus in both Japan and China. Masiningan has been reported to have significant PTP1B inhibitory activity and to affect cells in the insulin-signaling pathway. The aim of the present study is to identify the PTP1B inhibitory compounds in Masiningan. Bioactivity peaks were identified by analytical HPLC profiling and PTP1B inhibitory activity profiling of sub-fractions from Masiningan extract. The bioactive compounds were isolated by tracking two identified bioactive peaks, and the chemical structures were determined by spectroscopic analyses. The bioactive compounds were further investigated for their inhibitory effect against PTP1B by enzymatic kinetic analysis, molecular docking simulation, inhibitory selectivity against other PTPs, and cellular activity in the insulin signal transduction pathway. From Masiningan, magnolol (1) and chrysophanol (2) were isolated as compounds that exhibited significant dose-dependent inhibitory activities against PTP1B, with IC50 values of 24.6 and 12.3μM, respectively. Kinetic analysis revealed that 1 is a non-competitive and that 2 is a competitive PTP1B inhibitor. In the molecular docking simulation, compound 2 was stably positioned in the active pocket of PTP1B, and the CDOCKER energy was calculated to be 24.3411kcal/mol. Both compounds demonstrated remarkably high selectivity against four PTPs and revealed cellular activity against the insulin signal transduction pathway. Magnolol (1) and chrysophanol (2) were identified as the principle PTP1B inhibitory active compounds in Masiningan, and their actions were investigated in detail. These findings demonstrated the effectiveness of Masiningan on diabetes mellitus through the inhibition of PTP1B at a molecular level as well as the potential of magnolol (1) and chrysophanol (2) as lead compounds in future anti-diabetes drug development. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cytotoxic 20,24-epoxywithanolides from Physalis angulata.

PubMed

Maldonado, Emma; Hurtado, Norma E; Pérez-Castorena, Ana L; Martínez, Mahinda

2015-12-01

A new withanolide, physangulide B (1), was isolated from calyxes of Physalis angulata. This compound was also present in the aerial parts along with the known physangulide (4), which was isolated as the acetonide 3, and 24,25-epoxywithanolide D (6). Structures of these compounds were determined by analysis of their spectroscopic data, which indicated the presence of a 20,24-epoxy group in both physangulides. The structures of compounds 1 and 6 were confirmed by X-ray analysis of their corresponding acetyl derivatives 2 and 7. The structure of physangulide was originally described as the 22S withanolide 5, now its structure and configuration are revised to 4. Evaluation of the cytotoxic activity of compounds 1-3 against two human cancer cell lines indicated a potent activity of compound 1 and its derivative 2. Copyright © 2015 Elsevier Inc. All rights reserved.

Novel N-allyl/propargyl tetrahydroquinolines: Synthesis via Three-component Cationic Imino Diels-Alder Reaction, Binding Prediction, and Evaluation as Cholinesterase Inhibitors.

PubMed

Rodríguez, Yeray A; Gutiérrez, Margarita; Ramírez, David; Alzate-Morales, Jans; Bernal, Cristian C; Güiza, Fausto M; Romero Bohórquez, Arnold R

2016-10-01

New N-allyl/propargyl 4-substituted 1,2,3,4-tetrahydroquinolines derivatives were efficiently synthesized using acid-catalyzed three components cationic imino Diels-Alder reaction (70-95%). All compounds were tested in vitro as dual acetylcholinesterase and butyryl-cholinesterase inhibitors and their potential binding modes, and affinity, were predicted by molecular docking and binding free energy calculations (∆G) respectively. The compound 4af (IC50 = 72 μm) presented the most effective inhibition against acetylcholinesterase despite its poor selectivity (SI = 2), while the best inhibitory activity on butyryl-cholinesterase was exhibited by compound 4ae (IC50 = 25.58 μm) with considerable selectivity (SI = 0.15). Molecular docking studies indicated that the most active compounds fit in the reported acetylcholinesterase and butyryl-cholinesterase active sites. Moreover, our computational data indicated a high correlation between the calculated ∆G and the experimental activity values in both targets. © 2016 The Authors Chemical Biology & Drug Design Published by John Wiley & Sons Ltd.

Synthesis and biological evaluation of 1,3-diaryl pyrazole derivatives as potential antibacterial and anti-inflammatory agents.

PubMed

Li, Ya-Ru; Li, Chao; Liu, Jia-Chun; Guo, Meng; Zhang, Tian-Yi; Sun, Liang-Peng; Zheng, Chang-Ji; Piao, Hu-Ri

2015-11-15

Three series of 1,3-diaryl pyrazole derivatives bearing aminoguanidine or furan-2-carbohydrazide moieties have been synthesized, characterized and evaluated for antibacterial and anti-inflammatory activities. Most of the synthesized compounds showed potent inhibition of several Gram-positive bacterial strains (including multidrug-resistant clinical isolates) and Gram-negative bacterial strains with minimum inhibitory concentration values in the range of 1-64 μg/mL. Compounds 6g, 6l and 7l presented the most potent inhibitory activity against Gram-positive bacteria (e.g. Staphylococcus aureus 4220), Gram-negative bacteria (e.g. Escherichia coli 1924) and the fungus, Candida albicans 7535, with minimum inhibitory concentration values of 1 or 2 μg/mL. Compared with previous studies, these compounds exhibited a broad spectrum of inhibitory activity. Furthermore, compound 7l showed the greatest anti-inflammatory activity (93.59% inhibition, 30 min after intraperitoneal administration), which was more potent than the reference drugs ibuprofen and indomethacin. Copyright © 2015 Elsevier Ltd. All rights reserved.

Induction of quinone reductase (QR) by withanolides isolated from Physalis pubescens L. (Solanaceae).

PubMed

Ji, Long; Yuan, Yonglei; Ma, Zhongjun; Chen, Zhe; Gan, Lishe; Ma, Xiaoqiong; Huang, Dongsheng

2013-09-01

In the present study, it was demonstrated that the dichloromethane extract of Physalis pubescens L. (DEPP) had weak potential quinone reductase (QR) inducing activity, but an UPLC-ESI-MS method with glutathione (GSH) as the substrate revealed that the DEPP had electrophiles (with an α,β-unsaturated ketone moiety). These electrophiles could induce quinone reductase (QR) activity, which might be attributed to the modification of the highly reactive cysteine residues in Keap1. Herein, four withanolides, including three new compounds physapubescin B (2), physapubescin C (3), physapubescin D (4), together with one known steroidal compound physapubescin (1) were isolated. Structures of these compounds were determined by spectroscopic analysis and that of physapubescin C (3) was confirmed by a combination of molecular modeling and quantum chemical DFT-GIAO calculations. Evaluation of the QR inducing activities of all withanolides indicated potent activities of compounds 1 and 2, which had a common α,β-unsaturated ketone moiety. Copyright © 2013 Elsevier Ltd. All rights reserved.

Development of electrospun nanofibers containing chitosan/PEO blend and phenolic compounds with antibacterial activity.

PubMed

Kuntzler, Suelen Goettems; Costa, Jorge Alberto Vieira; Morais, Michele Greque de

2018-05-31

Electrospun nanofibers can be formed with chitosan as the polymers found in biological sources have antibacterial ability. The objective of this work was to evaluate whether chitosan/polyethylene oxide (PEO) blend nanofibers containing microalgal phenolic compounds exhibit antibacterial activity. Nanofibers produced with a 3% chitosan/2% PEO blend containing 1% phenolic compounds had an average diameter of 214 ± 37 nm, which resulted in a high temperature of maximum degradation, an important parameter for food packaging. The potential antibacterial activity of this nanofibers was confirmed by their inhibition of Staphylococcus aureus ATCC 25923 (6.4 ± 1.1 mm) and Escherichia coli ATCC 25972 (5.5 ± 0.4 mm). The polymeric nanofibers produced from chitosan and containing phenolic compounds have properties that therefore allow their application as active packaging. In addition, chitosan is an excellent polymer for packaging as it presents biodegradability, biocompatibility and, non-toxicity. Copyright © 2018. Published by Elsevier B.V.

Marine pharmacology in 2005–6: Marine Compounds with Anthelmintic, Antibacterial, Anticoagulant, Antifungal, Anti-inflammatory, Antimalarial, Antiprotozoal, Antituberculosis, and Antiviral Activities; affecting the Cardiovascular, Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action

PubMed Central

Mayer, Alejandro M. S.; Rodriguez, Abimael D.; Berlinck, Roberto G. S.; Hamann, Mark T.

2009-01-01

BACKGROUND The review presents the 2005–2006 peer-reviewed marine pharmacology literature, and follows a similar format to the authors’ 1998–2004 reviews. The preclinical pharmacology of chemically characterized marine compounds isolated from marine animals, algae, fungi and bacteria is systematically presented. RESULTS Anthelminthic, antibacterial, anticoagulant, antifungal, antimalarial, antiprotozoal, antituberculosis and antiviral activities were reported for 78 marine chemicals. Additionally 47 marine compounds were reported to affect the cardiovascular, immune and nervous system as well as possess anti-inflammatory effects. Finally, 58 marine compounds were shown to bind to a variety of molecular targets, and thus could potentially contribute to several pharmacological classes. CONCLUSIONS Marine pharmacology research during 2005–2006 was truly global in nature, involving investigators from 32 countries, and the United States, and contributed 183 marine chemical leads to the research pipeline aimed at the discovery of novel therapeutic agents. SIGNIFICANCE Continued preclinical and clinical research with marine natural products demonstrating a broad spectrum of pharmacological activity and will probably result in novel therapeutic agents for the treatment of multiple disease categories. PMID:19303911

Induction of apoptosis against cancer cell lines by four ascomycetes (endophytes) from Malaysian rainforest.

PubMed

Hazalin, Nurul Aqmar Mohamad Nor; Ramasamy, Kalavathy; Lim, Siong Meng; Cole, Anthony L J; Majeed, Abu Bakar Abdul

2012-05-15

Endophytic fungi have been shown to be a promising source of biologically active natural products. In the present study, extracts of four endophytic fungi isolated from plants of the National Park, Pahang were evaluated for their cytotoxic activity and the nature of their active compounds determined. Those extracts exhibiting activity with IC(50) values less than 17 μg/ml against HCT116, MCF-7 and K562 cell lines were shown to induce apoptosis in these cell lines. Molecular analysis, based on sequences of the rDNA internal transcribed spacers ITS1 and ITS4, revealed all four endophytic fungi to be ascomycetes: three sordariomycetes and a dothideomycete. Six known compounds, cytochalasin J, dechlorogriseofulvin, demethylharzianic-acid, griseofulvin, harzianic acid and 2-hexylidene-3-methyl-succinic acid were identified from a rapid dereplication technique for fungal metabolites using an in-house UV library. The results from the present study suggest the potential of endophytic fungi as cytotoxic agents, and there is an indication that the isolates contain bioactive compounds that mainly kill cancer cells by apoptosis. Copyright © 2012 Elsevier GmbH. All rights reserved.

Docking, synthesis and pharmacological activity of novel urea-derivatives designed as p38 MAPK inhibitors.

PubMed

de Oliveira Lopes, Raquel; Romeiro, Nelilma Correia; de Lima, Cleverton Kleiton F; Louback da Silva, Leandro; de Miranda, Ana Luisa Palhares; Nascimento, Paulo Gustavo B D; Cunha, Fernando Q; Barreiro, Eliezer J; Lima, Lídia Moreira

2012-08-01

p38 mitogen-activated protein kinase (p38 MAPK) is an important signal transducing enzyme involved in many cellular regulations, including signaling pathways, pain and inflammation. Several p38 MAPK inhibitors have been developed as drug candidates to treatment of autoimmune disorders, such as rheumatoid arthritis. In this paper we reported the docking, synthesis and pharmacological activity of novel urea-derivatives (4a-e) designed as p38 MAPK inhibitors. These derivatives presented good theoretical affinity to the target p38 MAPK, standing out compound 4e (LASSBio-998), which showed a better score value compared to the prototype GK-00687. This compound was able to reduce in vitro TNF-α production and was orally active in a hypernociceptive murine model sensible to p38 MAPK inhibitors. Otherwise, compound 4e presented a dose-dependent analgesic effect in a model of antigen (mBSA)-induced arthritis and anti-inflammatory profile in carrageenan induced paw edema, indicating its potential as a new antiarthritis prototype. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

De Novo Design of Bioactive Small Molecules by Artificial Intelligence

PubMed Central

Merk, Daniel; Friedrich, Lukas; Grisoni, Francesca

2018-01-01

Abstract Generative artificial intelligence offers a fresh view on molecular design. We present the first‐time prospective application of a deep learning model for designing new druglike compounds with desired activities. For this purpose, we trained a recurrent neural network to capture the constitution of a large set of known bioactive compounds represented as SMILES strings. By transfer learning, this general model was fine‐tuned on recognizing retinoid X and peroxisome proliferator‐activated receptor agonists. We synthesized five top‐ranking compounds designed by the generative model. Four of the compounds revealed nanomolar to low‐micromolar receptor modulatory activity in cell‐based assays. Apparently, the computational model intrinsically captured relevant chemical and biological knowledge without the need for explicit rules. The results of this study advocate generative artificial intelligence for prospective de novo molecular design, and demonstrate the potential of these methods for future medicinal chemistry. PMID:29319225

H1-A, a compound isolated from Fusarium oxysporum inhibits hepatitis C virus (HCV) NS3 serine protease.

PubMed

Yang, Li-Yuan; Lin, Jun; Zhou, Bin; Liu, Yan-Gang; Zhu, Bao-Quan

2016-04-01

The present study was aimed to isolate the active compounds from the fermentation products of Fusarium oxysporum, which had hepatitis C virus (HCV) NS3 protease inhibitory activity. A bioactive compound was isolated by reverse-phase silica-gel column chromatography, silica-gel column chromatography, semi-preparative reverse-phase High Performance Liquid Chromatography (HPLC), and then its molecular structure was elucidated based on the spectrosopic analysis. As a result, the compound (H1-A, 1) Ergosta-5, 8 (14), 22-trien-7-one, 3-hydroxy-,(3β, 22E) was isolated and identified. To the best of our knowledge, this was the first report on the isolation of H1-A from microorganisms with the inhibitory activity of NS3 protease. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Cerebroside D, a glycoceramide compound, improves experimental colitis in mice with multiple targets against activated T lymphocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Xue-Feng; Wu, Xing-Xin; Guo, Wen-Jie

2012-09-15

In the present paper, we aimed to examine the novel effects of cerebroside D, a glycoceramide compound, on murine experimental colitis. Cerebroside D significantly reduced the weight loss, mortality rate and alleviated the macroscopic and microscopic appearances of colitis induced by dexran sulfate sodium. This compound also decreased the levels of TNF-α, IFN-γ and IL-1β in intestinal tissue of mice with experimental colitis in a concentration-dependent manner, accompanied with markedly increased serum level of IL-10. Cerebroside D inhibited proliferation and induced apoptosis of T cells activated by concanavalin A or anti-CD3 plus anti-CD28 antibodies. The compound did not show anmore » effect on naive lymphocytes but prevented cells from entering S phase and G2/M phase during T cells activation. Moreover, the treatment of cerebroside D led to apoptosis of activated T cells with the cleavage of caspase 3, 9, 12 and PARP. These results showed multiple effects of cerebroside D against activated T cells for a novel approach to treatment of colonic inflammation. Highlights: ► Cerebroside D, a glycoceramide compound, alleviated DSS induced colitis. ► The mechanism of the compound involved multiple effects against activated T cells. ► It regulated cytokine profiles in mice with experimental colitis. ► It prevented T cells from entering S and G2/M phases during activation. ► It led to apoptosis of activated T cells with the cleavage of caspases and PARP.« less

1,4-Dihydropyridine Derivatives: Dihydronicotinamide Analogues—Model Compounds Targeting Oxidative Stress

PubMed Central

Velena, Astrida; Zarkovic, Neven; Gall Troselj, Koraljka; Bisenieks, Egils; Krauze, Aivars; Poikans, Janis; Duburs, Gunars

2016-01-01

Many 1,4-dihydropyridines (DHPs) possess redox properties. In this review DHPs are surveyed as protectors against oxidative stress (OS) and related disorders, considering the DHPs as specific group of potential antioxidants with bioprotective capacities. They have several peculiarities related to antioxidant activity (AOA). Several commercially available calcium antagonist, 1,4-DHP drugs, their metabolites, and calcium agonists were shown to express AOA. Synthesis, hydrogen donor properties, AOA, and methods and approaches used to reveal biological activities of various groups of 1,4-DHPs are presented. Examples of DHPs antioxidant activities and protective effects of DHPs against OS induced damage in low density lipoproteins (LDL), mitochondria, microsomes, isolated cells, and cell cultures are highlighted. Comparison of the AOA of different DHPs and other antioxidants is also given. According to the data presented, the DHPs might be considered as bellwether among synthetic compounds targeting OS and potential pharmacological model compounds targeting oxidative stress important for medicinal chemistry. PMID:26881016

Isolation and identification of antibacterial compound from the leaves of Cassia auriculata.

PubMed

Senthilkumar, P K; Reetha, D

2011-09-01

Antimicrobial properties of medicinal plants and plant parts such as flowers, roots, fruits, seeds and oils are being used to cure some chronic and acute diseases throughout the world. In the present study, an attempt has been made to isolate and identify the antibacterial compound present in the leaves of the Cassia auriculata. A preliminary screening of antibacterial activity was carried out with fine different plant extracts viz., Aegle marmelos, Chloris Virgata, Clausena anisata, Feronia limonia and Cassia auriculata against different human pathogenic bacteriae such as Escherichia coil, Salmonella typhi, Proteus mirabilis and Klebsiella pneumoniae at different concentrations. Based on the results, the plant Cassia auriculata was selected as the efficient plant, which shows antibacterial activity against the tested organisms. Further compound responsible for its antibacterial activity was isolated and identified by IR spectrum, 1HNMR, 13CNMR and Mass spectrum studies, as oleanolic acid, which has the molecular formula of C30H48O3.

Design, microwave-mediated synthesis and biological evaluation of novel 4-aryl(alkyl)amino-3-nitroquinoline and 2,4-diaryl(dialkyl)amino-3-nitroquinolines as anticancer agents.

PubMed

Chauhan, Monika; Rana, Anil; Alex, Jimi Marin; Negi, Arvind; Singh, Sandeep; Kumar, Raj

2015-02-01

Design, microwave-assisted synthesis of novel 4-aryl (alkyl)amino-3-nitroquinoline (1a-1l) and 2,4-diaryl (dialkyl)amino-3-nitroquinolines (2a-2k and 3a) via regioselective and complete nucleophilic substitution of 2,4-dichloro-3-nitroquinoline, respectively in water are presented. The newly synthesized compounds were evaluated for the first time for antiproliferative activity against EGFR overexpressing human lung (A-549 and H-460) and colon (HCT-116-wild type and HCT-116-p53 null) cancer cell lines. Some notions about structure-activity relationships (SAR) are presented. Compounds 2e, 2f, 2j and 3a overall exhibited excellent anticancer activity comparable to erlotinib which was used as a positive control. Molecular modeling studies disclosed the recognition pattern of the compounds and also supported the observed SAR. Copyright © 2014 Elsevier Inc. All rights reserved.

Novel gold(I) complexes with 5-phenyl-1,3,4-oxadiazole-2-thione and phosphine as potential anticancer and antileishmanial agents.

PubMed

Chaves, Joana Darc S; Tunes, Luiza Guimarães; de J Franco, Chris Hebert; Francisco, Thiago Martins; Corrêa, Charlane Cimini; Murta, Silvane M F; Monte-Neto, Rubens Lima; Silva, Heveline; Fontes, Ana Paula S; de Almeida, Mauro V

2017-02-15

The current anticancer and antileishmanial drug arsenal presents several limitations concerning their specificity, efficacy, costs and the emergence of drug-resistant cells lines, which encourages the urgent need to search for new alternatives. Inspired by the fact that gold(I)-based compounds are promising antitumoral and antileishmanial drug candidates, we synthesized novel gold(I) complexes containing phosphine and 5-phenyl-1,3,4-oxadiazole-2-thione and evaluated their anticancer and antileishmanial activities. Synthesis was performed by reacting 5-phenyl-1,3,4-oxadiazole-2-thione derivatives with chloro(triphenylphosphine)gold(I) and chloro(triethylphosphine)gold(I). The novel compounds were characterized by infrared, Raman, 1 H, 13 C nuclear magnetic resonance, high-resolution mass spectra, and x-ray crystallography. The coordination of the ligands to gold(I) occurred through the exocyclic sulfur atom. All gold(I) complexes were active at low micromolar or nanomolar range with IC 50 values ranging from <0.10 to 1.66 μM against cancer cell lines and from 0.9 to 4.2 μM for Leishmania infantum intracellular amastigotes. Compound (6-A) was very selective against murine melanoma B16F10, colon cancer CT26.WT cell lines and L. infantum intracellular amastigotes. Compound (7-B) presented the highest anticancer activity against both cancer cell lines while the promising antileishmanial lead was compound (6-A). Tiethylphosphine gold(I) complexes were more active than the conterparts triphenylphosphine derivatives for both anticancer and antileishmanial activities. Triethylphosphine gold(I) derivatives presented antimony cross-resistance in L. guyanensis demonstrating their potential to be used as chemical tools to better understand mechanisms of drug resistance and action. These findings revealed the anticancer and antileishmanial potential of gold(I) oxadiazole phosphine derivatives. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Design, synthesis, antiviral bioactivity and three-dimensional quantitative structure-activity relationship study of novel ferulic acid ester derivatives containing quinazoline moiety.

PubMed

Wu, Zengxue; Zhang, Jian; Chen, Jixiang; Pan, Jianke; Zhao, Lei; Liu, Dengyue; Zhang, Awei; Chen, Jin; Hu, Deyu; Song, Baoan

2017-10-01

Ferulic acid and quinazoline derivatives possess good antiviral activities. In order to develop novel compounds with high antiviral activities, a series of ferulic acid ester derivatives containing quinazoline were synthesized and evaluated for their antiviral activities. Bioassays indicated that some of the compounds exhibited good antiviral activities in vivo against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). One of the compounds demonstrated significant curative and protective activities against TMV and CMV, with EC 50 values of 162.14, 114.61 and 255.49, 138.81 mg L -1 , respectively, better than those of ningnanmycin (324.51, 168.84 and 373.88, 272.70 mg L -1 ). The values of q 2 and r 2 for comparative molecular field analysis and comparative molecular similarity index analysis in the TMV (0.508, 0.663 and 0.992, 0.930) and CMV (0.530, 0.626 and 0.997, 0.981) models presented good predictive abilities. Some of the title compounds demonstrated good antiviral activities. Three-dimensional quantitative structure-activity relationship models revealed that the antiviral activities depend on steric and electrostatic properties. These results could provide significant structural insights for the design of highly active ferulic acid derivatives. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Enhanced formulations for neutralization of chemical, biological and industrial toxants

DOEpatents

Tucker, Mark D [Albuqueque, NM

2008-06-24

An enhanced formulation and method of making that neutralizes the adverse health effects of both chemical and biological compounds, especially chemical warfare (CW) and biological warfare (BW) agents, and toxic industrial chemicals. The enhanced formulation according to the present invention is non-toxic and non-corrosive and can be delivered by a variety of means and in different phases. The formulation provides solubilizing compounds that serve to effectively render the chemical and biological compounds, particularly CW and BW compounds, susceptible to attack, and at least one reactive compound that serves to attack (and detoxify or kill) the compound. The formulation includes at least one solubilizing agent, a reactive compound, a bleaching activator and water.

Nuclear Factor Kappa B Activation and Peroxisome Proliferator-activated Receptor Transactivational Effects of Chemical Components of the Roots of Polygonum multiflorum.

PubMed

Sun, Ya Nan; Li, Wei; Song, Seok Bean; Yan, Xi Tao; Yang, Seo Young; Kim, Young Ho

2016-01-01

Polygonum multiflorum is well-known as "Heshouwu" in traditional Chinese herbal medicine. In Northeast Asia, it is often used as a tonic to prevent premature aging of the kidney and liver, tendons, and bones and strengthening of the lower back and knees. To research the anti-inflammatory activities of components from P. multiflorum. The compounds were isolated by a combination of silica gel and YMC R-18 column chromatography, and their structures were identified by analysis of spectroscopic data (1D, 2D-nuclear magnetic resonance, and mass spectrometry). The anti-inflammatory activities of the isolated compounds 1-15 were evaluated by luciferase reporter gene assays. Fifteen compounds (1-15) were isolated from the roots of P. multiflorum. Compounds 1-5 and 14-15 significantly inhibited tumor necrosis factor-α-induced nuclear factor kappa B-luciferase activity, with IC50 values of 24.16-37.56 μM. Compounds 1-5 also greatly enhanced peroxisome proliferator-activated receptors transcriptional activity with EC50 values of 18.26-31.45 μM. The anthraquinone derivatives were the active components from the roots of P. multiflorum as an inhibitor on inflammation-related factors in human hepatoma cells. Therefore, we suggest that the roots of P. multiflorum can be used to treat natural inflammatory diseases. This study presented that fifteen compounds (1-15) isolated from the roots of Polygonum multiflrum exert signifiant anti inflmmatory effects by inhibiting TNF α induced NF κB activation and PPARs transcription. Abbreviation used: NF κB: Nuclear factor kappa B, PPARs: Peroxisome proliferator activated receptors, PPREs: Peroxisome proliferator response elements, TNF α: Tumor necrosis factor α, ESI-MS: Electrospray ionization mass spectrometry, HepG2: Human hepatoma cells.

Biogas pre-upgrading by adsorption of trace compounds onto granular activated carbons and an activated carbon fiber-cloth.

PubMed

Boulinguiez, B; Le Cloirec, P

2009-01-01

The study assesses the adsorption onto activated carbon materials of selected volatile organic compounds -VOCs- (dichloromethane, 2-propanol, toluene, siloxane D4) in a biogas matrix composed of methane and carbon dioxide (55:45 v/v). Three different adsorbents are tested, two of them are granular activated carbon (GAC), and the last is an activated carbon fiber-cloth (ACFC). The adsorption isotherm data are fitted by different models by nonlinear regression. The Langmuir-Freundlich model appears to be the adequate one to describe the adsorption phenomena independently of the VOC considered or the adsorbent. The adsorbents present attractive adsorption capacity of the undesirable compounds in biogas atmosphere though the maximum adsorption capacities for a VOC are quite different from each other. The adsorption kinetics are characterized through three coefficients: the initial adsorption coefficient, the external film mass transfer coefficient and the internal diffusion coefficient of Weber. The ACFC demonstrates advanced kinetic yields compared to the granular activated carbon materials whatever VOC is considered. Therefore, pre-upgrading of biogas produced from wastewater sludge or co-digestion system by adsorption onto activated carbon appears worth investigating. Especially with ACFC material that presents correct adsorption capacities toward VOCs and concrete regeneration process opportunity to realize such process.

Virtual Screening Techniques to Probe the Antimalarial Activity of some Traditionally Used Phytochemicals.

PubMed

Shibi, Indira G; Aswathy, Lilly; Jisha, Radhakrishnan S; Masand, Vijay H; Gajbhiye, Jayant M

2016-01-01

Malaria parasites show resistance to most of the antimalarial drugs and hence developing antimalarials which can act on multitargets rather than a single target will be a promising strategy of drug design. Here we report a new approach by which virtual screening of 292 unique phytochemicals present in 72 traditionally important herbs is used for finding out inhibitors of plasmepsin-2 and falcipain-2 for antimalarial activity against P. falciparum. Initial screenings of the selected molecules by Random Forest algorithm model of Weka using the bioassay datasets AID 504850 and AID 2302 screened 120 out of the total 292 phytochemicals to be active against the targets. Toxtree scan cautioned 21 compounds to be either carcinogenic or mutagenic and were thus removed for further analysis. Out of the remaining 99 compounds, only 46 compounds offered drug-likeness as per the 'rule of five' criteria. Out of ten antimalarial drug targets, only two target proteins such as 3BPF and 3PNR of falcipain-2 and 1PFZ and 2BJU of plasmepsin-2 are selected as targets. The potential binding of the selected 46 compounds to the active sites of these four targets was analyzed using MOE software. The docked conformations and the interactions with the binding pocket residues of the target proteins were understood by 'Ligplot' analysis. It has been found that 8 compounds are dual inhibitors of falcipain-2 and plasmepsin-2, with the best binding energies. Compound 117 (6aR, 12aS)-12a-Hydroxy-9-methoxy-2,3-dimethylenedioxy-8-prenylrotenone (Usaratenoid C) present in the plant Millettia usaramensis showed maximum molecular docking score.

Improved solubility and bioactivity of theophylline (a bronchodilator drug) through its new nitrate salt analysed by experimental and theoretical approaches

NASA Astrophysics Data System (ADS)

Mary Novena, L.; Suresh Kumar, S.; Athimoolam, S.

2016-07-01

Synthesis, crystal structure, vibrational spectroscopy, quantum chemical studies and biological activity of the new semi organic compound, Theophyllinium Nitrate [C7H9N4 O2)+. (NO3)-], are reported here. Crystals of Theophyllinium nitrate (TN) were grown by slow solvent evaporation technique. The crystal packing is dominated by N-H···O intermolecular hydrogen bonds. The cations and anions are aggregated almost parallel leading to a lamellar structure. This molecular aggregation features two alternate hydrogen bonded chain C22(8) and C21(6) motifs. Further, a bifurcated ring R12(4) motifs is also seen. This aggregated molecular sheets are parallel to (2 bar 06) and (20 6 bar) planes of the crystal. The solubility test is carried out to enhance the physico-chemical activity of the compound. The atomic charge distribution on different atoms of TN has been calculated by Mulliken charge analysis. A detailed interpretation of FT-IR and FT-Raman spectra of TN show that most of the bands are matching between the experimental and theoretical methods. The strong intensity bands and shifting of bands due to intermolecular hydrogen bonds are also investigated. The NBO analysis is carried out to elucidate the stability of the molecule and charge delocalization within the molecule. The HOMO-LUMO analysis reveals molecular stability and chemical reactivity of the present compound. Also, the compound was examined for its antibacterial activity and found to exhibit notable activity against Pseudomonas aeruginosa. This shows that the present compound is a good candidate for the antimicrobial agent apart from its inherent Bronchodilator drug property. Hence, the new compound (TN) may be a good alternative for patients with Chronic Obstructive Pulmonary Disease (COPD) and bacterial infections.

Biological activity and molecular docking studies of curcumin-related α,β-unsaturated carbonyl-based synthetic compounds as anticancer agents and mushroom tyrosinase inhibitors.

PubMed

Bukhari, Syed Nasir Abbas; Jantan, Ibrahim; Unsal Tan, Oya; Sher, Muhammad; Naeem-Ul-Hassan, M; Qin, Hua-Li

2014-06-18

Hyperpigmentation in human skin and enzymatic browning in fruits, which are caused by tyrosinase enzyme, are not desirable. Investigations in the discovery of tyrosinase enzyme inhibitors and search for improved cytotoxic agents continue to be an important line in drug discovery and development. In present work, a new series of 30 compounds bearing α,β-unsaturated carbonyl moiety was designed and synthesized following curcumin as model. All compounds were evaluated for their effects on human cancer cell lines and mushroom tyrosinase enzyme. Moreover, the structure-activity relationships of these compounds are also explained. Molecular modeling studies of these new compounds were carried out to explore interactions with tyrosinase enzyme. Synthetic curcumin-like compounds (2a-b) were identified as potent anticancer agents with 81-82% cytotoxicity. Five of these newly synthesized compounds (1a, 8a-b, 10a-b) emerged to be the potent inhibitors of mushroom tyrosinase, providing further insight into designing compounds useful in fields of food, health, and agriculture.

Developing a novel dual PI3K–mTOR inhibitor from the prodrug of a metabolite

PubMed Central

Zhou, Yan; Zhang, Genyan; Wang, Feng; Wang, Jin; Ding, Yanwei; Li, Xinyu; Shi, Chongtie; Li, Jiakui; Shih, Chengkon; You, Song

2017-01-01

This study presents a process of developing a novel PI3K–mTOR inhibitor through the prodrug of a metabolite. The lead compound (compound 1) was identified with similar efficacy as that of NVP-BEZ235 in a tumor xenograft model, but the exposure of compound 1 was much lower than that of NVP-BEZ235. After reanalysis of the blood sample, a major metabolite (compound 2) was identified. Compound 2 exerted similar in vitro activity as compound 1, which indicated that compound 2 was an active metabolite and that the in vivo efficacy in the animal model came from compound 2 instead of compound 1. However, compound 1 was metabolized into compound 2 predominantly in the liver microsomes of mouse, but not in the liver microsomes of rat, dog, or human. In order to translate the efficacy in the animal model into clinical development or predict the pharmacokinetic/pharmacodynamic parameters in the clinical study using a preclinical model, we developed the metabolite (compound 2) instead of compound 1. Due to the low bioavailability of compound 2, its prodrug (compound 3) was designed and synthesized to improve the solubility. The prodrug was quickly converted to compound 2 through both intravenous and oral administrations. Because the prodrug (compound 3) did not improve the oral exposure of compound 2, developing compound 3 as an intravenous drug was considered by our team, and the latest results will be reported in the future. PMID:29118584

The cytotoxic constituents from marine-derived streptomyces 3320#

NASA Astrophysics Data System (ADS)

Ren, Hong; Gu, Qianqun; Cui, Chengbin; Zhu, Weiming

2006-01-01

The present work studies the chemical constituents from marine-derived streptomyces 3320# and their antitumor activities. The n-BuOH extract of the ferment broth of 3320# was chromatographed on silica gel, Sephadex LH-20, ODS columns and HPLC to separate the compounds with antitoumor activities. Their structures were identified using IR, UV, NMR, MS spectroscopic techniques and compared with published data. The antitumor activities of the isolates were assayed using SRB method and flow cytometry assay, accompanied with the morphological observation of the cells under light microscope against mammalian tsFT210 cells. Ten compounds, cyclo-(Ala-Leu) 1, cyclo-(Ala-Ile) 2, cyclo-(Ala-Val) 3, cyclo-(Phe- Pro) 4, cyclo-(Phe-Gly) 5, cyclo-(Leu-Pro) 6, 1-methyl-1, 2, 3, 4-tetrahydro-β-carboline-3-carboxylic acid 7, N-(4-hydroxyphenethyl) acetamide 8, 4-methyoxy-1-(2-hydroxy) ethylbenzene 9 and uridine 10, were isolated from the ferment broth of streptomyces 3320#. Among them, compounds 6, 7, 8 and 10 showed potent cytotoxicity against the tsFT210 cell with the IC50 values of 3.6, 7.2, 5.2 and 1.6 mmol L-1, respectively. Compounds 8, 10 also exhibited apoptosis inducing activity under 2.0 mmol L-1. Compounds 6, 7, 8 and 10 are the principle bioactive constituents responsible for the antitumor activities of marine streptomyces 3320#. Compound 7 was isolated from this species for the first time.

Anti-trypanosomal activity of pentacyclic triterpenes isolated from Austroplenckia populnea (Celastraceae).

PubMed

Duarte, Lucienir Pains; Vieira Filho, Sidney Augusto; Silva, Grácia Divina de Fátima; de Sousa, José Rego; Pinto, Artur da Silveira

2002-01-01

Four pentacyclic triterpenes isolated from Austroplenckia populnea and four compounds of known anti T. cruzi or anti-malarial activity were tested. Of those triterpenes tested 20alpha-hydroxy-tingenone showed high activity, epikatonic acid was less active, while populnilic and populninic acids were inactive against the trypanosome of the subgenus Schizotrypanum tested. Benzonidazole, nifurtimox, ketoconazole and primaquine presented a remarkable dose-dependent inhibitory effect reaching practically to a total growth inhibition of the parasite at the end of incubation time. The trypanosome tested appear to be a suitable model for preliminary screen for anti T. (S.) cruzi compounds.

In Vivo Anticonvulsant Activity of Extracts and Protopine from the Fumaria schleicheri Herb

PubMed Central

Prokopenko, Yuliya; Tsyvunin, Vadim; Shtrygol’, Sergey; Georgiyants, Victoriya

2015-01-01

The present study aimed to investigate the role of several biologically active compounds from Fumaria schleicheri Soy.-Will. in anticonvulsant models. The flavonoid fraction, alkaloid fraction, individual alkaloid protopine, and polysaccharide-protein complex were isolated from the Fumaria schleicheri herb and studied along with Fumaria schleicheri dry extract in mice with pentylenetetrazole-induced seizures. According to empirical results, the expressed anticonvulsant effect of Fumaria schleicheri dry extract depends on the synergism of biologically active compounds in herbal medicine, although some individual substances (mostly protopine and the protein-polysaccharide fraction) have shown moderate anti-seizure activity. PMID:28117320

In Vivo Anticonvulsant Activity of Extracts and Protopine from the Fumaria schleicheri Herb.

PubMed

Prokopenko, Yuliya; Tsyvunin, Vadim; Shtrygol', Sergey; Georgiyants, Victoriya

2015-12-06

The present study aimed to investigate the role of several biologically active compounds from Fumaria schleicheri Soy.-Will. in anticonvulsant models. The flavonoid fraction, alkaloid fraction, individual alkaloid protopine, and polysaccharide-protein complex were isolated from the Fumaria schleicheri herb and studied along with Fumaria schleicheri dry extract in mice with pentylenetetrazole-induced seizures. According to empirical results, the expressed anticonvulsant effect of Fumaria schleicheri dry extract depends on the synergism of biologically active compounds in herbal medicine, although some individual substances (mostly protopine and the protein-polysaccharide fraction) have shown moderate anti-seizure activity.

Skin bioavailability of dietary vitamin E, carotenoids, polyphenols, vitamin C, zinc and selenium.

PubMed

Richelle, Myriam; Sabatier, Magalie; Steiling, Heike; Williamson, Gary

2006-08-01

Dietary bioactive compounds (vitamin E, carotenoids, polyphenols, vitamin C, Se and Zn) have beneficial effects on skin health. The classical route of administration of active compounds is by topical application direct to the skin, and manufacturers have substantial experience of formulating ingredients in this field. However, the use of functional foods and oral supplements for improving skin condition is increasing. For oral consumption, some dietary components could have an indirect effect on the skin via, for example, secondary messengers. However, in the case of the dietary bioactive compounds considered here, we assume that they must pass down the gastrointestinal tract, cross the intestinal barrier, reach the blood circulation, and then be distributed to the different tissues of the body including the skin. The advantages of this route of administration are that the dietary bioactive compounds are metabolized and then presented to the entire tissue, potentially in an active form. Also, the blood continuously replenishes the skin with these bioactive compounds, which can then be distributed to all skin compartments (i.e. epidermis, dermis, subcutaneous fat and also to sebum). Where known, the distribution and mechanisms of transport of dietary bioactive compounds in skin are presented. Even for compounds that have been studied well in other organs, information on skin is relatively sparse. Gaps in knowledge are identified and suggestions made for future research.

Virtual screening and rational drug design method using structure generation system based on 3D-QSAR and docking.

PubMed

Chen, H F; Dong, X C; Zen, B S; Gao, K; Yuan, S G; Panaye, A; Doucet, J P; Fan, B T

2003-08-01

An efficient virtual and rational drug design method is presented. It combines virtual bioactive compound generation with 3D-QSAR model and docking. Using this method, it is possible to generate a lot of highly diverse molecules and find virtual active lead compounds. The method was validated by the study of a set of anti-tumor drugs. With the constraints of pharmacophore obtained by DISCO implemented in SYBYL 6.8, 97 virtual bioactive compounds were generated, and their anti-tumor activities were predicted by CoMFA. Eight structures with high activity were selected and screened by the 3D-QSAR model. The most active generated structure was further investigated by modifying its structure in order to increase the activity. A comparative docking study with telomeric receptor was carried out, and the results showed that the generated structures could form more stable complexes with receptor than the reference compound selected from experimental data. This investigation showed that the proposed method was a feasible way for rational drug design with high screening efficiency.

Antibacterial polyketides from Bacillus amyloliquefaciens associated with edible red seaweed Laurenciae papillosa.

PubMed

Chakraborty, Kajal; Thilakan, Bini; Raola, Vamshi Krishna; Joy, Minju

2017-03-01

Heterotrophic Bacillus amyloliquefaciens associated with edible red seaweed, Laurenciae papillosa was used to isolate antibacterial polyketide compounds. Antibacterial activity studies integrated with the outcome obtained by polyketide synthetase (pks) coding genes established that seaweed-affiliated bacterial flora had a wide-ranging antibacterial activities and potential natural product diversity, which proved that the bacterium is valuable reservoir of novel bioactive metabolites. Bioactivity-guided isolation of 3-(octahydro-9-isopropyl-2H-benzo[h]chromen-4-yl)-2-methylpropyl benzoate and methyl 8-(2-(benzoyloxy)-ethyl)-hexahydro-4-((E)-pent-2-enyl)-2H-chromene-6-carboxylate of polyketide origin, with activity against human opportunistic food pathogenic microbes, have been isolated from the ethyl acetate extract of B. amyloliquefaciens. Structure-activity relationship analysis revealed that hydrophobic descriptor of the polyketide compounds significantly contribute towards its antibacterial activity. Seaweed-associated microorganisms were shown to represent a potential source of antimicrobial compounds for food and health benefits. The antibacterial polyketide compounds described in the present study may find potential applications in the food industry to reduce food-borne pathogens. Copyright © 2016 Elsevier Ltd. All rights reserved.

Summaries of Research, Fiscal Year 1980.

DTIC Science & Technology

1980-10-01

separated from its subunits. The 1, 3- glucanse did not exhibit any dextranase or amylase activity when induced on a "limit- glucan " substrate. The greatest...by Surface Active Compounds." SHKLAIR, I. L. presented " Glucan Synthesis of S. mutans from Caries-Active and Caries-Free Naval Recruits." WIRTHLIN, M...I. L. presented "Relationship of Glucan Formation by S. mutans and Dental Caries Activity." WALTER, R. G. presented "Streptococcus mutans in Caries

Pyridine sulfonamide as a small key organic molecule for the potential treatment of type-II diabetes mellitus and Alzheimer's disease: In vitro studies against yeast α-glucosidase, acetylcholinesterase and butyrylcholinesterase.

PubMed

Riaz, Sadaf; Khan, Islam Ullah; Bajda, Marek; Ashraf, Muhammad; Qurat-Ul-Ain; Shaukat, Ayesha; Rehman, Tanzeel Ur; Mutahir, Sadaf; Hussain, Sajjad; Mustafa, Ghulam; Yar, Muhammad

2015-12-01

This paper presents the efficient high yield synthesis of novel pyridine 2,4,6-tricarbohydrazide derivatives (4a-4i) along with their α-glucosidase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition activities. The enzymes inhibition results showed the potential of synthesized compounds in controlling both type-II diabetes mellitus and Alzheimer's disease. In vitro biological investigations revealed that most of compounds were more active against yeast α-glucosidase than the reference compound acarbose (IC50 38.25±0.12μM). Among the tested series the compound 4c bearing 4-flouro benzyl group was noted to be the most active (IC50 25.6±0.2μM) against α-glucosidase, and it displayed weak inhibition activities against AChE and BChE. Compound 4a exhibited the most desired results against all three enzymes, as it was significantly active against all the three enzymes; α-glucosidase (IC50 32.2±0.3μM), AChE (IC50 50.2±0.8μM) and BChE (IC50 43.8±0.8μM). Due to the most favorable activity of 4a against the tested enzymes, for molecular modeling studies this compound was selected to investigate its pattern of interaction with α-glucosidase and AChE targets. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of koji fermented phenolic compounds on the oxidative stability of fish miso.

PubMed

Giri, Anupam; Osako, Kazufumi; Okamoto, Akira; Okazaki, Emiko; Ohshima, Toshiaki

2012-02-01

In the present study, Aspergillus oryzae-inoculated koji inhibited lipid oxidation in fermented fish paste rich in polyunsaturated fatty acids following a long fermentation period. The fermentation of koji by A. oryzae liberated several bioactive phenolic compounds, including kojic acid and ferulic acid, which were the most abundant. A linear correlation between several phenolic compounds and their bioactive properties, including their radical-scavenging activity, reducing power, metal-chelating activity, and ability to inhibit linoleic acid oxidation was observed. This suggested an important role of koji phenolics in the oxidative stability of fermented fish paste. The activities of different carbohydrate-cleaving enzymes, including α-amylase, cellulase, and β-glucosidase, were positively correlated with the liberation of several phenolic compounds through koji fermentation. Thus, the application of koji offers a novel strategy to enhance the oxidative stability of newly developed fermented fish miso. Application of traditional Japanese koji fermentation technique to develop an aroma enriched fish meat bases seasoning has been established. Aspergillus oryzae-inoculated koji releases several carbohydrate-cleaving enzymes, including α-amylase, cellulose, and β-glucosidase, which led to the liberation of several phenolic compounds during fermentation. Improvement of oxidative stability of the fermented fish meat paste by koji phenolics suggests a useful strategy to uplift the value of different trash fish meat-based seasoning through proper utilization of the present technique. © 2012 Institute of Food Technologists®

Synthesis of analogues of gingerol and shogaol, the active pungent principles from the rhizomes of Zingiber officinale and evaluation of their anti-platelet aggregation effects.

PubMed

Shih, Hung-Cheng; Chern, Ching-Yuh; Kuo, Ping-Chung; Wu, You-Cheng; Chan, Yu-Yi; Liao, Yu-Ren; Teng, Che-Ming; Wu, Tian-Shung

2014-03-04

The present study was aimed at discovering novel biologically active compounds based on the skeletons of gingerol and shogaol, the pungent principles from the rhizomes of Zingiber officinale. Therefore, eight groups of analogues were synthesized and examined for their inhibitory activities of platelet aggregation induced by arachidonic acid, collagen, platelet activating factor, and thrombin. Among the tested compounds, [6]-paradol (5b) exhibited the most significant anti-platelet aggregation activity. It was the most potent candidate, which could be used in further investigation to explore new drug leads.

Relationship between chemical structure and rat repellency

USGS Publications Warehouse

Bellack, E.; DeWitt, J.B.; Treichler, R.

1953-01-01

Repellent activity is defined as the activity of a compound in preventing consumption of, or gnawing attacks upon, foodstuffs or articles containing or treated with the candidate substance. Data are presented on repellency indices of 2700 compounds, and it is shown that repellency is associated with specific functional groups attached to alkyl, aryl, or heterocyclic nuclei. Functional groups containing nitrogen, sulfur or halogens are most active, with amines, imides, thiocyanates and thiocarbamates forming some of the most active classes. Activity of any functional group may be affected by molecular weight, unsaturation, or spatial configuration of the nucleus, or by the presence of additional substituent groups.

Synthesis of Analogues of Gingerol and Shogaol, the Active Pungent Principles from the Rhizomes of Zingiber officinale and Evaluation of Their Anti-Platelet Aggregation Effects

PubMed Central

Shih, Hung-Cheng; Chern, Ching-Yuh; Kuo, Ping-Chung; Wu, You-Cheng; Chan, Yu-Yi; Liao, Yu-Ren; Teng, Che-Ming; Wu, Tian-Shung

2014-01-01

The present study was aimed at discovering novel biologically active compounds based on the skeletons of gingerol and shogaol, the pungent principles from the rhizomes of Zingiber officinale. Therefore, eight groups of analogues were synthesized and examined for their inhibitory activities of platelet aggregation induced by arachidonic acid, collagen, platelet activating factor, and thrombin. Among the tested compounds, [6]-paradol (5b) exhibited the most significant anti-platelet aggregation activity. It was the most potent candidate, which could be used in further investigation to explore new drug leads. PMID:24599082

Analysis of phytochemical profile of Terminalia arjuna bark extract with antioxidative and antimicrobial properties.

PubMed

Mandal, Shreya; Patra, Arpita; Samanta, Animesh; Roy, Suchismita; Mandal, Arpita; Mahapatra, Tapasi Das; Pradhan, Shrabani; Das, Koushik; Nandi, Dilip Kumar

2013-12-01

To investigate phytochemical screening, antimicrobial activity and qualitative thin layer chromatographic separation of flavonoid components, antioxidant activity and total flavonoid compound of Terminalia arjuna. For phytochemical screening, some common and available standard tests were done. Antimicrobial bioassay was done through agar well diffusion method. Detection of antioxidant activity and flavonoid compounds were done through thin layer chromatography. Total antioxidant activity was measured by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) in colorimetric method. Aluminum chloride colorimetric method was used for total flavonoid determination. Phytochemical screening showed the active compounds presence in high concentration, such as phytosterol, lactones, flavonoids, phenolic compounds and tannins and glycosides. The antimicrobial activity of extract showed that greater inhibition zone against Gram negative bacteria than Gram positive bacteria. This methanolic extract showed a promising antioxidant activity, as absorption of DPPH redicles decreased in DPPH free radical scavenging assay. Flavonoids components having antioxidant property present in the methanol extract at a level of 199.00 mg quercetin equivalent/g of dried methanol extract in colorimetric method. The Terminalia arjuna bark extract revealed the presence of bio-active constituents which are known to exhibit medicinal as well as physiological activities. Copyright © 2013 Asian Pacific Tropical Biomedical Magazine. Published by Elsevier B.V. All rights reserved.

Compound C Inhibits Vascular Smooth Muscle Cell Proliferation and Migration in an AMP-Activated Protein Kinase-Independent Fashion

PubMed Central

Peyton, Kelly J.; Yu, Yajie; Yates, Benjamin; Shebib, Ahmad R.; Liu, Xiao-ming; Wang, Hong

2011-01-01

6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrazolo[1,5-a] pyrimidine (compound C) is a cell-permeable pyrrazolopyrimidine derivative that acts as a potent inhibitor of AMP-activated protein kinase (AMPK). Although compound C is often used to determine the role of AMPK in various physiological processes, it also evokes AMPK-independent actions. In the present study, we investigated whether compound C influences vascular smooth muscle cell (SMC) function through the AMPK pathway. Treatment of rat aortic SMCs with compound C (0.02–10 μM) inhibited vascular SMC proliferation and migration in a concentration-dependent fashion. These actions of compound C were not mimicked or affected by silencing AMPKα expression or infecting SMCs with an adenovirus expressing a dominant-negative mutant of AMPK. In contrast, the pharmacological activator of AMPK 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside inhibited the proliferation and migration of SMCs in a manner that was strictly dependent on AMPK activity. Flow cytometry experiments revealed that compound C arrested SMCs in the G0/G1 phase of the cell cycle, and this was associated with a decrease in cyclin D1 and cyclin A protein expression and retinoblastoma protein phosphorylation and an increase in p21 protein expression. Finally, local perivascular delivery of compound C immediately after balloon injury of rat carotid arteries markedly attenuated neointima formation. These studies identify compound C as a novel AMPK-independent regulator of vascular SMC function that exerts inhibitory effects on SMC proliferation and migration and neointima formation after arterial injury. Compound C represents a potentially new therapeutic agent in treating and preventing occlusive vascular disease. PMID:21566210

Compound C inhibits vascular smooth muscle cell proliferation and migration in an AMP-activated protein kinase-independent fashion.

PubMed

Peyton, Kelly J; Yu, Yajie; Yates, Benjamin; Shebib, Ahmad R; Liu, Xiao-ming; Wang, Hong; Durante, William

2011-08-01

6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrazolo[1,5-a] pyrimidine (compound C) is a cell-permeable pyrrazolopyrimidine derivative that acts as a potent inhibitor of AMP-activated protein kinase (AMPK). Although compound C is often used to determine the role of AMPK in various physiological processes, it also evokes AMPK-independent actions. In the present study, we investigated whether compound C influences vascular smooth muscle cell (SMC) function through the AMPK pathway. Treatment of rat aortic SMCs with compound C (0.02-10 μM) inhibited vascular SMC proliferation and migration in a concentration-dependent fashion. These actions of compound C were not mimicked or affected by silencing AMPKα expression or infecting SMCs with an adenovirus expressing a dominant-negative mutant of AMPK. In contrast, the pharmacological activator of AMPK 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside inhibited the proliferation and migration of SMCs in a manner that was strictly dependent on AMPK activity. Flow cytometry experiments revealed that compound C arrested SMCs in the G(0)/G(1) phase of the cell cycle, and this was associated with a decrease in cyclin D1 and cyclin A protein expression and retinoblastoma protein phosphorylation and an increase in p21 protein expression. Finally, local perivascular delivery of compound C immediately after balloon injury of rat carotid arteries markedly attenuated neointima formation. These studies identify compound C as a novel AMPK-independent regulator of vascular SMC function that exerts inhibitory effects on SMC proliferation and migration and neointima formation after arterial injury. Compound C represents a potentially new therapeutic agent in treating and preventing occlusive vascular disease.

In vitro function of the aryl hydrocarbon receptor predicts in vivo sensitivity of oviparous vertebrates to dioxin-like compounds

EPA Science Inventory

Differences in sensitivity to dioxin-like compounds (DLCs) among species and taxa presents a major challenge to ecological risk assessments. Activation of the aryl hydrocarbon receptor (AHR) regulates adverse effects associated with exposure to DLCs in vertebrates. Prior investig...

Microwave-assisted synthesis, structural characterization, DFT studies, antibacterial and antioxidant activity of 2-methyl-4-oxo-1,2,3,4-tetrahydroquinazoline-2-carboxylic acid

NASA Astrophysics Data System (ADS)

Obafemi, Craig A.; Fadare, Olatomide A.; Jasinski, Jerry P.; Millikan, Sean P.; Obuotor, Efere M.; Iwalewa, Ezekiel O.; Famuyiwa, Samson O.; Sanusi, Kayode; Yilmaz, Yusuf; Ceylan, Ümit

2018-03-01

In the present study a new tetrahydroquinazoline-2-carboxylic, C10H10N2O3, 1‧, was synthesized and its structure was characterized by elemental analysis, IR, 1H NMR, 13C NMR data and high-resolution mass spectrometry. The spectral results are in line with the proposed structure. Single crystal X-ray structural analysis of the compound showed that the crystal structure adopts a monoclinic space group P21/c, with the packing of the molecule stabilized by Cdbnd O … …Hsbnd O, Nsbnd H … ….Odbnd Csbnd Osbnd intermolecular hydrogen bonding. The theoretical geometrical parameters of the compound have been calculated using density functional (DFT) and time-dependent density functional (TD-DFT) theory methods and have been used to predict the thermodynamic one-electron redox potential and the electronic absorption property of the compound. The theoretical characterization matched the experimental measurements, showing a good correlation. The calculated HOMO-LUMO gap (4.79 eV) suggests that compound 1‧ could be a potential antioxidant. The synthesized compound was screened for its in vitro antimicrobial activity against selected bacterial strains and antioxidant activity using the TAC, FRAP, NO and ABTS models. In vitro antioxidant activity of 1' showed a moderate activity, but weaker scavenging activity than the standards of ascorbic acid and trolox. Results of the antibacterial activity of the tested compound showed that it possesses a higher activity against Bacillus anthracis, Bacillus cereus, Bacillus polymyxa, Bacillus subtilis and Staphylococcus aureus than the two standard drugs, streptomycin and tetracycline, and better activity than tetracycline against Escherichia coli.

Simple ortho- and para-hydroquinones as compounds neuroprotective against oxidative stress in a manner associated with specific transcriptional activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Satoh, Takumi; Saitoh, Sachie; Hosaka, Manami

2009-02-06

Electrophilic compounds protect neurons through the activation of the Keap1/Nrf2 pathway and the induction of phase-2 enzymes [T. Satoh, S.A. Lipton, Redox regulation of neuronal survival by electrophilic compounds, Trends Neurosci. 30 (2007) 38-45; T. Satoh, S. Okamoto, J. Cui, Y. Watanabe, K. Furuta, M. Suzuki, K. Tohyama, S.A. Lipton, Activation of the Keap1/Nrf2 pathway for neuroprotection by electrophilic phase II inducers. Proc. Natl. Acad. Sci. USA 103 (2006) 768-773]. Hydroquinone-type electrophilic compounds such as tert-butyl hydroquinone (TBHQ) and carnosic acid (CA) have attracted special attention, because the oxidative conversion of 'hydroquinone' to 'quinone' is essential for the transcriptional activationmore » of the above-mentioned enzymes [T. Satoh, K. Kosaka, K. Itoh, A. Kobayashi, M. Yamamoto, Y. Shimojo, C. Kitajima, J. Cui, J. Kamins, S. Okamoto, T. Shirasawa, S.A. Lipton, Carnosic acid, a catechol-type electrophilic compound, protect neurons both in vitro and in vivo through activation of the Keap1/Nrf2 pathway via S-alkylation of specific cysteine, J. Neurochem. 104 (2008) 1161-1131; A.D. Kraft, D.A. Johnson, J.A. Johnson, Nuclear factor E2-related factor 2-dependent antioxidant response element activation by tert-butylhydroquinone and sulforaphane occurring preferentially in astrocytes conditions neurons against oxidative insult, J. Neurosci. 24 (2004) 1101-1112]. In the present study, we examined the relationship between electrophilicity and the protective effects afforded by electrophilic compounds. Electrophilicity was assessed in terms of the ability of a compound to bind to a cysteine on bovine serum albumin, by which we found that neuroprotective hydroquinones [TBHQ (para-) and CA (ortho-)] had distinctive patterns of cysteine binding compared with other electrophilic compounds. Further, we found that isomers of simple ortho- and para-hydroquinones such as 2-methylhydroquinone (para-) and 4-methyl-catechol (ortho-) [not in abstract] had similar properties of cysteine binding as TBHQ and CA, which compounds were associated with the transcriptional activation and an increase in the level of reduced glutathione. These results suggest that para- and ortho-dihydroquinones may be neuroprotective compounds active against oxidative stress.« less

GDA, a web-based tool for Genomics and Drugs integrated analysis.

PubMed

Caroli, Jimmy; Sorrentino, Giovanni; Forcato, Mattia; Del Sal, Giannino; Bicciato, Silvio

2018-05-25

Several major screenings of genetic profiling and drug testing in cancer cell lines proved that the integration of genomic portraits and compound activities is effective in discovering new genetic markers of drug sensitivity and clinically relevant anticancer compounds. Despite most genetic and drug response data are publicly available, the availability of user-friendly tools for their integrative analysis remains limited, thus hampering an effective exploitation of this information. Here, we present GDA, a web-based tool for Genomics and Drugs integrated Analysis that combines drug response data for >50 800 compounds with mutations and gene expression profiles across 73 cancer cell lines. Genomic and pharmacological data are integrated through a modular architecture that allows users to identify compounds active towards cancer cell lines bearing a specific genomic background and, conversely, the mutational or transcriptional status of cells responding or not-responding to a specific compound. Results are presented through intuitive graphical representations and supplemented with information obtained from public repositories. As both personalized targeted therapies and drug-repurposing are gaining increasing attention, GDA represents a resource to formulate hypotheses on the interplay between genomic traits and drug response in cancer. GDA is freely available at http://gda.unimore.it/.

Synthesis and biological evaluation of pyrazolylthiazole carboxylic acids as potent anti-inflammatory-antimicrobial agents.

PubMed

Khloya, Poonam; Kumar, Satish; Kaushik, Pawan; Surain, Parveen; Kaushik, Dhirender; Sharma, Pawan K

2015-03-15

Current Letter presents design, synthesis and biological evaluation of a novel series of pyrazolylthiazole carboxylates 1a-1p and corresponding acid derivatives 2a-2p. All 32 novel compounds were tested for their in vivo anti-inflammatory activity by carrageenan-induced rat paw edema method as well as for in vitro antimicrobial activity. All the tested compounds exhibited excellent AI activity profile. Three compounds 1p (R=Cl, R(1)=Cl), 2c (R=H, R(1)=F) and 2n (R=Cl, R(1)=OCH3) were identified as potent anti-inflammatory agents exhibiting edema inhibition of 93.06-89.59% which is comparable to the reference drug indomethacin (91.32%) after 3h of carrageenan injection while most of the other compounds displayed inhibition ⩾80%. In addition, pyrazolylthiazole carboxylic acids (2a-2p) also showed good antimicrobial profile. Compound 2h (R=OCH3, R(1)=Cl) showed excellent antimicrobial activity (MIC 6.25μg/mL) against both Gram positive bacteria comparable with the reference drug ciprofloxacin (MIC 6.25μg/mL). Copyright © 2015 Elsevier Ltd. All rights reserved.

The pheromone production of female Plodia interpunctella is inhibited by tyraminergic antagonists.

PubMed

Hirashima, Akinori; Kimizu, Megumi; Shigeta, Yoko; Matsugu, Sachiko; Eiraku, Tomohiko; Kuwano, Eiichi; Eto, Morifusa

2004-11-01

Several compounds were found to suppress the calling behavior and in vitro pheromone biosynthesis of the Indian meal moth, Plodia interpunctella. The compounds were screened by means of a calling-behavior bioassay with female P. interpunctella. Five derivatives with activities in the nanomolar range were identified, in order of decreasing pheromonostatic activity: 4-hydroxybenzaldehyde semicarbazone (42) > 5-(4-methoxyphenyl)-1,3-oxazole (38) > 5-[4-(tert-butyl)phenyl]-1,3-oxazole (40) > 5-(3-methoxyphenyl)-1,3-oxazole (35) > 5-(4-cyanophenyl)-1,3-oxazole (36). These compounds also showed in vitro inhibitory activity in intracellular de novo pheromone biosynthesis, as determined with isolated pheromone-gland preparations that incorporated [1-(14)C]sodium acetate in the presence of the so-called pheromone-biosynthesis-activating neuropeptide (PBAN). The non-additive effect of the inhibitor with antagonist (yohimbine) for the tyramine (TA) receptor suggests that it could be a tyraminergic antagonist. Three-dimensional (3D) computer models were built from a set of compounds. Among the common-featured models generated by the program Catalyst/HipHop, aromatic-ring (AR) and H-bond-acceptor-lipophilic (HBAl) features were considered to be essential for inhibitory activity in the calling behavior and in vitro pheromone biosynthesis. Active compounds, including yohimbine, mapped well onto all the AR and HBAl features of the hypothesis. Less-active compounds were shown to be unable to achieve an energetically favorable conformation, consistent with our 3D common-feature pharmacophore models. The present hypothesis demonstrates that calling behavior and PBAN-stimulated incorporation of radioactivity are inhibited by tyraminergic antagonists.

Fe3O4 Nanoparticles Mediated Synthesis of Novel Isatin-dihydropyrimidinone Hybrid Molecules as Antioxidant and Cytotoxic Agents.

PubMed

Maddela, Srinubabu; Makula, Ajitha; Jayarambabu, N

2017-01-01

The present study emphasizes on designing a new series of isatin-dihydropyrimidinone derivatives by adopting a hybrid pharmacophore approach. Fe3O4 nanoparticles (Fe3O4 NP) are magnetically recoverable and are effective catalysts adequately used to synthesize Isatin-dihydropyrimidinones. Individual derivatives of Isatin and dihydropyrimidinone are equipotent to treat cytotoxicity. The present work was planned to fuse two pharmacophores (Isatin, dihydropyrimidinone) and to examine any synergistic effect in the anticancer activity. The individual compounds are synthesized by adopting appropriate synthetic routes like sandmayers and biginellis reaction and are fused together by using glacial acetic acid and Methanolic KOH to form novel Isatindihydropyrimidinone hybrids. All the new series of hybrids 7a-l were characterized by FT-IR, 1H NMR, 13C NMR, elemental analysis and Mass spectroscopy. The antioxidant activity of the synthesized compounds was assessed by using two models: 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) and Hydrogen peroxide (H2O2) scavenging assay. From the results it can be inferred that nearly all the synthesized compounds have shown antioxidant activity at the tested dose as correlated with the standard ascorbic acid. The in vitro cytotoxic activity was assayed by using MTT assay. Compound 7l with IC50 values 22.13, 25.68 and 35.59 μM has significantly greater potency against MCF- 7, HeLa and IMR-32 cell lines. The compounds with halogen and electron withdrawing groups at the C-5 position of isatin ring exhibited significant antioxidant and cytotoxic activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Quinolone-based HDAC inhibitors.

PubMed

Balasubramanian, Gopalan; Kilambi, Narasimhan; Rathinasamy, Suresh; Rajendran, Praveen; Narayanan, Shridhar; Rajagopal, Sridharan

2014-08-01

HDAC inhibitors emerged as promising drug candidates in combating wide variety of cancers. At present, two of the compounds SAHA and Romidepsin were approved by FDA for cutaneous T-cell lymphoma and many are in various clinical phases. A new quinolone cap structure was explored with hydroxamic acid as zinc-binding group (ZBG). The pan HDAC inhibitory and antiproliferative activities against three human cancer cell lines HCT-116 (colon), NCI-H460 (lung) and U251 (glioblastoma) of the compounds (4a-4w) were evaluated. Introduction of heterocyclic amines in CAP region increased the enzyme inhibitory and antiproliferative activities and few of the compounds tested are metabolically stable in both MLM and HLM.

A new antioxidant beverage produced with green tea and apple.

PubMed

Rubio-Perez, Jose M; Vidal-Guevara, Maria L; Zafrilla, Pilar; Morillas-Ruiz, Juana M

2014-08-01

Green tea and apple are natural products with health benefits. These healthy properties are linked closely to the antioxidant compounds, mainly phenolic compounds. These antioxidant compounds have a potential for preventing and treating cancer, cardiovascular, inflammatory and neurodegenerative diseases in humans. The aim of the present work was to design a new beverage with high antioxidant power combining extracts of green tea and apple, studying the antioxidant composition and activity, organoleptic properties (colour) and stability status during storage at different temperatures. The majority compounds identified in the beverage were flavan-3-ols, being the (-)-epigallocatechin-3-gallate which had the highest concentration. After storage, floridzine was the compound with lower decrease of concentration. The new designed beverage had a good colour, and high antioxidant activity and stability at room temperature, so that the beverage needs no refrigeration, showing potential for the development of new healthy functional beverages.

Development of sampling method and chromatographic analysis of volatile organic compounds emitted from human skin.

PubMed

Grabowska-Polanowska, Beata; Miarka, Przemysław; Skowron, Monika; Sułowicz, Joanna; Wojtyna, Katarzyna; Moskal, Karolina; Śliwka, Ireneusz

2017-10-01

The studies on volatile organic compounds emitted from skin are an interest for chemists, biologists and physicians due to their role in development of different scientific areas, including medical diagnostics, forensic medicine and the perfume design. This paper presents a proposal of two sampling methods applied to skin odor collection: the first one uses a bag of cellulose film, the second one, using cellulose sachets filled with active carbon. Volatile organic compounds were adsorbed on carbon sorbent, removed via thermal desorption and analyzed using gas chromatograph with mass spectrometer. The first sampling method allowed identification of more compounds (52) comparing to the second one (30). Quantitative analyses for acetone, butanal, pentanal and hexanal were done. The skin odor sampling method using a bag of cellulose film, allowed the identification of many more compounds when compared with the method using a sachet filled with active carbon.

Detection of Aryl Hydrocarbon Receptor Activation by Some Chemicals in Food Using a Reporter Gene Assay

PubMed Central

Amakura, Yoshiaki; Tsutsumi, Tomoaki; Yoshimura, Morio; Nakamura, Masafumi; Handa, Hiroshi; Matsuda, Rieko; Teshima, Reiko; Watanabe, Takahiro

2016-01-01

The purpose of this study was to examine whether a simple bioassay used for the detection of dioxins (DXNs) could be applied to detect trace amounts of harmful DXN-like substances in food products. To identify substances with possible DXN-like activity, we assessed the ability of various compounds in the environment to bind the aryl hydrocarbon receptor (AhR) that binds specifically to DXNs. The compounds tested included 19 polycyclic aromatic hydrocarbons (PAHs), 20 PAH derivatives (nitrated, halogenated, and aminated derivatives), 23 pesticides, six amino acids, and eight amino acid metabolites. The AhR binding activities (AhR activity) of these compounds were measured using the chemical activated luciferase gene expression (CALUX) reporter gene assay system. The majority of the PAHs exhibited marked AhR activity that increased in a concentration-dependent manner. Furthermore, there was a positive link between AhR activity and the number of aromatic rings in the PAH derivatives. Conversely, there appeared to be a negative correlation between AhR activity and the number of chlorine residues present on halogenated PAH derivatives. However, there was no correlation between AhR activity and the number and position of substituents among nitrated and aminated derivatives. Among the pesticides tested, the indole-type compounds carbendazim and thiabendazole showed high levels of activity. Similarly, the indole compound tryptamine was the only amino acid metabolite to induce AhR activity. The results are useful in understanding the identification and characterization of AhR ligands in the CALUX assay. PMID:28231110

Non-targeted workflow for identification of antimicrobial compounds in animal feed using bioassay-directed screening in combination with liquid chromatography-high resolution mass spectrometry.

PubMed

Wegh, Robin S; Berendsen, Bjorn J A; Driessen-Van Lankveld, Wilma D M; Pikkemaat, Mariël G; Zuidema, Tina; Van Ginkel, Leen A

2017-11-01

A non-targeted workflow is reported for the isolation and identification of antimicrobial active compounds using bioassay-directed screening and LC coupled to high-resolution MS. Suspect samples are extracted using a generic protocol and fractionated using two different LC conditions (A and B). The behaviour of the bioactive compound under these different conditions yields information about the physicochemical properties of the compound and introduces variations in co-eluting compounds in the fractions, which is essential for peak picking and identification. The fractions containing the active compound(s) obtained with conditions A and B are selected using a microbiological effect-based bioassay. The selected bioactive fractions from A and B are analysed using LC combined with high-resolution MS. Selection of relevant signals is automatically carried out by selecting all signals present in both bioactive fractions A and B, yielding tremendous data reduction. The method was assessed using two spiked feed samples and subsequently applied to two feed samples containing an unidentified compound showing microbial growth inhibition. In all cases, the identity of the compound causing microbiological inhibition was successfully confirmed.

Experimental and computational approaches of a novel methyl (2E)-2-{[N-(2-formylphenyl)(4-methylbenzene)sulfonamido]methyl}-3-(4-chlorophenyl)prop-2-enoate: A potential antimicrobial agent and an inhibition of penicillin-binding protein

NASA Astrophysics Data System (ADS)

Murugavel, S.; Vetri velan, V.; Kannan, Damodharan; Bakthadoss, Manickam

2016-07-01

The title compound methyl(2E)-2-{[N-(2-formylphenyl) (4-methylbenzene)sulfonamido]methyl}-3-(4-chlorophenyl) prop-2-enoate (MFMSC) has been synthesized and single crystals were grown by slow evaporation solution growth technique at room temperature. Structural and vibrational spectroscopic studies were carried out by using single crystal X-ray diffraction, FT-IR and NMR spectral analysis together with DFT method using GAUSSIAN'03 software. The detailed interpretation of the vibrational spectra has been carried out by VEDA program. NBO analysis, Mulliken charge analysis, HOMO-LUMO, MEP, Global chemical reactivity descriptors and thermodynamic properties have been analyzed. The hyperpolarisability calculation reveals the present material has a reasonably good propensity for nonlinear optical activity. The obtained antimicrobial activity results indicate that the compound shows good to moderate activity against all tested bacterial and fungal pathogens. A computational study was also carried out to predict the drug-likeness and ADMET properties of the title compound. Due to the different potential biological activity of the title compound, molecular docking study is also reported and the compound might exhibit inhibitory activity against penicillin-binding protein PBP-2X.

Antioxidant and antimicrobial effects of phenolic compounds extracts of Northeast Portugal honey.

PubMed

Estevinho, Letícia; Pereira, Ana Paula; Moreira, Leandro; Dias, Luís G; Pereira, Ermelinda

2008-12-01

Phenolic compounds of dark and clear honeys from Trás-os-Montes of Portugal were extracted with Amberlite XAD-2 and evaluated for their antioxidant and antimicrobial activities. The antioxidant effect was studied using the in vitro test capacity of scavenge the 2,2-diphenyl-1-picryhydrazyl (DPPH) free radical and of reducing power of iron (III)/ferricyanide complex. The antimicrobial activity was screened using three Gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus, Staphylococcus lentus) and three Gram-negative bacteria (Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli). The results obtained from the partial identification of honey phenolic compounds by high-performance liquid chromatography with a diode array detector showed that p-hydroxibenzoic acid, cinnamic acid, naringenin, pinocembrin and chrysin are the phenolic compounds present in most of the samples analyzed. Antioxidant potential was dependent of honey extract concentration and the results showed that dark honey phenolic compounds had higher activity than the obtained from clear honey. In the biological assays, results showed that S. aureus were the most sensitive microrganisms and B. subtilis, S. lentus, K. pneumoniae and E. coli were each moderately sensitive to the antimicrobial activity of honey extracts. Nevertheless, no antimicrobial activity was observed in the test with P. aeruginosa.

In vitro pharmacological activity of the tetrahydroisoquinoline salsolinol present in products from Theobroma cacao L. like cocoa and chocolate.

PubMed

Melzig, M F; Putscher, I; Henklein, P; Haber, H

2000-11-01

Cocoa and chocolate contain the tetrahydroisoquinoline alkaloid salsolinol up to a concentration of 25 microg/g. Salsolinol is a dopaminergic active compound which binds to the D(2) receptor family, especially to the D(3) receptor with a K(i) of 0.48+/-0.021 micromol/l. It inhibits the formation of cyclic AMP and the release of beta-endorphin and ACTH in a pituitary cell system. Taking the detected concentration and the pharmacological properties into account, salsolinol seems to be one of the main psychoactive compounds present in cocoa and chocolate and might be included in chocolate addiction.

Schistosomicidal Activity of Alkyl-phenols from the Cashew Anacardium occidentale against Schistosoma mansoni Adult Worms.

PubMed

Alvarenga, Tavane A; de Oliveira, Pollyanna F; de Souza, Julia M; Tavares, Denise C; Andrade E Silva, Márcio L; Cunha, Wilson R; Groppo, Milton; Januário, Ana H; Magalhães, Lizandra G; Pauletti, Patrícia M

2016-11-23

Bioassay-guided study of the ethanol extract from the cashew Anacardium occidentale furnished cardol triene (1), cardol diene (2), anacardic acid triene (3), cardol monoene (4), anacardic acid diene (5), 2-methylcardol triene (6), and 2-methylcardol diene (7). 1D- and 2D-NMR experiments and HRMS analysis confirmed the structures of compounds 1-7. Compounds 2 and 7 were active against Schistosoma mansoni adult worms in vitro, with LC 50 values of 32.2 and 14.5 μM and selectivity indices of 6.1 and 21.2, respectively. Scanning electron microscopy of the tegument of male worms in the presence of compound 7 at 25 μM after 24 h of incubation showed severe damage as well as peeling and reduction in the number of spine tubercles. Transmission electron microscopy analyses revealed swollen mitochondrial membrane, vacuoles, and altered tegument in worms incubated with compound 2 (25 μM after 24 h). Worms incubated with compound 7 (25 μM after 24 h) had lysed interstitial tissue, degenerated mitochondria, and drastically altered tegument. Together, the results indicated that compound 7 presents promising in vitro schistosomicidal activity.

Bond-based bilinear indices for computational discovery of novel trypanosomicidal drug-like compounds through virtual screening.

PubMed

Castillo-Garit, Juan Alberto; del Toro-Cortés, Oremia; Vega, Maria C; Rolón, Miriam; Rojas de Arias, Antonieta; Casañola-Martin, Gerardo M; Escario, José A; Gómez-Barrio, Alicia; Marrero-Ponce, Yovani; Torrens, Francisco; Abad, Concepción

2015-01-01

Two-dimensional bond-based bilinear indices and linear discriminant analysis are used in this report to perform a quantitative structure-activity relationship study to identify new trypanosomicidal compounds. A data set of 440 organic chemicals, 143 with antitrypanosomal activity and 297 having other clinical uses, is used to develop the theoretical models. Two discriminant models, computed using bond-based bilinear indices, are developed and both show accuracies higher than 86% for training and test sets. The stochastic model correctly indentifies nine out of eleven compounds of a set of organic chemicals obtained from our synthetic collaborators. The in vitro antitrypanosomal activity of this set against epimastigote forms of Trypanosoma cruzi is assayed. Both models show a good agreement between theoretical predictions and experimental results. Three compounds showed IC50 values for epimastigote elimination (AE) lower than 50 μM, while for the benznidazole the IC50 = 54.7 μM which was used as reference compound. The value of IC50 for cytotoxicity of these compounds is at least 5 times greater than their value of IC50 for AE. Finally, we can say that, the present algorithm constitutes a step forward in the search for efficient ways of discovering new antitrypanosomal compounds. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Glycyrrhiza glabra HPLC fractions: identification of Aldehydo Isoophiopogonone and Liquirtigenin having activity against multidrug resistant bacteria.

PubMed

Rahman, Hazir; Khan, Ilyas; Hussain, Anwar; Shahat, Abdelaaty Abdelaziz; Tawab, Abdul; Qasim, Muhammad; Adnan, Muhammad; Al-Said, Mansour S; Ullah, Riaz; Khan, Shahid Niaz

2018-05-02

Medicinal plants have been founded as traditional herbal medicine worldwide. Most of the plant's therapeutic properties are due to the presence of secondary metabolites such as alkaloids, glycosides, tannins and volatile oil. The present investigation analyzed the High-Pressure Liquid Chromatography (HPLC) fractions of Glycyrrhiza glabra (Aqueous, Chloroform, Ethanol and Hexane) against multidrug resistant human bacterial pathogens (Escherichia coli, Acinetobacter baumannii, Staphylococcus aureus and Pseudomonas aeruginosa). All the fractions showed antibacterial activity, were subjected to LC MS/MS analysis for identification of bioactive compounds. Among total HPLC fractions of G. glabra (n = 20), three HPLC fractions showed potential activity against multidrug resistant (MDR) bacterial isolates. Fraction 1 (F1) of aqueous extracts, showed activity against A. baumannii (15 ± 0.5 mm). F4 from hexane extract of G. glabra showed activity against S. aureus (10 ± 0.2 mm). However, F2 from ethanol extract exhibited activity against S. aureus (10 ± 0.3 mm). These active fractions were further processed by LC MS/MS analysis for the identification of compounds. Ellagic acid was identified in the F1 of aqueous extract while 6-aldehydo-isoophiopogonone was present in F4 of hexane extract. Similarly, Liquirtigenin was identified in F2 of ethanol. Glycyrrhiza glabra extracts HPLC fractions showed anti-MDR activity. Three bioactive compounds were identified in the study. 6-aldehydo-isoophiopogonone and Liquirtigenin were for the first time reported in G. glabra. Further characterization of the identified compounds will be helpful for possible therapeutic uses against infectious diseases caused by multidrug resistant bacteria.

A comparison of the phenolic profile and antioxidant activity of different Cichorium spinosum L. ecotypes.

PubMed

Petropoulos, Spyridon A; Fernandes, Ângela; Barros, Lillian; Ferreira, Isabel Cfr

2018-01-01

Wild greens are considered a rich source of phenolic compounds and antioxidants and an essential part of the so-called Mediterranean diet. In the present study, Cichorium spinosum L. ecotypes, cultivated or collected in situ from wild plants from the eastern Mediterranean, were evaluated regarding their phenolic composition and antioxidant activity. Significant differences were observed among the various studied ecotypes regarding their phenolic compound content and profile, especially between wild and cultivated ecotypes, as well as the phenolic acid content between commercial products and cultivated plants. The antioxidant activity also varied among the various studied ecotypes and growing conditions, with commercial products having the highest antioxidant activity, whereas wild ecotypes showed lower antioxidant activity. Cichorium spinosum leaves are a rich source of chicoric and 5-O-caffeoylquinic acid, while significant differences in total phenolic acids, flavonoids and phenolic compound content and in antioxidant activity were observed among the studied ecotypes, as well as between the tested growing conditions. According to the results of the present study, further valorization of C. spinosum species has great potential, since it could be used as a new alternative species in the food industry. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Antimalarial Activity of Potential Inhibitors of Plasmodium falciparum Lactate Dehydrogenase Enzyme Selected by Docking Studies

PubMed Central

Penna-Coutinho, Julia; Cortopassi, Wilian Augusto; Oliveira, Aline Alves; França, Tanos Celmar Costa; Krettli, Antoniana Ursine

2011-01-01

The Plasmodium falciparum lactate dehydrogenase enzyme (PfLDH) has been considered as a potential molecular target for antimalarials due to this parasite's dependence on glycolysis for energy production. Because the LDH enzymes found in P. vivax, P. malariae and P. ovale (pLDH) all exhibit ∼90% identity to PfLDH, it would be desirable to have new anti-pLDH drugs, particularly ones that are effective against P. falciparum, the most virulent species of human malaria. Our present work used docking studies to select potential inhibitors of pLDH, which were then tested for antimalarial activity against P. falciparum in vitro and P. berghei malaria in mice. A virtual screening in DrugBank for analogs of NADH (an essential cofactor to pLDH) and computational studies were undertaken, and the potential binding of the selected compounds to the PfLDH active site was analyzed using Molegro Virtual Docker software. Fifty compounds were selected based on their similarity to NADH. The compounds with the best binding energies (itraconazole, atorvastatin and posaconazole) were tested against P. falciparum chloroquine-resistant blood parasites. All three compounds proved to be active in two immunoenzymatic assays performed in parallel using monoclonals specific to PfLDH or a histidine rich protein (HRP2). The IC50 values for each drug in both tests were similar, were lowest for posaconazole (<5 µM) and were 40- and 100-fold less active than chloroquine. The compounds reduced P. berghei parasitemia in treated mice, in comparison to untreated controls; itraconazole was the least active compound. The results of these activity trials confirmed that molecular docking studies are an important strategy for discovering new antimalarial drugs. This approach is more practical and less expensive than discovering novel compounds that require studies on human toxicology, since these compounds are already commercially available and thus approved for human use. PMID:21779323

Preclinical Antileukemia Activity of Tramesan: A Newly Identified Bioactive Fungal Metabolite.

PubMed

Ricciardi, M R; Licchetta, R; Mirabilii, S; Scarpari, M; Parroni, A; Fabbri, A A; Cescutti, P; Reverberi, M; Fanelli, C; Tafuri, A

2017-01-01

Despite improvements that occurred in the last decades in the acute myeloid leukemia (AML) treatment, clinical results are still unsatisfactory. More effective therapies are required, and innovative approaches are ongoing, including the discovery of novel antileukemia natural compounds. Several studies have described the activity of extracts from mushrooms which produce compounds that exhibited immunological and antitumor activities. The latter has been demonstrated to be promoted in vitro by mushroom polysaccharides via induction of apoptosis. However, the antileukemia activity of these compounds on primary cells is still not reported. In the present study, we examined the in vitro effects of Tramesan (TR), a bioactive compound extracted from Trametes versicolor , on leukemic cell lines and primary cells. Our results demonstrated that TR induced a marked growth inhibition of leukemic cell lines and primary cells from AML patients. The antiproliferative effects of TR were associated in primary AML cells with a significant increase of apoptosis. No significant cytotoxic effects were observed in normal peripheral blood mononuclear cells (MNC) from healthy donors. Our data demonstrated a cytotoxic activity of TR on leukemia cells prompting further translational applications. Ongoing studies are elucidating the molecular mechanisms underlying its antileukemic activity.

Preclinical Antileukemia Activity of Tramesan: A Newly Identified Bioactive Fungal Metabolite

PubMed Central

Scarpari, M.; Parroni, A.; Fabbri, A. A.; Cescutti, P.; Reverberi, M.; Fanelli, C.

2017-01-01

Despite improvements that occurred in the last decades in the acute myeloid leukemia (AML) treatment, clinical results are still unsatisfactory. More effective therapies are required, and innovative approaches are ongoing, including the discovery of novel antileukemia natural compounds. Several studies have described the activity of extracts from mushrooms which produce compounds that exhibited immunological and antitumor activities. The latter has been demonstrated to be promoted in vitro by mushroom polysaccharides via induction of apoptosis. However, the antileukemia activity of these compounds on primary cells is still not reported. In the present study, we examined the in vitro effects of Tramesan (TR), a bioactive compound extracted from Trametes versicolor, on leukemic cell lines and primary cells. Our results demonstrated that TR induced a marked growth inhibition of leukemic cell lines and primary cells from AML patients. The antiproliferative effects of TR were associated in primary AML cells with a significant increase of apoptosis. No significant cytotoxic effects were observed in normal peripheral blood mononuclear cells (MNC) from healthy donors. Our data demonstrated a cytotoxic activity of TR on leukemia cells prompting further translational applications. Ongoing studies are elucidating the molecular mechanisms underlying its antileukemic activity. PMID:29270245

Quantum chemical and statistical study of megazol-derived compounds with trypanocidal activity

NASA Astrophysics Data System (ADS)

Rosselli, F. P.; Albuquerque, C. N.; da Silva, A. B. F.

In this work we performed a structure-activity relationship (SAR) study with the aim to correlate molecular properties of the megazol compound and 10 of its analogs with the biological activity against Trypanosoma cruzi (trypanocidal or antichagasic activity) presented by these molecules. The biological activity indication was obtained from in vitro tests and the molecular properties (variables or descriptors) were obtained from the optimized chemical structures by using the PM3 semiempirical method. It was calculated ˜80 molecular properties selected among steric, constitutional, electronic, and lipophilicity properties. In order to reduce dimensionality and investigate which subset of variables (descriptors) would be more effective in classifying the compounds studied, according to their degree of trypanocidal activity, we employed statistical methodologies (pattern recognition and classification techniques) such as principal component analysis (PCA), hierarchical cluster analysis (HCA), K-nearest neighbor (KNN), and discriminant function analysis (DFA). These methods showed that the descriptors molecular mass (MM), energy of the second lowest unoccupied molecular orbital (LUMO+1), charge on the first nitrogen at substituent 2 (qN'), dihedral angles (D1 and D2), bond length between atom C4 and its substituent (L4), Moriguchi octanol-partition coefficient (MLogP), and length-to-breadth ratio (L/Bw) were the variables responsible for the separation between active and inactive compounds against T. cruzi. Afterwards, the PCA, KNN, and DFA models built in this work were used to perform trypanocidal activity predictions for eight new megazol analog compounds.

Isolation and identification of antimicrobial compound from Mentha longifolia L. leaves grown wild in Iraq.

PubMed

Al-Bayati, Firas A

2009-06-12

Mentha longifolia L. (Lamiaceae) leaves have been traditionally implemented in the treatment of minor sore throat and minor mouth or throat irritation by the indigenous people of Iraq, although the compounds responsible for the medicinal properties have not been identified. In the present study, an antimicrobial compound was isolated and characterized, and its biological activity was assessed. The compound was isolated and characterized from the extracted essential oil using different spectral techniques: TLC, FTIR spectra and HPLC. Antimicrobial activity of the compound was assessed using both disc diffusion and microdilution method in 96 multi-well microtiter plates. A known compound was isolated from the essential oil of the plant and was identified as (-) menthol. The isolated compound was investigated for its antimicrobial activity against seven selected pathogenic and non-pathogenic microorganisms: Staphylococcus aureus, Streptococcus mutans, Streptococcus faecalis, Streptococcus pyogenis, Lactobacillus acidophilus, Pseudomonas aeruginosa and the yeast Candida albicans. Menthol at different concentrations (1:1, 1:5, 1:10, 1:20) was active against all tested bacteria except for P. aeruginosa, and the highest inhibitory effect was observed against S. mutans (zone of inhibition: 25.3 mm) using the disc diffusion method. Minimal inhibitory concentration MIC values ranged from 15.6-125.0 microg/ml, and the most promising results were observed against S. aureus and S. mutans (MIC 15.6 microg/ml) while, S. faecalis, S. pyogenis and L. acidophilus ranked next (MIC 31.2 microg/ml). Furthermore, menthol achieved considerable antifungal activity against the yeast C. albicans (zone of inhibition range: 7.1-18.5 mm; MIC: 125.0). The isolation of an antimicrobial compound from M. longifolia leaves validates the use of this plant in the treatment of minor sore throat and minor mouth or throat irritation.

Iron, copper, and manganese complexes with in vitro superoxide dismutase and/or catalase activities that keep Saccharomyces cerevisiae cells alive under severe oxidative stress.

PubMed

Ribeiro, Thales P; Fernandes, Christiane; Melo, Karen V; Ferreira, Sarah S; Lessa, Josane A; Franco, Roberto W A; Schenk, Gerhard; Pereira, Marcos D; Horn, Adolfo

2015-03-01

Due to their aerobic lifestyle, eukaryotic organisms have evolved different strategies to overcome oxidative stress. The recruitment of some specific metalloenzymes such as superoxide dismutases (SODs) and catalases (CATs) is of great importance for eliminating harmful reactive oxygen species (hydrogen peroxide and superoxide anion). Using the ligand HPClNOL {1-[bis(pyridin-2-ylmethyl)amino]-3-chloropropan-2-ol}, we have synthesized three coordination compounds containing iron(III), copper(II), and manganese(II) ions, which are also present in the active site of the above-noted metalloenzymes. These compounds were evaluated as SOD and CAT mimetics. The manganese and iron compounds showed both SOD and CAT activities, while copper showed only SOD activity. The copper and manganese in vitro SOD activities are very similar (IC50~0.4 μmol dm(-3)) and about 70-fold higher than those of iron. The manganese compound showed CAT activity higher than that of the iron species. Analyzing their capacity to protect Saccharomyces cerevisiae cells against oxidative stress (H2O2 and the O2(•-) radical), we observed that all compounds act as antioxidants, increasing the resistance of yeast cells mainly due to a reduction of lipid oxidation. Especially for the iron compound, the data indicate complete protection when wild-type cells were exposed to H2O2 or O2(•-) species. Interestingly, these compounds also compensate for both superoxide dismutase and catalase deficiencies; their antioxidant activity is metal ion dependent, in the order iron(III)>copper(II)>manganese(II). The protection mechanism employed by the complexes proved to be independent of the activation of transcription factors (such as Yap1, Hsf1, Msn2/Msn4) and protein synthesis. There is no direct relation between the in vitro and the in vivo antioxidant activities. Copyright © 2014 Elsevier Inc. All rights reserved.

Methods for the synthesis of aza(deaza)xanthines as a basis of biologically active compounds

NASA Astrophysics Data System (ADS)

Babkov, D. A.; Geisman, A. N.; Khandazhinskaya, A. L.; Novikov, M. S.

2016-03-01

The review covers methods for the synthesis of aza(deaza)xanthines, i.e., fused pyrrolo-, pyrazolo- and triazolopyrimidine heterocyclic systems, which are common core structures of various biologically active compounds. The extensive range of modern synthetic approaches is organized according to target structures and starting building blocks. The presented material is intended to benefit broad audience of specialists in the fields of organic, medicinal and pharmaceutical chemistry. The bibliography includes 195 references.

Polymethoxyflavones from Nicotiana plumbaginifolia (Solanaceae) Exert Antinociceptive and Neuropharmacological Effects in Mice

PubMed Central

Shajib, Md. Shafiullah; Rashid, Ridwan B.; Ming, Long C.; Islam, Shanta; Sarker, Md. Moklesur R.; Nahar, Lutfun; Sarker, Satyajit D.; Datta, Bidyut K.; Rashid, Mohammad A.

2018-01-01

Polymethoxylavones (PMFs) are known to exhibit significant anti-inflammatory and neuroprotective properties. Nicotiana plumbaginifolia, an annual Bangladeshi herb, is rich in polymethoxyflavones that possess significant analgesic and anxiolytic activities. The present study aimed to determine the antinociceptive and neuropharmacological activities of polyoxygenated flavonoids namely- 3,3′,5,6,7,8-hexamethoxy-4′,5′-methylenedioxyflavone (1), 3,3′,4′,5′,5,6,7,8-octamethoxyflavone (exoticin) (2), 6,7,4′,5′-dimethylenedioxy-3,5,3′-trimethoxyflavone (3), and 3,3′,4′,5,5′,8-hexamethoxy-6,7-methylenedioxyflavone (4), isolated and identified from N. plumbaginifolia. Antinociceptive activity was assessed using the acetic-acid induced writhing, hot plate, tail immersion, formalin and carrageenan-induced paw edema tests, whereas neuropharmacological effects were evaluated in the hole cross, open field and elevated plus maze test. Oral treatment of compounds 1, 3, and 4 (12.5–25 mg/kg b.w.) exhibited dose-dependent and significant (p < 0.01) antinociceptive activity in the acetic-acid, formalin, carrageenan, and thermal (hot plate)-induced pain models. The association of ATP-sensitive K+ channel and opioid systems in their antinociceptive effect was obvious from the antagonist effect of glibenclamide and naloxone, respectively. These findings suggested central and peripheral antinociceptive activities of the compounds. Compound 1, 3, and 4 (12.5 mg/kg b.w.) demonstrated significant (p < 0.05) anxiolytic-like activity in the elevated plus-maze test, while the involvement of GABAA receptor in the action of compound 3 and 4 was evident from the reversal effects of flumazenil. In addition, compounds 1 and 4 (12.5–25 mg/kg b.w) exhibited anxiolytic activity without altering the locomotor responses. The present study suggested that the polymethoxyflavones (1–4) from N. Plumbaginifolia could be considered as suitable candidates for the development of analgesic and anxiolytic agents. PMID:29515437

Polymethoxyflavones from Nicotiana plumbaginifolia (Solanaceae) Exert Antinociceptive and Neuropharmacological Effects in Mice.

PubMed

Shajib, Md Shafiullah; Rashid, Ridwan B; Ming, Long C; Islam, Shanta; Sarker, Md Moklesur R; Nahar, Lutfun; Sarker, Satyajit D; Datta, Bidyut K; Rashid, Mohammad A

2018-01-01

Polymethoxylavones (PMFs) are known to exhibit significant anti-inflammatory and neuroprotective properties. Nicotiana plumbaginifolia , an annual Bangladeshi herb, is rich in polymethoxyflavones that possess significant analgesic and anxiolytic activities. The present study aimed to determine the antinociceptive and neuropharmacological activities of polyoxygenated flavonoids namely- 3,3',5,6,7,8-hexamethoxy-4',5'-methylenedioxyflavone ( 1 ), 3,3',4',5',5,6,7,8-octamethoxyflavone (exoticin) ( 2 ), 6,7,4',5'-dimethylenedioxy-3,5,3'-trimethoxyflavone ( 3 ), and 3,3',4',5,5',8-hexamethoxy-6,7-methylenedioxyflavone ( 4 ), isolated and identified from N. plumbaginifolia . Antinociceptive activity was assessed using the acetic-acid induced writhing, hot plate, tail immersion, formalin and carrageenan-induced paw edema tests, whereas neuropharmacological effects were evaluated in the hole cross, open field and elevated plus maze test. Oral treatment of compounds 1 , 3 , and 4 (12.5-25 mg/kg b.w.) exhibited dose-dependent and significant ( p < 0.01) antinociceptive activity in the acetic-acid, formalin, carrageenan, and thermal (hot plate)-induced pain models. The association of ATP-sensitive K + channel and opioid systems in their antinociceptive effect was obvious from the antagonist effect of glibenclamide and naloxone, respectively. These findings suggested central and peripheral antinociceptive activities of the compounds. Compound 1 , 3 , and 4 (12.5 mg/kg b.w.) demonstrated significant ( p < 0.05) anxiolytic-like activity in the elevated plus-maze test, while the involvement of GABA A receptor in the action of compound 3 and 4 was evident from the reversal effects of flumazenil. In addition, compounds 1 and 4 (12.5-25 mg/kg b.w) exhibited anxiolytic activity without altering the locomotor responses. The present study suggested that the polymethoxyflavones ( 1-4 ) from N. Plumbaginifolia could be considered as suitable candidates for the development of analgesic and anxiolytic agents.

Olive Tree (Olea europeae L.) Leaves: Importance and Advances in the Analysis of Phenolic Compounds

PubMed Central

Abaza, Leila; Taamalli, Amani; Nsir, Houda; Zarrouk, Mokhtar

2015-01-01

Phenolic compounds are becoming increasingly popular because of their potential role in contributing to human health. Experimental evidence obtained from human and animal studies demonstrate that phenolic compounds from Olea europaea leaves have biological activities which may be important in the reduction in risk and severity of certain chronic diseases. Therefore, an accurate profiling of phenolics is a crucial issue. In this article, we present a review work on current treatment and analytical methods used to extract, identify, and/or quantify phenolic compounds in olive leaves. PMID:26783953

Volatile Compounds in Honey: A Review on Their Involvement in Aroma, Botanical Origin Determination and Potential Biomedical Activities

PubMed Central

Manyi-Loh, Christy E.; Ndip, Roland N.; Clarke, Anna M.

2011-01-01

Volatile organic compounds (VOCs) in honey are obtained from diverse biosynthetic pathways and extracted by using various methods associated with varying degrees of selectivity and effectiveness. These compounds are grouped into chemical categories such as aldehyde, ketone, acid, alcohol, hydrocarbon, norisoprenoids, terpenes and benzene compounds and their derivatives, furan and pyran derivatives. They represent a fingerprint of a specific honey and therefore could be used to differentiate between monofloral honeys from different floral sources, thus providing valuable information concerning the honey’s botanical and geographical origin. However, only plant derived compounds and their metabolites (terpenes, norisoprenoids and benzene compounds and their derivatives) must be employed to discriminate among floral origins of honey. Notwithstanding, many authors have reported different floral markers for honey of the same floral origin, consequently sensory analysis, in conjunction with analysis of VOCs could help to clear this ambiguity. Furthermore, VOCs influence honey’s aroma described as sweet, citrus, floral, almond, rancid, etc. Clearly, the contribution of a volatile compound to honey aroma is determined by its odor activity value. Elucidation of the aroma compounds along with floral origins of a particular honey can help to standardize its quality and avoid fraudulent labeling of the product. Although only present in low concentrations, VOCS could contribute to biomedical activities of honey, especially the antioxidant effect due to their natural radical scavenging potential. PMID:22272147

Unique DC-SIGN clustering activity of a small glycomimetic: A lesson for ligand design.

PubMed

Sutkeviciute, Ieva; Thépaut, Michel; Sattin, Sara; Berzi, Angela; McGeagh, John; Grudinin, Sergei; Weiser, Jörg; Le Roy, Aline; Reina, Jose J; Rojo, Javier; Clerici, Mario; Bernardi, Anna; Ebel, Christine; Fieschi, Franck

2014-06-20

DC-SIGN is a dendritic cell-specific C-type lectin receptor that recognizes highly glycosylated ligands expressed on the surface of various pathogens. This receptor plays an important role in the early stages of many viral infections, including HIV, which makes it an interesting therapeutic target. Glycomimetic compounds are good drug candidates for DC-SIGN inhibition due to their high solubility, resistance to glycosidases, and nontoxicity. We studied the structural properties of the interaction of the tetrameric DC-SIGN extracellular domain (ECD), with two glycomimetic antagonists, a pseudomannobioside (1) and a linear pseudomannotrioside (2). Though the inhibitory potency of 2, as measured by SPR competition experiments, was 1 order of magnitude higher than that of 1, crystal structures of the complexes within the DC-SIGN carbohydrate recognition domain showed the same binding mode for both compounds. Moreover, when conjugated to multivalent scaffolds, the inhibitory potencies of these compounds became uniform. Combining isothermal titration microcalorimetry, analytical ultracentrifugation, and dynamic light scattering techniques to study DC-SIGN ECD interaction with these glycomimetics revealed that 2 is able, without any multivalent presentation, to cluster DC-SIGN tetramers leading to an artificially overestimated inhibitory potency. The use of multivalent scaffolds presenting 1 or 2 in HIV trans-infection inhibition assay confirms the loss of potency of 2 upon conjugation and the equal efficacy of chemically simpler compound 1. This study documents a unique case where, among two active compounds chemically derived, the compound with the lower apparent activity is the optimal lead for further drug development.

Natural Bioactive Compounds from Winery By-Products as Health Promoters: A Review

PubMed Central

Teixeira, Ana; Baenas, Nieves; Dominguez-Perles, Raul; Barros, Ana; Rosa, Eduardo; Moreno, Diego A.; Garcia-Viguera, Cristina

2014-01-01

The relevance of food composition for human health has increased consumers’ interest in the consumption of fruits and vegetables, as well as foods enriched in bioactive compounds and nutraceuticals. This fact has led to a growing attention of suppliers on reuse of agro-industrial wastes rich in healthy plant ingredients. On this matter, grape has been pointed out as a rich source of bioactive compounds. Currently, up to 210 million tons of grapes (Vitis vinifera L.) are produced annually, being the 15% of the produced grapes addressed to the wine-making industry. This socio-economic activity generates a large amount of solid waste (up to 30%, w/w of the material used). Winery wastes include biodegradable solids namely stems, skins, and seeds. Bioactive compounds from winery by-products have disclosed interesting health promoting activities both in vitro and in vivo. This is a comprehensive review on the phytochemicals present in winery by-products, extraction techniques, industrial uses, and biological activities demonstrated by their bioactive compounds concerning potential for human health. PMID:25192288

Predicting the performance of fingerprint similarity searching.

PubMed

Vogt, Martin; Bajorath, Jürgen

2011-01-01

Fingerprints are bit string representations of molecular structure that typically encode structural fragments, topological features, or pharmacophore patterns. Various fingerprint designs are utilized in virtual screening and their search performance essentially depends on three parameters: the nature of the fingerprint, the active compounds serving as reference molecules, and the composition of the screening database. It is of considerable interest and practical relevance to predict the performance of fingerprint similarity searching. A quantitative assessment of the potential that a fingerprint search might successfully retrieve active compounds, if available in the screening database, would substantially help to select the type of fingerprint most suitable for a given search problem. The method presented herein utilizes concepts from information theory to relate the fingerprint feature distributions of reference compounds to screening libraries. If these feature distributions do not sufficiently differ, active database compounds that are similar to reference molecules cannot be retrieved because they disappear in the "background." By quantifying the difference in feature distribution using the Kullback-Leibler divergence and relating the divergence to compound recovery rates obtained for different benchmark classes, fingerprint search performance can be quantitatively predicted.

A computational investigation on the antioxidant potential of myricetin 3,4'-di-O-α-L-rhamnopyranoside.

PubMed

Mendes, Rodrigo A; Almeida, Shawan K C; Soares, Iuri N; Barboza, Cristina A; Freitas, Renato G; Brown, Alex; de Souza, Gabriel L C

2018-05-11

In this work, we present a computational study on the antioxidant potential of myricetin 3,4[Formula: see text]-di-O-α-L-rhamnopyranoside (Compound M). A density functional theory (DFT) approach with the B3LYP and LC-ωPBE functionals and with both the 6-311G(d,p) and 6-311+G(d,p) basis sets was used. The focus of the investigation was on the structural and energetic parameters including both bond dissociation enthalpies (BDEs) and ionization potentials (IPs), which provide information on the potential antioxidant activity. The properties computed were compared with BDEs and IPs available in the literature for myricetin, a compound well known for presenting antioxidant activity (and the parent molecule of the compound of interest in the present work). Myricetin 3,4[Formula: see text]-di-O-α-L-rhamnopyranoside presented the lowest BDE to be 79.13 kcal/mol (as determined using B3LYP/6-311G(d,p) in water) while myricetin has a quite similar value (within 3.4 kcal/mol). IPs computed in the gas phase [B3LYP/6-311G(d,p)] are 157.18 and 161.4 kcal/mol for myricetin 3,4[Formula: see text]-di-O-α-L-rhamnopyranoside and myricetin, respectively. As the values of BDEs are considerably lower than the ones probed for IPs (in the gas phase or in any given solvent environment), the hydrogen atom transfer mechanism is preferred over the single electron transfer mechanism. The BDEs obtained suggest that myricetin 3,4[Formula: see text]-di-O-α-L-rhamnopyranoside can present antioxidant potential as good as the parent molecule myricetin (a well-known antioxidant). Therefore, experimental tests on the antioxidant activity of Compound M are encouraged.

Apple Pomace as Potential Source of Natural Active Compounds.

PubMed

Waldbauer, Katharina; McKinnon, Ruxandra; Kopp, Brigitte

2017-08-01

Apple pomace is a waste product of the apple manufacturing industry that has been in the focus of life sciences as it represents a low-cost source of fruit-derived compounds. High fruit consumption is associated with beneficial health effects, and therefore, apple pomace and its constituents raise therapeutic interest. The present work reviews (i) the chemical constituents of apple pomace, (ii) optimized extraction methods of apple pomace compounds, and (iii) biological activities of apple pomace. Current evidence of apple pomace influence on digestion and metabolism, cholesterol and triglyceride homeostasis, diabetes, and sex hormones is summarized. Furthermore, studies regarding its antioxidative, anti-inflammatory, antiproliferative, antibacterial and antiviral effects are presented. The review concludes that apple pomace is an underutilized waste product of the apple industry with the potential of being processed for its nutritional and pharmaceutical value. Georg Thieme Verlag KG Stuttgart · New York.

Basics of Compounding with Dilutions and Concentrates.

PubMed

Allen, Loyd V

2017-01-01

Pharmacists use various sources for obtaining the active pharmaceutical ingredient for compounding medications. In many cases, it is the pure drug (United States Pharmacopeia, National Formulary, or similar grade); in some cases, it can be a commercial dosage form; and, in some cases, it may be a dilution or concentrate. If the drug is not present at full strength, then adjustments may be necessary to obtain the required quantity of drug. Also, in many cases, it is necessary to use a dilution or a concentrate of a drug due to safety and quality reasons. Presented within this article are new sources of active pharmaceutical ingredients that are now available to aid pharmacists in meeting future United States Pharmacopeia <800> standards. It is critical that the pharmacist be aware of the strength of the drug and any other excipients that may be available. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Benzofuran-pyran hybrids: A new class of potential bone anabolic agents.

PubMed

Gupta, Sampa; Adhikary, Sulekha; Modukuri, Ram K; Choudhary, Dharmendra; Trivedi, Ritu; Sashidhara, Koneni V

2018-06-01

Benzofuran moiety is an important pharmacophore showing positive effects on bone health. In the present study, sixteen benzofuran-pyran hybrids were synthesized and were evaluated for their osteogenic effects on primary osteoblast cells isolated from calvaria. Compounds 22 and 24 were found potent in stimulating osteoblast differentiation as assessed by the alkaline phosphatase activity. These compounds were also found to be nontoxic to osteoblast cells as compared to the control cells in MTT assay. Further, Alizarin Red-S staining for visualization of calcium nodules demonstrated compounds 22 and 34 as active in enhancing mineralization in osteoblast cells. Additionally, transcriptional analysis of these compounds on osteoblast cells revealed that compound 22 up-regulated the expression of osteogenic genes RUNX2, BMP-2, COL-1, thus substantiating that compound 22 having two geminal methyl groups in its R 3 position is a potent osteogenic agent. Additionally, compound 22 enhanced the ability of bone marrow stromal cells to differentiate towards osteoblast lineage and therefore can be further studied in vivo in bone loss model. Copyright © 2018 Elsevier Ltd. All rights reserved.

Determination of sulfur and nitrogen compounds during the processing of dry fermented sausages and their relation to amino acid generation.

PubMed

Corral, Sara; Leitner, Erich; Siegmund, Barbara; Flores, Mónica

2016-01-01

The identification of odor-active sulfur and nitrogen compounds formed during the processing of dry fermented sausages was the objective of this study. In order to elucidate their possible origin, free amino acids (FAAs) were also determined. The volatile compounds present in the dry sausages were extracted using solvent assisted flavor evaporation (SAFE) and monitored by one and two-dimensional gas chromatography with different detectors: mass spectrometry (MS), nitrogen phosphorous (NPD), flame photometric (FPD) detectors, as well as gas chromatography-olfactometry. A total of seventeen sulfur and nitrogen compounds were identified and quantified. Among them, 2-acetyl-1-pyrroline was the most potent odor active compound, followed by methional, ethylpyrazine and 2,3-dihydrothiophene characterized by toasted, cooked potato, and nutty notes. The degradation of FAAs, generated during processing, was related to the production of aroma compounds, such as methionine forming methional and benzothiazole while ornithine was the precursor compound for 2-acetyl-1-pyrroline and glycine for ethylpyrazine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Plant seeds as sources of potential industrial chemicals, pharmaceuticals, and pest control agents.

PubMed

Powell, Richard G

2009-03-27

Investigations of natural products isolated from seeds have resulted in a remarkable variety of compounds having unusual structures. Seeds of many plant species contain uncommon fatty acids and lipids, some of which have found uses in the cosmetic industry or as renewable (non-petroleum based) industrial raw materials. In addition to proteins and energy storage substances such as carbohydrates and lipids, seeds generally contain, or have the ability to produce, protective compounds that are active as plant growth regulators, fungicides, insecticides, and repellents of herbivores; seeds occasionally contain compounds that are toxic to most other organisms. These compounds may also be present in other plant parts, but often are found at higher concentrations in seeds. Other compounds of interest have been associated with plant-endophyte interactions that are of mutual benefit to both organisms. Tests of seed extracts for cytotoxic and antitumor activity, toxicity to insects, and relationships to several animal disease syndromes have been revealing. Examples of compounds isolated from plant seeds that have served as lead compounds for additional research, or that continue to be of interest to researchers in multiple areas, are reviewed.

Advances in the development of AMPK-activating compounds.

PubMed

Sriwijitkamol, Apiradee; Musi, Nicolas

2008-10-01

AMP-activated protein kinase (AMPK) is an energy sensing enzyme that controls glucose and lipid metabolism. This review summarizes the present data on AMPK as a pharmacologic target for the treatment of metabolic disorders. The mechanisms governing AMPK activity and how this enzyme controls different metabolic pathways are reviewed briefly, and details about the effect that AMPK activators have on glucose metabolism are provided. Evidence obtained using the AMPK-activating compound 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) suggests that AMPK promotes glucose transport into skeletal muscles and that this enzyme inhibits hepatic glucose production. AICAR also induces fatty acid oxidation in muscle and inhibits cholesterol synthesis in the liver. The metabolic effects of AICAR on glucose and lipid metabolism indicate that AMPK may be a good pharmacologic target for the treatment of type 2 diabetes and hypercholesterolemia. Novel AMPK-specific compounds are allowing researchers to examine whether this enzyme is a useful pharmacologic target for the treatment of human disease and whether chronic activation of AMPK will be safe.

Spectral investigations, DFT computations and molecular docking studies of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-{3-[4-(2-methylphenyl)piperazin-1-yl]propyl}-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione

NASA Astrophysics Data System (ADS)

Resmi, K. S.; Mary, Y. Sheena; Varghese, Hema Tresa; Panicker, C. Yohannan; Pakosińska-Parys, Magdalena; Alsenoy, C. Van

2015-10-01

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of the title compound have been investigated experimentally and theoretically. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analysed using NBO analysis. The hyperpolarisability calculation reveals the present material has a reasonably good propensity for nonlinear optical activity. Due to the different potential biological activity of the title compound, molecular docking study is also reported and the compound might exhibit inhibitory activity against human M2 muscarinic acetylcholine receptor.

Antioxidant phenolic compounds from the rhizomes of Astilbe rivularis.

PubMed

Hori, Kengo; Wada, Mikiyo; Yahara, Shoji; Watanabe, Takashi; Devkota, Hari Prasad

2018-02-01

The rhizomes of Astilbe rivularis, commonly known as 'Thulo Okhati' are widely used in Nepal as tonic for uterine and menstrual disorders. In our preliminary study, the 70% MeOH extract of the rhizomes showed potent antioxidant activity. Hence, present study was aimed for the isolation of potent antioxidant constituents. Bergenin (1), 11-O-galloylbergenin (2), (+)-catechin (3), (-)-catechin (4), (-)-afzelechin (5), (-)-epiafzelechin (6) and 2-(β-D-glucopyranosyloxy)-4-hydroxylbenzenacetonitrile (7) were isolated from the rhizomes. Structures of these compounds were elucidated on the basis of spectroscopic methods. All these isolated compounds were evaluated for their in vitro antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. 11-O-Galloylbergenin (2), (+)-catechin (3), (-)-catechin (4), (-)-afzelechin (5) and (-)-epiafzelechin (6) showed potent antioxidant activity.

Brown Algae Padina sanctae-crucis Børgesen: A Potential Nutraceutical

PubMed Central

Nogueira, Raquel B. S. S.; Tomaz, Anna Cláudia A.; Pessoa, Déborah R.; Xavier, Aline L.; Pita, João Carlos L. R.; Sobral, Marianna V.; Pontes, Marcela L. C.; Pessôa, Hilzeth L. F.; Diniz, Margareth F. F. M.; Miranda, George Emmanuel C.; Vieira, Maria Aparecida R.; Marques, Marcia O. M.; Souza, Maria de Fátima V.; Cunha, Emídio V. L.

2017-01-01

Padina sanctae-crucis Børgesen is distributed worldwide in tropical and subtropical seas; belongs to the Dictyotaceae family, and has proven to be an exceptional source of biologically active compounds. Four compounds were isolated and identified, namely: dolastane diterpene new for the genus Padina; phaeophytin and hidroxy-phaeophytin new for the family Dictyotaceae, and; mannitol first described in this species. Saturated fatty acids as compared to the percentages of unsaturated fatty acids were shown to be present in greater abundance. Palmitic and linolenic acid were the main saturated and unsaturated acids, respectively. Cytotoxic and antioxidant activities were evaluated using human erythrocytes. In vivo evaluations of acute toxicity and genotoxicity were performed in mice. Methanolic extract of P. sanctae-crucis presented antioxidant activity and did not induce cytotoxicity, genotoxicity or acute toxicity. Since Padina sanctae-crucis is already used as food, has essential fatty acids for the nutrition of mammals, does not present toxicity and has antioxidant activity, it can be considered as a potential nutraceutical. PMID:28954390

Antitumour, antimicrobial and catalytic activity of gold nanoparticles synthesized by different pH propolis extracts

NASA Astrophysics Data System (ADS)

Gatea, Florentina; Teodor, Eugenia Dumitra; Seciu, Ana-Maria; Covaci, Ovidiu Ilie; Mănoiu, Sorin; Lazăr, Veronica; Radu, Gabriel Lucian

2015-07-01

The Romanian propolis was extracted in five different media, respectively, in water (pH 6.8), glycine buffer (pH 2.5), acetate buffer (pH 5), phosphate buffer (pH 7.4) and carbonate buffer (pH 9.2). The extracts presented different amounts of flavonoids and phenolic acids, increasing pH leading to higher concentrations of active compounds. Five variants of gold nanoparticles suspensions based on different pH Romanian propolis aqueous extracts were successfully synthesized. The obtained nanoparticles presented dimensions between 20 and 60 nm in dispersion form and around 18 nm in dried form, and different morphologies (spherical, hexagonal, triangular). Fourier transform infrared spectroscopy proved the attachment of organic compounds from propolis extracts to the colloidal gold suspensions and X-ray diffraction certified that the suspensions contain metallic gold. The obtained propolis gold nanoparticles do not exhibit any antibacterial or antifungal activity, but presented different catalytic activities and toxicity on tumour cells.

Novel Anthra[1,2-c][1,2,5]Thiadiazole-6,11-Diones as Promising Anticancer Lead Compounds: Biological Evaluation, Characterization & Molecular Targets Determination.

PubMed

Ali, Ahmed Atef Ahmed; Lee, Yu-Ru; Chen, Tsung-Chih; Chen, Chun-Liang; Lee, Chia-Chung; Shiau, Chia-Yang; Chiang, Chiao-Hsi; Huang, Hsu-Shan

2016-01-01

The novel compounds NSC745885 and NSC757963 developed at our laboratory were tested against a panel of 60 cancer cell lines at the National Cancer Institute, USA, and a panel of 39 cancer cell lines at the Japanese Foundation of Cancer Research. Both compounds demonstrated selective unique multi-log differential patterns of activity, with GI50 values in the sub-micro molar range against cancer cells rather than normal cardiac cells. NSC757963 showed high selectivity towards the leukemia subpanel. Activities of both compounds strongly correlated to expression of NFKB1 and CSNK2B genes, implying that they may inhibit the NF-κB pathway. Immunocytochemical microscopy of OVCAR-3 cells showed clear cytosolic accumulation of the NF-κB p65 subunit following treatment. Western blotting showed dose dependent inhibition of the nuclear expression of the NF-κB p65 subunit with subsequent accumulation in the cytosol following treatment. Docking experiments showed binding of both compounds to the NF-κB activator IKKβ subunit preventing its translocation to the nucleus. Collectively, these results confirm the ability of our compounds to inhibit the constitutively active NF-κB pathway of OVCAR-3 cells. Furthermore, COMPARE analysis indicated that the activity of NSC757963 is similar to the antituberculosis agent rifamycin SV, this was confirmed by testing the antimycobacterial activity of NSC757963 against Mycobacterium tuberculosis, results revealed potent activity suitable for use in clinical practice. Molecular properties and Lipinski's parameters predicted acceptable bioavailability properties with no indication of mutagenicity, tumorigenicity, irritability and reproductive effects. Oral absorption experiments using the human Caco-2 model showed high intestinal absorption of NSC745885 by passive transport mechanism with no intestinal efflux or active transport mechanisms. The unique molecular characterization as well as the illustrated anticancer spectra of activity and bioavailability properties warrant further development of our compounds and present a foundation brick in the pre-clinical investigations to implement such compounds in clinical practice.

Does Compound I Vary Significantly between Isoforms of Cytochrome P450?

PubMed Central

2011-01-01

The cytochrome P450 (CYP) enzymes are important in many areas, including pharmaceutical development. Subtle changes in the electronic structure of the active species, Compound I, have been postulated previously to account partly for the experimentally observed differences in reactivity between isoforms. Current predictive models of CYP metabolism typically assume an identical Compound I in all isoforms. Here we present a method to calculate the electronic structure and to estimate the Fe–O bond enthalpy of Compound I, and apply it to several human and bacterial CYP isoforms. Conformational flexibility is accounted for by sampling large numbers of structures from molecular dynamics simulations, which are subsequently optimized with density functional theory (B3LYP) based quantum mechanics/molecular mechanics. The observed differences in Compound I between human isoforms are small: They are generally smaller than the spread of values obtained for the same isoform starting from different initial structures. Hence, it is unlikely that the variation in activity between human isoforms is due to differences in the electronic structure of Compound I. A larger difference in electronic structure is observed between the human isoforms and P450cam and may be explained by the slightly different hydrogen-bonding environment surrounding the cysteinyl sulfur. The presence of substrate in the active site of all isoforms studied appears to cause a slight decrease in the Fe–O bond enthalpy, apparently due to displacement of water out of the active site, suggesting that Compound I is less stable in the presence of substrate. PMID:21863858

Natural compounds isolated from Brazilian plants are potent inhibitors of hepatitis C virus replication in vitro.

PubMed

Jardim, A C G; Igloi, Z; Shimizu, J F; Santos, V A F F M; Felippe, L G; Mazzeu, B F; Amako, Y; Furlan, M; Harris, M; Rahal, P

2015-03-01

Compounds extracted from plants can provide an alternative approach to new therapies. They present characteristics such as high chemical diversity, lower cost of production and milder or inexistent side effects compared with conventional treatment. The Brazilian flora represents a vast, largely untapped, resource of potential antiviral compounds. In this study, we investigate the antiviral effects of a panel of natural compounds isolated from Brazilian plants species on hepatitis C virus (HCV) genome replication. To do this we used firefly luciferase-based HCV sub-genomic replicons of genotypes 2a (JFH-1), 1b and 3a and the compounds were assessed for their effects on both HCV replication and cellular toxicity. Initial screening of compounds was performed using the maximum non-toxic concentration and 4 compounds that exhibited a useful therapeutic index (favourable ratio of cytotoxicity to antiviral potency) were selected for extra analysis. The compounds APS (EC50=2.3μM), a natural alkaloid isolated from Maytrenus ilicifolia, and the lignans 3(∗)43 (EC50=4.0μM), 3(∗)20 (EC50=8.2μM) and 5(∗)362 (EC50=38.9μM) from Peperomia blanda dramatically inhibited HCV replication as judged by reductions in luciferase activity and HCV protein expression in both the subgenomic and infectious systems. We further show that these compounds are active against a daclatasvir resistance mutant subgenomic replicon. Consistent with inhibition of genome replication, production of infectious JFH-1 virus was significantly reduced by all 4 compounds. These data are the first description of Brazilian natural compounds possessing anti-HCV activity and further analyses are being performed in order to investigate the mode of action of those compounds. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Adaption of Ehrlich’s Reagent to a HPLC post-column reaction system for the quantification of limonoid glucosides (abstract)

USDA-ARS?s Scientific Manuscript database

Citrus limonoid glucosides are found in large quantities in citrus fruits and seeds. Characterization and quantification of these compounds is important because they contribute to citrus quality and are reported to be biologically active. Unlike other bioactive compounds (e.g., flavonoids) present...

Phytochemical screening and in-vitro antioxidant activity isolated bioactive compounds from Tridax procumbens Linn.

PubMed

Saxena, Manjusha; Mir, Abrar Hussain; Sharma, Manik; Malla, Mohd Yousu; Qureshi, Sumeerah; Mir, Mohd Iqbal; Chaturvedi, Yogesh

2013-12-15

Tridax procumbens L., Asteraceae, has been extensively used for various ailments in the Ayurvedic system of medicine. Previous studies have revealed remarkable phytoconstituents from Tridax procumbens L. with significant antioxidant activity. The aim of the present study is to measure the anti-DPPH activity of the purified isolated compounds from n butanol soluble part and ethyl acetate soluble part of successive methanolic extract of Tridax procumbens L. We thus quantified the total phenolic and total flavonoids in different purified isolated compounds, the whole of the tests were evaluated with a sample cone. of 100 microg mL(-1) and were determined spectrophotometrically using Folin-ciocaltue and AlCl3 reagents, respectively. DPPH (1,1-diphenyl, 2-picryl hydrazyl) assay was used to determine the in vitro antioxidant activity of different isolated compounds. Isolated compounds, one from ethyl acetate soluble part (EF-I) and one from n butanol soluble part (BF-II) were reported to possess a significant anti DPPH activity with lowest IC50 values 67.26 and 80.90 microg mL(-1), respectively while comparable to standard ascorbic acid with IC50 value of 59.62 microg mL(-1), due to the high concentration of phenols 146.4 microg mL(-1) from EF-I and 142.2 microg mL(-1) from BF-II and flavonoids 48 and 42.5 microg mL(-1) found in EF-I and BF-II isolated compounds, respectively.

Comparison of the free and bound phenolic profiles and cellular antioxidant activities of litchi pulp extracts from different solvents

PubMed Central

2014-01-01

Background The phenolic contents and antioxidant activities of fruits could be underestimated if the bound phenolic compounds are not considered. In the present study, the extraction efficiencies of various solvents were investigated in terms of the total content of the free and bound phenolic compounds, as well as the phenolic profiles and antioxidant activities of the extracts. Methods Five different solvent mixtures were used to extract the free phenolic compounds from litchi pulp. Alkaline and acidic hydrolysis methods were compared for the hydrolysis of bound phenolic compounds from litchi pulp residue. The phenolic compositions of the free and bound fractions from the litchi pulp were identified using HPLC-DAD. The antioxidant activities of the litchi pulp extracts were determined by oxygen radical absorbance capacity (ORAC) and cellular antioxidant activity (CAA) assays. Results Of the solvents tested, aqueous acetone extracted the largest amount of total free phenolic compounds (210.7 mg GAE/100 g FW) from litchi pulp, followed sequentially by aqueous mixtures of methanol, ethanol and ethyl acetate, and water itself. The acid hydrolysis method released twice as many bound phenolic compounds as the alkaline hydrolysis method. Nine phenolic compounds were detected in the aqueous acetone extract. In contrast, not all of these compounds were found in the other four extracts. The classification and content of the bound phenolic compounds released by the acid hydrolysis method were higher than those achieved by the alkaline hydrolysis. The aqueous acetone extract showing the highest ORAC value (3406.9 μmol TE/100 g FW) for the free phenolic extracts. For the CAA method, however, the aqueous acetone and methanol extracts (56.7 and 55.1 μmol QE/100 g FW) showed the highest levels of activity of the five extracts tested. The ORAC and CAA values of the bound phenolic compounds obtained by acid hydrolysis were 2.6- and 1.9-fold higher than those obtained using the alkaline hydrolysis method. Conclusions The free and bound phenolic contents and profiles and antioxidant activities of the extracts were found to be dependent on the extraction solvent used. Litchi exhibited good cellular antioxidant activity and could be a potentially useful natural source of antioxidants. PMID:24405977

Quantification of major compounds from Ixeris dentata, Ixeris dentata Var. albiflora, and Ixeris sonchifolia and their comparative anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7 cells.

PubMed

Karki, Subash; Park, Hee-Juhn; Nugroho, Agung; Kim, Eon Ji; Jung, Hyun Ah; Choi, Jae Sue

2015-01-01

The aim of the present study was to evaluate the comparative anti-inflammatory activities of Ixeris dentata (ID), Ixeris dentata var. albiflora (IDA), and Ixeris sonchifolia (IS) and to identify the main compounds present in extracts. The anti-inflammatory activity was evaluated through lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 murine macrophages. Five main compounds consisting of chlorogenic acid, caffeic acid, luteolin 7-O-glucoside, luteolin 7-O-glucuronide, and luteolin were used for simultaneous high-performance liquid chromatography quantification. The total phenolic content present in ID (30 mg/g GAE), IDA (35.33 mg/g GAE), and IS (43.79 mg/g GAE) was correlated to the corresponding LPS-induced NO production inhibitory effect in RAW 264.7 cells as expressed with IC(50) values 26.19, 21.43, and 7.59 μg/mL, respectively. Luteolin 7-O-glucoside was found as the major compound in ID (8.76 mg/g dry weight) and IDA (10.35 mg/g dry weight) and luteolin 7-O-glucuronide was the major compound in IS (34.66 mg/g dry weight). Luteolin 7-O-glucoside and luteolin 7-O-glucuronide inhibited LPS-induced NO production with IC(50) values of 30 and 4.5 μM, respectively. Furthermore, luteolin, luteolin 7-O-glucoside, and luteolin 7-O-glucuronide suppressed the expression of iNOS and COX-2, and t-BHP-induced ROS generation in LPS-stimulated RAW 264.7 cells. These results clearly showed that the anti-inflammatory potential of ID, IDA, and IS extract are primarily due to their contents of luteolin 7-O-glucoside and luteolin 7-O-glucuronide, respectively.

Regulatory domain phosphorylation to distinguish the mechanistic basis underlying acute CFTR modulators

PubMed Central

Pyle, Louise C.; Ehrhardt, Annette; Mitchell, Lisa High; Fan, LiJuan; Ren, Aixia; Naren, Anjaparavanda P.; Li, Yao; Clancy, J. P.; Bolger, Graeme B.; Sorscher, Eric J.

2011-01-01

Modulator compounds intended to overcome disease-causing mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) show significant promise in clinical testing for cystic fibrosis. However, the mechanism(s) of action underlying these compounds are not fully understood. Activation of CFTR ion transport requires PKA-regulated phosphorylation of the regulatory domain (R-D) and dimerization of the nucleotide binding domains. Using a newly developed assay, we evaluated nine compounds including both CFTR potentatiators and activators discovered via various high-throughput screening strategies to acutely augment CFTR activity. We found considerable differences in the effects on R-D phosphorylation. Some (including UCCF-152) stimulated robust phosphorylation, and others had little effect (e.g., VRT-532 and VX-770). We then compared CFTR activation by UCCF-152 and VRT-532 in Ussing chamber studies using two epithelial models, CFBE41o− and Fischer rat thyroid cells, expressing various CFTR forms. UCCF-152 activated wild-type-, G551D-, and rescued F508del-CFTR currents but did not potentiate cAMP-mediated CFTR activation. In contrast, VRT-532 moderately activated CFTR short-circuit current and strongly potentiated forskolin-mediated current. Combined with the result that UCCF-152, but not VRT-532 or VX-770, acts by increasing CFTR R-D phosphorylation, these findings indicate that potentiation of endogenous cAMP-mediated activation of mutant CFTR is not due to a pathway involving augmented R-D phosphorylation. This study presents an assay useful to distinguish preclinical compounds by a crucial mechanism underlying CFTR activation, delineates two types of compound able to acutely augment CFTR activity (e.g., activators and potentiators), and demonstrates that a number of different mechanisms can be successfully employed to activate mutant CFTR. PMID:21724857

Synthesis and biological evaluations of a series of thaxtomin analogues.

PubMed

Zhang, Hongbo; Wang, Qingpeng; Ning, Xin; Hang, Hang; Ma, Jing; Yang, Xiande; Lu, Xiaolin; Zhang, Jiabao; Li, Yonghong; Niu, Congwei; Song, Haoran; Wang, Xin; Wang, Peng George

2015-04-15

Thaxtomins are a unique family of phytotoxins with unique 4-nitroindole and diketopiperazine fragments possessing potential herbicidal activities. This work presents the total synthesis of natural product thaxtomin C and its analogues. The extensive structure-activity relationship study screens four effective compounds, including thaxtomin A and thaxtomin C. It is indicated that 4-nitro indole fragment is essential for phytotoxicity, while benzyl and m-hydroxybenzyl substituents on the diketopiperazine ring are favorable for the efficacy. The N-methylations on indole and diketopiperazine show weak influence on the herbicidal activities. The four selected compounds show effective herbicidal activities against Brassica campestris, Amaranthus retroflexus, and Abutilon theophrasti, which are comparable or better than dichlobenil, even at a dosage of 187.5 g ha(-1). Moreover, these four compounds show good crop-selective properties to different crops and exhibit moderate protoporphyrinogen oxidase (PPO) enzyme inhibition. The antifungal results indicate that thaxtomin C displays inhibition to a wide range of fungi.

Phenolic profiles and antioxidant activity of Turkish Tombul hazelnut samples (natural, roasted, and roasted hazelnut skin).

PubMed

Pelvan, Ebru; Olgun, Elmas Öktem; Karadağ, Ayşe; Alasalvar, Cesarettin

2018-04-01

The phenolic profiles and antioxidant status of hazelnut samples [natural (raw) hazelnut, roasted hazelnut, and roasted hazelnut skin] were compared. Free and bound (ester-linked and glycoside-linked) phenolic acids were examined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Comprehensive identification of phenolics was carried out using Q-exactive hybrid quadrupole-orbitrap mass spectrometer (Q-OT-MS). Samples were also assessed for their total phenolics and antioxidant activities using three different assays. Ten free and bound phenolic acids were quantified in hazelnut samples. Roasted hazelnut skin contained the highest content of total phenolic acids, followed by natural and roasted hazelnuts. The majority of phenolic acids were present in the bound form. Using a Q-OT-MS, 22 compounds were tentatively identified, 16 of which were identified for the first time in hazelnut samples. The newly identified compounds consisted of flavonoids, phenolic acids and related compounds, hydrolysable tannins and related compounds, and other phenolics. Three antioxidant assays demonstrated similar trends that roasted hazelnut skin rendered the highest activity. The present work suggests that roasted hazelnut skin is a rich source of phenolics and can be considered as a value-added co-product for use as functional food ingredient and antioxidant. Copyright © 2017 Elsevier Ltd. All rights reserved.

Trypanocidal and Leishmanicidal Activities of Sesquiterpene Lactones from Ambrosia tenuifolia Sprengel (Asteraceae) ▿

PubMed Central

Sülsen, Valeria P.; Frank, Fernanda M.; Cazorla, Silvia I.; Anesini, Claudia A.; Malchiodi, Emilio L.; Freixa, Blanca; Vila, Roser; Muschietti, Liliana V.; Martino, Virginia S.

2008-01-01

Bioassay-guided fractionation of the organic extract of Ambrosia tenuifolia Sprengel (Asteraceae) led to the isolation of two bioactive sesquiterpene lactones with significant trypanocidal and leishmanicidal activities. By spectroscopic methods (1H- and 13C-nuclear magnetic resonance, distortionless enhancement by polarization transfer, correlated spectroscopy, heteronuclear multiple-quantum coherence, electron impact-mass spectrometry, and infrared spectroscopy), these compounds were identified as psilostachyin and peruvin. Both compounds showed a marked in vitro trypanocidal activity against Trypanosoma cruzi epimastigotes with 50% inhibitory concentration (IC50) values of less than 2 μg/ml. Psilostachyin exerted a significant in vitro activity against the trypomastigote forms of T. cruzi (IC50, 0.76 μg/ml) and was selected for in vivo testing. Psilostachyin-treated mice had a survival of 100% and lower parasitemia values than control mice. Both compounds were also tested on Leishmania sp. promastigotes: psilostachyin (IC50, 0.12 μg/ml) and peruvin (IC50, 0.39 μg/ml) exerted significant leishmanicidal activities. This is the first time that the trypanocidal and leishmanicidal activities of these compounds have been reported. The selectivity index (SI) was employed to evaluate the cytotoxic effect of lactones on T lymphocytes. Although the SIs of both compounds were high for T. cruzi epimastigotes, psilostachyin was more selective against trypomastigotes (SI, 33.8) while peruvin showed no specificity for this parasite. Both compounds presented high selectivity for Leishmania spp. The results shown herein suggest that psilostachyin and peruvin could be considered potential candidates for the development of new antiprotozoal agents against Chagas' disease and leishmaniasis. PMID:18443111

Selective activators of protein phosphatase 5 target the auto-inhibitory mechanism.

PubMed

Haslbeck, Veronika; Drazic, Adrian; Eckl, Julia M; Alte, Ferdinand; Helmuth, Martin; Popowicz, Grzegorz; Schmidt, Werner; Braun, Frank; Weiwad, Matthias; Fischer, Gunter; Gemmecker, Gerd; Sattler, Michael; Striggow, Frank; Groll, Michael; Richter, Klaus

2015-04-20

Protein phosphatase 5 (PP5) is an evolutionary conserved serine/threonine phosphatase. Its dephosphorylation activity modulates a diverse set of cellular factors including protein kinases and the microtubule-associated tau protein involved in neurodegenerative disorders. It is auto-regulated by its heat-shock protein (Hsp90)-interacting tetratricopeptide repeat (TPR) domain and its C-terminal α-helix. In the present study, we report the identification of five specific PP5 activators [PP5 small-molecule activators (P5SAs)] that enhance the phosphatase activity up to 8-fold. The compounds are allosteric modulators accelerating efficiently the turnover rate of PP5, but do barely affect substrate binding or the interaction between PP5 and the chaperone Hsp90. Enzymatic studies imply that the compounds bind to the phosphatase domain of PP5. For the most promising compound crystallographic comparisons of the apo PP5 and the PP5-P5SA-2 complex indicate a relaxation of the auto-inhibited state of PP5. Residual electron density and mutation analyses in PP5 suggest activator binding to a pocket in the phosphatase/TPR domain interface, which may exert regulatory functions. These compounds thus may expose regulatory mechanisms in the PP5 enzyme and serve to develop optimized activators based on these scaffolds. © 2015 Authors.

Spectral characterization and antibacterial activity of an isolated compound from Memecylon edule leaves.

PubMed

Srinivasan, R; Natarajan, D; Shivakumar, M S

2017-03-01

Memecylon edule Roxb. (Melastamataceae family) is a small evergreen tree reported as having ethnobotanical and pharmacological properties. The present study was aimed to investigate the spectral characterization and antibacterial activity of isolated pure compound (3β-hydroxyurs-12-en-28-oic acid (ursolic acid)) from Memecylon edule leaves by performing bioassay guided isolation method. The structure derivation of isolated compound was done by different spectral studies like UV, FT-IR, LC-MS, CHNS analysis, 1D ( 1 H, 13 C and DEPT-135) and 2D-NMR (HSQC and HMBC), respectively. About 99.29% purity of the compound was found in LC analysis. 1 H NMR spectrum results of compound shown 48 protons appear at different shielded region and most of the protons were present in aliphatic region. Whereas, 13 C NMR spectral data resulted seven methyl carbons (CH3), nine methylene carbons (CH2), seven methine carbons (CH) and six non-hydrogenated carbons (C) which are characteristic of pentacyclic triterpene. The isolated pure compound was tested for its antibacterial properties against targeted human pathogens by performing agar well diffusion, MIC and MBC assays and the result exhibits better growth inhibitory effects against S. epidermidis and S. pneumoniae, with the MIC values of 1.56 and 3.15μg/ml. The outcome of this study suggests that the bioactive compound is used for development of plant based drugs in pharmaceutical industry for combating microbial mediated diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Design and synthesis of some new pyrazolyl-pyrazolines as potential anti-inflammatory, analgesic and antibacterial agents.

PubMed

Viveka, Shivapura; Dinesha; Shama, Prasanna; Nagaraja, Gundibasappa Karikannar; Ballav, Shuvankar; Kerkar, Savita

2015-08-28

In the present study, an efficient synthesis of some new substituted pyrazoline derivatives linked to a substituted pyrazole scaffold was performed by a multistep reaction sequences and compounds were screened for their anti-inflammatory, analgesic and antibacterial activities. The preliminary results revealed that the N-acylated (5e, 5h) and nitro substituted N-phenyl (6f) pyrazolyl-pyrazolines derivatives exhibited a very promising anti-inflammatory activity whereas 5h, 6f were interesting analgesic agents. The compounds with halo substituted phenyl group at C-3 of the pyrazoline ring (4a, 5g, 5h, 6a and 6b) were found to be active against clinical bacterial pathogens with MIC in the range of 0.2-0.4 mg/mL. Compound containing N-propionyl pyrazolyl-pyrazoline (5h) could be identified as the most active member within this study with a dual anti-inflammatory and antibacterial profile. Taken together, this study has led to the development of promising compounds. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Inhibition of dengue virus replication by novel inhibitors of RNA-dependent RNA polymerase and protease activities.

PubMed

Pelliccia, Sveva; Wu, Yu-Hsuan; Coluccia, Antonio; La Regina, Giuseppe; Tseng, Chin-Kai; Famiglini, Valeria; Masci, Domiziana; Hiscott, John; Lee, Jin-Ching; Silvestri, Romano

2017-12-01

Dengue virus (DENV) is the leading mosquito-transmitted viral infection in the world. With more than 390 million new infections annually, and up to 1 million clinical cases with severe disease manifestations, there continues to be a need to develop new antiviral agents against dengue infection. In addition, there is no approved anti-DENV agents for treating DENV-infected patients. In the present study, we identified new compounds with anti-DENV replication activity by targeting viral replication enzymes - NS5, RNA-dependent RNA polymerase (RdRp) and NS3 protease, using cell-based reporter assay. Subsequently, we performed an enzyme-based assay to clarify the action of these compounds against DENV RdRp or NS3 protease activity. Moreover, these compounds exhibited anti-DENV activity in vivo in the ICR-suckling DENV-infected mouse model. Combination drug treatment exhibited a synergistic inhibition of DENV replication. These results describe novel prototypical small anti-DENV molecules for further development through compound modification and provide potential antivirals for treating DENV infection and DENV-related diseases.

α-Amylase inhibitors: a review of raw material and isolated compounds from plant source.

PubMed

Sales, Paloma Michelle; Souza, Paula Monteiro; Simeoni, Luiz Alberto; Silveira, Damaris

2012-01-01

Inhibition of α-amylase, enzyme that plays a role in digestion of starch and glycogen, is considered a strategy for the treatment of disorders in carbohydrate uptake, such as diabetes and obesity, as well as, dental caries and periodontal diseases. Plants are an important source of chemical constituents with potential for inhibition of α-amylase and can be used as therapeutic or functional food sources. A review about crude extracts and isolated compounds from plant source that have been tested for α-amylase inhibitory activity has been done. The analysis of the results shows a variety of crude extracts that present α-amylase inhibitory activity and some of them had relevant activity when compared with controls used in the studies. Amongst the phyto-constituents that have been investigated, flavonoids are one of them that demonstrated the highest inhibitory activities with the potential of inhibition related to number of hydroxyl groups in the molecule of the compound. Several phyto-constituents and plant species as α-amylase inhibitors are being reported in this article. Majority of studies have focused on the anti-amylase phenolic compounds.

Synthesis, Structural Characterization and Antinociceptive Activities of New Arylated Quinolines via Suzuki-Miyaura Cross Coupling Reaction.

PubMed

Ullah, Malik A; Adeel, Muhammad; Tahir, Muhammad N; Rauf, Abdur; Akram, Muhammad; Hadda, Taibi B; Mabkhot, Yahia N; Muhammad, Naveed; Naseer, Fehmida; Mubarak, Mohammad S

2017-01-01

The quinoline ring system is one of the most commonly encountered heterocycles in medicinal chemistry, due to the pharmaceutical and medicinal uses of derivatives containing this ring. These quinoline-based compounds have remarkable biological activity, as they are employed as antimalarial, antibacterial, antifungal, and antitumor agents. The quinoline nucleus can be synthesized by various traditional methods such as the Skraup reaction, Friedlaender synthesis, Combes quinoline synthesis, Larock quinoline synthesis, among others. The aim of the present work is to synthesize a number of new arylated quninolines having significant antinoceciptive effect through the Suzuki-Miyaura cross coupling reaction using 3- bromoquinoline as a starting material. A number of new quinoline derivatives have been synthesized. Structures of the newly synthesized compounds were confirmed by means of IR, NMR, and mass spectrometry, and by elemental analysis. In addition, the molecular structures of two representative derivatives were determined with the aid of X-ray crystallography. Additionally, the antinociceptive activity of the prepared compounds was evaluated in vivo; results revealed that most of the tested compounds exhibited a dosedependent antinociceptive effect. Prepared compounds were found to exhibit significant antinociceptive activities and could be used as potential analgesic agents. Further work, however, may be required to establish the safety and efficacy of these compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Coumarins from the roots of Angelica dahurica cause anti-allergic inflammation

PubMed Central

Li, Dong; Wu, Li

2017-01-01

Allergic inflammation is induced by allergens and leads to various allergic diseases, including rhinitis, asthma and conjunctivitis. Histamine is important in the pathogenesis of an immunoglobulin E-dependent allergic reaction and results in the secretion of cytokines associated with inflammation. Angelica dahurica (A. dahurica) is a medicinal plant widely used in China for the treatment of symptoms related to allergic inflammation. The present study investigated the chemical constituents from A. dahurica and evaluated their reductive effect on allergic inflammation. As a result, 15 compounds including 13 coumarins have been identified as isoimperatorin (1), imperatorin (2), oxypeucedanin (3), oxypeucedanin hydrate (4), bergapten (5), byakangelicin (6), phellopterin (7), byakangelicol (8), isopimpinellin (9), xanthotoxol (10), xanthotoxin (11), pimpinellin (12), scopoletin (13), β-sitosterol (14) and daucosterol (15). Compounds 1–13 were able to reduce the release of histamine, with compounds 4–6 exhibiting the most potent activity. Furthermore, compounds 1–12 were able to inhibit the secretion of tumor necrosis factor-α, interleukin (IL)-1β and IL-4, with compounds 5 and 7 exhibiting the strongest inhibitory effects. These compounds implemented the inhibitory effects on the expression of inflammatory cytokine genes through the inhibition of nuclear factor-κB activation. Virtual screening by a docking program indicated that compound 3 is a potent histamine H1 receptor antagonist. Additionally, the calculated physicochemical properties of these compounds support most furanocoumarins to be delivered to binding sites and permeate the cell membrane. The present findings contribute to understanding how A. dahurica attenuates allergic inflammation. PMID:28673013

Understanding the potential benefits of thyme and its derived products for food industry and consumer health: From extraction of value-added compounds to the evaluation of bioaccessibility, bioavailability, anti-inflammatory, and antimicrobial activities.

PubMed

Lorenzo, Jose M; Mousavi Khaneghah, Amin; Gavahian, Mohsen; Marszałek, Krystian; Eş, Ismail; Munekata, Paulo E S; Ferreira, Isabel C F R; Barba, Francisco J

2018-05-17

Natural bioactive compounds isolated from several aromatic plants have been studied for centuries due to their unique characteristics that carry great importance in food, and pharmaceutical, and cosmetic industries. For instance, several beneficial activities have been attributed to some specific compounds found in Thymus such as anti-inflammatory, antioxidant, antimicrobial, and antiseptic properties. Moreover, these compounds are classified as Generally Recognized as Safe (GRAS) which means they can be used as an ingrident of may food producs. Conventional extraction processes of these compounds and their derived forms from thyme leaves are well established. Hoewever, they present some important drawbacks such as long extraction time, low yield, high solvent consumption and degradation thermolabile compounds. Therefore, innovative extraction techniques such as ultrasound, microwave, enzyme, ohmic and heat-assisted methods can be useful strategies to enhance the exytraction yield and to reduce processing temperature, extraction time, and energy and solvent consumption. Furthermore, bioaccessibility and bioavailability aspects of these bioactive compounds as well as their metabolic fates are crucial for developing novel functional foods. Additionally, immobilization methods to improve stability, solubility, and the overall bioavailability of these valuable compounds are necessary for their commercial applications. This review aims to give an overall perspective of innovative extraction techniques to extract the targeted compounds with anti-inflammatory and antimicrobial activities. Moreover, the bioaccessi-bility and bioavailability of these compounds before and after processing discussed. In addition, some of the most important characteristics of thyme and their derived products discussed in this paper.

New Isoflavonoids from the extract of Rhynchosia precatoria (Humb. & Bonpl. ex Willd.) DC. and their antimycobacterial activity.

PubMed

Coronado-Aceves, Enrique Wenceslao; Gigliarelli, Giulia; Garibay-Escobar, Adriana; Zepeda, Ramón Enrique Robles; Curini, Massimo; López Cervantes, Jaime; Inés Espitia-Pinzón, Clara Inés; Superchi, Stefano; Vergura, Stefania; Marcotullio, Maria Carla

2017-07-12

The evaluation of the antimycobacterial activity of extracts of medicinal plants used by Mayos against tuberculosis and respiratory problems, allowed the identification of Rhynchosia precatoria (Humb. & Bonpl. ex Willd.) DC (Fabaceae) as the best candidate to find new antimycobacterial compounds. To isolate and characterize the compounds of R. precatoria responsible for the inhibitory and bactericidal activity against Mycobacterium tuberculosis H37Rv and Mycobacterium smegmatis ATCC 700084. To determine antimycobacterial synergistic effect of pure compounds and their selectivity index towards Vero cells. A total of six flavonoids were purified by silica gel column chromatography. Structural elucidation of the isolated compounds was achieved by using 1D and 2D NMR spectroscopy techniques. The configuration at the C-3 chiral center was established by quantum mechanical calculation of the electronic circular dichroism (ECD) spectrum. In vitro inhibitory and bactericidal activity against M. tuberculosis and M. smegmatis were determined with the redox indicator Alamar Blue (resazurin). Synergy was determined by X/Y quotient. Cytotoxicity was measured by MTT assay. The isolated compounds were identified as precatorin A (1), precatorin B (2), precatorin C (3), lupinifolin (4), cajanone (5) and lupinifolinol (6). Compounds 1-3 are new. Compounds 1 to 5 inhibited the growth of M. tuberculosis (MIC ≥31.25µg/mL); compounds 1, 2, 4 and 5 killed the bacteria (MBC ≥31.25µg/mL) and also inhibited M. smegmatis (MIC ≥125µg/mL), while 1 and 4 also resulted bactericidal (MBC ≥125µg/mL). Compounds 4 and 5 presented synergistic effect (X/Y quotient value <0.5) at a concentration of 1/2 MIC of each compound in the combination. Cytotoxicity in murine macrophages (RAW 264.7 cells) gave IC 50 values of 13.3-46.98µM, for compounds 1-5. In this work we isolated two new isoflavanones (1 and 2), and one new isoflavone (3) with a weak antimycobacterial activity. The (3R) absolute configuration was assigned to 1 by computational analysis of its ECD spectrum and to 2 and 5 by similarity of their ECD spectra with that of 1. We are also reporting by first time, activity against virulent strain of M. tuberculosis for compounds 4 and 5 and their antimycobacterial synergistic effect. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Dinuclear RuII(bipy)2 Derivatives: Structural, Biological, and in Vivo Zebrafish Toxicity Evaluation.

PubMed

Lenis-Rojas, Oscar A; Roma-Rodrigues, Catarina; Fernandes, Alexandra R; Marques, Fernanda; Pérez-Fernández, David; Guerra-Varela, Jorge; Sánchez, Laura; Vázquez-García, Digna; López-Torres, Margarita; Fernández, Alberto; Fernández, Jesús J

2017-06-19

Ruthenium-based drugs exhibit interesting properties as potential anticancer pharmaceuticals. We herein present the synthesis and characterization of a new family of ruthenium complexes with formulas [{Ru(bipy) 2 } 2 (μ-L)][CF 3 SO 3 ] 4 (L = bptz, 1a) and [{Ru(bipy) 2 } 2 (μ-L)][CF 3 SO 3 ] 2 (L = arphos, 2a; dppb, 3a; dppf, 4a), which were synthesized from the Ru(II) precursor compound cis-Ru(bipy) 2 Cl 2 . The complexes were characterized by elemental analysis, mass spectrometry, 1 H and 31 P{ 1 H} NMR, IR spectroscopy, and conductivity measurements. The molecular structures for three Ru(II) compounds were determined by single-crystal X-ray diffraction. The newly developed compounds interact with CT-DNA by intercalation, in particular, 2a, 3a, and 4a, which also seemed to induce some extent of DNA degradation. This effect seemed to be related with the formation of reactive oxygen species. The cytotoxic activity was evaluated against A2780, MCF7, and MDAMB231 human tumor cells. Compounds 2a and 4a were the most cytotoxic with activity compared to cisplatin (∼2 μM, 72 h) in the A2780 cisplatin sensitive cells. All the compounds induced A2780 cell death by apoptosis, however, to a lesser extent for compounds 4a and 2a. For these compounds, the mechanism of cell death in addition to apoptosis seemed to involve autophagy. In vivo toxicity was evaluated using the zebrafish embryo model. LC 50 estimates varied from 5.397 (3a) to 39.404 (1a) mg/L. Considering the in vivo toxicity in zebrafish embryos and the in vitro cytotoxicity in cancer cells, compound 1a seems to be the safest having no effect on dechirionation and presenting a good antiproliferative activity against ovarian carcinoma cells.

The development of novel inhibitors of tumor necrosis factor-alpha production based on substituted [5,5]-bicyclic pyrozolones

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laufersweiler, Matthew; Brugel, Todd; Clark, Michael

Novel substituted [5,5]-bicyclic pyrzazolones are presented as inhibitors of tumor necrosis factor-{alpha} (TNF-{alpha}) production. Many of these compounds show low nanomolar activity against lipopolysaccaride (LPS)-induced TNF-{alpha} production in THP-1 cells. This class of molecules was co-crystallized with mutated p38, and several analogs showed good oral bioavailability in the rat. Oral activity of these compounds in the rat iodoacetate model for osteoarthritis is discussed.

Determination of the In Vitro and In Vivo Activity of Compounds Tested Against Punta Toro Virus.

DTIC Science & Technology

1987-12-29

were performed on 295 AVS compounds in LLC-MK2 cells with inhibition of viral cytopathic effect (CPE) as initial endpoint and reduction of virus...ineffective doses of ribavirin were highly active against the infection. 11. Publications and Presentations: One manuscript describing work performed on...USERS unclassifie 22a N4AME QP RESPONSIBE INDIIDUAL 22b. TELEPHONE WInd Area Code) 22. OFFICE SYMBOL WF ir ginia M. Miller- - DD FORM 1473,s4Mat 83

Allelopathy of Bracken Fern (Pteridium arachnoideum): New Evidence from Green Fronds, Litter, and Soil

PubMed Central

Juliano Gualtieri, Sonia Cristina; Rodrigues-Filho, Edson; Macías, Francisco Antonio

2016-01-01

The neotropical bracken fern Pteridium arachnoideum (Kaulf.) Maxon. (Dennstaedtiaceae) is described as an aggressive pioneer plant species. It invades abandoned or newly burned areas and represents a management challenge at these invaded sites. Native to the Atlantic Forest and Cerrado (Tropical Savanna) Brazilian biomes, P. arachnoideum has nevertheless become very problematic in these conservation hotspots. Despite some reports suggesting a possible role of allelopathy in this plant’s dominance, until now there has been little evidence of isolated and individually identified compounds with phytotoxic activities present in its tissues or in the surrounding environment. Thus, the aim of this study was to investigate the allelopathic potential of P. arachnoideum by isolating and identifying any secondary metabolites with phytotoxic activity in its tissues, litter, and soil. Bioguided phytochemical investigation led to the isolation and identification of the proanthocyanidin selligueain A as the major secondary compound in the green fronds and litter of this fern. It is produced by P. arachnoideum in its green fronds, remains unaltered during the senescence process, and is the major secondary compound present in litter. Selligueain A showed phytotoxic activity against the selected target species sesame (Sesamum indicum) early development. In particular, the compound inhibited root and stem growth, and root metaxylem cell size but did not affect chlorophyll content. This compound can be considered as an allelochemical because it is present in the soil under P. arachnoideum patches as one of the major compounds in the soil solution. This is the first report of the presence of selligueain A in any member of the Dennstaedtiaceae family and the first time an isolated and identified allelochemical produced by members of the Pteridium species complex has been described. This evidence of selligueain A as a putative allelochemical of P. arachnoideum reinforces the role of allelopathy in the dominance processes of this plant in the areas where it occurs. PMID:27552161

Synthesis and evaluation of 2-(3-arylureido)pyridines and 2-(3-arylureido)pyrazines as potential modulators of Aβ-induced mitochondrial dysfunction in Alzheimer's disease.

PubMed

Elkamhawy, Ahmed; Park, Jung-Eun; Hassan, Ahmed H E; Pae, Ae Nim; Lee, Jiyoun; Park, Beoung-Geon; Roh, Eun Joo

2018-01-20

A series of 2-(3-arylureido)pyridines and 2-(3-benzylureido)pyridines were synthesized and evaluated as potential modulators for amyloid beta (Aβ)-induced mitochondrial dysfunction in Alzheimer's disease (AD). The blocking activities of forty one small molecules against Aβ-induced mitochondrial permeability transition pore (mPTP) opening were evaluated by JC-1 assay which measures the change of mitochondrial membrane potential (ΔΨm). The inhibitory activity of twenty five compounds against Aβ-induced mPTP opening was superior to that of the standard cyclosporin A (CsA). Six hit compounds have been identified as likely safe in regards to mitochondrial and cellular safety and subjected to assessment for their protective effect against Aβ-induced deterioration of ATP production and cytotoxicity. Among them, compound 7fb has been identified as a lead compound protecting neuronal cells against 67% of neurocytotoxicity and 43% of suppression of mitochondrial ATP production induced by 5 μM concentrations of Aβ. Using CDocker algorithm, a molecular docking model presented a plausible binding mode for these compounds with cyclophilin D (CypD) receptor as a major component of mPTP. Hence, this report presents compound 7fb as a new nonpeptidyl mPTP blocker which would be promising for further development of Alzheimer's disease (AD) therapeutics. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Brazilian fruit pulps as functional foods and additives: evaluation of bioactive compounds.

PubMed

Paz, Mário; Gúllon, Patricia; Barroso, M Fátima; Carvalho, Ana P; Domingues, Valentina F; Gomes, Ana M; Becker, Helena; Longhinotti, Elisane; Delerue-Matos, Cristina

2015-04-01

Eight tropical fruit pulps from Brazil were simultaneously characterised in terms of their antioxidant and antimicrobial properties. Antioxidant activity was screened by DPPH radical scavenging activity (126-3987 mg TE/100g DW) and ferric reduction activity power (368-20819 mg AAE/100g DW), and complemented with total phenolic content (329-12466 mg GAE/100g DW) and total flavonoid content measurements (46-672 mg EE /100g DW), whereas antimicrobial activity was tested against the most frequently found food pathogens. Acerola and açaí presented the highest values for the antioxidant-related measurements. Direct correlations between these measurements could be observed for some of the fruits. Tamarind exhibited the broadest antimicrobial potential, having revealed growth inhibition of Pseudomonas aeruginosa. Escherichia coli, Listeria monocytogenes, Salmonella sp. and Staphylococcus aureus. Açaí and tamarind extracts presented an inverse relationship between antibacterial and antioxidant activities, and therefore, the antibacterial activity cannot be attributed (only) to phenolic compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.

Monitoring the apple polyphenol oxidase-modulated adduct formation of phenolic and amino compounds.

PubMed

Reinkensmeier, Annika; Steinbrenner, Katrin; Homann, Thomas; Bußler, Sara; Rohn, Sascha; Rawel, Hashadrai M

2016-03-01

Minimally processed fruit products such as smoothies are increasingly coming into demand. However, they are often combined with dairy ingredients. In this combination, phenolic compounds, polyphenoloxidases, and amino compounds could interact. In this work, a model approach is presented where apple serves as a source for a high polyphenoloxidase activity for modulating the reactions. The polyphenoloxidase activity ranged from 128 to 333nakt/mL in different apple varieties. From these, 'Braeburn' was found to provide the highest enzymatic activity. The formation and stability of resulting chromogenic conjugates was investigated. The results show that such adducts are not stable and possible degradation mechanisms leading to follow-up products formed are proposed. Finally, apple extracts were used to modify proteins and their functional properties characterized. There were retaining antioxidant properties inherent to phenolic compounds after adduct formation. Consequently, such interactions may also be utilized to improve the textural quality of food products. Copyright © 2015 Elsevier Ltd. All rights reserved.

De Novo Design of Bioactive Small Molecules by Artificial Intelligence.

PubMed

Merk, Daniel; Friedrich, Lukas; Grisoni, Francesca; Schneider, Gisbert

2018-01-01

Generative artificial intelligence offers a fresh view on molecular design. We present the first-time prospective application of a deep learning model for designing new druglike compounds with desired activities. For this purpose, we trained a recurrent neural network to capture the constitution of a large set of known bioactive compounds represented as SMILES strings. By transfer learning, this general model was fine-tuned on recognizing retinoid X and peroxisome proliferator-activated receptor agonists. We synthesized five top-ranking compounds designed by the generative model. Four of the compounds revealed nanomolar to low-micromolar receptor modulatory activity in cell-based assays. Apparently, the computational model intrinsically captured relevant chemical and biological knowledge without the need for explicit rules. The results of this study advocate generative artificial intelligence for prospective de novo molecular design, and demonstrate the potential of these methods for future medicinal chemistry. © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Naturally Occurring Cinnamic Acid Sugar Ester Derivatives.

PubMed

Tian, Yuxin; Liu, Weirui; Lu, Yi; Wang, Yan; Chen, Xiaoyi; Bai, Shaojuan; Zhao, Yicheng; He, Ting; Lao, Fengxue; Shang, Yinghui; Guo, Yu; She, Gaimei

2016-10-24

Cinnamic acid sugar ester derivatives (CASEDs) are a class of natural product with one or several phenylacrylic moieties linked with the non-anomeric carbon of a glycosyl skeleton part through ester bonds. Their notable anti-depressant and brains protective activities have made them a topic of great interest over the past several decades. In particular the compound 3',6-disinapoylsucrose, the index component of Yuanzhi (a well-known Traditional Chinese Medicine or TCM), presents antidepressant effects at a molecular level, and has become a hotspot of research on new lead drug compounds. Several other similar cinnamic acid sugar ester derivatives are reported in traditional medicine as compounds to calm the nerves and display anti-depression and neuroprotective activity. Interestingly, more than one third of CASEDs are distributed in the family Polygalaceae . This overview discusses the isolation of cinnamic acid sugar ester derivatives from plants, together with a systematic discussion of their distribution, chemical structures and properties and pharmacological activities, with the hope of providing references for natural product researchers and draw attention to these interesting compounds.

Qualitative comparison of active compounds between red and green Mariposa Christia Vespertillonis leaves extracts

NASA Astrophysics Data System (ADS)

Osman, M. S.; Ghani, Z. A.; Ismail, N. F.; Razak, N. A. A.; Jaapar, J.; Ariff, M. A. M.

2017-09-01

At present time, Mariposa Christia Vespertillonis (MCV) leave has become popular for its anti-cancer and thus is used widely among the traditional medicine in Malaysia. There are several types of MCV plants and the one that is currently well-known for traditional medicine in Malaysia is the green MCV (GMCV). Red MCV (RMCV) is another type of MCV plant which can also be found easily in Malaysia. In this study, the active compounds for GMCV and RMCV will be compared and analyzed by using Liquid Chromatography - Mass Spectrometry (LC-MS). The active compounds will be extracted from the MCV leaves by using Supercritical Fluid Extraction (SFE). The findings of this study indicates the global yield of the MCV oils is 31 mg/g while the compound identification indicates the presence of anti-cancer, anti-inflammatory and beneficial phytochemicals. This work is an explorative study to reveal the potential of MCV to be extracted using SFE method as potential therapeutic plants for the traditional medicine in Malaysia.

Identification of lipid fraction constituents from grasshopper (Chorthippus spp.) abdominal secretion with potential activity in wound healing with the use of GC-MS/MS technique.

PubMed

Buszewska-Forajta, Magdalena; Siluk, Danuta; Struck-Lewicka, Wiktoria; Raczak-Gutknecht, Joanna; Markuszewski, Michał J; Kaliszan, Roman

2014-02-01

In recent years biologically active compounds isolated from insects call special interest of drug researchers. According to some Polish etnopharmacological observations, secretion from the grasshopper's abdomen (Orthoptera family) is believed to speed up the process of wound healing. In the present work we focused on determination of main components of the lipid fraction of material from grasshopper abdomen using GC-MS/MS. Samples were qualitatively analyzed using gas chromatography coupled with mass spectrometry. Both liquid-liquid extraction and solid-phase extraction pretreatment methods were used to concentrate and fractionate the compounds from the insect. In the derivatized fractions ca. 350 compounds were identified, including substances of known biological activity. The potential agents affecting wound healing have been indicated. A set of compounds characteristic for all the studied Chorthippus spp., have been identified. Data analysis revealed different lipidomic profiles of grasshoppers depending on the insects origin and collection area. Copyright © 2013 Elsevier B.V. All rights reserved.

Study of the Gastroprotective Effect of Extracts and Semipurified Fractions of Chresta martii DC. and Identification of Its Principal Compounds

PubMed Central

Franco, E. S.; Mélo, M. E. B.; Jatobá, B. J. A.; Santana, A. L. B. D.; Silva, A. A. R.; Silva, T. G.; Nascimento, M. S.; Maia, M. B. S.

2015-01-01

Chresta martii (Asteraceae) is a species widely used by the population of the Xingu region of Sergipe, Brazil, in the form of a decoction (aerial parts) for the treatment of gastrointestinal diseases. The study aims to assess the gastroprotective activity of organic extracts and semipurified fractions and identify the principal compounds present in C. martii responsible for such activity. The organic extracts (cyclohexane: ECCm, ethyl acetate: EACm, and ethanol: EECm) were obtained from the dried aerial parts (500 g) of C. martii. For evaluation of the gastroprotective activity of extracts (50, 100, or 200 mg/kg; p.o.), male Swiss Webster mice (25–30 g) were used which had gastric ulcers induced by indomethacin (40 mg/kg, s.c.) or ethanol (0.2 mL/animal; p.o.). Among the extracts evaluated, EACm exhibited significant (P < 0.05) gastroprotective activity in the models used. The fractionation of EACm was performed in a silica gel column 60 eluted with the following compounds: [chloroform—F1 yield (10%)], [chloroform/ethyl acetate (1/1)—F2 yield (6%)], [ethyl acetate—F3 yield (8%)], and [ethyl/methanol acetate (1/1)—F4 yield (5%)]. Of the fractions described above, the F1 (25 mg/kg; p.o.) had greater gastroprotective activity (P < 0.05) than that displayed by ranitidine (80 mg/kg; p.o.) in the ethanol-induced ulcer model. The refractionation of F1 produced 23 subfractions and from these two yellow amorphous compounds were obtained by recrystallization, Rf: 0.46 and 0.31 (ethyl acetate : chloroform 5 : 5). The compounds isolated were characterized by nuclear magnetic resonance spectroscopy (1H-NMR and 13C-NMR) and identified as flavones: chrysoeriol (yield: 0.43%) and 3′,4′-dimethoxyluteolin (yield: 0.58%). Conclusion. Flavone 3′,4′-dimethoxyluteolin is the principal compound present in the species C. martii and is probably responsible for gastroprotective activity observed in this species. PMID:25866537

Study of the Gastroprotective Effect of Extracts and Semipurified Fractions of Chresta martii DC. and Identification of Its Principal Compounds.

PubMed

Franco, E S; Mélo, M E B; Jatobá, B J A; Santana, A L B D; Silva, A A R; Silva, T G; Nascimento, M S; Maia, M B S

2015-01-01

Chresta martii (Asteraceae) is a species widely used by the population of the Xingu region of Sergipe, Brazil, in the form of a decoction (aerial parts) for the treatment of gastrointestinal diseases. The study aims to assess the gastroprotective activity of organic extracts and semipurified fractions and identify the principal compounds present in C. martii responsible for such activity. The organic extracts (cyclohexane: ECCm, ethyl acetate: EACm, and ethanol: EECm) were obtained from the dried aerial parts (500 g) of C. martii. For evaluation of the gastroprotective activity of extracts (50, 100, or 200 mg/kg; p.o.), male Swiss Webster mice (25-30 g) were used which had gastric ulcers induced by indomethacin (40 mg/kg, s.c.) or ethanol (0.2 mL/animal; p.o.). Among the extracts evaluated, EACm exhibited significant (P < 0.05) gastroprotective activity in the models used. The fractionation of EACm was performed in a silica gel column 60 eluted with the following compounds: [chloroform-F1 yield (10%)], [chloroform/ethyl acetate (1/1)-F2 yield (6%)], [ethyl acetate-F3 yield (8%)], and [ethyl/methanol acetate (1/1)-F4 yield (5%)]. Of the fractions described above, the F1 (25 mg/kg; p.o.) had greater gastroprotective activity (P < 0.05) than that displayed by ranitidine (80 mg/kg; p.o.) in the ethanol-induced ulcer model. The refractionation of F1 produced 23 subfractions and from these two yellow amorphous compounds were obtained by recrystallization, Rf: 0.46 and 0.31 (ethyl acetate : chloroform 5 : 5). The compounds isolated were characterized by nuclear magnetic resonance spectroscopy ((1)H-NMR and (13)C-NMR) and identified as flavones: chrysoeriol (yield: 0.43%) and 3',4'-dimethoxyluteolin (yield: 0.58%). Conclusion. Flavone 3',4'-dimethoxyluteolin is the principal compound present in the species C. martii and is probably responsible for gastroprotective activity observed in this species.

Structure Diversity, Synthesis, and Biological Activity of Cyathane Diterpenoids in Higher Fungi.

PubMed

Tang, Hao-Yu; Yin, Xia; Zhang, Cheng-Chen; Jia, Qian; Gao, Jin-Ming

2015-01-01

Cyathane diterpenoids, occurring exclusively in higher basidiomycete (mushrooms), represent a structurally diverse class of natural products based on a characteristic 5-6-7 tricyclic carbon scaffold, including 105 members reported to date. These compounds show a diverse range of biological activities, such as antimicrobial, anti-MRSA, agonistic toward the kappa-opioid receptor, antiinflammatory, anti-proliferative and nerve growth factor (NGF)-like properties. The present review focuses on the structure diversity, structure elucidation and biological studies of these compounds, including mechanisms of actions and structure-activity relationships (SARs). In addition, new progress in chemical synthesis of cyathane diterpenoids is discussed.

Selection of representative emerging micropollutants for drinking water treatment studies: a systematic approach.

PubMed

Jin, Xiaohui; Peldszus, Sigrid

2012-01-01

Micropollutants remain of concern in drinking water, and there is a broad interest in the ability of different treatment processes to remove these compounds. To gain a better understanding of treatment effectiveness for structurally diverse compounds and to be cost effective, it is necessary to select a small set of representative micropollutants for experimental studies. Unlike other approaches to-date, in this research micropollutants were systematically selected based solely on their physico-chemical and structural properties that are important in individual water treatment processes. This was accomplished by linking underlying principles of treatment processes such as coagulation/flocculation, oxidation, activated carbon adsorption, and membrane filtration to compound characteristics and corresponding molecular descriptors. A systematic statistical approach not commonly used in water treatment was then applied to a compound pool of 182 micropollutants (identified from the literature) and their relevant calculated molecular descriptors. Principal component analysis (PCA) was used to summarize the information residing in this large dataset. D-optimal onion design was then applied to the PCA results to select structurally representative compounds that could be used in experimental treatment studies. To demonstrate the applicability and flexibility of this selection approach, two sets of 22 representative micropollutants are presented. Compounds in the first set are representative when studying a range of water treatment processes (coagulation/flocculation, oxidation, activated carbon adsorption, and membrane filtration), whereas the second set shows representative compounds for ozonation and advanced oxidation studies. Overall, selected micropollutants in both lists are structurally diverse, have wide-ranging physico-chemical properties and cover a large spectrum of applications. The systematic compound selection approach presented here can also be adjusted to fit individual research needs with respect to type of micropollutants, treatment processes and number of compounds selected. Copyright © 2011 Elsevier B.V. All rights reserved.

Bioactivity of compounds from Acmella oleracea against Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) and selectivity to two non-target species.

PubMed

Moreno, Shaiene C; Carvalho, Geraldo A; Picanço, Marcelo C; Morais, Elisangela G F; Pereira, Rogério M

2012-03-01

Tropical plants are recognised sources of bioactive compounds that can be used for pest control. The objective of this study was to evaluate the biological activity of compounds present in Acmella oleracea (Asteracea) against Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), which is the main pest of tomato crops in Latin America. The selectivity of these compounds to the predator Solenopsis saevissima (Smith) (Hymenoptera: Formicidae) and to the pollinator Tetragonisca angustula (Latr.) (Hymenoptera: Apidae: Meliponinae) was also of interest. A bioassay screening with hexane and ethanol extracts from 23 plants was performed. The hexane extract of A. oleraceae was the most active of the extracts and was selected for further study. The following three alkamides were isolated from a hexane extract of the aerial parts of A. oleracea: spilanthol, (E)-N-isobutylundeca-2-en-8,10-diynamide and (R, E)-N-(2-methylbutyl)undeca-2-en-8,10-diynamide. All of the isolated compounds showed insecticidal activity, with spilanthol being the most active (LD(50) = 0.13 µg mg(-1) ) against T. absoluta. The alkamides were selective to both beneficial species studied. The crude hexane extract of A. oleraceae showed high insecticidal activity and can be used to control T. absoluta in organic or conventional crops. Quantification of LD(50) values of isolated compounds against T. absoluta showed that alkamides could serve as potent insecticides for T. absoluta control programmes. Spilanthol was the main alkamide active isolated. This alkamide is the most promising as it has the highest insecticidal activity and is selective to non-target organisms. Copyright © 2011 Society of Chemical Industry.

Graph Theoretical Analysis, In Silico Modeling, Synthesis, Anti-Microbial and Anti-TB Evaluation of Novel Quinoxaline Derivatives.

PubMed

Saravanan, Govindaraj; Selvam, Theivendren Panneer; Alagarsamy, Veerachamy; Kunjiappan, Selvaraj; Joshi, Shrinivas D; Indhumathy, Murugan; Kumar, Pandurangan Dinesh

2018-05-01

We designed to synthesize a number of 2-(2-(substituted benzylidene) hydrazinyl)-N-(4-((3-(phenyl imino)-3,4-dihydro quinoxalin-2(1 H)-ylidene)amino) phenyl) acetamide S1-S13: with the hope to obtain more active and less toxic anti-microbial and anti-TB agents. A series of novel quinoxaline Schiff bases S1-S13: were synthesized from o-phenylenediamine and oxalic acid by a multistep synthesis. In present work, we are introducing graph theoretical analysis to identify drug target. In the connection of graph theoretical analysis, we utilised KEGG database and Cytoscape software. All the title compounds were evaluated for their in-vitro anti-microbial activity by using agar well diffusion method at three different concentration levels (50, 100 and 150 µg/ml). The MIC of the compounds was also determined by agar streak dilution method. The identified study report through graph theoretical analysis were highlights that the key virulence factor for pathogenic mycobacteria is a eukaryotic-like serine/threonine protein kinase, termed PknG. All compounds were found to display significant activity against entire tested bacteria and fungi. In addition the synthesized scaffolds were screened for their in vitro antituberculosis (anti-TB) activity against Mycobacterium tuberculosis (Mtb) strain H 37 Ra using standard drug Rifampicin. A number of analogs found markedly potent anti-microbial and anti-TB activity. The relationship between the functional group variation and the biological activity of the evaluated compounds were well discussed. The observed study report was showing that the compound S6: (4-nitro substitution) exhibited most potent effective anti-microbial and anti-TB activity out of various tested compounds. © Georg Thieme Verlag KG Stuttgart · New York.

Polyphenolic content, in vitro antioxidant activity and chemical composition of extract from Nephelium lappaceum L. (Mexican rambutan) husk.

PubMed

Hernández, Cristian; Ascacio-Valdés, Juan; De la Garza, Heliodoro; Wong-Paz, Jorge; Aguilar, Cristóbal Noé; Martínez-Ávila, Guillermo Cristian; Castro-López, Cecilia; Aguilera-Carbó, Antonio

2017-12-01

To determinate the recovery of total polyphenolic compounds content, in vitro antioxidant activity and HPLC/ESI/MS characterization of extract from Nephelium lappaceum L. (Mexican rambutan). The rambutan husk extract was obtained by aqueous extraction and a polyphenolic fraction was recovered using Amberlite XAD-16. The total polyphenolic compounds content was determined by the Folin Ciocalteu and butanol-HCI methods. In vitro antioxidant activity was performed using ABTS and ferric reducing antioxidant power methods. Mexican rambutan husk showed a total polyphenolic content of 582 mg/g and an evident antioxidant activity by ABTS and ferric reducing antioxidant power analysis. The HPLC/ESI/MS assay allowed the identification of 13 compounds, most of which belong to ellagitannins. Geraniin, corilagin and ellagic acid were present in the sample; the mineral composition was also evaluated. Rambutan husk cultivated in Mexico is a promising source for the recovery of added value bioactive compounds with antioxidant activity, which have potential applications as bioactive antioxidant agents for the treatment of diseases. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Novel propanamides as fatty acid amide hydrolase inhibitors.

PubMed

Deplano, Alessandro; Morgillo, Carmine Marco; Demurtas, Monica; Björklund, Emmelie; Cipriano, Mariateresa; Svensson, Mona; Hashemian, Sanaz; Smaldone, Giovanni; Pedone, Emilia; Luque, F Javier; Cabiddu, Maria G; Novellino, Ettore; Fowler, Christopher J; Catalanotti, Bruno; Onnis, Valentina

2017-08-18

Fatty acid amide hydrolase (FAAH) has a key role in the control of the cannabinoid signaling, through the hydrolysis of the endocannabinoids anandamide and in some tissues 2-arachidonoylglycerol. FAAH inhibition represents a promising strategy to activate the cannabinoid system, since it does not result in the psychotropic and peripheral side effects characterizing the agonists of the cannabinoid receptors. Here we present the discovery of a novel class of profen derivatives, the N-(heteroaryl)-2-(4-((2-(trifluoromethyl)pyridin-4-yl)amino)phenyl)propanamides, as FAAH inhibitors. Enzymatic assays showed potencies toward FAAH ranging from nanomolar to micromolar range, and the most compounds lack activity toward the two isoforms of cyclooxygenase. Extensive structure-activity studies and the definition of the binding mode for the lead compound of the series are also presented. Kinetic assays in rat and mouse FAAH on selected compounds of the series demonstrated that slight modifications of the chemical structure could influence the binding mode and give rise to competitive (TPA1) or non-competitive (TPA14) inhibition modes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Antibacterial activity of isolated phenolic compounds from cranberry (Vaccinium macrocarpon) against Escherichia coli.

PubMed

Rodríguez-Pérez, Celia; Quirantes-Piné, Rosa; Uberos, José; Jiménez-Sánchez, Cecilia; Peña, Alejandro; Segura-Carretero, Antonio

2016-03-01

Phenolic compounds from a cranberry extract were isolated in order to assess their contribution to the antibacterial activity against uropathogenic strains of Escherichia coli (UPEC). With this purpose, a total of 25 fractions from a cranberry extract were isolated using semipreparative high performance liquid chromatography (HPLC) and characterized based on the results obtained by reversed-phase HPLC coupled to mass spectrometry detection. Then, the effects on UPEC surface hydrophobicity and biofilm formation of the cranberry extract as well as the purest fractions (a total of 13) were tested. As expected, the whole extract presented a powerful antibacterial activity against UPEC while the selected fractions presented a different behavior. Myricetin and quercitrin significantly decreased (p < 0.05) E. coli biofilm formation compared with the control, while dihydroferulic acid glucuronide, procyanidin A dimer, quercetin glucoside, myricetin and prodelphinidin B led to a significant decrease of the surface hydrophobicity compared with the control. The results suggest that apart from proanthocyanidins, other compounds, mainly flavonoids, can act against E. coli biofilm formation and also modify UPEC surface hydrophobicity in vitro, one of the first steps of adhesion.

Comparative studies on extracts from Hericium erinaceus by different polarity reagents to gain higher antioxidant activities.

PubMed

Jiang, Shengjuan; Wang, Yuliang; Zhang, Xiaolong

2016-07-01

Hericium erinaceus (H. erinaceus) is a source of exogenous antioxidants that has been traditionally used in China for the prevention and treatment of oxidative stress-associated disease. In the present study, the bioactive compounds of H. erinaceus were extracted with the following eight representative reagents: n-Hexane, xylene, chloroform, anhydrous ether, ethyl acetate, acetone, anhydrous ethanol and distilled water. The in vitro antioxidant activities were also evaluated. All of the extracted compounds exhibited reducing power and scavenging activity against 1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide anion free radicals. In addition, the antioxidant capacities varied with the used chemical reagents and exhibited dose-dependent effects. Extracts from anhydrous ethanol, chloroform and acetone were capable of inhibiting lipid peroxidation. The anhydrous ethanol extracts were observed to have significant levels of antioxidant compounds since they had a strong reducing power, high scavenging rates against DPPH and superoxide anion-free radicals (>90%), and high inhibition rates on lipid peroxidation (>60%). The present study will provide reference data for the antioxidant applications of H. erinaceus in pharmaceutical use and disease prevention.

Comparative studies on extracts from Hericium erinaceus by different polarity reagents to gain higher antioxidant activities

PubMed Central

JIANG, SHENGJUAN; WANG, YULIANG; ZHANG, XIAOLONG

2016-01-01

Hericium erinaceus (H. erinaceus) is a source of exogenous antioxidants that has been traditionally used in China for the prevention and treatment of oxidative stress-associated disease. In the present study, the bioactive compounds of H. erinaceus were extracted with the following eight representative reagents: n-Hexane, xylene, chloroform, anhydrous ether, ethyl acetate, acetone, anhydrous ethanol and distilled water. The in vitro antioxidant activities were also evaluated. All of the extracted compounds exhibited reducing power and scavenging activity against 1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide anion free radicals. In addition, the antioxidant capacities varied with the used chemical reagents and exhibited dose-dependent effects. Extracts from anhydrous ethanol, chloroform and acetone were capable of inhibiting lipid peroxidation. The anhydrous ethanol extracts were observed to have significant levels of antioxidant compounds since they had a strong reducing power, high scavenging rates against DPPH and superoxide anion-free radicals (>90%), and high inhibition rates on lipid peroxidation (>60%). The present study will provide reference data for the antioxidant applications of H. erinaceus in pharmaceutical use and disease prevention. PMID:27347087

Identification of volatile components of bobcat (Lynx rufus) urine.

PubMed

Mattina, M J; Pignatello, J J; Swihart, R K

1991-02-01

Bobcat (Lynx rufus) urine reduces scent-marking activity of woodchucks (Marmota monax) and feeding activity of snowshoe hares (Lepus americanus) and deer (Odocoileus virginianus, O. hemionus). In order to identify the semiochemicals responsible for these behavior modifications, a dichloromethane extract of the bobcat urine was analyzed by GC-MS. Among the known compounds identified in the extract are phenol, indole, dimethyl sulfone, and 3-mercapto-3-methylbutanol. Compounds for which spectroscopic data are presented for the first time include one sulfide, two disulfides, and two trisulfides. The sulfur compounds are derived from an amino acid,S-(l,1-dimethyl-3-hydroxypropyl)cysteine ("felinine"), which was identified several years ago in the urine of the domestic cat (Felis domesticus).

Screening for Antiviral Activities of Isolated Compounds from Essential Oils

PubMed Central

Astani, Akram; Reichling, Jürgen; Schnitzler, Paul

2011-01-01

Essential oil of star anise as well as phenylpropanoids and sesquiterpenes, for example, trans-anethole, eugenol, β-eudesmol, farnesol, β-caryophyllene and β-caryophyllene oxide, which are present in many essential oils, were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro. Antiviral activity was analyzed by plaque reduction assays and mode of antiviral action was determined by addition of the drugs to uninfected cells, to the virus prior to infection or to herpesvirus-infected cells. Star anise oil reduced viral infectivity by >99%, phenylpropanoids inhibited HSV infectivity by about 60–80% and sesquiterpenes suppressed herpes virus infection by 40–98%. Both, star anise essential oil and all isolated compounds exhibited anti-HSV-1 activity by direct inactivation of free virus particles in viral suspension assays. All tested drugs interacted in a dose-dependent manner with herpesvirus particles, thereby inactivating viral infectivity. Star anise oil, rich in trans-anethole, revealed a high selectivity index of 160 against HSV, whereas among the isolated compounds only β-caryophyllene displayed a high selectivity index of 140. The presence of β-caryophyllene in many essential oils might contribute strongly to their antiviral ability. These results indicate that phenylpropanoids and sesquiterpenes present in essential oils contribute to their antiviral activity against HSV. PMID:20008902

Synthesis and biological activity of imidazopyridine anticoccidial agents: part I.

PubMed

Scribner, Andrew; Dennis, Richard; Hong, Jean; Lee, Shuliang; McIntyre, Donald; Perrey, David; Feng, Dennis; Fisher, Michael; Wyvratt, Matthew; Leavitt, Penny; Liberator, Paul; Gurnett, Anne; Brown, Chris; Mathew, John; Thompson, Donald; Schmatz, Dennis; Biftu, Tesfaye

2007-01-01

Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance to current anticoccidials has prompted the search for new therapeutic agents with potent in vitro and in vivo activity against Eimeria. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we present the synthesis and biological activity of imidazo[1,2-a]pyridine anticoccidial agents. From this series, several compounds showed subnanomolar in vitro activity and commercial levels of in vivo activity. However, the potential genotoxicity of these compounds precludes them from further development.

Toxicology, an STS Approach.

ERIC Educational Resources Information Center

Wagner, Richard

1990-01-01

Presented are activities suggested through Project L.A.B.S. that involve the topic of toxicology. Activities include suggested research, the risk benefit seesaw, human-made compounds, legislation, a historical perspective, and health. A suggested readings list is provided. (KR)

In Vitro Anti-Toxoplasma gondii and Antimicrobial Activity of Amides Derived from Cinnamic Acid.

PubMed

Silveira, Graziela Rangel; Campelo, Karoline Azerêdo; Lima, Gleice Rangel Silveira; Carvalho, Lais Pessanha; Samarão, Solange Silva; Vieira-da-Motta, Olney; Mathias, Leda; Matos, Carlos Roberto Ribeiro; Vieira, Ivo José Curcino; Melo, Edesio José Tenório de; Maria, Edmilson José

2018-03-28

Most cinnamic acids, their esters, amides, aldehydes, and alcohols present several therapeutic actions through anti-inflammatory, antitumor, and inhibitory activity against a great variety of microorganisms. In this work, eight amines derived from cinnamic acid were synthesized and tested against host cells infected with Toxoplasma gondii and the bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and three strains of Staphylococcus aureus . Compounds 3 and 4 showed the best result against intracellular T. gondii , presenting antiparasitic activity at low concentrations (0.38 and 0.77 mM). The antibacterial activity of these compounds was also evaluated by the agar microdilution method, and amides 2 and 5 had a minimum inhibitory concentration of 250 µg mL -1 against two strains of S. aureus (ATCC 25923 and bovine strain LSA 88). These also showed synergistic action along with a variety of antibiotics, demonstrating that amines derived from cinnamic acid have potential as pharmacological agents.

Identification of pyrogallol as an antiproliferative compound present in extracts from the medicinal plant Emblica officinalis: effects on in vitro cell growth of human tumor cell lines.

PubMed

Khan, Mahmud Tareq Hassan; Lampronti, Ilaria; Martello, Dino; Bianchi, Nicoletta; Jabbar, Shaila; Choudhuri, Mohammad Shahabuddin Kabir; Datta, Bidduyt Kanti; Gambari, Roberto

2002-07-01

In this study we compared the in vitro antiproliferative activity of extracts from medicinal plants toward human tumor cell lines, including human erythromyeloid K562, B-lymphoid Raji, T-lymphoid Jurkat, erythroleukemic HEL cell lines. Extracts from Emblica officinalis were the most active in inhibiting in vitro cell proliferation, after comparison to those from Terminalia arjuna, Aphanamixis polystachya, Oroxylum indicum, Cuscuta reflexa, Aegle marmelos, Saraca asoka, Rumex maritimus, Lagerstroemia speciosa, Red Sandalwood. Emblica officinalis extracts have been studied previously, due to their hepatoprotective, antioxidant, antifungal, antimicrobial and anti-inflammatory medicinal activities. Gas chromatography/mass spectrometry analyses allowed to identify pyrogallol as the common compound present both in unfractionated and n-butanol fraction of Emblica officinalis extracts. Antiproliferative effects of pyrogallol were therefore determined on human tumor cell lines thus identifying pyrogallol as an active component of Emblica officinalis extracts.

Carbonic anhydrase inhibition of Schiff base derivative of imino-methyl-naphthalen-2-ol: Synthesis, structure elucidation, molecular docking, dynamic simulation and density functional theory calculations

NASA Astrophysics Data System (ADS)

Abbas, Saghir; Nasir, Hafiza Huma; Zaib, Sumera; Ali, Saqib; Mahmood, Tariq; Ayub, Khurshid; Tahir, Muhammad Nawaz; Iqbal, Jamshed

2018-03-01

In the present study, we have designed and synthesized a Schiff base derivative 3 and characterized by FT-IR, 1H and 13C NMR spectroscopy. Single crystal X-ray diffraction and NMR studies were also performed. The synthetic compound was screened for its inhibitory potential against carbonic anhydrase II. The experimental results were validated by molecular docking and dynamic simulations of compound 3 in the active pocket of enzyme. Important binding interactions with the key residues in the active site of the carbonic anhydrase enzyme were revealed. Moreover, supramolecular assembly of the title compound was analyzed by density functional theory (DFT) calculations. These studies rendered a more clear understanding for the demonstration of novel molecular mechanism involved in CA II inhibition by the synthesized compound.

Tetraphenylphosphonium allyldithiocarbimates derived from Morita-Baylis-Hillman adducts: Synthesis, characterization, crystal structure and antifungal activity

NASA Astrophysics Data System (ADS)

Tavares, Eder C.; Rubinger, Mayura M. M.; Filho, Eclair V.; Oliveira, Marcelo R. L.; Piló-Veloso, Dorila; Ellena, Javier; Guilardi, Silvana; Souza, Rafael A. C.; Zambolim, Laércio

2016-02-01

Botrytis blight is a very destructive disease caused by Botrytis spp., infecting flowers, trees, vegetables and fruits. Twelve new compounds were prepared by the reaction of potassium N-aryl-sulfonyldithiocarbimates with Morita-Baylis-Hillman derivatives bearing phenyl and furyl groups. These are the first examples of allyldithiocarbimate anions and were isolated as tetraphenylphosphonium salts. The new compounds were characterized by HRMS, NMR and Infrared spectroscopy. Further, the structures of three allyldithiocarbimates were determined by single crystal X-ray diffraction. The compounds are isostructural and crystallize in the space group P21/c of the monoclinic system, and the allyldithiocarbimate anions present Z configuration. All the compounds were active against Botrytis cinerea. The best results were achieved with the tetraphenylphosphonium (Z)-3-(furan-2-yl)-2-(methoxycarbonyl)allyl-(4-chlorophenylsulfonyl)dithiocarbimate (IC50 38 μM).

Tributyltin or triphenyltin inhibits aromatase activity in the human granulosa-like tumor cell line KGN.

PubMed

Saitoh, M; Yanase, T; Morinaga, H; Tanabe, M; Mu, Y M; Nishi, Y; Nomura, M; Okabe, T; Goto, K; Takayanagi, R; Nawata, H

2001-11-23

The superimposition of male sex organs (penis and vas deferens) in a female gastropod, called imposex, is widely attributed to the exposure to tributyltin (TBT) compounds, used world-wide in antifouling paints for ships. It has been hypothesized that the TBT-induced imposex is mediated by an increasing androgen level relative to the estrogen level, namely a decreased conversion of androgens to estrogens (i.e., aromatization). In the present study, we tested this hypothesis by examining the effects of TBT or triphenyltin (TPT) on the aromatase activity in a cultured human granulosa-like tumor cell line, KGN, which was recently established by our group. Treatment with more than 1000 ng/ml TBT compounds was very toxic to the cells and caused immediate cell death within 24 h, while 200 ng/ml was found to cause apoptosis of the cells. Treatment of the KGN cells for more than 48 h with 20 ng/ml TBT or TPT, which is a concentration level reported to cause imposex in marine species, did not affect cell proliferation but significantly suppressed the aromatase activity determined by a [(3)H]H(2)O release assay. Treatment with 20 ng/ml TBT compounds for 7 days also resulted in a reduction of the E2 production from Delta 4-androstenedione stimulated by db-cAMP. The changes in the aromatase activity by TBT compounds were associated with comparable changes in P450arom mRNA assessed by RT-PCR. The luciferase activity of the P450arom promoter II (1 kb) decreased after the addition of 20 ng/ml TBT compounds in transfected KGN cells either in a basic state or in states stimulated by db-cAMP. The Ad4BP-dependent increase in the luciferase activity of P450arom promoter II was also downregulated by such treatments. These results indicate that TBT compounds inhibited the aromatase activity and also decreased the P450arom mRNA level at the transcriptional level in KGN cells. The direct inhibitory effect of TBT compounds on the aromatase activity may therefore partly explain the induction of imposex by these compounds in female species. Copyright 2001 Academic Press.

A flavonoid isolated from Streptomyces sp. (ERINLG-4) induces apoptosis in human lung cancer A549 cells through p53 and cytochrome c release caspase dependant pathway.

PubMed

Balachandran, C; Sangeetha, B; Duraipandiyan, V; Raj, M Karunai; Ignacimuthu, S; Al-Dhabi, N A; Balakrishna, K; Parthasarathy, K; Arulmozhi, N M; Arasu, M Valan

2014-12-05

The aim of this study was to investigate the anticancer activity of a flavonoid type of compound isolated from soil derived filamentous bacterium Streptomyces sp. (ERINLG-4) and to explore the molecular mechanisms of action. Cytotoxic properties of ethyl acetate extract was carried out against A549 lung cancer cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cytotoxic properties of isolated compound were investigated in A549 lung cancer cell line, COLO320DM cancer cell line and Vero cells. The compound showed potent cytotoxic properties against A549 lung cancer cell line and moderate cytotoxic properties against COLO320DM cancer cell line. Isolated compound showed no toxicity up to 2000 μg/mL in Vero cells. So we have chosen the A549 lung cancer cell line for further anticancer studies. Intracellular visualization was done by using a laser scanning confocal microscope. Apoptosis was measured using DNA fragmentation technique. Treatment of the A549 cancer cells with isolated compound significantly reduced cell proliferation, increased formation of fragmented DNA and apoptotic body. Activation of caspase-9 and caspase-3 indicated that compound may be inducing intrinsic and extrinsic apoptosis pathways. Bcl-2, p53, pro-caspases, caspase-3, caspase-9 and cytochrome c release were detected by western blotting analysis after compound treatment (123 and 164 μM). The activities of pro-caspases-3, caspase-9 cleaved to caspase-3 and caspase-9 gradually increased after the addition of isolated compound. But Bcl-2 protein was down regulated after treatment with isolated compound. Molecular docking studies showed that the compound bound stably to the active sites of caspase-3 and caspase-9. These results strongly suggest that the isolated compound induces apoptosis in A549 cancer cells via caspase activation through cytochrome c release from mitochondria. The present results might provide helpful suggestions for the design of antitumor drugs toward lung cancer treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Actinobacteria from Termite Mounds Show Antiviral Activity against Bovine Viral Diarrhea Virus, a Surrogate Model for Hepatitis C Virus

PubMed Central

Padilla, Marina Aiello; Rodrigues, Rodney Alexandre Ferreira; Bastos, Juliana Cristina Santiago; Martini, Matheus Cavalheiro; Barnabé, Ana Caroline de Souza; Kohn, Luciana Konecny; Uetanabaro, Ana Paula Trovatti; Bomfim, Getúlio Freitas; Afonso, Rafael Sanches; Fantinatti-Garboggini, Fabiana; Arns, Clarice Weis

2015-01-01

Extracts from termite-associated bacteria were evaluated for in vitro antiviral activity against bovine viral diarrhea virus (BVDV). Two bacterial strains were identified as active, with percentages of inhibition (IP) equal to 98%. Both strains were subjected to functional analysis via the addition of virus and extract at different time points in cell culture; the results showed that they were effective as posttreatments. Moreover, we performed MTT colorimetric assays to identify the CC50, IC50, and SI values of these strains, and strain CDPA27 was considered the most promising. In parallel, the isolates were identified as Streptomyces through 16S rRNA gene sequencing analysis. Specifically, CDPA27 was identified as S. chartreusis. The CDPA27 extract was fractionated on a C18-E SPE cartridge, and the fractions were reevaluated. A 100% methanol fraction was identified to contain the compound(s) responsible for antiviral activity, which had an SI of 262.41. GC-MS analysis showed that this activity was likely associated with the compound(s) that had a peak retention time of 5 min. Taken together, the results of the present study provide new information for antiviral research using natural sources, demonstrate the antiviral potential of Streptomyces chartreusis compounds isolated from termite mounds against BVDV, and lay the foundation for further studies on the treatment of HCV infection. PMID:26579205

Actinobacteria from Termite Mounds Show Antiviral Activity against Bovine Viral Diarrhea Virus, a Surrogate Model for Hepatitis C Virus.

PubMed

Padilla, Marina Aiello; Rodrigues, Rodney Alexandre Ferreira; Bastos, Juliana Cristina Santiago; Martini, Matheus Cavalheiro; Barnabé, Ana Caroline de Souza; Kohn, Luciana Konecny; Uetanabaro, Ana Paula Trovatti; Bomfim, Getúlio Freitas; Afonso, Rafael Sanches; Fantinatti-Garboggini, Fabiana; Arns, Clarice Weis

2015-01-01

Extracts from termite-associated bacteria were evaluated for in vitro antiviral activity against bovine viral diarrhea virus (BVDV). Two bacterial strains were identified as active, with percentages of inhibition (IP) equal to 98%. Both strains were subjected to functional analysis via the addition of virus and extract at different time points in cell culture; the results showed that they were effective as posttreatments. Moreover, we performed MTT colorimetric assays to identify the CC50, IC50, and SI values of these strains, and strain CDPA27 was considered the most promising. In parallel, the isolates were identified as Streptomyces through 16S rRNA gene sequencing analysis. Specifically, CDPA27 was identified as S. chartreusis. The CDPA27 extract was fractionated on a C18-E SPE cartridge, and the fractions were reevaluated. A 100% methanol fraction was identified to contain the compound(s) responsible for antiviral activity, which had an SI of 262.41. GC-MS analysis showed that this activity was likely associated with the compound(s) that had a peak retention time of 5 min. Taken together, the results of the present study provide new information for antiviral research using natural sources, demonstrate the antiviral potential of Streptomyces chartreusis compounds isolated from termite mounds against BVDV, and lay the foundation for further studies on the treatment of HCV infection.

Isolation and structural characterisation of two antibacterial free fatty acids from the marine diatom, Phaeodactylum tricornutum.

PubMed

Desbois, Andrew P; Lebl, Tomas; Yan, Liming; Smith, Valerie J

2008-12-01

One solution to the global crisis of antibiotic resistance is the discovery of novel antimicrobial compounds for clinical application. Marine organisms are an attractive and, as yet, relatively untapped resource of new natural products. Cell extracts from the marine diatom, Phaeodactylum tricornutum, have antibacterial activity and the fatty acid, eicosapentaenoic acid (EPA), has been identified as one compound responsible for this activity. During the isolation of EPA, it became apparent that the extracts contained further antibacterial compounds. The present study was undertaken to isolate these additional antibacterial factors using silica column chromatography and reverse-phase high-performance liquid chromatography. Two antibacterial fractions, each containing a pure compound, were isolated and their chemical structures were investigated by mass spectrometry and nuclear magnetic resonance spectroscopy. The antibacterial compounds were identified as the monounsaturated fatty acid (9Z)-hexadecenoic acid (palmitoleic acid; C16:1 n-7) and the relatively unusual polyunsaturated fatty acid (6Z, 9Z, 12Z)-hexadecatrienoic acid (HTA; C16:3 n-4). Both are active against Gram-positive bacteria with HTA further inhibitory to the growth of the Gram-negative marine pathogen, Listonella anguillarum. Palmitoleic acid is active at micro-molar concentrations, kills bacteria rapidly, and is highly active against multidrug-resistant Staphylococcus aureus. These free fatty acids warrant further investigation as a new potential therapy for drug-resistant infections.

Molecular descriptors calculation as a tool in the analysis of the antileishmanial activity achieved by two series of diselenide derivatives. An insight into its potential action mechanism.

PubMed

Font, María; Baquedano, Ylenia; Plano, Daniel; Moreno, Esther; Espuelas, Socorro; Sanmartín, Carmen; Palop, Juan Antonio

2015-07-01

A molecular modeling study has been carried out on two previously reported series of symmetric diselenide derivatives that show remarkable antileishmanial in vitro activity against Leishmania infantum intracellular amastigotes and in infected macrophages (THP-1 cells), in addition to showing favorable selectivity indices. Series 1 consists of compounds that can be considered as central scaffold constructed with a diaryl/dialkylaryl diselenide central nucleus, decorated with different substituents located on the aryl rings. Series 2 consists of compounds constructed over a diaryl diselenide central nucleus, decorated in 4 and 4' positions with an aryl or heteroaryl sulfonamide fragment, thus forming the diselenosulfonamide derivatives. With regard to the diselenosulfonamide derivatives (2 series), the activity can be related, as a first approximation, with (a) the ability to release bis(4-aminophenyl) diselenide, the common fragment which can be ultimately responsible for the activity of the compounds. (b) the anti-parasitic activity achieved by the sulfonamide pharmacophore present in the analyzed derivatives. The data that support this connection include the topography of the molecules, the conformational behavior of the compounds, which influences the bond order, as well as the accessibility of the hydrolysis point, and possibly the hydrophobicity and polarizability of the compounds. Copyright © 2015 Elsevier Inc. All rights reserved.

Synthesis, crystal structure, cytotoxic, antileishmanial activities and docking studies on N,N‧-(ethane-1,2-diyl)bis(3-methylbenzamide)

NASA Astrophysics Data System (ADS)

Aziz, Hamid; Saeed, Aamer; Jabeen, Farukh; Simpson, Jim; Munawar, Amna; Qasim, Muhammad

2018-03-01

Amide derivatives have gained considerable attention because of their extensive range of biological activities and pharmaceutical applications. The current paper presents the synthesis of N, N‧-(ethane-1,2-diyl) bis (3-methylbenzamide), (I), its molecular and crystal structure and an evaluation of its likely biological activity, including cytotoxicity (LD50 = 37.21 μg/ml) and antileishmanial activity (IC50 = 5.77 μg/ml). Moreover, a docking simulation was used to determine the possible interaction sites of the compound (I) with TryR, an enzyme involved in the redox metabolism of the leishmania parasite. Docking computations demonstrate that the compound established prominent binding interactions with the key residues of the TryR and possess the potential to effectively inhibit the catalytic activities of the enzyme. Thus the results suggest that this compound can serve as a potential scaffold for the treatment of leishmaniasis and deserves further development.

Synthesis, crystal structure and larvicidal activity of novel diamide derivatives against Culex pipiens.

PubMed

Wu, Rui; Zhu, Cong; Du, Xiu-Jiang; Xiong, Li-Xia; Yu, Shu-Jing; Liu, Xing-Hai; Li, Zheng-Ming; Zhao, Wei-Guang

2012-09-11

Culex is an important mosquito as vectors for the transmission of serious diseases, such as filariasis, West Nile virus, dengue, yellow fever, chikungunya and other encephalitides. Nearly one billion people in the developing countries are at risk. In order to discover new bioactive molecules and pesticides acting on mosquito, we designed active amide structure and synthesized a series of novel diamide derivatives. A series of novel diamide derivatives were designed and synthesized. Their structures were characterized by 1 H NMR, FTIR and HRMS. The single crystal structure of compound 6n was determined to further elucidate the structure. Biological activities of these compounds were tested. Most of them exhibited higher mosquito larvicidal activity. Especially compound 6r displayed relatively good activity to reach 70% at 2 μg/mL. A practical synthetic route to amide derivatives by the reaction of amide with another acid is presented. This study suggests that the diamide derivatives exhibited good effective against mosquito.

Activity of bis(7-hydroxycoumarin) Mannich bases against bovine viral diarrhoea virus.

PubMed

Ibrahim, Munjed M; Mazzei, Mauro; Delogu, Ilenia; Szabó, Róbert; Sanna, Giuseppina; Loddo, Roberta

2016-10-01

Some Mannich bases of 7-hydroxycoumarins (3-6) with piperazine or other amines bearing two secondary amine groups were prepared and tested against viruses representative of RNA families. All compounds were symmetrical and possessed two identical coumarin moieties with respect to one diamine. In the series of 7-hydroxy derivatives, 3a was endowed with a significant activity against BVDV. Then, some of these double Mannich bases were alkylated and acylated. Among the propyloxy derivatives, only 3f showed a modest activity against BVDV. Among the acyl derivatives, the p-nitrobenzoyl derivative 3i emerged as the most active compound; in this series, the p-nitrobenzoyl derivative 3j also exhibited good action against BVDV and modest activity against CVB-5. On the whole, the compounds presented here show some differences, with respect to previous studies in terms of SAR from similar Mannich bases of 7-hydroxycoumarin. Copyright © 2016 Elsevier B.V. All rights reserved.

Studies on the antioxidant activities of natural vanilla extract and its constituent compounds through in vitro models.

PubMed

Shyamala, B N; Naidu, M Madhava; Sulochanamma, G; Srinivas, P

2007-09-19

Vanilla extract was prepared by extraction of cured vanilla beans with aqueous ethyl alcohol (60%). The extract was profiled by HPLC, wherein major compounds, viz., vanillic acid, 4-hydroxybenzyl alcohol, 4-hydroxy-3-methoxybenzyl alcohol, 4-hydroxybenzaldehyde and vanillin, could be identified and separated. Extract and pure standard compounds were screened for antioxidant activity using beta-carotene-linoleate and DPPH in vitro model systems. At a concentration of 200 ppm, the extract showed 26% and 43% of antioxidant activity by beta-carotene-linoleate and DPPH methods, respectively, in comparison to corresponding values of 93% and 92% for BHA. Interestingly, 4-hydroxy-3-methoxybenzyl alcohol and 4-hydroxybenzyl alcohol exhibited antioxidant activity of 65% and 45% by beta-carotene-linoleate method and 90% and 50% by DPPH methods, respectively. In contrast, pure vanillin exhibited much lower antioxidant activity. The present study points toward the potential use of vanilla extract components as antioxidants for food preservation and in health supplements as nutraceuticals.

Antimicrobial activity of Olea europaea Linné extracts and their applicability as natural food preservative agents.

PubMed

Thielmann, J; Kohnen, S; Hauser, C

2017-06-19

The antimicrobial activity of phenolic compounds from Olea (O.) europaea Linné (L.) is part of the scientific discussion regarding the use of natural plant extracts as alternative food preservative agents. Although, the basic knowledge on the antimicrobial potential of certain molecules such as oleuropein, hydroxytyrosol or elenolic acid derivatives is given, there is still little information regarding their applicability for food preservation. This might be primarily due to the lack of information regarding the full antimicrobial spectrum of the compounds, their synergisms in natural or artificial combinations and their interaction with food ingredients. The present review accumulates available literature from the past 40 years, investigating the antimicrobial activity of O. europaea L. derived extracts and compounds in vitro and in food matrices, in order to evaluate their food applicability. In summary, defined extracts from olive fruit or leaves, containing the strongest antimicrobial compounds hydroxytyrosol, oleacein or oleacanthal in considerable concentrations, appear to be suitable for food preservation. Nonetheless there is still need for consequent research on the compounds activity in food matrices, their effect on the natural microbiota of certain foods and their influence on the sensorial properties of the targeted products. Copyright © 2017 Elsevier B.V. All rights reserved.

Design, synthesis and biological activity of novel donepezil derivatives bearing N-benzyl pyridinium moiety as potent and dual binding site acetylcholinesterase inhibitors.

PubMed

Lan, Jin-Shuai; Zhang, Tong; Liu, Yun; Yang, Jing; Xie, Sai-Sai; Liu, Jing; Miao, Ze-Yang; Ding, Yue

2017-06-16

A series of new donepezil derivatives were designed synthesized and evaluated as multifunctional cholinesterase inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of them exhibited significant potency to inhibit acetylcholinesterase and self-induced β-amyloid (Aβ) aggregation, and moderate antioxidant activity. Especially, compound 5b presented the greatest ability to inhibit cholinesterase (IC 50 , 1.9 nM for eeAChE and 0.8 nM for hAChE), good inhibition of Aβ aggregation (53.7% at 20 μM) and good antioxidant activity (0.54 trolox equivalents). Kinetic and molecular modeling studies indicated that compound 5b was a mixed-type inhibitor, binding simultaneously to the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, compound 5b could reduce PC12 cells death induced by oxidative stress and Aβ (1-42). Moreover, in vivo experiments showed that compound 5b was nontoxic and tolerated at doses up to 2000 mg/kg. These results suggested that compound 5b might be an excellent multifunctional agent for AD treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Sesquiterpene Lactones from Cynara cornigera: Acetyl Cholinesterase Inhibition and In Silico Ligand Docking.

PubMed

Hegazy, Mohamed-Elamir F; Ibrahim, Abeer Y; Mohamed, Tarik A; Shahat, Abdelaaty A; El Halawany, Ali M; Abdel-Azim, Nahla S; Alsaid, Mansour S; Paré, Paul W

2016-01-01

Wild artichoke (Cynara cornigera), a thistle-like perennial belonging to the Asteraceae family, is native to the Mediterranean region, northwestern Africa, and the Canary Islands. While the pleasant, albeit bitter, taste of the leaves and flowers is attributed to the sesquiterpene lactones cynaropicrin and cynarin, a comprehensive phytochemical investigation still needs to be reported. In this study seven sesquiterpene lactones were isolated from an aqueous methanol plant extract, including a new halogenated metabolite (1), the naturally isolated compound sibthorpine (2), and five metabolites isolated for the first time from C. cornigera. Structures were established by spectroscopic methods, including HREIMS, (1 )H, (13 )C, DEPT, (1 )H-(1 )H COSY, HMQC, and HMBC-NMR experiments as well as by X-ray analysis. The isolated bioactive nutrients were analyzed for their antioxidant and metal chelating activity. Compound 1 exhibited a potent metal chelating activity as well as a high antioxidant capacity. Moreover, select compounds were effective as acetyl cholinesterase inhibitors presenting the possibility for such compounds to be examined for anti-neurodegenerative activity. A computational pharmacophore elucidation and docking study was performed to estimate the pharmacophoric features and binding conformation of isolated compounds in the acetyl cholinesterase active site. Georg Thieme Verlag KG Stuttgart · New York.

Bacteriological profiling of diphenylureas as a novel class of antibiotics against methicillin-resistant Staphylococcus aureus

PubMed Central

Younis, Waleed; Ezzat, Hany G.; Peters, Christine E.; AbdelKhalek, Ahmed; Cooper, Bruce; Pogliano, Kit; Pogliano, Joe; Mayhoub, Abdelrahman S.; Seleem, Mohamed N.

2017-01-01

Bacterial resistance to antibiotics remains an imposing global public health challenge. Of the most serious pathogens, methicillin-resistant Staphylococcus aureus (MRSA) is problematic given strains have emerged that exhibit resistance to several antibiotic classes including β-lactams and agents of last resort such as vancomycin. New antibacterial agents composed of unique chemical scaffolds are needed to counter this public health challenge. The present study examines two synthetic diphenylurea compounds 1 and 2 that inhibit growth of clinically-relevant isolates of MRSA at concentrations as low as 4 µg/mL and are non-toxic to human colorectal cells at concentrations up to 128 μg/mL. Both compounds exhibit rapid bactericidal activity, completely eliminating a high inoculum of MRSA within four hours. MRSA mutants exhibiting resistance to 1 and 2 could not be isolated, indicating a low likelihood of rapid resistance emerging to these compounds. Bacterial cytological profiling revealed the diphenylureas exert their antibacterial activity by targeting bacterial cell wall synthesis. Both compounds demonstrate the ability to resensitize vancomycin-resistant Staphylococcus aureus to the effect of vancomycin. The present study lays the foundation for further investigation and development of diphenylurea compounds as a new class of antibacterial agents. PMID:28797064

Discovery of potent and selective cytotoxic activity of new quinazoline-ureas against TMZ-resistant glioblastoma multiforme (GBM).

PubMed

Elkamhawy, Ahmed; Viswanath, Ambily Nath Indu; Pae, Ae Nim; Kim, Hyeon Young; Heo, Jin-Chul; Park, Woo-Kyu; Lee, Chong-Ock; Yang, Heekyoung; Kim, Kang Ho; Nam, Do-Hyun; Seol, Ho Jun; Cho, Heeyeong; Roh, Eun Joo

2015-10-20

Herein, we report new quinazoline-urea based compounds with potent cytotoxic activities against TMZ-resistant glioblastoma multiforme (GBM) cells. Low micromolar IC₅₀ values were exhibited over a panel of three primary GBM patient-derived cell cultures belonging to proneural (GBM-1), mesenchymal (GBM-2), and classical (GBM-3) subtypes. Eight compounds showed excellent selectivity indices for GBM cells comparing to a normal astrocyte cell line. In JC-1 assay, analogues 11, 12, 20, 22, and 24 exerted promising rates of mPTP opening induction towards proneural GBM subtype. Compounds 11, 20, and 24 bound to the translocator protein 18 kDa (TSPO) in submicromolar range using [(3)H] PK-11195 binding affinity assay. A homology model was built and docked models of 11, 12, 20, 22 and 24 were generated for describing their plausible binding modes in TSPO. In 3D clonogenic assay, compound 20 manifested potent tumoricidal effects on TMZ-resistant GBM cells even at submicromolar concentrations. In addition, CYP450 and hERG assays presented a safe toxicity profile of 20. Taken as a whole, this report presents compound 20 as a potent, selective and safe GBM cytotoxic agent which constitutes a promising direction against TMZ-resistant GBM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Characterization of the Key Aroma Volatile Compounds in Cranberry (Vaccinium macrocarpon Ait.) Using Gas Chromatography-Olfactometry (GC-O) and Odor Activity Value (OAV).

PubMed

Zhu, JianCai; Chen, Feng; Wang, LingYing; Niu, YunWei; Chen, HeXing; Wang, HongLin; Xiao, ZuoBing

2016-06-22

The volatile compounds of cranberries obtained from four cultivars (Early Black, Y1; Howes, Y2; Searles, Y3; and McFarlin, Y4) were analyzed by gas chromatography-olfactometry (GC-O), gas chromatography-mass spectrometry (GC-MS), and GC-flame photometric detection (FPD). The result presented that a total of thirty-three, thirty-four, thirty-four, and thirty-six odor-active compounds were identified by GC-O in the Y1, Y2, Y3, and Y4, respectively. In addition, twenty-two, twenty-two, thirty, and twenty-seven quantified compounds were demonstrated as important odorants according to odor activity values (OAVs > 1). Among these compounds, hexanal (OAV: 27-60), pentanal (OAV: 31-51), (E)-2-heptenal (OAV: 17-66), (E)-2-hexenal (OAV: 18-63), (E)-2-octenal (OAV: 10-28), (E)-2-nonenal (OAV: 8-77), ethyl 2-methylbutyrate (OAV: 10-33), β-ionone (OAV: 8-73), 2-methylbutyric acid (OAV: 18-37), and octanal (OAV: 4-24) contributed greatly to the aroma of cranberry. Partial least-squares regression (PLSR) was used to process the mean data accumulated from sensory evaluation by the panelists, odor-active aroma compounds (OAVs > 1), and samples. Sample Y3 was highly correlated with the sensory descriptors "floral" and "fruity". Sample Y4 was greatly related to the sensory descriptors "mellow" and "green and grass". Finally, an aroma reconstitution (Model A) was prepared by mixing the odor-active aroma compounds (OAVs > 1) based on their measured concentrations in the Y1 sample, indicating that the aroma profile of the reconstitution was pretty similar to that of the original sample.

Discovery of a novel and potent class of F. tularensis enoyl-reductase (FabI) inhibitors by molecular shape and electrostatic matching

PubMed Central

Hevener, Kirk E.; Mehboob, Shahila; Su, Pin-Chih; Truong, Kent; Boci, Teuta; Deng, Jiangping; Ghassemi, Mahmood; Cook, James L.; Johnson, Michael E.

2011-01-01

Enoyl-acyl carrier protein (ACP) reductase, FabI, is a key enzyme in the bacterial fatty acid biosynthesis pathway (FAS II). FabI is an NADH-dependent oxidoreductase that acts to reduce enoyl-ACP substrates in a final step of the pathway. The absence of this enzyme in humans makes it an attractive target for the development of new antibacterial agents. FabI is known to be unresponsive to structure-based design efforts due to a high degree of induced fit and a mobile flexible loop encompassing the active site. Here we discuss the development, validation, and careful application of a ligand-based virtual screen used for the identification of novel inhibitors of the Francisella tularensis FabI target. In this study, four known classes of FabI inhibitors were used as templates for virtual screens that involved molecular shape and electrostatic matching. The program ROCS was used to search a high-throughput screening library for compounds that matched any of the four molecular shape queries. Matching compounds were further refined using the program EON, which compares and scores compounds by matching electrostatic properties. Using these techniques, 50 compounds were selected, ordered, and tested. The tested compounds possessed novel chemical scaffolds when compared to the input query compounds. Several hits with low micromolar activity were identified and follow-up scaffold-based searches resulted in the identification of a lead series with sub-micromolar enzyme inhibition, high ligand efficiency, and a novel scaffold. Additionally, one of the most active compounds showed promising whole-cell antibacterial activity against several Gram-positive and Gram-negative species, including the target pathogen. The results of a preliminary structure-activity relationship analysis are presented. PMID:22098466

Betulin derivatives impair Leishmania braziliensis viability and host-parasite interaction.

PubMed

Alcazar, Wilmer; López, Adrian Silva; Alakurtti, Sami; Tuononen, Maija-Liisa; Yli-Kauhaluoma, Jari; Ponte-Sucre, Alicia

2014-11-01

Leishmaniasis is a public health problem in tropical and subtropical areas of the world, including Venezuela. The incidence of treatment failure and the number of cases with Leishmania-HIV co-infection underscore the importance of developing alternative, economical and effective therapies against this disease. The work presented here analyzed whether terpenoids derived from betulin are active against New World Leishmania parasites. Initially we determined the concentration that inhibits the growth of these parasites by 50% or IC50, and subsequently evaluated the chemotactic effect of four compounds with leishmanicidal activity in the sub-micromolar and micromolar range. That is, we measured the migratory capacity of Leishmania (V.) braziliensis in the presence of increasing concentrations of compounds. Finally, we evaluated their cytotoxicity against the host cell and their effect on the infectivity of L. (V.) braziliensis. The results suggest that (1) compounds 14, 17, 18, 25 and 27 are active at concentrations lower than 10 μM; (2) compound 26 inhibits parasite growth with an IC50 lower than 1 μM; (3) compounds 18, 26 and 27 inhibit parasite migration at pico- to nanomolar concentrations, suggesting that they impair host-parasite interaction. None of the tested compounds was cytotoxic against J774.A1 macrophages thus indicating their potential as starting points to develop compounds that might affect parasite-host cell interaction, as well as being leishmanicidal. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of 6-chloro-N-[3,4-disubstituted-1,3-thiazol-2(3H)-ylidene]-1,3-benzothiazol-2-amine Using Drug Design Concept for Their Targeted Activity Against Colon Cancer Cell Lines HCT-116, HCT15, and HT29.

PubMed

Zhu, Ming-Li; Wang, Cui-Yue; Xu, Cheng-Mian; Bi, Wei-Ping; ZHou, Xiu-Ying

2017-03-05

BACKGROUND Colorectal adenocarcinoma is the second leading cause of cancer-related death in the world. The stage of the disease is related to the survival of the patient, and in early phases surgery is the main modality of treatment. The main aim of modern medicinal chemistry is to synthesize small molecules via drug designing, especially by targeting tumor cells. MATERIAL AND METHODS A new series of 19 compounds containing benzothiazole and thiazole were designed. Molecular docking studies were performed on the designed series of molecules. Compounds showing good binding affinity towards the EGFR receptor were selected for synthetic studies. Characterization of the synthesized compounds was done by FTIR, 1HNMR, Mass and C, H, N, analysis. RESULTS The anticancer evaluation of the synthesized compounds was done at NIC, USA at a single dose against colon cancer cell lines HCT 116, HCT15, and HC 29. The active compounds were further evaluated for the 5-dose testing. Compounds were designed by using docking analysis. To ascertain the interaction of EGFR tyrosine kinase binding, energy calculation was used. CONCLUSIONS The results of the present study indicate that the designed compounds show good activity against colon cancer cell lines, which may be further studied to design new potential molecules.

Design, synthesis and biological assessment of new thiazolylhydrazine derivatives as selective and reversible hMAO-A inhibitors.

PubMed

Can, Nafiz Öncü; Osmaniye, Derya; Levent, Serkan; Sağlık, Begüm Nurpelin; Korkut, Büşra; Atlı, Özlem; Özkay, Yusuf; Kaplancıklı, Zafer Asım

2018-01-20

In the recent works, it was shown that numerous thiazolylhydrazine derivatives display hMAO inhibitory activity in the range of micromolar concentration. Hence, in the present study a new series of new thiazole-hydrazines (3a-3n) were designed, synthesized, characterized and screened for their hMAO-A and hMAO-B inhibitory activity by an in vitro flurometric method. The enzyme inhibition assay revealed that most of the synthesized compounds have selective inhibition potency against hMAO-A. The compounds 3f and 3h showed promising hMAO-A inhibition with an IC 50 values of 0.012 μM and 0.011 μM and significant selectivity indexes of 1214 and 1601 towards hMAO-A, respectively. The mechanism of hMAO-A inhibition of compounds 3f and 3h was investigated by Lineweaver-Burk graphics and reversible-competitive inhibition of hMAO-A was determined. Cytotoxicity and genotoxicity studies were carried out and the compound 3h was found as non-cytotoxic and non-genotoxic. Theoretical calculation of ADME properties suggested that synthesized compounds may have a good pharmacokinetic profile. The docking study of compound 3f and 3h revealed that there is a strong interaction between the active sites of hMAO-A and analyzed compound. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Beneficial Effects of Marine Algal Compounds in Cosmeceuticals

PubMed Central

Thomas, Noel Vinay; Kim, Se-Kwon

2013-01-01

The name “cosmeceuticals” is derived from “cosmetics and pharmaceuticals”, indicating that a specific product contains active ingredients. Marine algae have gained much importance in cosmeceutical product development due to their rich bioactive compounds. In the present review, marine algal compounds (phlorotannins, sulfated polysaccharides and tyrosinase inhibitors) have been discussed toward cosmeceutical application. In addition, atopic dermatitis and the possible role of matrix metalloproteinase (MMP) in skin-related diseases have been explored extensively for cosmeceutical products. The proper development of marine algae compounds will be helpful in cosmeceutical product development and in the development of the cosmeceutical industry. PMID:23344156

Synthesis and P-glycoprotein induction activity of colupulone analogs.

PubMed

Bharate, Jaideep B; Batarseh, Yazan S; Wani, Abubakar; Sharma, Sadhana; Vishwakarma, Ram A; Kaddoumi, Amal; Kumar, Ajay; Bharate, Sandip B

2015-05-21

Brain amyloid-beta (Aβ) plaques are one of the primary hallmarks associated with Alzheimer's disease (AD) pathology. Efflux pump proteins located at the blood-brain barrier (BBB) have been reported to play an important role in the clearance of brain Aβ, among which the P-glycoprotein (P-gp) efflux transporter pump has been shown to play a crucial role. Thus, P-gp has been considered as a potential therapeutic target for treatment of AD. Colupulone, a prenylated phloroglucinol isolated from Humulus lupulus, is known to activate pregnane-X-receptor (PXR), which is a nuclear receptor controlling P-gp expression. In the present work, we aimed to synthesize and identify analogs of colupulone that are potent P-gp inducer(s) with an ability to enhance Aβ transport across the BBB. A series of colupulone analogs were synthesized by modifications at both prenyl as well as acyl domains. All compounds were screened for P-gp induction activity using a rhodamine 123 based efflux assay in the P-gp overexpressing human adenocarcinoma LS-180 cells, wherein all compounds showed significant P-gp induction activity at 5 μM. In the western blot studies in LS-180 cells, compounds 3k and 5f were able to induce P-gp as well as LRP1 at 1 μM. The effect of compounds on the Aβ uptake and transport was then evaluated. Among all tested compounds, diprenylated acyl phloroglucinol displayed a significant increase (29%) in Aβ transport across bEnd3 cells grown on inserts as a BBB model. The results presented here suggest the potential of this scaffold to enhance clearance of brain Aβ across the BBB and thus its promise for development as a potential anti-Alzheimer agent.

Isolation of quercetin from the methanolic extract of Lagerstroemia speciosa by HPLC technique, its cytotoxicity against MCF-7 cells and photocatalytic activity.

PubMed

Sai Saraswathi, V; Saravanan, D; Santhakumar, K

2017-06-01

The flavonoids present in the leaves of Lagerstroemia speciosa were extracted, characterized by spectral methods and studied for its cytotoxicity activity against MCF-cell lines and photocatalytic activity against azo dye. Direct and sequential soxhlet extraction was performed and its concentrated crude extract was subjected to high performance liquid chromatography. The yield obtained by the isolated compound (MEI-quercetin) from leaves of L. speciosa was found to be 1.8g from the methanolic extract. The phytochemical analysis and the Rf value of the isolated flavonoid was found to be 3.59. The isolated compound was characterized by Infrared Spectroscopy, NMR and Mass. Based on the characterization, the structure was elucidated as quercetin - a flavonoid. The isolated compound showed the significant in vitro cytotoxicity activity against MCF-7 cell lines at 500μg/ml when compared to the crude extract. Among the various concentrations (25, 50, 100, 250, and 500μg/ml), at higher concentration the cell viability was pronounced and also compared with that of the control. It was first time to report that the isolated flavonoid showed photocatalytic against azo dye-methyl orange. The dye degradation was monitored by UV-Vis spectrophotometry. The isolated compound showed dye degradation of 91.66% with the crude extract 82.47% at 160min. Hence in the present findings, the photocatalytic degradation of MO dye under UV irradiation was investigated over isolated compound of L. speciosa. Hence we expect that this can be used to treat the waste water in near future based on the photocatalytic technique. Copyright © 2017 Elsevier B.V. All rights reserved.

Biomimetic synthesis, antimicrobial, antileishmanial and antimalarial activities of euglobals and their analogues.

PubMed

Bharate, Sandip B; Bhutani, Kamlesh K; Khan, Shabana I; Tekwani, Babu L; Jacob, Melissa R; Khan, Ikhlas A; Singh, Inder Pal

2006-03-15

In the present communication, naturally occurring phloroglucinol-monoterpene adducts, euglobals G1-G4 (3b/a and 4a/b) and 16 new analogues (13a/b-18a/b and 19-22) were synthesized by biomimetic approach. These synthetic compounds differ from natural euglobals in the nature of monoterpene and acyl functionality. All of these compounds were evaluated for their antibacterial, antifungal, antileishmanial and antimalarial activities. Analogue 17b possessed good antibacterial activity against methicillin-resistant Staphylococcus aureus, while analogues 19-22 possessed potent antifungal activity against Candida glabrata with IC50s ranging from 1.5 to 2.5 microg/mL. Euglobals along with all synthesized analogues exhibited antileishmanial activity. Amongst these, euglobal G2 (3a), G3 (4a) and analogues 13a and 14a showed potent antileishmanial activity with IC50s ranging from 2.8 to 3.9 microg/mL. Analogue 16a possessed antimalarial activity against chloroquine sensitive D6 clone of Plasmodium falciparum. None of the compounds showed toxicity against mammalian kidney fibroblasts (vero cells) upto the concentration of 4.76 microg/ml.

Anti-inflammatory properties of clovamide and Theobroma cacao phenolic extracts in human monocytes: evaluation of respiratory burst, cytokine release, NF-κB activation, and PPARγ modulation.

PubMed

Zeng, Huawu; Locatelli, Monica; Bardelli, Claudio; Amoruso, Angela; Coisson, Jean Daniel; Travaglia, Fabiano; Arlorio, Marco; Brunelleschi, Sandra

2011-05-25

There is a great interest in the potential health benefits of biologically active phenolic compounds in cocoa (Theobroma cacao) and dark chocolate. We investigated the anti-inflammatory potential of clovamide (a N-phenylpropenoyl-L-amino acid amide present in cocoa beans) and two phenolic extracts from unroasted and roasted cocoa beans, by evaluating superoxide anion (O(2)(-)) production, cytokine release, and NF-κB activation in human monocytes stimulated by phorbol 12-myristate 13-acetate (PMA). The effects of rosmarinic acid are shown for comparison. Clovamide and rosmarinic acid inhibited PMA-induced O(2)(-) production and cytokine release (with a bell-shaped curve and maximal inhibition at 10-100 nM), as well as PMA-induced NF-κB activation; the two cocoa extracts were less effective. In all tests, clovamide was the most potent compound and also enhanced peroxisome proliferator-activated receptor-γ (PPARγ) activity, which may exert anti-inflammatory effects. These findings indicate clovamide as a possible bioactive compound with anti-inflammatory activity in human cells.

Procaspase-activating compound 1 induces a caspase-3-dependent cell death in cerebellar granule neurons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aziz, Gulzeb; Akselsen, Oyvind W.; Hansen, Trond V.

2010-09-15

Procaspase-activating compound 1, PAC-1, has been introduced as a direct activator of procaspase-3 and has been suggested as a therapeutic agent against cancer. Its activation of procaspase-3 is dependent on the chelation of zinc. We have tested PAC-1 and an analogue of PAC-1 as zinc chelators in vitro as well as their ability to activate caspase-3 and induce cell death in chicken cerebellar granule neuron cultures. These neurons are non-dividing, primary cells with normal caspase-3. The results reported herein show that PAC-1 chelates zinc, activates procaspase-3, and leads to caspase-3-dependent cell death in neurons, as the specific caspase-3-inhibitor Ac-DEVD-cmk inhibitedmore » both the caspase-3 activity and cell death. Thus, chicken cerebellar granule neurons is a suitable model to study mechanisms of interference with apoptosis of PAC-1 and similar compounds. Furthermore, the present study also raises concern about potential neurotoxicity of PAC-1 if used in cancer therapy.« less

Characterization of ToxCast Phase II compounds disruption of spontaneous network activity in cortical networks grown on multi-well microelectrode array (mwMEA) plates.

EPA Science Inventory

The development of multi-well microelectrode array (mwMEA) systems has increased in vitro screening throughput making them an effective method to screen and prioritize large sets of compounds for potential neurotoxicity. In the present experiments, a multiplexed approach was used...

Novel pregnenolone derivatives modulate apoptosis via Bcl-2 family genes in hepatocellular carcinoma in vitro.

PubMed

Elhinnawi, Manar A; Mohareb, Rafat M; Rady, Hanaa M; Khalil, Wagdy K B; Abd Elhalim, Mervat M; Elmegeed, Gamal A

2018-06-10

A series of pregnenolone derivatives were synthesized and assessed for anti-cancer activity against hepatocellular carcinoma cell line (HepG2). The synthesized hetero-steroids (compounds 3, 4, 5, 6, 7, 8a and 8b) were evaluated for their cytotoxic activities using MTT (3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide) assay. Apoptotic activity was assessed using dual acridine orange/ethidium bromide staining method and DNA fragmentation assay. Pro-apoptotic genes (Bax and Bak) and anti-apoptotic genes (Bcl-2 and Bcl-xL) were analyzed using quantitative real time PCR. The results revealed that compounds 4 and 6 displayed cytotoxic activity (IC 50s , 36.97 ± 2.18 and 18.46 ± 0.64 µM, respectively), while compounds 5 and 7 exhibited weak cytotoxic activity (IC 50s , 93.87 ± 8.30 µM and 93.48 ± 4.14 µM, respectively). All synthesized heterocyclic pregnenolone derivatives induced apoptosis through DNA fragmentation. Compounds 4 and 6 increased early and late apoptotic cell percentages while compounds 3, 5, 7 and 8b increased either early or late apoptotic cell percentage. Moreover, compounds 3, 6 and 8b up-regulated the expression level of Bak gene. On the other hand, compounds 4, 5, 7 and 8a down-regulated the Bcl-2 expression level, besides, compounds 5, 7 and 8a down-regulated the Bcl-xL expression level. Compounds 5, 7, 8a and 8b increased the Bak/Bcl-xL ratio, besides, compound 8a raised the Bax/Bcl-xL ratio whereas compound 5 elevated Bax/Bcl-2 and Bak/Bcl-2 ratios. The present work introduced novel pro-apoptotic pregnenolone derivatives that acted against HepG2 cells through DNA fragmentation, apoptotic morphological changes and were able to increase the pro-apoptotic/anti-apoptotic ratios of Bcl-2 family genes. This study particularly revealed that the cytotoxic compound 4 is the most promising pro-apoptotic compound among other synthesized derivatives where it induced apoptosis (late and early) through the down-regulation of Bcl-2 gene expression level. Copyright © 2018 Elsevier Ltd. All rights reserved.

In Vitro Wound Healing Potential and Identification of Bioactive Compounds from Moringa oleifera Lam

PubMed Central

Muhammad, Abubakar Amali; Pauzi, Nur Aimi Syarina; Arulselvan, Palanisamy; Abas, Faridah; Fakurazi, Sharida

2013-01-01

Moringa oleifera Lam. (M. oleifera) from the monogeneric family Moringaceae is found in tropical and subtropical countries. The present study was aimed at exploring the in vitro wound healing potential of M. oleifera and identification of active compounds that may be responsible for its wound healing action. The study included cell viability, proliferation, and wound scratch test assays. Different solvent crude extracts were screened, and the most active crude extract was further subjected to differential bioguided fractionation. Fractions were also screened and most active aqueous fraction was finally obtained for further investigation. HPLC and LC-MS/MS analysis were used for identification and confirmation of bioactive compounds. The results of our study demonstrated that aqueous fraction of M. oleifera significantly enhanced proliferation and viability as well as migration of human dermal fibroblast (HDF) cells compared to the untreated control and other fractions. The HPLC and LC-MS/MS studies revealed kaempferol and quercetin compounds in the crude methanolic extract and a major bioactive compound Vicenin-2 was identified in the bioactive aqueous fraction which was confirmed with standard Vicenin-2 using HPLC and UV spectroscopic methods. These findings suggest that bioactive fraction of M. oleifera containing Vicenin-2 compound may enhance faster wound healing in vitro. PMID:24490175

Characterization of anticancer agents by their growth inhibitory activity and relationships to mechanism of action and structure.

PubMed

Keskin, O; Bahar, I; Jernigan, R L; Beutler, J A; Shoemaker, R H; Sausville, E A; Covell, D G

2000-04-01

An analysis of the growth inhibitory potency of 122 anticancer agents available from the National Cancer Institute anticancer drug screen is presented. Methods of singular value decomposition (SVD) were applied to determine the matrix of distances between all compounds. These SVD-derived dissimilarity distances were used to cluster compounds that exhibit similar tumor growth inhibitory activity patterns against 60 human cancer cell lines. Cluster analysis divides the 122 standard agents into 25 statistically distinct groups. The first eight groups include structurally diverse compounds with reactive functionalities that act as DNA-damaging agents while the remaining 17 groups include compounds that inhibit nucleic acid biosynthesis and mitosis. Examination of the average activity patterns across the 60 tumor cell lines reveals unique 'fingerprints' associated with each group. A diverse set of structural features are observed for compounds within these groups, with frequent occurrences of strong within-group structural similarities. Clustering of cell types by their response to the 122 anticancer agents divides the 60 cell types into 21 groups. The strongest within-panel groupings were found for the renal, leukemia and ovarian cell panels. These results contribute to the basis for comparisons between log(GI(50)) screening patterns of the 122 anticancer agents and additional tested compounds.

β-lactam substituted polycyclic fused pyrrolidine/pyrrolizidine derivatives eradicate C. albicans in an ex vivo human dentinal tubule model by inhibiting sterol 14-α demethylase and cAMP pathway.

PubMed

Gowri, Meiyazhagan; Sofi Beaula, Winfred; Biswal, Jayashree; Dhamodharan, Prabhu; Saiharish, Raghavan; Rohan prasad, Surabi; Pitani, Ravishankar; Kandaswamy, Deivanayagam; Raghunathan, Ragavachary; Jeyakanthan, Jeyaraman; Rayala, Suresh K; Venkatraman, Ganesh

2016-04-01

Further quest for new anti-fungal compounds with proven mechanisms of action arises due to resistance and dose limiting toxicity of existing agents. Among the human fungal pathogens C. albicans predominate by infecting several sites in the body and in particular oral cavity and root canals of human tooth. In the present study, we screened a library of β-lactam substituted polycyclic fused pyrrolidine/pyrrolizidine compounds against Candida sp. Detailed molecular studies were carried out with the active compound 3 on C. albicans. Morphological damage and antibiofilm activity of compound 3 on C. albicans was studied using scanning electron microscopy (SEM). Biochemical evidence for membrane damage was studied using flow cytometry. In silico docking studies were carried out to elucidate the mechanism of action of compound 3. Further, the antifungal activity of compound 3 was evaluated in an ex vivo dentinal tubule infection model. Screening data showed that several new compounds were active against Candida sp. Among them, Compound 3 was most potent and exerted time kill effect at 4h, post antifungal effect up to 6h. When used in combination with fluconazole or nystatin, compound 3 revealed an minimum inhibitory concentration (MIC) decrease by 4 fold for both drugs used. In-depth molecular studies with compound 3 on C. albicans showed that this compound inhibited yeast to hyphae (Y-H) conversion and this involved the cAMP pathway. Further, SEM images of C. albicans showed that compound 3 caused membrane damage and inhibited biofilm formation. Biochemical evidence for membrane damage was confirmed by increased propidium iodide (PI) uptake in flow cytometry. Further, in silico studies revealed that compound 3 docks with the active site of the key enzyme 14-α-demethylase and this might inhibit ergosterol synthesis. In support of this, ergosterol levels were found to be decreased by 32 fold in compound 3 treated samples as analyzed by high performance liquid chromatography (HPLC). Further, the antifungal activity of compound 3 was evaluated in an ex vivo dentinal tubule infection model, which mimics human tooth root canal infection. Confocal laser scanning microscopy studies showed 83% eradication of C. albicans and a 6 log reduction in colony forming unit (CFU) after 24h treatment in the infected tooth samples in this model. Compound 3 was found to be very effective in eradicating C. albicans by inhibiting cAMP pathway and ergosterol biosynthesis. The results of this study can pave the way for developing new antifungal agents with well deciphered mechanisms of action and can be a promising antifungal agent or medicament against root canal infection. Copyright © 2015 Elsevier B.V. All rights reserved.

QSAR Accelerated Discovery of Potent Ice Recrystallization Inhibitors

NASA Astrophysics Data System (ADS)

Briard, Jennie G.; Fernandez, Michael; de Luna, Phil; Woo, Tom. K.; Ben, Robert N.

2016-05-01

Ice recrystallization is the main contributor to cell damage and death during the cryopreservation of cells and tissues. Over the past five years, many small carbohydrate-based molecules were identified as ice recrystallization inhibitors and several were shown to reduce cryoinjury during the cryopreservation of red blood cells (RBCs) and hematopoietic stems cells (HSCs). Unfortunately, clear structure-activity relationships have not been identified impeding the rational design of future compounds possessing ice recrystallization inhibition (IRI) activity. A set of 124 previously synthesized compounds with known IRI activities were used to calibrate 3D-QSAR classification models using GRid INdependent Descriptors (GRIND) derived from DFT level quantum mechanical calculations. Partial least squares (PLS) model was calibrated with 70% of the data set which successfully identified 80% of the IRI active compounds with a precision of 0.8. This model exhibited good performance in screening the remaining 30% of the data set with 70% of active additives successfully recovered with a precision of ~0.7 and specificity of 0.8. The model was further applied to screen a new library of aryl-alditol molecules which were then experimentally synthesized and tested with a success rate of 82%. Presented is the first computer-aided high-throughput experimental screening for novel IRI active compounds.

Dillapiole as antileishmanial agent: discovery, cytotoxic activity and preliminary SAR studies of dillapiole analogues.

PubMed

Parise-Filho, Roberto; Pasqualoto, Kerly Fernanda Mesquita; Magri, Fátima Maria Motter; Ferreira, Adilson Kleber; da Silva, Bárbara Athayde Vaz Galvão; Damião, Mariana Celestina Frojuello Costa Bernstorff; Tavares, Maurício Temotheo; Azevedo, Ricardo Alexandre; Auada, Aline Vivian Vatti; Polli, Michelle Carneiro; Brandt, Carlos Alberto

2012-12-01

In this paper, the isolation of dillapiole (1) from Piper aduncum was reported as well as the semi-synthesis of two phenylpropanoid derivatives [di-hydrodillapiole (2), isodillapiole (3)], via reduction and isomerization reactions. Also, the compounds' molecular properties (structural, electronic, hydrophobic, and steric) were calculated and investigated to establish some preliminary structure-activity relationships (SAR). Compounds were evaluated for in vitro antileishmanial activity and cytotoxic effects on fibroblast cells. Compound 1 presented inhibitory activity against Leishmania amazonensis (IC(50)  = 69.3 µM) and Leishmania brasiliensis (IC(50)  = 59.4 µM) and induced cytotoxic effects on fibroblast cells mainly in high concentrations. Compounds 2 (IC(50)  = 99.9 µM for L. amazonensis and IC(50)  = 90.5 µM for L. braziliensis) and 3 (IC(50)  = 122.9 µM for L. amazonensis and IC(50)  = 109.8 µM for L. brasiliensis) were less active than dillapiole (1). Regarding the molecular properties, the conformational arrangement of the side chain, electronic features, and the hydrophilic/hydrophobic balance seem to be relevant for explaining the antileishmanial activity of dillapiole and its analogues. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Variation of antioxidant activity and the levels of bioactive compounds in lipophilic and hydrophilic extracts from hot pepper (Capsicum spp.) cultivars.

PubMed

Bae, Haejin; Jayaprakasha, G K; Jifon, John; Patil, Bhimanagouda S

2012-10-15

Peppers (Capsicum spp.) are a rich source of diverse bioactive compounds with potential health-promoting properties. This study investigated the extraction efficiency of five solvents on antioxidant activities from cayenne (CA408 and Mesilla), jalapeño (Ixtapa) and serrano (Tuxtlas) pepper cultivars. Freeze-dried peppers were extracted using a Soxhlet extractor with five solvents: hexane, ethyl acetate, acetone, methanol, and methanol:water (80:20). The levels of specific bioactive compounds (phenolics, capsaicinoids, carotenoids and flavonoids) were determined by HPLC and antioxidant activities were assayed by three methods. For all pepper cultivars tested, hexane extracts had the highest levels of capsaicinoids and carotenoids, but methanol extracts had the maximum levels of flavonoids. Hexane extracts showed higher 2,2-diphenyl-1-pricrylhydrozyl (DPPH) radical-scavenging activity and higher reducing power, and acetone extracts (from Mesilla pepper) had a high reducing power. All pepper extracts, except hexane, were effective in preventing deoxyribose degradation, and the inhibition was increased by high concentrations of extracts. The results of the present study indicated that, among the different measures of antioxidant activity, DPPH radical-scavenging activity was strongly correlated with total bioactive compounds (capsaicinoids, carotenoids, flavonoids and total phenolics) in pepper cultivars. Copyright © 2012 Elsevier Ltd. All rights reserved.

QSAR Accelerated Discovery of Potent Ice Recrystallization Inhibitors

PubMed Central

Briard, Jennie G.; Fernandez, Michael; De Luna, Phil; Woo, Tom. K.; Ben, Robert N.

2016-01-01

Ice recrystallization is the main contributor to cell damage and death during the cryopreservation of cells and tissues. Over the past five years, many small carbohydrate-based molecules were identified as ice recrystallization inhibitors and several were shown to reduce cryoinjury during the cryopreservation of red blood cells (RBCs) and hematopoietic stems cells (HSCs). Unfortunately, clear structure-activity relationships have not been identified impeding the rational design of future compounds possessing ice recrystallization inhibition (IRI) activity. A set of 124 previously synthesized compounds with known IRI activities were used to calibrate 3D-QSAR classification models using GRid INdependent Descriptors (GRIND) derived from DFT level quantum mechanical calculations. Partial least squares (PLS) model was calibrated with 70% of the data set which successfully identified 80% of the IRI active compounds with a precision of 0.8. This model exhibited good performance in screening the remaining 30% of the data set with 70% of active additives successfully recovered with a precision of ~0.7 and specificity of 0.8. The model was further applied to screen a new library of aryl-alditol molecules which were then experimentally synthesized and tested with a success rate of 82%. Presented is the first computer-aided high-throughput experimental screening for novel IRI active compounds. PMID:27216585

QSAR Accelerated Discovery of Potent Ice Recrystallization Inhibitors.

PubMed

Briard, Jennie G; Fernandez, Michael; De Luna, Phil; Woo, Tom K; Ben, Robert N

2016-05-24

Ice recrystallization is the main contributor to cell damage and death during the cryopreservation of cells and tissues. Over the past five years, many small carbohydrate-based molecules were identified as ice recrystallization inhibitors and several were shown to reduce cryoinjury during the cryopreservation of red blood cells (RBCs) and hematopoietic stems cells (HSCs). Unfortunately, clear structure-activity relationships have not been identified impeding the rational design of future compounds possessing ice recrystallization inhibition (IRI) activity. A set of 124 previously synthesized compounds with known IRI activities were used to calibrate 3D-QSAR classification models using GRid INdependent Descriptors (GRIND) derived from DFT level quantum mechanical calculations. Partial least squares (PLS) model was calibrated with 70% of the data set which successfully identified 80% of the IRI active compounds with a precision of 0.8. This model exhibited good performance in screening the remaining 30% of the data set with 70% of active additives successfully recovered with a precision of ~0.7 and specificity of 0.8. The model was further applied to screen a new library of aryl-alditol molecules which were then experimentally synthesized and tested with a success rate of 82%. Presented is the first computer-aided high-throughput experimental screening for novel IRI active compounds.

Activated persulfate for organic chemical degradation: A review.

PubMed

Matzek, Laura W; Carter, Kimberly E

2016-05-01

Activated persulfate reactions have widespread application for groundwater and environmental remediation, as many of these reactions involve destruction of environmental contaminants. Within the last five years, knowledge of activated persulfate degradation reactions has grown to include novel means of activating persulfate for enhanced removal of organic species. These current studies cover a long list of organic analytes, including pharmaceuticals, pesticides, halogenated compounds and dyes. An extensive review of recently published experimental parameters and results for the destruction of organic compounds via activated persulfate is presented. Focus is placed on emerging methodologies and manipulation of traditional activation techniques. Knowledge gaps are identified and discussed, as despite the number of publications on this subject, more broad-reaching guidelines are needed for optimizing applications of activated persulfate in water treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Superoxide radical-generating compounds activate a predicted promoter site for paraquat-inducible genes of the Chromobacterium violaceum bacterium in a dose-dependent manner.

PubMed

Gabriel, J E; Guerra-Slompo, E P; de Souza, E M; de Carvalho, F A L; Madeira, H M F; de Vasconcelos, A T R

2015-08-21

The purpose of the present study was to functionally evaluate the influence of superoxide radical-generating compounds on the heterologous induction of a predicted promoter region of open reading frames for paraquat-inducible genes (pqi genes) revealed during genome annotation analyses of the Chromobacterium violaceum bacterium. A 388-bp fragment corresponding to a pqi gene promoter of C. violaceum was amplified using specific primers and cloned into a conjugative vector containing the Escherichia coli lacZ gene without a promoter. Assessments of the expression of the β-galactosidase enzyme were performed in the presence of menadione (MEN) and phenazine methosulfate (PMS) compounds at different final concentrations to evaluate the heterologous activation of the predicted promoter region of interest in C. violaceum induced by these substrates. Under these experimental conditions, the MEN reagent promoted highly significant increases in the expression of the β-galactosidase enzyme modulated by activating the promoter region of the pqi genes at all concentrations tested. On the other hand, significantly higher levels in the expression of the β-galactosidase enzyme were detected exclusively in the presence of the PMS reagent at a final concentration of 50 μg/mL. The findings described in the present study demonstrate that superoxide radical-generating compounds can activate a predicted promoter DNA motif for pqi genes of the C. violaceum bacterium in a dose-dependent manner.

Effects of Phytochemically Characterized Extracts From Syringa vulgaris and Isolated Secoiridoids on Mediators of Inflammation in a Human Neutrophil Model.

PubMed

Woźniak, Marta; Michalak, Barbara; Wyszomierska, Joanna; Dudek, Marta K; Kiss, Anna K

2018-01-01

Aim of the study: The aim of the present study was to investigate the effects of phytochemically characterized extracts connected with the traditional use (infusions and ethanolic extracts) of different parts of Syringa vulgaris (common lilac) on the pro-inflammatory functions of neutrophils. Active compounds were isolated from the most promising extract(s) using bioassay-guided fractionation, and their activity and molecular mechanisms of action were determined. Methods: The extracts were characterized using a HPLC-DAD- MS n method. The effects on ROS, MMP-9, TNF-α, IL-8, and MCP-1 production by neutrophils were measured using luminol-dependent chemiluminescence and enzyme-linked immunosorbent assay (ELISA) methods. The effects on p38MAPK, ERK1/2, JNK phosphorylation, and NF- k B p65 translocation were determined using western blots. Results: The major compounds detected in the extracts and infusions belong to structural groups, including caffeic acid derivatives, flavonoids, and iridoids. All extracts and infusions were able to significantly reduce ROS and IL-8 production. Bioassay-guided fractionation led to the isolation of the following secoiridoids: 2″-epiframeroside, oleonuezhenide, oleuropein, ligstroside, neooleuropein, hydroxyframoside, and framoside. Neooleuropein appeared to be the most active compound in the inhibition of cytokine production by attenuating the MAP kinase pathways. Conclusion: The present study demonstrated that common lilac, which is a traditionally used medicinal plant in Europe, is a valuable source of active compounds, especially neooleuropein.

Streamlined system for purifying and quantifying a diverse library of compounds and the effect of compound concentration measurements on the accurate interpretation of biological assay results.

PubMed

Popa-Burke, Ioana G; Issakova, Olga; Arroway, James D; Bernasconi, Paul; Chen, Min; Coudurier, Louis; Galasinski, Scott; Jadhav, Ajit P; Janzen, William P; Lagasca, Dennis; Liu, Darren; Lewis, Roderic S; Mohney, Robert P; Sepetov, Nikolai; Sparkman, Darren A; Hodge, C Nicholas

2004-12-15

As part of an overall systems approach to generating highly accurate screening data across large numbers of compounds and biological targets, we have developed and implemented streamlined methods for purifying and quantitating compounds at various stages of the screening process, coupled with automated "traditional" storage methods (DMSO, -20 degrees C). Specifically, all of the compounds in our druglike library are purified by LC/MS/UV and are then controlled for identity and concentration in their respective DMSO stock solutions by chemiluminescent nitrogen detection (CLND)/evaporative light scattering detection (ELSD) and MS/UV. In addition, the compound-buffer solutions used in the various biological assays are quantitated by LC/UV/CLND to determine the concentration of compound actually present during screening. Our results show that LC/UV/CLND/ELSD/MS is a widely applicable method that can be used to purify, quantitate, and identify most small organic molecules from compound libraries. The LC/UV/CLND technique is a simple and sensitive method that can be easily and cost-effectively employed to rapidly determine the concentrations of even small amounts of any N-containing compound in aqueous solution. We present data to establish error limits for concentration determination that are well within the overall variability of the screening process. This study demonstrates that there is a significant difference between the predicted amount of soluble compound from stock DMSO solutions following dilution into assay buffer and the actual amount present in assay buffer solutions, even at the low concentrations employed for the assays. We also demonstrate that knowledge of the concentrations of compounds to which the biological target is exposed is critical for accurate potency determinations. Accurate potency values are in turn particularly important for drug discovery, for understanding structure-activity relationships, and for building useful empirical models of protein-ligand interactions. Our new understanding of relative solubility demonstrates that most, if not all, decisions that are made in early discovery are based upon missing or inaccurate information. Finally, we demonstrate that careful control of compound handling and concentration, coupled with accurate assay methods, allows the use of both positive and negative data in analyzing screening data sets for structure-activity relationships that determine potency and selectivity.

Synthesis, characterization and antioxidant/cytotoxic activity of oxovanadium(IV) complexes of methyliminodiacetic acid and ethylenediaminetetracetic acid

NASA Astrophysics Data System (ADS)

Ibrahim, Mohamed M.; Mersal, Gaber A. M.; Ramadan, Abdel-Motaleb M.; Shaban, Shaban Y.; Mohamed, Mahmoud A.; Al-Juaid, Salih

2017-06-01

Two oxovanadium(IV) complexes, viz., [VO(Me-IDA)(H2O)2] (1) and NaH[VO(EDTA)]·4H2O (2) (Me-IDA = methyliminodiacetic acid and EDTA = ethylenediaminetetraacetic acid) have been synthesized and characterized by FT-IR, UV-Vis, mass spectrometry, elemental analysis, magnetic moment and thermal analysis, as well as electrochemical measurements including cyclic voltammetry. Both compounds are monomeric with distorted octahedral geometries. Compound 2 has been structurally characterized by using X-ray crystallography. It shows an octahedral V(O)N2O3 coordination geometry, which exhibits chemically significant hydrogen bonding interactions besides showing coordination polymer formation. Compounds 1 and 2 show an irreversible redox peak around +0.80 V versus Ag/AgCl corresponding to one-electron oxidation of V(IV) to V(V). The free radical scavenging activity of compounds 1 and 2 were done using 2,2-diphenyl- 1-picrylhydrazyl (DPPH). Both compounds have shown encouraging ROS scavenging activities. The cytotoxicity effects of both compounds toward two different tumor cells (HePG2 and MCF-7) have been also studied by MTT assay. The IC50 values obtained, after 48 h incubation at 37 °C for HepG2 and MCF-7 cell lines were 74.23 and 42.04 μg/mL for compound 1 and 65.56 and 48.34 μg/mL for compound 2, respectively. Conclusively, the present investigation provides preliminary results which suggest that such compounds can be promising alternative antitumor agents.

An iterative approach for compound detection in an unknown pharmaceutical drug product: Application on Raman microscopy.

PubMed

Boiret, Mathieu; Gorretta, Nathalie; Ginot, Yves-Michel; Roger, Jean-Michel

2016-02-20

Raman chemical imaging provides both spectral and spatial information on a pharmaceutical drug product. Even if the main objective of chemical imaging is to obtain distribution maps of each formulation compound, identification of pure signals in a mixture dataset remains of huge interest. In this work, an iterative approach is proposed to identify the compounds in a pharmaceutical drug product, assuming that the chemical composition of the product is not known by the analyst and that a low dose compound can be present in the studied medicine. The proposed approach uses a spectral library, spectral distances and orthogonal projections to iteratively detect pure compounds of a tablet. Since the proposed method is not based on variance decomposition, it should be well adapted for a drug product which contains a low dose product, interpreted as a compound located in few pixels and with low spectral contributions. The method is tested on a tablet specifically manufactured for this study with one active pharmaceutical ingredient and five excipients. A spectral library, constituted of 24 pure pharmaceutical compounds, is used as a reference spectral database. Pure spectra of active and excipients, including a modification of the crystalline form and a low dose compound, are iteratively detected. Once the pure spectra are identified, multivariate curve resolution-alternating least squares process is performed on the data to provide distribution maps of each compound in the studied sample. Distributions of the two crystalline forms of active and the five excipients were in accordance with the theoretical formulation. Copyright © 2015 Elsevier B.V. All rights reserved.

Mastering tricyclic ring systems for desirable functional cannabinoid activity

PubMed Central

Petrov, Ravil R.; Knight, Lindsay; Chen, Shao-Rui; Wager-Miller, Jim; McDaniel, Steven W.; Diaz, Fanny; Barth, Francis; Pan, Hui-Lin; Mackie, Ken; Cavasotto, Claudio N.; Diaz, Philippe

2013-01-01

There is growing interest in using cannabinoid receptor 2 (CB2) agonists for the treatment of neuropathic pain and other indications. In continuation of our ongoing program aiming for the development of new small molecule cannabinoid ligands, we have synthesized a novel series of carbazole and γ-carboline derivatives. The affinities of the newly synthesized compounds were determined by a competitive radioligand displacement assay for human CB2 cannabinoid receptor and rat CB1 cannabinoid receptor. Functional activity and selectivity at human CB1 and CB2 receptors were characterized using receptor internalization and [35S]GTP-γ-S assays. The structure-activity relationship and optimization studies of the carbazole series have led to the discovery of a non-selective CB1 and CB2 agonist, compound 4. Our subsequent research efforts to increase CB2 selectivity of this lead compound have led to the discovery of CB2 selective compound 64, which robustly internalized CB2 receptors. Compound 64 had potent inhibitory effects on pain hypersensitivity in a rat model of neuropathic pain. Other potent and CB2 receptor–selective compounds, including compounds 63 and 68, and a selective CB1 agonist, compound 74 were also discovered. In addition, we identified the CB2 ligand 35 which failed to promote CB2 receptor internalization and inhibited compound CP55,940-induced CB2 internalization despite a high CB2 receptor affinity. The present study provides novel tricyclic series as a starting point for further investigations of CB2 pharmacology and pain treatment. PMID:24125850

Design, synthesis and biological evaluation of novel ring-opened cromakalim analogues with relaxant effects on vascular and respiratory smooth muscles and as stimulators of elastin synthesis.

PubMed

Bouhedja, Mourad; Peres, Basile; Fhayli, Wassim; Ghandour, Zeinab; Boumendjel, Ahcène; Faury, Gilles; Khelili, Smail

2018-01-20

Two new series of ring-opened analogues of cromakalim bearing sulfonylurea moieties (series A: with N-unmethylated sulfonylureas, series B: with N-methylated sulfonylureas) were synthesized and tested as relaxants of vascular and respiratory smooth muscles (rat aorta and trachea, respectively). Ex vivo biological evaluations indicated that the most active compounds, belonging to series B, displayed a marked vasorelaxant activity on endothelium-intact aortic rings and the trachea. A majority of series B compounds exhibited a higher vasorelaxant activity (EC 50  < 22 μM) than that of the reference compound diazoxide (EC 50  = 24 μM). Interestingly, several tested compounds of series B also presented stronger relaxant effects on the trachea than the reference compound cromakalim (EC 50  = 124 μM), in particular compounds B4, B7 and B16 (EC 50  < 10 μM). By contrast, series A derivatives were poorly active on aortic rings (EC 50  > 57 μM for all, and EC 50  > 200 μM for a majority of them), but some of them showed an interesting relaxing effect on trachea (i.e. A15 and A33, EC 50  = 30 μM). The most potent compounds of both series, i.e. A15, A33 and B16, tested on aortic rings in the presence of glibenclamide or 80 mM KCl, suggested that they acted as voltage-gated Ca 2+ channel blockers, like verapamil, instead of being ATP-potassium channel activators, as is cromakalim, the parent molecule. Further investigations on cultured vascular smooth muscle cells showed a strong stimulating effect on elastin synthesis, especially compound B16, which was more active at 20 μM than diazoxide, a reference ATP-sensitive potassium channel activator. Taken together, our results show that the N-methylation of the sulfonylurea moieties of ring-opened cromakalim analogues led to new compounds blocking calcium-gated channels, which had a major impact on the arterial and tracheal activities as well as selectivity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Degradation of phenolic compounds by the lignocellulose deconstructing thermoacidophilic bacterium Alicyclobacillus Acidocaldarius

DOE PAGES

Aston, John E.; Apel, William A.; Lee, Brady D.; ...

2015-11-05

Alicyclobacillus acidocaldarius, a thermoacidophilic bacterium, has a repertoire of thermo- and acid-stable enzymes that deconstruct lignocellulosic compounds. The work presented here describes the ability of A. acidocaldarius to reduce the concentration of the phenolic compounds: phenol, ferulic acid, ρ-coumaric acid and sinapinic acid during growth conditions. The extent and rate of the removal of these compounds were significantly increased by the presence of micro-molar copper concentrations, suggesting activity by copper oxidases that have been identified in the genome of A. acidocaldarius. Substrate removal kinetics was first order for phenol, ferulic acid, ρ-coumaric acid and sinapinic acid in the presence ofmore » 50 μM copper sulfate. In addition, laccase enzyme assays of cellular protein fractions suggested significant activity on a lignin analog between the temperatures of 45 and 90 °C. As a result, this work shows the potential for A. acidocaldarius to degrade phenolic compounds, demonstrating potential relevance to biofuel production and other industrial processes.« less

1,2-Benzisoselenazol-3(2H)-one Derivatives As a New Class of Bacterial Urease Inhibitors.

PubMed

Macegoniuk, Katarzyna; Grela, Ewa; Palus, Jerzy; Rudzińska-Szostak, Ewa; Grabowiecka, Agnieszka; Biernat, Monika; Berlicki, Łukasz

2016-09-08

Urease inhibitors are considered promising compounds for the treatment of ureolytic bacterial infections, particularly infections resulting from Helicobacter pylori in the gastric tract. Herein, we present the synthesis and the inhibitory activity of novel and highly effective organoselenium compounds as inhibitors of Sporosarcina pasteurii and Helicobacter pylori ureases. These studied compounds represent a class of competitive reversible urease inhibitors. The most active compound, 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen), displayed Ki values equal to 2.11 and 226 nM against S. pasteurii and H. pylori enzymes, respectively, indicating ebselen as one of the most potent low-molecular-weight inhibitors of bacterial ureases reported to date. Most of these molecules penetrated through the cell membrane of the Gram-negative bacteria Escherichia coli (pGEM::ureOP) in vitro. Furthermore, whole-cell studies on the H. pylori J99 reference strain confirmed the high efficiency of the examined organoselenium compounds as urease inhibitors against pathogenic bacteria.

Efficient Synthesis and Discovery of Schiff Bases as Potent Cholinesterase Inhibitors.

PubMed

Razik, Basma M Abd; Osman, Hasnah; Ezzat, Mohammed O; Basiri, Alireza; Salhin, Abdussalam; Kia, Yalda; Murugaiyah, Vikneswaran

2016-01-01

The search for new cholinesterase inhibitors is still a promising approach for management of Alzheimer`s disease. Schiff bases are considered as important class of organic compounds, which have wide range of applications including as enzyme inhibitors. In the present study, a new green ionic liquid mediated strategy was developed for convenient synthesis of two series of Schiff bases 3(a-j) and 5(a-j) as potential cholinesterase inhibitors using aromatic aldehydes and primary amines in [bmim]Br. The synthesized compounds were evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potential by modified Ellman's method. The molecular interactions between the most active compound and the enzyme were analyzed by molecular docking. Among them, 3j displayed higher inhibitory activities than reference drug, galanthamine, with IC50 values of 2.05 and 5.77 µM, for AChE and BChE, respectively. Interestingly, all the compounds except 3b displayed higher BChE inhibitions than galanthamine with IC50 values ranging from 5.77 to 18.52 µM. Molecular docking of compound 3j inside the TcAChE and hBChE completely coincided with the inhibitory activities observed. The compound forms strong hydrogen bonding at the peripheral anionic site of AChE whereas on BChE, it had hydrophobic and mild polar interactions. An efficient and eco-friendly synthetic methodology has been developed to synthesize Schiff bases in a very short reaction time and excellent yields in ionic solvent, whereby the compounds from series 3 showed promising cholinesterase inhibitory activity.

Cancer sniffer dogs: how can we translate this peculiarity in laboratory medicine? Results of a pilot study on gastrointestinal cancers.

PubMed

Panebianco, Concetta; Kelman, Edgar; Vene, Kristel; Gioffreda, Domenica; Tavano, Francesca; Vilu, Raivo; Terracciano, Fulvia; Pata, Illar; Adamberg, Kaarel; Andriulli, Angelo; Pazienza, Valerio

2017-11-27

Identification of cancer biomarkers to allow early diagnosis is an urgent need for many types of tumors, whose prognosis strongly depends on the stage of the disease. Canine olfactory testing for detecting cancer is an emerging field of investigation. As an alternative, here we propose to use GC-Olfactometry (GC/O), which enables the speeding up of targeted biomarker identification and analysis. A pilot study was conducted in order to determine odor-active compounds in urine that discriminate patients with gastrointestinal cancers from control samples (healthy people). Headspace solid phase microextraction (HS-SPME)-GC/MS and GC-olfactometry (GC/O) analysis were performed on urine samples obtained from gastrointestinal cancer patients and healthy controls. In total, 91 key odor-active compounds were found in the urine samples. Although no odor-active biomarkers present were found in cancer carrier's urine, significant differences were discovered in the odor activities of 11 compounds in the urine of healthy and diseased people. Seven of above mentioned compounds were identified: thiophene, 2-methoxythiophene, dimethyl disulphide, 3-methyl-2-pentanone, 4-(or 5-)methyl-3-hexanone, 4-ethyl guaiacol and phenylacetic acid. The other four compounds remained unknown. GC/O has a big potential to identify compounds not detectable using untargeted GC/MS approach. This paves the way for further research aimed at improving and validating the performance of this technique so that the identified cancer-associated compounds may be introduced as biomarkers in clinical practice to support early cancer diagnosis.

Synthesis and biological evaluation of benzo[d]isothiazole, benzothiazole and thiazole Schiff bases.

PubMed

Vicini, Paola; Geronikaki, Athina; Incerti, Matteo; Busonera, Bernadetta; Poni, Graziella; Cabras, Carla Alba; La Colla, Paolo

2003-11-03

Three new series of benzo[d]isothiazole, benzothiazole and thiazole Schiff bases were synthesized and tested in vitro with the aim of identifying novel lead compounds active against emergent and re-emergent human and cattle infectious diseases (AIDS, hepatitis B and C, tuberculosis, bovine viral diarrhoea) or against drug-resistant cancers (leukaemia, carcinoma, melanoma, MDR tumors) for which no definitive cure or efficacious vaccine is available at present. In particular, these compounds were evaluated in vitro against representatives of different virus classes, such as a HIV-1 (Retrovirus), a HBV (Hepadnavirus) and the single-stranded RNA(+) viruses Yellow fever virus (YFV) and Bovine viral diarrhoea virus (BVDV), both belonging to Flaviviridae. Title compounds were also tested against representatives of Gram-positive and Gram-negative bacteria (Staphylococcus aureus, Salmonella spp.), various atypic mycobacterial strains (Mycobacterium fortuitum and Mycobacterium smegmatis), yeast (Candida albicans) and mould (Aspergillus fumigatus). None of the compounds showed antiviral or antimicrobial activity. The benzo[d]isothiazole compounds showed a marked cytotoxicity (CC(50)=4-9 microM) against the human CD4(+) lymphocytes (MT-4) that were used to support HIV-1 growth. For this reason, the most cytotoxic compounds of this series were evaluated for their antiproliferative activity against a panel of human cell lines derived from haematological and solid tumors. The results highlighted that all the benzo[d]isothiazole derivatives inhibited the growth of leukaemia cell lines, whereas only one of the above mentioned compounds (1e) showed antiproliferative activity against two solid tumor-derived cell lines.

Predictive Array Design. A method for sampling combinatorial chemistry library space.

PubMed

Lipkin, M J; Rose, V S; Wood, J

2002-01-01

A method, Predictive Array Design, is presented for sampling combinatorial chemistry space and selecting a subarray for synthesis based on the experimental design method of Latin Squares. The method is appropriate for libraries with three sites of variation. Libraries with four sites of variation can be designed using the Graeco-Latin Square. Simulated annealing is used to optimise the physicochemical property profile of the sub-array. The sub-array can be used to make predictions of the activity of compounds in the all combinations array if we assume each monomer has a relatively constant contribution to activity and that the activity of a compound is composed of the sum of the activities of its constitutive monomers.

Advances toward multifunctional cholinesterase and β-amyloid aggregation inhibitors.

PubMed

Panek, Dawid; Wichur, Tomasz; Godyń, Justyna; Pasieka, Anna; Malawska, Barbara

2017-10-01

The emergence of a multitarget design approach in the development of new potential anti-Alzheimer's disease agents has resulted in the discovery of many multifunctional compounds focusing on various targets. Among them the largest group comprises inhibitors of both cholinesterases, with additional anti-β-amyloid aggregation activity. This review describes recent advances in this research area and presents the most interesting compounds reported over a 2-year span (2015-2016). The majority of hybrids possess heterodimeric structures obtained by linking structurally active fragments interacting with different targets. Multipotent cholinesterase inhibitors with β-amyloid antiaggregating activity may additionally possess antioxidative, neuroprotective or metal-chelating properties or less common features such as anti-β-secretase or τ-antiaggregation activity.

TIPdb-3D: the three-dimensional structure database of phytochemicals from Taiwan indigenous plants

PubMed Central

Tung, Chun-Wei; Lin, Ying-Chi; Chang, Hsun-Shuo; Wang, Chia-Chi; Chen, Ih-Sheng; Jheng, Jhao-Liang; Li, Jih-Heng

2014-01-01

The rich indigenous and endemic plants in Taiwan serve as a resourceful bank for biologically active phytochemicals. Based on our TIPdb database curating bioactive phytochemicals from Taiwan indigenous plants, this study presents a three-dimensional (3D) chemical structure database named TIPdb-3D to support the discovery of novel pharmacologically active compounds. The Merck Molecular Force Field (MMFF94) was used to generate 3D structures of phytochemicals in TIPdb. The 3D structures could facilitate the analysis of 3D quantitative structure–activity relationship, the exploration of chemical space and the identification of potential pharmacologically active compounds using protein–ligand docking. Database URL: http://cwtung.kmu.edu.tw/tipdb. PMID:24930145

Solid-state studies and antioxidant properties of the γ-cyclodextrin·fisetin inclusion compound.

PubMed

Pais, Joana M; Barroca, Maria João; Marques, Maria Paula M; Almeida Paz, Filipe A; Braga, Susana S

2017-01-01

Fisetin is a natural antioxidant with a wide range of nutraceutical properties, including antidiabetic, neuroprotecting, and suppression or prevention of tumors. The present work describes the preparation of a water-soluble, solid inclusion compound of fisetin with gamma-cyclodextrin (γ-CD), a cyclic oligosaccharide approved for human consumption. A detailed physicochemical analysis of the product is carried out using elemental analysis, powder X-ray diffraction (PXRD), Raman, infrared and 13 C{ 1 H} CP-MAS NMR spectroscopies, and thermal analysis (TGA) to verify fisetin inclusion and to present a hypothetical structural arrangement for the host-guest units. The antioxidant activity of the γ-CD·fisetin inclusion compound is evaluated by the DPPH assay.

Promiscuity and selectivity of bitter molecules and their receptors.

PubMed

Di Pizio, Antonella; Niv, Masha Y

2015-07-15

Bitter taste is essential for survival, as it protects against consuming poisonous compounds, which are often bitter. Bitter taste perception is mediated by bitter taste receptors (TAS2Rs), a subfamily of G-protein coupled receptors (GPCRs). The number of TAS2R subtypes is species-dependent, and varies from 3 in chicken to 50 in frog. TAS2Rs present an intriguing case for studying promiscuity: some of the receptors are still orphan, or have few known agonists, while others can be activated by numerous, structurally dissimilar compounds. The ligands also vary in the repertoire of TAS2Rs that they activate: some bitter compounds are selective toward a single TAS2R, while others activate multiple TAS2Rs. Selectivity/promiscuity profile of bitter taste receptors and their compounds was explored by a chemoinformatic approach. TAS2R-promiscuous and TAS2R-selective bitter molecules were found to differ in chemical features, such as AlogP, E-state, total charge, number of rings, globularity, and heavy atom count. This allowed the prediction of bitter ligand selectivity toward TAS2Rs. Interestingly, while promiscuous TAS2Rs are activated by both TAS2R-promiscuous and TAS2R-selective compounds, almost all selective TAS2Rs in human are activated by promiscuous compounds, which are recognized by other TAS2Rs anyway. Thus, unique ligands, that may have been the evolutionary driving force for development of selective TAS2Rs, still need to be unraveled. Copyright © 2015 Elsevier Ltd. All rights reserved.

The antitumor activity screening of chemical constituents from Camellia nitidissima Chi

PubMed Central

Yang, Rui; Qi, Jing; Huang, Yue; Feng, Shuyun; Wu, Yao; Lin, Sensen; Liu, Zhixin; Jia, Ai-Qun; Yuan, Shengtao; Sun, Li

2018-01-01

Chemotherapy is the preferred and most common treatment for cancer in clinical practice. An increasing number of researchers all over the world are focusing on natural medicines to find new antitumor drugs, and several reports have shown that Camellia nitidissima (C. nitidis-sima) Chi could reduce blood-lipid, decrease blood pressure, resist oxidation, prevent carcinogenesis and inhibit tumors. Therefore, the pharmacodynamics of the chemical constituents in C. nitidissima need to be investigated further. In the present study, 16 chemical constituents were isolated from the leaves of C. nitidissima, of which 6 compounds are reported to be found in this plant for the first time. Furthermore, all these phytochemicals were screened for antitumor activity on 4 common cancer cell lines, while compound 3, one oleanane-type triterpene, exhibited the most potential antitumor effects. Interestingly, to our knowledge, this was the first report that compound 3 inhibits cancer cells. Compound 3 inhibited EGFR-mutant lung cancer cell line, NCI-H1975 via apoptosis effect, with an IC50 of 13.37±2.05 µM at 48 h. Based on the data, compound 3 showed potential for antitumor drug development, suggesting the scientific basis for the antitumor activity of C. nitidissima. PMID:29484370

Characterization of phenolic compounds and antinociceptive activity of Sempervivum tectorum L. leaf juice.

PubMed

Alberti, Ágnes; Béni, Szabolcs; Lackó, Erzsébet; Riba, Pál; Al-Khrasani, Mahmoud; Kéry, Ágnes

2012-11-01

Sempervivum tectorum L. (houseleek) leaf juice has been known as a traditional herbal remedy. The aim of the present study was the chemical characterization of its phenolic compounds and to develop quantitation methods for its main flavonol glycoside, as well as to evaluate its antinociceptive activity. Lyophilized houseleek leaf juice was studied by HPLC-DAD coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) to identify flavonol glycosides, hydroxy-benzoic and hydroxy-cinnamic acids. Ten flavonol glycosides and sixteen phenolic acid compounds were identified or tentatively characterized. Structure of the main flavonol compound was identified by nuclear magnetic resonance spectroscopy. Three characteristic kaempferol glycosides were isolated and determined by LC-ESI-MS/MS with external calibration method, using the isolated compounds as standard. The main flavonol glycoside was also determined by HPLC-DAD. Validated HPLC-DAD and LC-ESI-MS/MS methods were developed to quantify kaempferol-3-O-rhamnosyl-glucoside-7-O-rhamnoside and two other kaempferol glycosides. Antinociceptive activity of houseleek leaf juice was investigated by writhing test of mice. Sempervivum extract significantly reduced pain in the mouse writhing test. Copyright © 2012 Elsevier B.V. All rights reserved.

Influence of phenolic compounds on the growth and arginine deiminase system in a wine lactic acid bacterium

PubMed Central

Alberto, María R.; de Nadra, María C. Manca; Arena, Mario E.

2012-01-01

The influence of seven phenolic compounds, normally present in wine, on the growth and arginine deiminase system (ADI) of Lactobacillus hilgardii X1B, a wine lactic acid bacterium, was established. This system provides energy for bacterial growth and produces citrulline that reacts with ethanol forming the carcinogen ethyl carbamate (EC), found in some wines. The influence of phenolic compounds on bacterial growth was compound dependent. Growth and final pH values increased in presence of arginine. Arginine consumption decreased in presence of protocatechuic and gallic acids (31 and 17%, respectively) and increased in presence of quercetin, rutin, catechin and the caffeic and vanillic phenolic acids (between 10 and 13%, respectively). ADI enzyme activities varied in presence of phenolic compounds. Rutin, quercetin and caffeic and vanillic acids stimulated the enzyme arginine deiminase about 37–40%. Amounts of 200 mg/L gallic and protocatechuic acids inhibited the arginine deiminase enzyme between 53 and 100%, respectively. Ornithine transcarbamylase activity was not modified at all concentrations of phenolic compounds. As gallic and protocatechuic acids inhibited the arginine deiminase enzyme that produces citrulline, precursor of EC, these results are important considering the formation of toxic compounds. PMID:24031815

New phthalimide-appended Schiff bases: Studies of DNA binding, molecular docking and antioxidant activities.

PubMed

Nayab, Pattan Sirajuddin; Akrema; Ansari, Istikhar A; Shahid, Mohammad; Rahisuddin

2017-08-01

Herein, we investigated new phthalimide-based Schiff base molecules as promising DNA-binding and free radical scavenging agents. Physicochemical properties of these molecules were demonstrated on the basis of elemental analysis, ultraviolet-visible (UV-Vis), infra-red (IR), 1 H and 13 C nuclear magnetic resonance (NMR) spectroscopy. All spectral data are agreed well with the proposed Schiff base framework. The DNA-binding potential of synthesized compounds were investigated by means of UV-visible, fluorescence, iodide quenching, circular dichroism, viscosity and thermal denaturation studies. The intrinsic binding constants (K b ) were calculated from absorption studies were found to be 1.1 × 10 4 and 1.0 × 10 4  M -1 for compounds 2a and 2b suggesting that compound 2a binding abilities with DNA were stronger than the compound 2b. Our studies showed that the presented compounds interact with DNA through groove binding. Molecular docking studies were carried out to predict the binding between Ct-DNA and test compounds. Interestingly, in silico predictions were corroborated with in vitro DNA-binding conclusions. Furthermore, the title compounds displayed remarkable antioxidant activity compared with reference standard. Copyright © 2016 John Wiley & Sons, Ltd.

Traditional medicine and gastroprotective crude drugs.

PubMed

Schmeda-Hirschmann, Guillermo; Yesilada, Erdem

2005-08-22

A frequent question when dealing with the search for gastroprotective compounds from natural sources is how far or close are both the plant preparations and extract amounts from the doses recommended in traditional medicine and what should be considered realistic levels for experimental studies. The administration way is oral and therefore extracts and products should be administered by gavage when looking for validation of ethnopharmacological uses. Suggestions of doses for both crude extracts and pure compounds are presented and discussed. For plant extracts prepared from single herbs and herbal mixtures, dose-response studies in the range between 100 and 300 mg/kg are suggested, with more than a single gastric ulcer model either in rats or mice. A suitable reference compound should be used according to the ulcer model and in doses resembling those used for human patients. For pure compounds and structure-activity studies or trends, dose-response results should be provided for at least a parent compound in order to select a reasonable dose for comparison purposes. We suggest an evaluation of the activity of the parent compound in the 50-300 mg/kg range and to look for structural modification leading to derivatives with similar or higher gastroprotective effects than the reference antiulcer compounds.

Biting deterrence and insecticidal activity of hydrazide-hydrazones and their corresponding 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles against Aedes aegypti.

PubMed

Tabanca, Nurhayat; Ali, Abbas; Bernier, Ulrich R; Khan, Ikhlas A; Kocyigit-Kaymakcioglu, Bedia; Oruç-Emre, Emine E; Unsalan, Seda; Rollas, Sevim

2013-06-01

Taking into account the improvement in insecticidal activity by the inclusion of fluorine in the hydrazone moiety, the authors synthesized new 4-fluorobenzoic acid hydrazides and 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles, substituting a phenyl group or a heteroaryl ring carrying one or two atoms of F, Cl and Br, and investigated their biting deterrent and larvicidal activities against Aedes aegypti for the first time. The compound 3-acetyl-5-(4-fluorophenyl)-2-[4-(dimethylamino)phenyl]-2,3-dihydro-1,3,4-oxadiazole (17) produced the highest biting deterrent activity (BDI = 1.025) against Ae. Aegypti, followed by 4-fluorobenzoic acid [(phenyl)methylene] hydrazide (1). These activity results were similar to those of N,N-diethyl-meta-toluamide (DEET), which showed a proportion not biting of 0.8-0.92. When compounds 1 and 17 were tested on cloth worn on human volunteers, compound 1 was not repellent for some volunteers until present in excess of 500 nmol cm(-2) , while compound 17 was not repellent at the highest concentration tested (1685 nmol cm(-2) ). In the larvicidal screening bioassays, only compounds 10, 11, 12 and 17 showed 100% mortality at the highest screening dose of 100 ppm against Ae. aegypti larvae. Compounds 11 and 12 with LD50 values of 24.1 and 30.9 ppm showed significantly higher mortality than 10 (80.3 ppm) and 17 (58.7 ppm) at 24-h post-treatment. The insecticidal and biting deterrent activities were correlated with the presence of a halogen atom on the phenyl or heteroaryl substituent of the hydrazone moiety. © 2012 Society of Chemical Industry.

Phytosterols isolated from Clinacanthus nutans induce immunosuppressive activity in murine cells.

PubMed

Le, Cheng-Foh; Kailaivasan, Thina Hareesh; Chow, Sek-Chuen; Abdullah, Zunoliza; Ling, Sui-Kiong; Fang, Chee-Mun

2017-03-01

Clinacanthus nutans (Burm. f.) Lindau is a traditional medicinal plant belonging to the Acanthaceae family. Its therapeutic potentials have been increasingly documented particularly the antiviral activity against Herpes Simplex Virus (HSV), anti-cancer, anti-oxidant, anti-inflammatory and immunomodulatory activities. However, majority of these studies used crude or fractionated extracts and not much is known about individual compounds from these extracts and their biological activities. In the present study, we have isolated four compounds (CN1, CN2, CN3 and CN4) from the hexane fractions of C. nutans leaves. Using NMR spectroscopic analysis, these compounds were identified to be shaftoside (CN1), stigmasterol (CN2), β-sitosterol (CN3) and a triterpenoid lupeol (CN4). To determine the immunosuppressive potential of these compounds, their effects on mitogens induced T and B lymphocyte proliferation and the secretion of helper T cell cytokines were examined. Among the four compounds, stigmasterol (CN2) and β-sitosterol (CN3) were shown to readily inhibit T cell proliferation mediated by Concanavalin A (ConA). However, only β-sitosterol (CN3) and not stigmasterol (CN2) blocks the secretion of T helper 2 (Th2) cytokines (IL-4 and IL-10). Both compounds have no effect on the secretion of Th1 cytokines (IL-2 and IFN-γ), suggesting that β-sitosterol treatment selectively suppresses Th2 activity and promotes a Th1 bias. CN3 was also found to significantly reduce the proliferation of both T helper cells (CD4 + CD25 + ) and cytotoxic T cells (CD8 + CD25 + ) following T cell activation induced by ConA. These results suggested that phytosterols isolated from C. nutans possess immunomodulatory effects with potential development as immunotherapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

Ginsenoside Compound K suppresses the hepatic gluconeogenesis via activating adenosine-5'monophosphate kinase: A study in vitro and in vivo.

PubMed

Wei, Shengnan; Li, Wei; Yu, Yang; Yao, Fan; A, Lixiang; Lan, Xiaoxin; Guan, Fengying; Zhang, Ming; Chen, Li

2015-10-15

Compound K (CK) is a final intestinal metabolite of protopanaxadiol-type ginsenoside. We have reported that CK presented anti-diabetic effect via diminishing the expressions of hepatic gluconeogenesis key enzyme. Here, we further explore the possible mechanism of CK on suppression hepatic gluconeogenesis via activation of adenosine-5'monophosphate kinase (AMPK) on type 2 diabetes mice in vivo and in HepG2 cells. Type 2 diabetes mice model was developed by high fat diet combined with STZ injection. 30mg/kg/d CK was orally administrated for 4weeks, the fasting blood glucose level and 2h OGTT were conducted, and the protein expression of AMPK, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase) were examined. The mechanism of Compound K on hepatic gluconeogenesis was further explored in HepG2 hepatocytes. Glucose production, the protein expression of AMPK, PEPCK, G6pase and PGC-1α, hepatic nuclear factor 4α (HNF-4α) and forkhead transcription factor O1 (FOXO1) were determined after Compound K treatment at the presence of AMPK inhibitor Compound C. We observed that CK inhibited the expression of PEPCK and G6Pase in the liver and in HepG2 hepatocytes. Meanwhile, CK treatment remarkably increased the activation of AMPK, while decreasing the expressions of PGC-1α, HNF-4α and FOXO1. However, AMPK inhibitor Compound C could reverse these effects of CK on gluconeogenesis in part. The results indicated that the effect of CK on suppression hepatic gluconeogenesis might be via the activation the AMPK activity. Copyright © 2015. Published by Elsevier Inc.

Synthesis of new bioactive aminophosphonates and study of their antioxidant, anti-inflammatory and antibacterial activities as well the assessment of their toxicological activity

NASA Astrophysics Data System (ADS)

Damiche, Rebiha; Chafaa, Salah

2017-02-01

Two new categories of α-aminophosphonates molecules were synthesized and characterized by UV-Vis, IR, and NMR. Their spectral properties show a perfect convergence. Their biological activities were evaluated. Molecules 1a, 2a, and 1d present a greater antioxidant potential than BHT and vitamin C. The best anti-inflammatory activity is shown by the 2b molecule and that of 1a, 2a, and 2c molecules are closely comparable to that of diclofenac. The antibacterial activity of the synthesized compounds is significantly higher than the antibiotic amoxicillin. The hemolysis rate HR of compounds 1b, 1c, 2b, and 2c was lower than 5%.

Honey: Chemical composition, stability and authenticity.

PubMed

da Silva, Priscila Missio; Gauche, Cony; Gonzaga, Luciano Valdemiro; Costa, Ana Carolina Oliveira; Fett, Roseane

2016-04-01

The aim of this review is to describe the chemical characteristics of compounds present in honey, their stability when heated or stored for long periods of time and the parameters of identity and quality. Therefore, the chemical characteristics of these compounds were examined, such as sugars, proteins, amino acids, enzymes, organic acids, vitamins, minerals, phenolic and volatile compounds present in honey. The stability of these compounds in relation to the chemical reactions that occur by heating or prolonged storage were also discussed, with increased understanding of the behavior regarding the common processing of honey that may compromise its quality. In addition, the identity and quality standards were described, such as sugars, moisture, acidity, ash and electrical conductivity, color, 5-HMF and diastase activity, along with the minimum and maximum limits established by the Codex Alimentarius. Copyright © 2015 Elsevier Ltd. All rights reserved.

Design and synthesis of aloe-emodin derivatives as potent anti-tyrosinase, antibacterial and anti-inflammatory agents.

PubMed

Liu, Jinbing; Wu, Fengyan; Chen, Changhong

2015-11-15

Twenty aloe-emodin derivatives were designed, synthesized, and their biological activities were evaluated. Some compounds displayed potent tyrosinase inhibitory activities, especially, compounds with thiosemicarbazide moiety showed more potent inhibitory effects than the other compounds. The structure-activity relationships (SARs) were preliminarily discussed. The inhibition mechanism of selected compounds 1 and 13 were investigated. The results showed compound 1 was reversible inhibitor, however, compound 13 was irreversible. Kinetic analysis indicated that compound 1 was competitive tyrosinase inhibitor. Furthermore, the antibacterial activities and anti-inflammatory activities of some selected compounds were also screened. The results showed that compound 3 exhibited more potent antibacterial activity than the aloe-emodin, compounds 5 and 6 possessed more potent anti-inflammatory activities than the diacerein. Copyright © 2015 Elsevier Ltd. All rights reserved.

Large enhancement of skeletal muscle cell glucose uptake and suppression of hepatocyte glucose-6-phosphatase activity by weak uncouplers of oxidative phosphorylation.

PubMed

Martineau, Louis C

2012-02-01

Perturbation of energy homeostasis in skeletal muscle and liver resulting from a transient inhibition of mitochondrial energy transduction can produce effects of relevance for the control of hyperglycemia through activation of the AMP-activated protein kinase, as exemplified by the antidiabetic drug metformin. The present study focuses on uncoupling of oxidative phosphorylation rather than its inhibition as a trigger for such effects. The reference weak uncoupler 2,4-dinitrophenol, fourteen naturally-occurring phenolic compounds identified as uncouplers in isolated rat liver mitochondria, and fourteen related compounds with little or no uncoupling activity were tested for enhancement of glucose uptake in differentiated C2C12 skeletal muscle cells following 18 h of treatment at 25-100 μM. A subset of compounds were tested for suppression of glucose-6-phosphatase (G6Pase) activity in H4IIE hepatocytes following 16 h at 12.5-25 μM. Metformin (400 μM) was used as a standard in both assays. Dinitrophenol and nine of eleven compounds that induced 50% or more uncoupling at 100 μM in isolated mitochondria enhanced basal glucose uptake by 53 to 269%; the effect of the 4'-hydroxychalcone butein was more than 6-fold that of metformin; negative control compounds increased uptake by no more than 25%. Dinitrophenol and four 4'-hydroxychalconoids also suppressed hepatocyte G6Pase as well as, or more effectively than metformin, whereas the unsubstituted parent compound chalcone, devoid of uncoupling activity, had no effect. Activities key to glycemic control can be induced by a wide range of weak uncouplers, including compounds free of difficult-to-metabolize groups typically associated with uncouplers. Uncoupling represents a valid and possibly more efficient alternative to inhibition for triggering cytoprotective effects of therapeutic relevance to insulin resistance in both muscle and liver. Identification of actives of natural origin and the insights into their structure-activity relationship reported herein may lead to alternatives to metformin. Copyright © 2011 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Shi-Wei; Wu, Chun-Ying; Wang, Yen-Ting

Compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), has been reported to cause apoptotic cell death in myeloma, breast cancer cells and glioma cells. In this study, we have demonstrated that compound C not only induced autophagy in all tested skin cancer cell lines but also caused more apoptosis in p53 wildtype skin cancer cells than in p53-mutant skin cancer cells. Compound C can induce upregulation, phosphorylation and nuclear translocalization of the p53 protein and upregulate expression of p53 target genes in wildtype p53-expressing skin basal cell carcinoma (BCC) cells. The changes of p53more » status were dependent on DNA damage which was caused by compound C induced reactive oxygen species (ROS) generation and associated with activated ataxia-telangiectasia mutated (ATM) protein. Using the wildtype p53-expressing BCC cells versus stable p53-knockdown BCC sublines, we present evidence that p53-knockdown cancer cells were much less sensitive to compound C treatment with significant G2/M cell cycle arrest and attenuated the compound C-induced apoptosis but not autophagy. The compound C induced G2/M arrest in p53-knockdown BCC cells was associated with the sustained inactive Tyr15 phosphor-Cdc2 expression. Overall, our results established that compound C-induced apoptosis in skin cancer cells was dependent on the cell's p53 status. - Highlights: ► Compound C caused more apoptosis in p53 wildtype than p53-mutant skin cancer cells. ► Compound C can upregulate p53 expression and induce p53 activation. ► Compound C induced p53 effects were dependent on ROS induced DNA damage pathway. ► p53-knockdown attenuated compound C-induced apoptosis but not autophagy. ► Compound C-induced apoptosis in skin cancer cells was dependent on p53 status.« less

Aegeline inspired synthesis of novel β3-AR agonist improves insulin sensitivity in vitro and in vivo models of insulin resistance.

PubMed

Rajan, Sujith; Satish, Sabbu; Shankar, Kripa; Pandeti, Sukanya; Varshney, Salil; Srivastava, Ankita; Kumar, Durgesh; Gupta, Abhishek; Gupta, Sanchita; Choudhary, Rakhi; Balaramnavar, Vishal M; Narender, Tadigoppula; Gaikwad, Anil N

2018-03-07

In our drug discovery program of natural product, earlier we have reported Aegeline that is N-acylated-1-amino-2- alcohol, which was isolated from the leaves of Aeglemarmelos showed anti-hyperlipidemic activity for which the QSAR studies predicted the compound to be the β3-AR agonist, but the mechanism of its action was not elucidated. In our present study, we have evaluated the β3-AR activity of novel N-acyl-1-amino-3-arylopropanol synthetic mimics of aegeline and its beneficial effect in insulin resistance. In this study, we have proposed the novel pharmacophore model using reported molecules for antihyperlipidemic activity. The reported pharmacophore features were also compared with the newly developed pharmacophore model for the observed biological activity. Based on 3D pharmacophore modeling of known β3AR agonist, we screened 20 synthetic derivatives of Aegeline from the literature. From these, the top scoring compound 10C was used for further studies. The in-slico result was further validated in HEK293T cells co-trransfected with human β3-AR and CRE-Luciferase reporter plasmid for β3-AR activity.The most active compound was selected and β3-AR activity was further validated in white and brown adipocytes differentiated from human mesenchymal stem cells (hMSCs). Insulin resistance model developed in hMSC derived adipocytes was used to study the insulin sensitizing property. 8 week HFD fed C57BL6 mice was given 50 mg/Kg of the selected compound and metabolic phenotyping was done to evaluate its anti-diabetic effect. As predicted by in-silico 3D pharmacophore modeling, the compound 10C was found to be the most active and specific β3-AR agonist with EC 50 value of 447 nM. The compound 10C activated β3AR pathway, induced lipolysis, fatty acid oxidation and increased oxygen consumption rate (OCR) in human adipocytes. Compound 10C induced expression of brown adipocytes specific markers and reverted chronic insulin induced insulin resistance in white adipocytes. The compound 10C also improved insulin sensitivity and glucose tolerance in 8 week HFD fed C57BL6 mice. This study enlightens the use of in vitro insulin resistance model close to human physiology to elucidates the insulin sensitizing activity of the compound 10C and edifies the use of β3AR agonist as therapeutic interventions for insulin resistance and type 2 diabetes. Copyright © 2018. Published by Elsevier Inc.

Ameliorative effects of amide derivatives of 1,3,4-thiadiazoles on scopolamine induced cognitive dysfunction.

PubMed

Kulshreshtha, Akanksha; Piplani, Poonam

2016-10-21

The present study reports the effect of amide derivatives of 1,3,4-thiadizoles on scopolamine induced deficit cholinergic neurotransmission and oxidative stress serving as promising leads for the therapeutics of cognitive dysfunction. Fourteen compounds (2c-8d) have been synthesised and evaluated against behavioural alterations using step down passive avoidance protocol and morris water maze and at a dose of 0.5 mg/kg with reference to the standard, Rivastigmine. All the synthesised compounds were evaluated for their in vitro acetylcholinesterase (AChE) inhibition at five different concentrations using mice brain homogenate as the source of the enzyme. Biochemical estimation of markers of oxidative stress (lipid peroxidation, superoxide dismutase, glutathione, plasma nitrite, catalase) has also been carried out to assess the role of synthesised molecules on the oxidative damage induced by scopolamine. The compounds 5c, 6c and 8c displayed appreciable activity with an IC50 value of 3 μM, 3.033 μM and 2.743 μM, respectively towards acetylcholinesterase inhibition. These compounds also decreased scopolamine induced oxidative stress, thus serving as promising leads for the amelioration of oxidative stress induced cognitive decline. The molecular docking study performed to predict the binding mode of the compounds also suggested that these compounds bind appreciably with the amino acids present in the active site of recombinant human acetylcholinesterase (rhAChE). The results indicated that these compounds could be further traversed as inhibitors of AChE and oxidative stress for the treatment of cognitive dysfunction. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Chemical Composition and in-Vitro Evaluation of the Antimicrobial and Antioxidant Activities of Essential Oils Extracted from Seven Eucalyptus Species.

PubMed

Ghaffar, Abdul; Yameen, Muhammad; Kiran, Shumaila; Kamal, Shagufta; Jalal, Fatima; Munir, Bushra; Saleem, Sadaf; Rafiq, Naila; Ahmad, Aftab; Saba, Iram; Jabbar, Abdul

2015-11-18

Eucalyptus is well reputed for its use as medicinal plant around the globe. The present study was planned to evaluate chemical composition, antimicrobial and antioxidant activity of the essential oils (EOs) extracted from seven Eucalyptus species frequently found in South East Asia (Pakistan). EOs from Eucalyptus citriodora, Eucalyptus melanophloia, Eucalyptus crebra, Eucalyptus tereticornis, Eucalyptus globulus, Eucalyptus camaldulensis and Eucalyptus microtheca were extracted from leaves through hydrodistillation. The chemical composition of the EOs was determined through GC-MS-FID analysis. The study revealed presence of 31 compounds in E. citriodora and E. melanophloia, 27 compounds in E. crebra, 24 compounds in E. tereticornis, 10 compounds in E. globulus, 13 compounds in E. camaldulensis and 12 compounds in E. microtheca. 1,8-Cineole (56.5%), α-pinene (31.4%), citrinyl acetate (13.3%), eugenol (11.8%) and terpenene-4-ol (10.2%) were the highest principal components in these EOs. E. citriodora exhibited the highest antimicrobial activity against the five microbial species tested (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Aspergillus niger and Rhizopus solani). Gram positive bacteria were found more sensitive than Gram negative bacteria to all EOs. The diphenyl-1-picrylhydazyl (DPPH) radical scavenging activity and percentage inhibition of linoleic acid oxidation were highest in E. citriodora (82.1% and 83.8%, respectively) followed by E. camaldulensis (81.9% and 83.3%, respectively). The great variation in chemical composition of EOs from Eucalyptus, highlight its potential for medicinal and nutraceutical applications.

Ganoboninketals A-C, Antiplasmodial 3,4-seco-27-Norlanostane Triterpenes from Ganoderma boninense Pat.

PubMed

Ma, Ke; Ren, Jinwei; Han, Junjie; Bao, Li; Li, Li; Yao, Yijian; Sun, Chen; Zhou, Bing; Liu, Hongwei

2014-08-22

Three new nortriterpenes, ganoboninketals A-C (1-3), featuring rearranged 3,4-seco-27-norlanostane skeletons and highly complex polycyclic systems were isolated from the medicinal mushroom Ganoderma boninense. The structures of the new metabolites were established by spectroscopic methods. The absolute configurations in 1-3 were assigned by electronic circular dichroism (ECD) calculations. Compounds 1-3 showed antiplasmodial activity against Plasmodium falciparum with IC50 values of 4.0, 7.9, and 1.7 μM, respectively. Compounds 1 and 3 also displayed weak cytotoxicity against A549 cell line with IC50 values of 47.6 and 35.8 μM, respectively. Compound 2 showed weak cytotoxicity toward HeLa cell line with an IC50 value of 65.5 μM. Compounds 1-3 also presented NO inhibitory activity in the LPS-induced macrophages with IC50 values of 98.3, 24.3, and 60.9 μM, respectively.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aston, John E.; Apel, William A.; Lee, Brady D.

Alicyclobacillus acidocaldarius, a thermoacidophilic bacterium, has a repertoire of thermo- and acid-stable enzymes that deconstruct lignocellulosic compounds. The work presented here describes the ability of A. acidocaldarius to reduce the concentration of the phenolic compounds: phenol, ferulic acid, ρ-coumaric acid and sinapinic acid during growth conditions. The extent and rate of the removal of these compounds were significantly increased by the presence of micro-molar copper concentrations, suggesting activity by copper oxidases that have been identified in the genome of A. acidocaldarius. Substrate removal kinetics was first order for phenol, ferulic acid, ρ-coumaric acid and sinapinic acid in the presence ofmore » 50 μM copper sulfate. In addition, laccase enzyme assays of cellular protein fractions suggested significant activity on a lignin analog between the temperatures of 45 and 90 °C. As a result, this work shows the potential for A. acidocaldarius to degrade phenolic compounds, demonstrating potential relevance to biofuel production and other industrial processes.« less

Variation in bioactive compounds, antioxidant enzymes and radical-scavenging activity during flower development of Rosa hybrida

NASA Astrophysics Data System (ADS)

Zhang, Yong; Luo, Ya; Wang, Xiaorong; Chen, Qing; Sun, Bo; Wang, Yan; Liu, Zejing; Tang, Haoru

2018-04-01

Roses are one of the most important ornamental plants and have long been used for edible and medicinal flowers. In the present study, the effect of growth and florescence on changes in anthocyanins, proanthocyanidins (PAs), and the activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxide (APX) and glutathione reductase (GR) of two different colored Rosa hybrida genotypes were determined. Four complementary assays, l,l-diphenyl-2-picrylhydrazyl (DPPH), superoxide and hydroxyl radicals scavenging capacity, ferric reducing antioxidant power (FRAP) assay were used to screen the antioxidant activity of rose flower extracts. Significant variations in bioactive compounds, antioxidant enzymes and radical-scavenging activity were observed at six different developmental stages. No significant difference in antioxidant activity between the white cultivar and red cultivar was found. During flower development, total antioxidant activity and involved compounds decreased, however some antioxidant components such as anthocyanins increased. Overall, rose flowers from flower-bud stage to initiating bloom stage possess the high functional benefit and thus would be the appropriate harvesting stage in the view of nutritional consideration.

Synthesis, antimicrobial evaluation and theoretical prediction of NMR chemical shifts of thiazole and selenazole derivatives with high antifungal activity against Candida spp.

NASA Astrophysics Data System (ADS)

Łączkowski, Krzysztof Z.; Motylewska, Katarzyna; Baranowska-Łączkowska, Angelika; Biernasiuk, Anna; Misiura, Konrad; Malm, Anna; Fernández, Berta

2016-03-01

Synthesis and investigation of antimicrobial activities of novel thiazoles and selenazoles is presented. Their structures were determined using NMR, FAB(+)-MS, HRMS and elemental analyses. To support the experiment, theoretical calculations of the 1H NMR shifts were carried out for representative systems within the DFT B3LYP/6-311++G** approximation which additionally confirmed the structure of investigated compounds. Among the derivatives, compounds 4b, 4h, 4j and 4l had very strong activity against reference strains of Candida albicans ATCC and Candida parapsilosis ATCC 22019 with MIC = 0.49-7.81 μg/ml. In the case of compounds 4b, 4c, 4h - 4j and 4l, the activity was very strong against of Candida spp. isolated from clinical materials, i.e. C. albicans, Candida krusei, Candida inconspicua, Candida famata, Candida lusitaniae, Candida sake, C. parapsilosis and Candida dubliniensis with MIC = 0.24-15.62 μg/ml. The activity of several of these was similar to the activity of commonly used antifungal agent fluconazole. Additionally, compounds 4m - 4s were found to be active against Gram-positive bacteria, both pathogenic staphylococci Staphylococcus aureus ATCC with MIC = 31.25-125 μg/ml and opportunistic bacteria, such as Staphylococcus epidermidis ATCC 12228 and Micrococcus luteus ATCC 10240 with MIC = 7.81-31.25 μg/ml.

Synthesis, computational studies and enzyme inhibitory kinetics of substituted methyl[2-(4-dimethylamino-benzylidene)-hydrazono)-4-oxo-thiazolidin-5-ylidene]acetates as mushroom tyrosinase inhibitors.

PubMed

Channar, Pervaiz Ali; Saeed, Aamer; Larik, Fayaz Ali; Rafiq, Muhammad; Ashraf, Zaman; Jabeen, Farukh; Fattah, Tanzeela Abdul

2017-11-01

The present article describes the synthesis and enzyme inhibitory kinetics of methyl[2-(arylmethylene-hydrazono)-4-oxo-thiazolidin-5-ylidene]acetates 5a-j as mushroom tyrosinase inhibitors. The title compounds were synthesized via cyclocondensation of thiosemicarbazones 3a-j with dimethyl but-2-ynedioate (DMAD) 4 in good yields under solvent-free conditions. The synthesized compounds were evaluated for their potential to inhibit the activity of mushroom tyrosinase. It was unveiled that compounds 5i showed excellent enzyme inhibitory activity with IC 50 3.17µM while IC 50 of standard kojic acid is 15.91µM. The presence of heterocyclic pyridine ring in compound 5i play important role in enzyme inhibitory activity as rest of the functional groups are common in all synthesized compounds. The enzyme inhibitory kinetics of the most potent derivative 5i determined by Lineweaver-Burk plots and Dixon plots showed that it is non-competitive inhibitor with Ki value 1.5µM. It was further investigated that the wet lab results are in good agreement with the computational results. The molecular docking of the synthesized compounds was performed against tyrosinase protein (PDBID 2Y9X) to delineate ligand-protein interactions at molecular level. The docking results showed that the major interacting residues are His244, His85, His263, Val 283, His 296, Asn260, Val248, His260, His261 and Phe264 which are located in active binding site of the protein. The molecular modeling demonstrates that the oxygen atom of the compound 5i coordinated with the key residues in the active site of mushroom tyrosinase contribute significantly against inhibitory ability and diminishing the human melanin synthesis. These results evident that compound 5i is a lead structure in developing most potent mushroom tyrosinase inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Isolation and identification of antimicrobial compound from Mentha longifolia L. leaves grown wild in Iraq

PubMed Central

Al-Bayati, Firas A

2009-01-01

Background Mentha longifolia L. (Lamiaceae) leaves have been traditionally implemented in the treatment of minor sore throat and minor mouth or throat irritation by the indigenous people of Iraq, although the compounds responsible for the medicinal properties have not been identified. In the present study, an antimicrobial compound was isolated and characterized, and its biological activity was assessed. Methods The compound was isolated and characterized from the extracted essential oil using different spectral techniques: TLC, FTIR spectra and HPLC. Antimicrobial activity of the compound was assessed using both disc diffusion and microdilution method in 96 multi-well microtiter plates. Results A known compound was isolated from the essential oil of the plant and was identified as (-) menthol. The isolated compound was investigated for its antimicrobial activity against seven selected pathogenic and non-pathogenic microorganisms: Staphylococcus aureus, Streptococcus mutans, Streptococcus faecalis, Streptococcus pyogenis, Lactobacillus acidophilus, Pseudomonas aeruginosa and the yeast Candida albicans. Menthol at different concentrations (1:1, 1:5, 1:10, 1:20) was active against all tested bacteria except for P. aeruginosa, and the highest inhibitory effect was observed against S. mutans (zone of inhibition: 25.3 mm) using the disc diffusion method. Minimal inhibitory concentration MIC values ranged from 15.6–125.0 μg/ml, and the most promising results were observed against S. aureus and S. mutans (MIC 15.6 μg/ml) while, S. faecalis, S. pyogenis and L. acidophilus ranked next (MIC 31.2 μg/ml). Furthermore, menthol achieved considerable antifungal activity against the yeast C. albicans (zone of inhibition range: 7.1–18.5 mm; MIC: 125.0). Conclusion The isolation of an antimicrobial compound from M. longifolia leaves validates the use of this plant in the treatment of minor sore throat and minor mouth or throat irritation. PMID:19523224

Effect of zinc compounds on Fusarium verticillioides growth, hyphae alterations, conidia, and fumonisin production.

PubMed

Savi, Geovana D; Vitorino, Vinícius; Bortoluzzi, Adailton J; Scussel, Vildes M

2013-10-01

Several strategies are used to eliminate toxigenic fungi that produce fumonisins in grains. Fusarium verticillioides can be controlled by the application of synthetic fungicides in the field or during storage. However, there may also be residuals, which may remain in the foods. Inorganic compounds such as zinc are cheap, stable and could present strong antifungal activity. Some Zn compounds can be utilized as dietary supplements and are authorized for the fortification of foods. Knowing the advantages and that low concentrations of Zn can have antimicrobial activity, our objective was to evaluate the effects of Zn compounds on the growth of F. verticillioides and the production of fumonisin and conidia. In addition, we aimed to verify that Zn compounds cause morphological alterations of the hyphae, mortality and production of reactive oxygen species. Zn compounds efficiently reduced fungal growth and fumonisin production. Treatment using zinc perchlorate gave the best results. All treatments inhibited conidia production and caused morphological alterations of the hyphae. It was possible to observe cell death and production of reactive oxygen species. Zn compounds have advantages compared to other antifungal compounds. In particular, they are non-toxic for the organism in appropriate amounts. They could be studied further as potential fungicides in agriculture. © 2013 Society of Chemical Industry.

In Vitro Test for Potential Inhibitors of Plasmepsin II and IV as Anti-malarial Agents

NASA Astrophysics Data System (ADS)

Kang, Hee-Kyoung; Hwang, Soon-Wook; Kim, Do-Won; Breton, Vincent; Kim, Doman

Plasmepsins (PMs) are involved in the degradation of host cell hemoglobin during malaria infection. PM II and IV initiate the degradative process, and have been suggested as attractive targets for treatment of malaria. Previously, 30 compounds were identified by post-processing the results of a large docking screen of commercially available compounds using an automated procedure based on molecular dynamics refinement and binding free-energy estimation using MM-PBSA and MM-GBSA (Degliesposti et al., 2009). Presently, these were experimentally validated using an inhibition assay based on fluorescence resonance energy transfer (FRET) and hemoglobin substrate degradation. Remarkably, 26 of the 30 tested compounds were active as PM II inhibitors, with FRET IC50 values ranging from 4.3 nM to 1.8 μM. Also, IC50 value for PM IV inhibition ranged from 9.34 nM to 83 μM and the best inhibitor among the 30 compounds was compound 7. Hemoglobin degradation by recombinant PM II and IV was completely inhibited by 100 μM of compound 7. The newly identified compounds, and one in particular (compound 7), can inhibit PM II and IV activity and hemoglobin degradation in vitro. These experiments suggest an overall approach in the design of powerful and selective PM II and IV inhibitors.

Deciphering the underlying mechanisms of Diesun Miaofang in traumatic injury from a systems pharmacology perspective

PubMed Central

ZHENG, CHUN-SONG; FU, CHANG-LONG; PAN, CAI-BIN; BAO, HONG-JUAN; CHEN, XING-QIANG; YE, HONG-ZHI; YE, JIN-XIA; WU, GUANG-WEN; LI, XI-HAI; XU, HUI-FENG; XU, XIAO-JIE; LIU, XIAN-XIANG

2015-01-01

Diesun Miaofang (DSMF) is a traditional herbal formula, which has been reported to activate blood, remove stasis, promote qi circulation and relieve pain. DSMF holds a great promise for the treatment of traumatic injury in an integrative and holistic manner. However, its underlying mechanisms remain to be elucidated. In the present study, a systems pharmacology model, which integrated cluster ligands, human intestinal absorption and aqueous solution prediction, chemical space mapping, molecular docking and network pharmacology techniques were used. The compounds from DSMF were diverse in the clusters and chemical space. The majority of the compounds exhibited drug-like properties. A total of 59 compounds were identified to interact with 16 potential targets. In the herb-compound-target network, the majority of compounds acted on only one target; however, a small number of compounds acted on a large number of targets, up to a maximum of 12. The comparison of key topological properties in compound-target networks associated with the above efficacy intuitively demonstrated that potential active compounds possessed diverse functions. These results successfully explained the polypharmcological mechanism underlying the efficiency of DSMF for the treatment of traumatic injury as well as provided insight into potential novel therapeutic strategies for traumatic injury from herbal medicine. PMID:25891262

Involvement of CYP4F2 in the Metabolism of a Novel Monophosphate Ester Prodrug of Gemcitabine and Its Interaction Potential In Vitro.

PubMed

Wang, Yedong; Li, Yuan; Lu, Jia; Qi, Huixin; Cheng, Isabel; Zhang, Hongjian

2018-05-16

Compound- 3 is an oral monophosphate prodrug of gemcitabine. Previous data showed that Compound- 3 was more potent than gemcitabine and it was orally active in a tumor xenograft model. In the present study, the metabolism of Compound- 3 was investigated in several well-known in vitro matrices. While relatively stable in human and rat plasma, Compound- 3 demonstrated noticeable metabolism in liver and intestinal microsomes in the presence of NADPH and human hepatocytes. Compound- 3 could also be hydrolyzed by alkaline phosphatase, leading to gemcitabine formation. Metabolite identification using accurate mass- and information-based scan techniques revealed that Compound- 3 was subjected to sequential metabolism, forming alcohol, aldehyde and carboxylic acid metabolites, respectively. Results from reaction phenotyping studies indicated that cytochrome P450 4F2 (CYP4F2) was a key CYP isozyme involved in Compound- 3 metabolism. Interaction assays suggested that CYP4F2 activity could be inhibited by Compound- 3 or an antiparasitic prodrug pafuramidine. Because CYP4F2 is a key CYP isozyme involved in the metabolism of eicosanoids and therapeutic drugs, clinical relevance of drug-drug interactions mediated via CYP4F2 inhibition warrants further investigation.

Fruit wastes fermentation for phenolic antioxidants production and their application in manufacture of edible coatings and films.

PubMed

Martinez-Avila, G C G; Aguilera, A F; Saucedo, S; Rojas, R; Rodriguez, R; Aguilar, C N

2014-01-01

Agro-industrial by-products are important sources of potent bioactive phenolic compounds. These compounds are of extreme relevance for food and pharmacological industries due to their great variety of biological activities. Fermentation represents an environmentally clean technology for production and extraction of these bioactive compounds, providing high quality and high activity extracts, which can be incorporated in foods using coatings/films wax-based in order to avoid alterations in their quality. In this document is presented an overview about importance and benefits of solid-state fermentation, pointing out this bioprocess as an alternative technology for use agro-industrial by-products as substrates to produce valuable secondary metabolites and their applications as food quality conservatives.

The Extent of Fermentative Transformation of Phenolic Compounds in the Bioanode Controls Exoelectrogenic Activity in a Microbial Electrolysis Cell

DOE PAGES

Zeng, Xiaofei; Collins, Maya; Borole, Abhijeet P.; ...

2016-11-27

Phenolic compounds in hydrolysate/pyrolysate and wastewater streams produced during the pretreatment of lignocellulosic biomass for biofuel production present a significant challenge in downstream processes. Bioelectrochemical systems are increasingly recognized as an alternative technology to handle biomass-derived streams and to promote water reuse in biofuel production. Thus, a thorough understanding of the fate of phenolic compounds in bioanodes is urgently needed. The present study investigated the biotransformation of three structurally similar phenolic compounds (syringic acid, SA; vanillic acid, VA; 4-hydroxybenzoic acid, HBA), and their individual contribution to exoelectrogenesis in a microbial electrolysis cell (MEC) bioanode. Fermentation of SA resulted in themore » highest exoelectrogenic activity among the three compounds tested, with 50% of the electron equivalents converted to current, compared to 12 and 9% for VA and HBA, respectively. The biotransformation of SA, VA and HBA was initiated by demethylation and decarboxylation reactions common to all three compounds, resulting in their corresponding hydroxylated analogs. SA was transformed to pyrogallol (1,2,3-trihydroxybenzene), whose aromatic ring was then cleaved via a phloroglucinol pathway, resulting in acetate production, which was then used in exoelectrogenesis. In contrast, more than 80% of VA and HBA was converted to catechol (1,2-dihydroxybenzene) and phenol (hydroxybenzene) as their respective dead-end products. The persistence of catechol and phenol is explained by the fact that the phloroglucinol pathway does not apply to di- or mono-hydroxylated benzenes. Previously reported, alternative ring-cleaving pathways were either absent in the bioanode microbial community or unfavorable due to high energy-demand reactions. With the exception of acetate oxidation, all biotransformation steps in the bioanode occurred via fermentation, independently of exoelectrogenesis. Therefore, the observed exoelectrogenic activity in batch runs conducted with SA, VA and HBA was controlled by the extent of fermentative transformation of the three phenolic compounds in the bioanode, which is related to the number and position of the methoxy and hydroxyl substituents.« less

[Chemotherapeutic characterization of new nitrosourea compounds].

PubMed

Zeller, W J; Berger, M R; Eisenbrand, G; Petru, E

1988-01-01

The development of new nitrosoureas is described using selected examples. Results obtained with water-soluble analogs and with compounds linked to biomolecules as for instance amino acids, oligopeptides and steroids, are presented. The pronounced antineoplastic effect of some water-soluble analogs is paralleled by an increased rate of DNA-interstrand cross-links and by an increased suppression of hematopoietic stem cells. The suppression of bone marrow stem cells is followed by their rapid regeneration. Water-soluble nitrosoureas induce significant less inhibition of glutathione reductase as compared with established compounds. With regard to long-term toxicity and carcinogenicity water-soluble are superior to established compounds as for instance BCNU. Linking of the nitrosourea moiety to amino acids and oligopeptides led to some analogs with outstanding therapeutic ratio. Out of a group of steroid-linked nitrosoureas, CNC-L-alanine-estradiol-17-ester (CNC-ala-17-E2) is chosen to demonstrate the possibility of reducing bone marrow toxicity despite unchanged or increased therapeutic activity by attachment of the nitrosourea moiety to a steroid. Results of a comparative interspecies in vitro evaluation of CNC-ala-17-E2 in transplanted MXT mammary carcinoma of the mouse, MNU-induced autochthonous rat mammary carcinoma and primary human mammary carcinomas are presented and the question is discussed to what extent in vitro activity of such receptor agents using the tumor stem cell assay reflects their in vivo activity.

Identification of anti-proliferative kinase inhibitors as potential therapeutic agents to treat canine osteosarcoma.

PubMed

Mauchle, Ulrike; Selvarajah, Gayathri T; Mol, Jan A; Kirpensteijn, Jolle; Verheije, Monique H

2015-08-01

Osteosarcoma is the most common primary bone tumour in dogs but various forms of therapy have not significantly improved clinical outcomes. As dysregulation of kinase activity is often present in tumours, kinases represent attractive molecular targets for cancer therapy. The purpose of this study was to identify novel compounds targeting kinases with the potential to induce cell death in a panel of canine osteosarcoma cell lines. The ability of 80 well-characterized kinase inhibitor compounds to inhibit the proliferation of four canine osteosarcoma cell lines was investigated in vitro. For those compounds with activity, the mechanism of action and capability to potentiate the activity of doxorubicin was further evaluated. The screening showed 22 different kinase inhibitors that induced significant anti-proliferative effects across the four canine osteosarcoma cell lines investigated. Four of these compounds (RO 31-8220, 5-iodotubercidin, BAY 11-7082 and an erbstatin analog) showed significant cell growth inhibitory effects across all cell lines in association with variable induction of apoptosis. RO 31-8220 and 5-iodotubercidin showed the highest ability to potentiate the effects of doxorubicin on cell viability. In conclusion, the present study identified several potent kinase inhibitors targeting the PKC, CK1, PKA, ErbB2, mTOR and NF-κB pathways, which may warrant further investigations for the treatment of osteosarcoma in dogs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Facial Regioselective Synthesis of Novel Bioactive Spiropyrrolidine/Pyrrolizine-Oxindole Derivatives via a Three Components Reaction as Potential Antimicrobial Agents.

PubMed

Hassaneen, Huwaida M E; Eid, Elshimaa M; Eid, Hamid A; Farghaly, Thoraya A; Mabkhot, Yahia Nasser

2017-02-26

This article presents the synthesis of new derivatives of spirooxindole-spiropiperidinone- pyrrolidines 6a - j and spirooxindole-spiropiperidinone-pyrrolizines 8a - j, through a 1,3-dipolar cycloaddition reaction of azomethineylides generated from isatin, sarcosine, and l-proline, through a decarboxylative route with dipolarophile 4a - j . All of the newly synthesized compounds were evaluated for their antimicrobial activities and their minimum inhibitory concentration (MIC) against most of the test organisms. The tested compounds displayed excellent activity against all of the tested microorganisms.

NSAID-derived gamma-secretase modulators. Part III: Membrane anchoring.

PubMed

Baumann, Stefanie; Höttecke, Nicole; Schubenel, Robert; Baumann, Karlheinz; Schmidt, Boris

2009-12-15

Selective lowering of Abeta(42) levels with small-molecule substrate targeting gamma-secretase modulators (sGSMs), such as some non-steroidal anti-inflammatory drugs, is a promising therapeutic approach for Alzheimer's disease. Here we present N-substituted carbazole- and O-substituted fenofibrate-derived sGSMs and their activity data. Seven out of 19 screened compounds exhibited promising activity against Abeta(42) secretion at a low micromolar level. We presume that the sGSMs interact with lys624 at the membrane interface and that the lipophilic substituents anchor the compound orientation in the membrane.

Computational ligand-based rational design: Role of conformational sampling and force fields in model development.

PubMed

Shim, Jihyun; Mackerell, Alexander D

2011-05-01

A significant number of drug discovery efforts are based on natural products or high throughput screens from which compounds showing potential therapeutic effects are identified without knowledge of the target molecule or its 3D structure. In such cases computational ligand-based drug design (LBDD) can accelerate the drug discovery processes. LBDD is a general approach to elucidate the relationship of a compound's structure and physicochemical attributes to its biological activity. The resulting structure-activity relationship (SAR) may then act as the basis for the prediction of compounds with improved biological attributes. LBDD methods range from pharmacophore models identifying essential features of ligands responsible for their activity, quantitative structure-activity relationships (QSAR) yielding quantitative estimates of activities based on physiochemical properties, and to similarity searching, which explores compounds with similar properties as well as various combinations of the above. A number of recent LBDD approaches involve the use of multiple conformations of the ligands being studied. One of the basic components to generate multiple conformations in LBDD is molecular mechanics (MM), which apply an empirical energy function to relate conformation to energies and forces. The collection of conformations for ligands is then combined with functional data using methods ranging from regression analysis to neural networks, from which the SAR is determined. Accordingly, for effective application of LBDD for SAR determinations it is important that the compounds be accurately modelled such that the appropriate range of conformations accessible to the ligands is identified. Such accurate modelling is largely based on use of the appropriate empirical force field for the molecules being investigated and the approaches used to generate the conformations. The present chapter includes a brief overview of currently used SAR methods in LBDD followed by a more detailed presentation of issues and limitations associated with empirical energy functions and conformational sampling methods.

Toward an Increased Functionality in Oyster ( Pleurotus) Mushrooms Produced on Grape Marc or Olive Mill Wastes Serving as Sources of Bioactive Compounds.

PubMed

Koutrotsios, Georgios; Kalogeropoulos, Nick; Kaliora, Andriana C; Zervakis, Georgios I

2018-06-20

Pleurotus ostreatus, P. eryngii, and P. nebrodensis were cultivated on nonconventional substrates containing grape marc (GMC) or olive mill byproducts (OMB); wheat straw (WHS) served as control. GMC-based media demonstrated equal/better mushroom productivity than WHS for P. eryngii and P. nebrodensis, while the cultivation performance of P. eryngii was improved in OMB-based media. Both GMC and OMB substrates led to large increase of fruit-bodies content in phenolic acids, resveratrol, triterpenic compounds, and ergosterol; in particular, P. eryngii mushrooms presented significantly more total phenolics and exhibited much higher antioxidant activity (2- to 8-fold increase). Furthermore, substrates containing GMC or OMB presented up to 27% increase in mushroom β-glucans. Overall, Pleurotus species responded in a different and mostly substrate-specific manner by selectively absorbing organic compounds. Phenolics and squalene content of substrates correlated very well with mushrooms antioxidant activity and ergosterol, respectively; the same was observed for triterpenics' content of substrates and mushrooms.

In vitro penetration through the skin layers of topically applied glucocorticoids.

PubMed

Carrer, Victor; Alonso, Cristina; Oliver, Marc Adrià; Coderch, Luisa

2018-05-22

Corticoids are actives widely used in the treatment of skin diseases. This work aims to study the penetration of three corticoids (betamethasone, clobetasol and flurandrenolide), their relationship with their Log D values and the effects of the vehicles. The three compounds were applied on a Franz-type diffusion cell in propylene glycol solution and their respective commercial creams and ointments. The active amounts found in the stratum corneum, epidermal and dermal layers of the skin were investigated. Their diffusions were greatly affected by the formulation, moreover higher amounts of substance in the epidermis and dermis were detected in ointments than in creams. The enhancement effect of propylene glycol was also observed. Moreover, the differences between the three substances could be related to their lipophilicity, molecular structure and molecular weight. The more hydrophobic compounds (clobetasol and betamethasone) are present in higher amounts in the epidermis and dermis, while the hydrophilic compound (flurandrenolide) is mostly present in the receptor fluid. This article is protected by copyright. All rights reserved.

QSAR, docking and ADMET studies of artemisinin derivatives for antimalarial activity targeting plasmepsin II, a hemoglobin-degrading enzyme from P. falciparum.

PubMed

Qidwai, Tabish; Yadav, Dharmendra K; Khan, Feroz; Dhawan, Sangeeta; Bhakuni, R S

2012-01-01

This work presents the development of quantitative structure activity relationship (QSAR) model to predict the antimalarial activity of artemisinin derivatives. The structures of the molecules are represented by chemical descriptors that encode topological, geometric, and electronic structure features. Screening through QSAR model suggested that compounds A24, A24a, A53, A54, A62 and A64 possess significant antimalarial activity. Linear model is developed by the multiple linear regression method to link structures to their reported antimalarial activity. The correlation in terms of regression coefficient (r(2)) was 0.90 and prediction accuracy of model in terms of cross validation regression coefficient (rCV(2)) was 0.82. This study indicates that chemical properties viz., atom count (all atoms), connectivity index (order 1, standard), ring count (all rings), shape index (basic kappa, order 2), and solvent accessibility surface area are well correlated with antimalarial activity. The docking study showed high binding affinity of predicted active compounds against antimalarial target Plasmepsins (Plm-II). Further studies for oral bioavailability, ADMET and toxicity risk assessment suggest that compound A24, A24a, A53, A54, A62 and A64 exhibits marked antimalarial activity comparable to standard antimalarial drugs. Later one of the predicted active compound A64 was chemically synthesized, structure elucidated by NMR and in vivo tested in multidrug resistant strain of Plasmodium yoelii nigeriensis infected mice. The experimental results obtained agreed well with the predicted values.

A Multi-species Bait for Chagas Disease Vectors

PubMed Central

Mota, Theo; Vitta, Ana C. R.; Lorenzo-Figueiras, Alicia N.; Barezani, Carla P.; Zani, Carlos L.; Lazzari, Claudio R.; Diotaiuti, Liléia; Jeffares, Lynne; Bohman, Björn; Lorenzo, Marcelo G.

2014-01-01

Background Triatomine bugs are the insect vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. These insects are known to aggregate inside shelters during daylight hours and it has been demonstrated that within shelters, the aggregation is induced by volatiles emitted from bug feces. These signals promote inter-species aggregation among most species studied, but the chemical composition is unknown. Methodology/Principal Findings In the present work, feces from larvae of the three species were obtained and volatile compounds were identified by solid phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS). We identified five compounds, all present in feces of all of the three species: Triatoma infestans, Panstrongylus megistus and Triatoma brasiliensis. These substances were tested for attractivity and ability to recruit insects into shelters. Behaviorally active doses of the five substances were obtained for all three triatomine species. The bugs were significantly attracted to shelters baited with blends of 160 ng or 1.6 µg of each substance. Conclusions/Significance Common compounds were found in the feces of vectors of Chagas disease that actively recruited insects into shelters, which suggests that this blend of compounds could be used for the development of baits for early detection of reinfestation with triatomine bugs. PMID:24587457

Human aldo-keto reductases 1B1 and 1B10: a comparative study on their enzyme activity toward electrophilic carbonyl compounds.

PubMed

Shen, Yi; Zhong, Linlin; Johnson, Stephen; Cao, Deliang

2011-05-30

Aldo-keto reductase family 1 member B1 (AKR1B1, 1B1 in brief) and aldo-keto reductase family 1 member B10 (AKR1B10, 1B10 in brief) are two proteins with high similarities in their amino acid sequences, stereo structures, and substrate specificity. However, these two proteins exhibit distinct tissue distributions; 1B10 is primarily expressed in the gastrointestinal tract and adrenal gland, whereas 1B1 is ubiquitously present in all tissues/organs, suggesting their difference in biological functions. This study evaluated in parallel the enzyme activity of 1B1 and 1B10 toward alpha, beta-unsaturated carbonyl compounds with cellular and dietary origins, including acrolein, crotonaldehyde, 4-hydroxynonenal, trans-2-hexenal, and trans-2,4-hexadienal. Our results showed that 1B10 had much better enzyme activity and turnover rates toward these chemicals than 1B1. By detecting the enzymatic products using high-performance liquid chromatography, we measured their activity to carbonyl compounds at low concentrations. Our data showed that 1B10 efficiently reduced the tested carbonyl compounds at physiological levels, but 1B1 was less effective. Ectopically expressed 1B10 in 293T cells effectively eliminated 4-hydroxynonenal at 5 μM by reducing to 1,4-dihydroxynonene, whereas endogenously expressed 1B1 did not. The 1B1 and 1B10 both showed enzyme activity to glutathione-conjugated carbonyl compounds, but 1B1 appeared more active in general. Together our data suggests that 1B10 is more effectual in eliminating free electrophilic carbonyl compounds, but 1B1 seems more important in the further detoxification of glutathione-conjugated carbonyl compounds. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Validation of ethnomedicinal potential of Tinospora cordifolia for anticancer and immunomodulatory activities and quantification of bioactive molecules by HPTLC.

PubMed

Bala, Manju; Pratap, Kunal; Verma, Praveen Kumar; Singh, Bikram; Padwad, Yogendra

2015-12-04

Tinospora cordifolia (Willd.) Miers ex Hook. f. & Thomas. (Menispermaceae) is one of the most widely used plants in various traditional medicinal systems including "Ayurveda". The plant is used for the treatment of jaundice, rheumatism, urinary disorder, skin diseases, diabetes and anemia. The phytoconstituents present in the plant belongs to different class of compounds such as alkaloids, diterpenoids lactones, glycosides, steroids, phenol, aliphatic compounds and polysaccharides. The aim of present study was the isolation, structure elucidation, quantification and pharmacological evaluation of secondary metabolites from T. cordifolia for anticancer and immunomodulatory activities. Different extracts and fractions were prepared from the stem of T. cordifolia. Pure molecules were isolated using normal phase chromatography and characterized on the basis of NMR and mass spectroscopic techniques. The anti-cancer and immunomodulatory activities of different extracts, fractions and isolated compounds were evaluated against four different human cancer cell lines, KB (human oral squamous carcinoma), CHOK-1 (hamster ovary), HT-29 (human colon cancer) and SiHa (human cervical cancer) and murine primary cells respectively. A simple, normal phase HPTLC method was also developed for the quantification of three bioactive compounds i.e N-formylannonain (1), 11-hydroxymustakone (5) and yangambin (8) in the stem of T. cordifolia hosted on fifteen different plants. Chromatographic purification of different fractions led to the isolation of eight pure molecules i.e N-formylannonain (1), magnoflorine (2), jatrorrhizine (3) palmatine (4), 11-hydroxymustakone (5), cordifolioside A (6), tinocordiside (7) and yangambin (8). All extracts and fractions were active against KB and CHOK-1 cells whereas among the pure molecules palmatine (4) was found to be active against KB and HT-29; tinocordiside (7) against KB and CHOK-1; yangambin (8) against KB cells however N-formylannonain (1) and 11-hydroxymustakone (5), was found active for immunomodulatory activity. HPTLC quantification of three active molecules i.e N-formylannonain (1), 11-hydroxymustakone (5), and yangambin (8) were found in highest quantity in the stem of T. cordifolia hosted on Mangifera indica, however, other two active molecules were not quantified due to their insufficient quantity. Eight compounds have been isolated and characterized belonging to different classes. The pharmacological evaluation of extract, fractions and pure molecules revealed the ethnomedicinal value of T. cordifolia for anticancer and immunomodulatory activities. Copyright © 2015. Published by Elsevier Ireland Ltd.

Polyhydroxybutyrate and phenolic compounds microalgae electrospun nanofibers: A novel nanomaterial with antibacterial activity.

PubMed

Kuntzler, Suelen Goettems; Almeida, Ana Claudia Araujo de; Costa, Jorge Alberto Vieira; Morais, Michele Greque de

2018-07-01

Polymer nanofibers produced by electrospinning are promising for use in food packaging because of their nanometric diameter, which provides a barrier to external conditions above the possible incorporation of the active compounds. The microalga Spirulina sp. LEB 18 synthesizes bioproducts, such as polyhydroxybutyrate (PHB), which is biodegradable and has similar mechanical and thermal properties to polymers of petrochemical origin. Moreover, phenolic compounds of microalgae have antibacterial, antifungal, and antioxidant activities, which is a differential for the development of packaging. The objective of the study was to develop a nanomaterial with antibacterial action from bioproducts of microalgal origin. PHB nanofibers containing phenolic compounds presented average diameter of 810±85nm exhibited hydrophobicity, which gave protection to the food relative to the moisture outside the package. These nanofibers showed inhibition of the growth of Staphylococcus aureus ATCC 25923 with a zone of 7.5±0.4mm. Thermal and mechanical properties have confirmed the potential applicability of this material as food packaging. This new nanomaterial combines a packaging function to protect products and to be biodegradable with the antibacterial activity that prevents the proliferation of microorganisms and ensures the quality and preservation of food. Published by Elsevier B.V.

Effects of extraction methods on the antioxidant activities of polysaccharides from Agaricus blazei Murrill.

PubMed

Jia, Shaoyi; Li, Feng; Liu, Yong; Ren, Haitao; Gong, Guili; Wang, Yanyan; Wu, Songhai

2013-11-01

Five polysaccharides were obtained from Agaricus blazei Murrill (ABM) through different extraction methods including hot water extraction, single enzyme extraction (pectinase, cellulase or papain) and compound enzymes extraction (cellulase:pectinase:papain). Their characteristics such as the polysaccharide yield, polysaccharide content, protein content, infrared spectra were determined, and antioxidant activities were investigated on the basis of hydroxyl radical, DPPH free radical, ABTS free radical and reducing power. The results showed that five extracts exhibited antioxidant activities in a concentration-dependent manner. Compared with other methods, the compound enzymes extraction method was found to present the highest polysaccharides yield (17.44%). Moreover, compound enzymes extracts exhibited the strongest reducing power and highest scavenging rates on hydroxyl radicals, DPPH radicals and ABTS radicals. On the contrary, hot water extraction method had the lowest polysaccharides yield of 11.95%, whose extracts also exhibited the lowest antioxidant activities. Overall, the available data obtained in vitro models suggested that ABM extracts were natural antioxidants and compound enzymes extraction was an appropriate, mild and effective extracting method for obtaining the polysaccharide extracts from Agaricus blazei Murrill (ABM). Copyright © 2013 Elsevier B.V. All rights reserved.

Multicomponent synthesis of some new (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-dithiocarbamates and their in vitro anti-proliferative activity against CaSki, MDA-MB-231 and SK-Lu-1 tumour cells as apoptosis inducing agents without necrosis.

PubMed

Laskar, Sujay; Sánchez-Sánchez, Luis; López-Ortiz, Manuel; López-Muñoz, Hugo; Escobar-Sánchez, María L; Sánchez, Arturo T; Regla, Ignacio

2017-12-01

Identification of a new class of antitumor agent capable to induce apoptosis without triggering necrotic cell death event is challenging. The present communication describes the multicomponent synthesis of seven new (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-dithiocarbamates and their in vitro antiproliferative activity on cervical cancer cell line (CaSki), breast cancer cell line (MDA-MB231), lung cancer cell line (SK-Lu-1) and human lymphocytes. Among the synthesized dithiocarbamates, compound 9e displayed significant antiproliferative activity without inducing any necrotic cell death (both on tumour cells and lymphocytes) and induced apoptosis in tumor cells by the caspase dependent apoptotic pathway. The compound 9e also exhibited greater tumor selectivity than human lymphocytes. In silico ADME predictions revealed that compound 9e has the potential to be developed as a drug candidate. Rapid chemical modifications of this lead are thus highly necessary for further investigation as a drug like safer antitumor candidate and also to achieve compounds with better activity profile.

Ginger Phytochemicals Inhibit Cell Growth and Modulate Drug Resistance Factors in Docetaxel Resistant Prostate Cancer Cell.

PubMed

Liu, Chi-Ming; Kao, Chiu-Li; Tseng, Yu-Ting; Lo, Yi-Ching; Chen, Chung-Yi

2017-09-05

Ginger has many bioactive compounds with pharmacological activities. However, few studies are known about these bioactive compounds activity in chemoresistant cells. The aim of the present study was to investigate the anticancer properties of ginger phytochemicals in docetaxel-resistant human prostate cancer cells in vitro. In this study, we isolated 6-gingerol, 10-gingerol, 4-shogaol, 6-shogaol, 10-shogaol, and 6-dehydrogingerdione from ginger. Further, the antiproliferation activity of these compounds was examined in docetaxel-resistant (PC3R) and sensitive (PC3) human prostate cancer cell lines. 6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol at the concentration of 100 μM significantly inhibited the proliferation in PC3R but 6-gingerol, 6-shogaol, and 10-shogaol displayed similar activity in PC3. The protein expression of multidrug resistance associated protein 1 (MRP1) and glutathione-S-transferase (GSTπ) is higher in PC3R than in PC3. In summary, we isolated the bioactive compounds from ginger. Our results showed that 6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol inhibit the proliferation of PC3R cells through the downregulation of MRP1 and GSTπ protein expression.

Noscapinoids with anti-cancer activity against human acute lymphoblastic leukemia cells (CEM): a three dimensional chemical space pharmacophore modeling and electronic feature analysis.

PubMed

Naik, Pradeep K; Santoshi, Seneha; Joshi, Harish C

2012-01-01

We have identified a new class of microtubule-binding compounds-noscapinoids-that alter microtubule dynamics at stoichiometric concentrations without affecting tubulin polymer mass. Noscapinoids show great promise as chemotherapeutic agents for the treatment of human cancers. To investigate the structural determinants of noscapinoids responsible for anti-cancer activity, we tested 36 structurally diverse noscapinoids in human acute lymphoblastic leukemia cells (CEM). The IC(50) values of these noscapinoids vary from 1.2 to 56.0 μM. Pharmacophore models of anti-cancer activity were generated that identify two hydrogen bond acceptors, two aromatic rings, two hydrophobic groups, and one positively charged group as essential structural features. Additionally, an atom-based quantitative structure-activity relationship (QSAR) model was developed that gave a statistically satisfying result (R(2) = 0.912, Q(2) = 0.908, Pearson R = 0.951) and effectively predicts the anti-cancer activity of training and test set compounds. The pharmacophore model presented here is well supported by electronic property analysis using density functional theory at B3LYP/3-21*G level. Molecular electrostatic potential, particularly localization of negative potential near oxygen atoms of the dimethoxy isobenzofuranone ring of active compounds, matched the hydrogen bond acceptor feature of the generated pharmacophore. Our results further reveal that all active compounds have smaller lowest unoccupied molecular orbital (LUMO) energies concentrated over the dimethoxy isobenzofuranone ring, azido group, and nitro group, which is indicative of the electron acceptor capacity of the compounds. Results obtained from this study will be useful in the efficient design and development of more active noscapinoids.

Caatinga plants: Natural and semi-synthetic compounds potentially active against Trichomonas vaginalis.

PubMed

Vieira, Patrícia de Brum; Silva, Nícolas Luiz Feijó; da Silva, Gloria Narjara Santos; Silva, Denise Brentan; Lopes, Norberto Peporine; Gnoatto, Simone Cristina Baggio; da Silva, Márcia Vanusa; Macedo, Alexandre José; Bastida, Jaume; Tasca, Tiana

2016-05-01

Trichomonas vaginalis causes trichomoniasis; the most common but overlooked non-viral sexually transmitted disease worldwide. The treatment is based at 5'-nitroimidazoles, however, failure are related to resistance of T. vaginalis to chemotherapy. Caatinga is a uniquely Brazilian region representing a biome with type desert vegetation and plants present diverse biological activity, however, with few studies. The aim of this study was to investigate the activity against T. vaginalis of different plants from Caatinga and identify the compounds responsible by the activity. A bioguided fractionation of Manilkara rufula was performed and four major compounds were identified: caproate of α-amyrin (1b), acetate of β-amyrin (2a), caproate of β-amyrin (2b), and acetate of lupeol (3a). In addition, six derivatives of α-amyrin (1), β-amyrin (2) and lupeol (3) were synthesized and tested against the parasite. Ursolic acid (5) reduced about 98% of parasite viability after 2h of incubation and drastic ultrastructural alterations were observed by scanning electron microscopy. Moreover, 5 presented high cytotoxicity to HMVII and HeLa cell line and low cytotoxicity against Vero line at 50 μM (MIC against the parasite). Metronidazole effect against T. vaginalis resistant isolate was improved when in association with 5. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anti-inflammatory effect of anthocyanins via modulation of nuclear factor-κB and mitogen-activated protein kinase signaling cascades.

PubMed

Vendrame, Stefano; Klimis-Zacas, Dorothy

2015-06-01

Anthocyanins are a group of bioactive compounds present in plant foods. Although they have consistently shown an anti-inflammatory effect both in vitro and in vivo, their mechanisms of action are not fully understood and have only recently begun to be elucidated. The aim of this review is to highlight the anti-inflammatory activity of anthocyanins, including their effect on the expression of several genes involved in inflammation. The available evidence suggests that their anti-inflammatory action can be attributed primarily to their antioxidant properties, which result in downregulation of the redox-sensitive nuclear factor-κB signaling pathway. Other pathways at least partly involved in the inflammatory response, particularly the mitogen-activated protein kinase pathways, also appear to play a role. A discussion is presented on the most effective dose of anthocyanins, the differential contribution of specific compounds, the comparative effects of anthocyanins versus other anti-inflammatory phenolic compounds, and the extent to which the observed biological activities are exerted by anthocyanins themselves or their metabolites. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Potential application of aromatic plant extracts to prevent cheese blowing.

PubMed

Librán, C M; Moro, A; Zalacain, A; Molina, A; Carmona, M; Berruga, M I

2013-07-01

This study aimed to inhibit the growth of Escherichia coli and Clostridium tyrobutyricum, common bacteria responsible for early and late cheese blowing defects respectively, by using novel aqueous extracts obtained by dynamic solid-liquid extraction and essential oils obtained by solvent free microwave extraction from 12 aromatic plants. In terms of antibacterial activity, a total of 13 extracts inhibited one of the two bacteria, and only two essential oils, Lavandula angustifolia Mill. and Lavandula hybrida, inhibited both. Four aqueous extracts were capable of inhibiting C. tyrobutyricum, but none were effective against E. coli. After extracts' chemical composition identification, relationship between the identified compounds and their antibacterial activity were performed by partial least square regression models revealing that compounds such as 1,8 cineole, linalool, linalyl acetate, β-phellandrene or verbene (present in essential oils), pinocarvone, pinocamphone or coumaric acid derivate (in aqueous extracts) were compounds highly correlated to the antibacterial activity.

Red wines and flavonoids diminish Staphylococcus aureus virulence with anti-biofilm and anti-hemolytic activities.

PubMed

Cho, Hyun Seob; Lee, Jin-Hyung; Cho, Moo Hwan; Lee, Jintae

2015-01-01

The emergence of antibiotic resistant Staphylococcus aureus presents a worldwide problem that requires non-antibiotic strategies. This study investigated the anti-biofilm and anti-hemolytic activities of four red wines and two white wines against three S. aureus strains. All red wines at 0.5-2% significantly inhibited S. aureus biofilm formation and hemolysis by S. aureus, whereas the two white wines had no effect. Furthermore, at these concentrations, red wines did not affect bacterial growth. Analyses of hemolysis and active component identification in red wines revealed that the anti-biofilm compounds and anti-hemolytic compounds largely responsible were tannic acid, trans-resveratrol, and several flavonoids. In addition, red wines attenuated S. aureus virulence in vivo in the nematode Caenorhabditis elegans, which is killed by S. aureus. These findings show that red wines and their compounds warrant further attention in antivirulence strategies against persistent S. aureus infection.

UV light induced surface modification of HDPE films with bioactive compounds

NASA Astrophysics Data System (ADS)

Daniloska, Vesna; Blazevska-Gilev, Jadranka; Dimova, Vesna; Fajgar, Radek; Tomovska, Radmila

2010-01-01

The development of different techniques for surface modification of polymers becomes popular in a last decade. These techniques preserve useful bulk polymer properties unchanged, while the activation of the polymer surface offers more possibilities for polymer applications. In this work, a new, one-step method for bio-activation of HDPE (high density polyethylene) surface by UV irradiation is presented. HDPE films coupled with selected active compound and a photoinitiator was treated by UV lamp, emitting light at 254 nm. For surface functionalization of HDPE films, the following compounds were employed: 2-aminopyridine (AP), N 1-(2-pyridylaminomethyl)-1,2,4-triazole (TA) and benzocaine (BC). The influence of irradiation time on the extent of surface changes was investigated. The modified polymer surfaces were investigated by Fourier transformed infrared (FTIR) and Raman spectroscopy, scanning electron microscopy (SEM) and contact angle measurements, demonstrating successful functionalization of HDPE surface.

Novel 2-Phenoxyanilide Congeners Derived from a Hit Structure of the TCAMS: Synthesis and Evaluation of Their in Vitro Activity against Plasmodium falciparum.

PubMed

Weidner, Thomas; Nasereddin, Abed; Preu, Lutz; Grünefeld, Johann; Dzikowski, Ron; Kunick, Conrad

2016-02-17

The Tres Cantos Antimalarial Compound Set (TCAMS) is a publicly available compound library which contains 13533 hit structures with confirmed activity against Plasmodium falciparum, the infective agent responsible for malaria tropica. The TCAMS provides a variety of starting points for the investigation of new antiplasmodial drug leads. One of the promising compounds is TCMDC-137332, which seemed to be a good starting point due to its antiplasmodial potency and its predicted physicochemical properties. Several new analogues based on a 2-phenoxyanilide scaffold were synthesized by standard amide coupling reactions and were fully characterized regarding their identity and purity by spectroscopic and chromatographic methods. Furthermore, the results of the biological evaluation of all congeners against Plasmodium falciparum NF54 strains are presented. The findings of our in vitro screening could not confirm the presumed nanomolar antiplasmodial activity of TCMDC-137332 and its derivatives.

Synthesis and biological activity evaluation of cytidine-5'-deoxy-5-fluoro-N-[(alkoxy/aryloxy)] carbonyl-cyclic 2',3'-carbonates.

PubMed

Jhansi Rani, V; Raghavendra, A; Kishore, P; Nanda Kumar, Y; Hema Kumar, K; Jagadeeswarareddy, K

2012-08-01

Capecitabine, an oral prodrug of 5-FU was developed to improve the tumor selectivity and tolerability. To enhance the efficacy of capacitabine, a series of 5'-deoxy-5-fluorocytidine derivatives 5a-e were synthesized. In the present study, we investigated antitumor activity of 5'-deoxy-5-fluorocytidine derivatives both in vivo and in vitro methods. Title compounds were non-mutagenic to Salmonella typhimurium tester strain in Ames test. Compounds 5d and 5e are potent to inhibit the proliferation of NCI-69, PZ-HPV-7, MCF-7 and HeLa cells in MTT assay. In particular, 5d and 5e showed potent antitumor activities against L1210 leukemia cell line. Collectively, these findings suggest that 5d and 5e are more potent anti-cancer compounds than capecitabine. Published by Elsevier Masson SAS.

Synthesis, antimalarial evaluation and molecular docking studies of some thiolactone derivatives

NASA Astrophysics Data System (ADS)

Sainy, Jitendra; Sharma, Rajesh

2017-04-01

In present study novel thiolactone derivatives were designed, synthesized and characterized by various analytical techniques such as IR, 1H NMR, 13C NMR, mass spectral data and elemental analysis. All synthesized compounds were evaluated for in vitro antimalarial activity against Dd2 and 3d7 strain of P. falciparum. All synthesized compounds were also subjected for molecular docking study with pf KASI/II enzyme to analyze their binding orientation in the active site of the enzyme. Compounds 5d, 5e, and 5i found to be most potent with IC50 in the range of 0.09-0.19 μM and 0.03-0.04 μM against the Dd2 strain and 3D7 strain respectively as well as they showed good binding affinities with the residues of the active site of pf KASI/II.

Novel oxime based flavanone, naringin-oxime: synthesis, characterization and screening for antioxidant activity.

PubMed

Ozyürek, Mustafa; Akpınar, Damla; Bener, Mustafa; Türkkan, Baki; Güçlü, Kubilay; Apak, Reşat

2014-04-05

Recent interest in polyphenolic antioxidants due to their involvement in health benefits has led to the investigation of new polyphenolic compounds with enhanced antioxidant activity. Naringin (4',5,7-trihydroxyflavanone-7-β-l-rhamnoglucoside-(1,2)-α-d-glucopyranoside) is one of the major flavanones in citrus and grapefruit. The present study aimed to synthesize naringin oxime from naringin and to evaluate its antioxidant and anticancer potential using in vitro assay system. The structure of the synthesized compound, naringin oxime, was elucidated by FT-IR, (1)H NMR, elemental analysis and UV-vis spectroscopy. Antioxidant capacity of naringin oxime, as measured by the cupric reducing antioxidant capacity (CUPRAC) method, was found to be higher than that of the parent compound naringin. Other parameters of antioxidant activity (scavenging effects on OH, O2(-), and H2O2) of naringin and naringin oxime were also determined. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Metagenomic approaches to exploit the biotechnological potential of the microbial consortia of marine sponges.

PubMed

Kennedy, Jonathan; Marchesi, Julian R; Dobson, Alan D W

2007-05-01

Natural products isolated from sponges are an important source of new biologically active compounds. However, the development of these compounds into drugs has been held back by the difficulties in achieving a sustainable supply of these often-complex molecules for pre-clinical and clinical development. Increasing evidence implicates microbial symbionts as the source of many of these biologically active compounds, but the vast majority of the sponge microbial community remain uncultured. Metagenomics offers a biotechnological solution to this supply problem. Metagenomes of sponge microbial communities have been shown to contain genes and gene clusters typical for the biosynthesis of biologically active natural products. Heterologous expression approaches have also led to the isolation of secondary metabolism gene clusters from uncultured microbial symbionts of marine invertebrates and from soil metagenomic libraries. Combining a metagenomic approach with heterologous expression holds much promise for the sustainable exploitation of the chemical diversity present in the sponge microbial community.

Antiviral Activity of Natural Products Extracted from Marine Organisms

PubMed Central

Uzair, Bushra; Mahmood, Zahra; Tabassum, Sobia

2011-01-01

Many epidemics have broken out over the centuries. Hundreds and thousands of humans have died over a disease. Available treatments for infectious diseases have always been limited. Some infections are more deadly than the others, especially viral pathogens. These pathogens have continuously resisted all kinds of medical treatment, due to a need for new treatments to be developed. Drugs are present in nature and are also synthesized in vitro and they help in combating diseases and restoring health. Synthesizing drugs is a hard and time consuming task, which requires a lot of man power and financial aid. However, the natural compounds are just lying around on the earth, may it be land or water. Over a thousand novel compounds isolated from marine organisms are used as antiviral agents. Others are being pharmacologically tested. Today, over forty antiviral compounds are present in the pharmacological market. Some of these compounds are undergoing clinical and preclinical stages. Marine compounds are paving the way for a new trend in modern medicine. PMID:23678429

Marine Cyanobacteria Compounds with Anticancer Properties: A Review on the Implication of Apoptosis

PubMed Central

Costa, Margarida; Costa-Rodrigues, João; Fernandes, Maria Helena; Barros, Piedade; Vasconcelos, Vitor; Martins, Rosário

2012-01-01

Marine cyanobacteria have been considered a rich source of secondary metabolites with potential biotechnological applications, namely in the pharmacological field. Chemically diverse compounds were found to induce cytoxicity, anti-inflammatory and antibacterial activities. The potential of marine cyanobacteria as anticancer agents has however been the most explored and, besides cytotoxicity in tumor cell lines, several compounds have emerged as templates for the development of new anticancer drugs. The mechanisms implicated in the cytotoxicity of marine cyanobacteria compounds in tumor cell lines are still largely overlooked but several studies point to an implication in apoptosis. This association has been related to several apoptotic indicators such as cell cycle arrest, mitochondrial dysfunctions and oxidative damage, alterations in caspase cascade, alterations in specific proteins levels and alterations in the membrane sodium dynamics. In the present paper a compilation of the described marine cyanobacterial compounds with potential anticancer properties is presented and a review on the implication of apoptosis as the mechanism of cell death is discussed. PMID:23170077

Chemical Variability and Biological Activities of Brassica rapa var. rapifera Parts Essential Oils Depending on Geographic Variation and Extraction Technique.

PubMed

Saka, Boualem; Djouahri, Abderrahmane; Djerrad, Zineb; Terfi, Souhila; Aberrane, Sihem; Sabaou, Nasserdine; Baaliouamer, Aoumeur; Boudarene, Lynda

2017-06-01

In the present work, the Brassica rapa var. rapifera parts essential oils and their antioxidant and antimicrobial activities were investigated for the first time depending on geographic origin and extraction technique. Gas-chromatography (GC) and GC/mass spectrometry (MS) analyses showed several constituents, including alcohols, aldehydes, esters, ketones, norisoprenoids, terpenic, nitrogen and sulphur compounds, totalizing 38 and 41 compounds in leaves and root essential oils, respectively. Nitrogen compounds were the main volatiles in leaves essential oils and sulphur compounds were the main volatiles in root essential oils. Qualitative and quantitative differences were found among B. rapa var. rapifera parts essential oils collected from different locations and extracted by hydrodistillation and microwave-assisted hydrodistillation techniques. Furthermore, our findings showed a high variability for both antioxidant and antimicrobial activities. The highlighted variability reflects the high impact of plant part, geographic variation and extraction technique on chemical composition and biological activities, which led to conclude that we should select essential oils to be investigated carefully depending on these factors, in order to isolate the bioactive components or to have the best quality of essential oil in terms of biological activities and preventive effects in food. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Pyrrole Alkaloids with Potential Cancer Chemopreventive Activity Isolated from a Goji Berry-Contaminated Commercial Sample of African Mango

PubMed Central

2015-01-01

Bioassay-guided fractionation of a commercial sample of African mango (Irvingia gabonensis) that was later shown to be contaminated with goji berry (Lycium sp.) led to the isolation of a new pyrrole alkaloid, methyl 2-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]propanoate, 1, along with seven known compounds, 2–8. The structures of the isolated compounds were established by analysis of their spectroscopic data. The new compound 1g showed hydroxyl radical-scavenging activity with an ED50 value of 16.7 μM, whereas 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid (2) was active in both the hydroxyl radical-scavenging (ED50 11.9 μM) and quinone reductase-induction [CD (concentration required to double QR activity) 2.4 μM)] assays used. The isolated compounds were shown to be absent in a taxonomically authenticated African mango sample but present in three separate authentic samples of goji berry (Lycium barbarum) using LC-MS and 1H NMR fingerprinting analysis, including one sample that previously showed inhibitory activity in vivo in a rat esophageal cancer model induced with N-nitrosomethylbenzylamine. Additionally, microscopic features characteristic of goji berry were observed in the commercial African mango sample. PMID:24792835

UPLC-Q-TOF-MS analysis of non-volatile migrants from new active packaging materials.

PubMed

Aznar, M; Rodriguez-Lafuente, A; Alfaro, P; Nerin, C

2012-10-01

Ultra-performance liquid chromatography (UPLC) coupled to mass spectrometry (MS) is a useful tool in the analysis of non-volatile compounds, and the use of a quadrupole-time-of-flight (Q-TOF) mass analyzer allows a high sensitivity and accuracy when acquiring full fragment mode, providing a high assurance of correct identification of unknown compounds. In this work, UPLC-Q-TOF-MS technology has been applied to the analysis of non-volatile migrants from new active packaging materials. The materials tested were based on polypropylene (PP), ethylene-vinyl alcohol copolymer (EVOH), and poly(ethylene terephthalate) (PET). The active packaging materials studied were one PP film containing a natural antioxidant, and two PP/EVOH films, two PET/EVOH films and one coextruded PP/EVOH/PP film containing natural antimicrobials. The chemical structure of several compounds was unequivocally identified. The analysis revealed the migration of some of the active substances used in the manufacture of active packaging, such as caffeine (0.07 ± 0.01 μg/g), carvacrol (0.31 ± 0.03 μg/g) and citral (0.20 ± 0.01 μg/g). Unintentionally added substances were also found, such as citral reaction compounds, or citral impurities present in the raw materials.

A Comprehensive Review on the Phytochemical Constituents and Pharmacological Activities of Pogostemon cablin Benth.: An Aromatic Medicinal Plant of Industrial Importance.

PubMed

Swamy, Mallappa Kumara; Sinniah, Uma Rani

2015-05-12

Pogostemon cablin Benth. (patchouli) is an important herb which possesses many therapeutic properties and is widely used in the fragrance industries. In traditional medicinal practices, it is used to treat colds, headaches, fever, nausea, vomiting, diarrhea, abdominal pain, insect and snake bites. In aromatherapy, patchouli oil is used to relieve depression, stress, calm nerves, control appetite and to improve sexual interest. Till now more than 140 compounds, including terpenoids, phytosterols, flavonoids, organic acids, lignins, alkaloids, glycosides, alcohols, aldehydes have been isolated and identified from patchouli. The main phytochemical compounds are patchouli alcohol, α-patchoulene, β-patchoulene, α-bulnesene, seychellene, norpatchoulenol, pogostone, eugenol and pogostol. Modern studies have revealed several biological activities such as antioxidant, analgesic, anti-inflammatory, antiplatelet, antithrombotic, aphrodisiac, antidepressant, antimutagenic, antiemetic, fibrinolytic and cytotoxic activities. However, some of the traditional uses need to be verified and may require standardizing and authenticating the bioactivity of purified compounds through scientific methods. The aim of the present review is to provide comprehensive knowledge on the phytochemistry and pharmacological activities of essential oil and different plant extracts of patchouli based on the available scientific literature. This information will provide a potential guide in exploring the use of main active compounds of patchouli in various medical fields.

Calculation and application of activity discriminants in lead optimization.

PubMed

Luo, Xincai; Krumrine, Jennifer R; Shenvi, Ashok B; Pierson, M Edward; Bernstein, Peter R

2010-11-01

We present a technique for computing activity discriminants of in vitro (pharmacological, DMPK, and safety) assays and the application to the prediction of in vitro activities of proposed synthetic targets during the lead optimization phase of drug discovery projects. This technique emulates how medicinal chemists perform SAR analysis and activity prediction. The activity discriminants that are functions of 6 commonly used medicinal chemistry descriptors can be interpreted easily by medicinal chemists. Further, visualization with Spotfire allows medicinal chemists to analyze how the query molecule is related to compounds tested previously, and to evaluate easily the relevance of the activity discriminants to the activities of the query molecule. Validation with all compounds synthesized and tested in AstraZeneca Wilmington since 2006 demonstrates that this approach is useful for prioritizing new synthetic targets for synthesis. Copyright © 2010 Elsevier Inc. All rights reserved.

Glycycoumarin exerts anti-liver cancer activity by directly targeting T-LAK cell-originated protein kinase.

PubMed

Song, Xinhua; Yin, Shutao; Zhang, Enxiang; Fan, Lihong; Ye, Min; Zhang, Yong; Hu, Hongbo

2016-10-04

Glycycoumarin (GCM) is a major bioactive coumarin compound isolated from licorice and the anti-cancer activity of GCM has not been scientifically addressed. In the present study, we have tested the anti-liver cancer activity of GCM using both in vitro and in vivo models and found for the first time that GCM possesses a potent activity against liver cancer evidenced by cell growth inhibition and apoptosis induction in vitro and tumor reduction in vivo. Mechanistically, GCM was able to bind to and inactivate oncogenic kinase T-LAK cell-originated protein kinase (TOPK), which in turn led to activation of p53 pathway. Our findings supported GCM as a novel active compound that contributed to the anti-cancer activity of licorice and TOPK could be an effective target for hepatocellular carcinoma (HCC) treatment.

Effects of Two Fullerene Derivatives on Monocytes and Macrophages

PubMed Central

Pacor, Sabrina; Grillo, Alberto; Đorđević, Luka; Zorzet, Sonia; Da Ros, Tatiana; Prato, Maurizio

2015-01-01

Two fullerene derivatives (fullerenes 1 and 2), bearing a hydrophilic chain on the pyrrolidinic nitrogen, were developed with the aim to deliver anticancer agents to solid tumors. These two compounds showed a significantly different behaviour on human neoplastic cell lines in vitro in respect to healthy leukocytes. In particular, the pyrrolidinium ring on the fullerene carbon cage brings to a more active compound. In the present work, we describe the effects of these fullerenes on primary cultures of human monocytes and macrophages, two kinds of immune cells representing the first line of defence in the immune response to foreign materials. These compounds are not recognized by circulating monocytes while they get into macrophages. The evaluation of the pronecrotic or proapoptotic effects, analysed by means of analysis of the purinergic receptor P2X7 activation and of ROS scavenging activity, has allowed us to show that fullerene 2, but not its analogue fullerene 1, displays toxicity, even though at concentrations higher than those shown to be active on neoplastic cells. PMID:26090460

Antibacterial activities of plant-derived compounds and essential oils toward Cronobacter sakazakii and Cronobacter malonaticus.

PubMed

Fraňková, Adéla; Marounek, Milan; Mozrová, Věra; Weber, Jaroslav; Klouček, Pavel; Lukešová, Daniela

2014-10-01

Cronobacter sakazakii and C. malonaticus are opportunistic pathogens that cause infections in children and immunocompromised adults. In the present study, the antibacterial activity of 19 plant-derived compounds, 5 essential oils, and an extract of propolis were assessed against C. sakazakii and C. malonaticus. The effects of most of these antimicrobials have not been reported previously. Both strains were susceptible to thymol, carvacrol, thymoquinone, p-cymene, linalool, camphor, citral, eugenol, and trans-cinnamaldehyde as well as cinnamon, lemongrass, oregano, clove, and laurel essential oils; their minimum inhibitory concentrations varied between 0.1 and 2.0 mg/mL. As an alternative treatment method, vapors of the volatiles were tested as an indirect treatment. Vapors of trans-cinnamaldehyde, eugenol, oregano, and cinnamon essential oils inhibited both tested strains, while vapors of linalool were only active against C. sakazakii. To our knowledge, this study is the first time that the inhibitory activity of the vapors of these compounds and essential oils has been reported against Cronobacter spp.

Supercritical fluid extraction of grape seeds: extract chemical composition, antioxidant activity and inhibition of nitrite production in LPS-stimulated Raw 264.7 cells.

PubMed

Pérez, Concepción; Ruiz del Castillo, María Luisa; Gil, Carmen; Blanch, Gracia Patricia; Flores, Gema

2015-08-01

Grape by-products are a rich source of bioactive compounds having broad medicinal properties, but are usually wasted from juice/wine processing industries. The present study investigates the use of supercritical fluid extraction (SFE) for obtaining an extract rich in bioactive compounds. First, some variables involved in the extraction were applied. SFE conditions were selected based on the oil mass yield, fatty acid profile and total phenolic composition. As a result, 40 °C and 300 bar were selected as operational conditions. The phenolic composition of the grape seed oil was determined using LC-DAD. The antioxidant activity was determined by ABTS and DPPH assays. For the anti-inflammatory activity the inhibition of nitrite production was assessed. The grape seed oil extracted was rich in phenolic compounds and fatty acids with significant antioxidant and anti-inflammatory activities. From these results, added economic value to this agroindustrial residue is proposed using environmentally friendly techniques.

Phenolic profile, antioxidant activity and palynological analysis of stingless bee honey from Amazonas, Northern Brazil.

PubMed

da Silva, Isnandia Andréa Almeida; da Silva, Tania Maria Sarmento; Camara, Celso Amorim; Queiroz, Neide; Magnani, Marciane; de Novais, Jaílson Santos; Soledade, Luiz Edmundo Bastos; Lima, Edeltrudes de Oliveira; de Souza, Antonia Lucia; de Souza, Antonio Gouveia

2013-12-15

In this study honey samples produced by Melipona (Michmelia) seminigra merrillae, collected in seven counties distributed in the central and southern region of Amazonas state in Brazil, were analysed for their botanical origin, content and profile of phenolic compounds, and antioxidant and antimicrobial activities. Twenty-two pollen types were identified. The total phenolic content ranged from 17 to 66 mg GAE/g of extract; the highest contents were found in honeys produced from pollen types such as Clidemia and Myrcia. The antioxidant activity was higher in the samples that contained higher quantities of phenolic compounds. In relation to the antibacterial activity, samples CAD3, CAD4 and SAD3 presented the best results. Fourteen phenolic compounds were determined. Among them, we identified the flavonoid taxifolin, which has not previously been described in honeys from stingless bees, and we report the identification of catechol in Brazilian honey samples for the first time. Copyright © 2013 Elsevier Ltd. All rights reserved.

Assessment of the antioxidant and antibacterial activities of different olive processing wastewaters

PubMed Central

Tan, Shiau Pin; El-Abbassi, Abdelilah; Kiai, Hajar; Hafidi, Abdellatif; O’Donovan, Orla; McLoughlin, Peter

2017-01-01

Olive processing wastewaters (OPW), namely olive mill wastewater (OMW) and table-olive wastewaters (TOW) were evaluated for their antibacterial activity against five Gram-positive and two Gram-negative bacteria using the standard disc diffusion and thin layer chromatography (TLC)-bioautography assays. Disc diffusion screening and bioautography of OMW were compared to the phenolic extracts of table-olive brines. Positive activity against S. aureus was demonstrated. The optimization of chromatographic separation revealed that hexane/acetone in the ratio of 4:6 was the most effective for phenolic compounds separation. A HPLC-MS analysis was performed showing that only two compounds, hydroxytyrosol and tyrosol, were the predominant phenolic compounds in all OPW. The phenolic extract of OMW generated by a semi-modern process showed the highest free radical-scavenging activity (DPPH assay) compared to the other phenolic extracts. It is apparent from the present study that OPW are a rich source of antioxidants suitable for use in food, cosmetic or pharmaceutical applications. PMID:28873097

New Thiazolyl-triazole Schiff Bases: Synthesis and Evaluation of the Anti-Candida Potential.

PubMed

Stana, Anca; Enache, Alexandra; Vodnar, Dan Cristian; Nastasă, Cristina; Benedec, Daniela; Ionuț, Ioana; Login, Cezar; Marc, Gabriel; Oniga, Ovidiu; Tiperciuc, Brîndușa

2016-11-22

In the context of the dangerous phenomenon of fungal resistance to the available therapies, we present here the chemical synthesis of a new series of thiazolyl-triazole Schiff bases B1 - B15 , which were in vitro assessed for their anti- Candida potential. Compound B10 was found to be more potent against Candida spp. when compared with the reference drugs Fluconazole and Ketoconazole. A docking study of the newly synthesized Schiff bases was performed, and results showed good binding affinity in the active site of co-crystallized Itraconazole-lanosterol 14α-demethylase isolated from Saccharomyces cerevisiae . An in silico ADMET (absorption, distribution, metabolism, excretion, toxicity) study was done in order to predict some pharmacokinetic and pharmacotoxicological properties. The Schiff bases showed good drug-like properties. The results of in vitro anti- Candida activity, a docking study and ADMET prediction revealed that the newly synthesized compounds have potential anti- Candida activity and evidenced the most active derivative, B10 , which can be further optimized as a lead compound.

Design, synthesis and biological evaluation of piperazinyl-β-carbolinederivatives as anti-leishmanial agents.

PubMed

Ashok, Penta; Chander, Subhash; Smith, Terry K; Sankaranarayanan, Murugesan

2018-04-25

Molecular hybridization is a ligand based drug design approach is well known recent medicinal chemistry to design anti-parasitic agents. In the present study, we have designed a series of (1-phenyl-9H-pyrido [3,4-b]indol-3-yl) (4-phenylpiperazin-1-yl)methanone derivatives using molecular hybridization approach. Designed analogues were evaluated for cytotoxicity and inhibition activity against Leishmania infantum and Leishmania donovani. Among these reported analogues 7b, 7d, 7e, 7f and 7m displayed potent inhibition of both L. infantum and L. donovani. Compounds 7i and 7k exhibited selective potent inhibition of L. donovani. Especially, compounds 7e and 7k showed most potent anti-leishmanial activity against L. infantum and L. donovani respectively. Anti-leishmanial activity of these compounds is comparable with standard drugs miltefosine and pentamidine. SAR studies revealed that, electron donating group substitution on phenyl ring recommended for potent anti-leishmanial activity. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Isolation and Quantification of Ginsenoside Rh23, a New Anti-Melanogenic Compound from the Leaves of Panax ginseng.

PubMed

Lee, Dae Young; Kim, Hyoung-Geun; Lee, Yeong-Geun; Kim, Jin Hee; Lee, Jae Won; Choi, Bo-Ram; Jang, In-Bae; Kim, Geum-Soog; Baek, Nam-In

2018-01-29

A new ginsenoside, named ginsenoside Rh23 ( 1 ), and 20- O -β-d-glucopyranosyl-3β,6α,12β,20β,25-pentahydroxydammar-23-ene ( 2 ) were isolated from the leaves of hydroponic Panax ginseng . Compounds were isolated by various column chromatography and their structures were determined based on spectroscopic methods, including high resolution quadrupole/time of flight mass spectrometry (HR-QTOF/MS), nuclear magnetic resonance (NMR) spectroscopy, and infrared (IR) spectroscopy. To determine anti-melanogenic activity, the change in the melanin content in melan-a cells treated with identified compounds was tested. Additionally, we investigated the melanin inhibitory effects of ginsenoside Rh23 on pigmentation in a zebrafish in vivo model. Compound 1 inhibited potent melanogenesis in melan-a cells with 37.0% melanogenesis inhibition at 80 µM and also presented inhibition on the body pigmentation in zebrafish model. Although compound 2 showed slightly lower inhibitory activity than compound 1 , it also showed significantly decreased melanogenesis in melan-a cell and in zebrafish model. These results indicated that compounds isolated from hydroponic P. ginseng may be used as new skin whitening compound through the in vitro and in vivo systems. Furthermore, this study demonstrated the utility of MS-based compound 1 for the quantitative analysis. Ginsenoside Rh23 ( 1 ) was found at a level of 0.31 mg/g in leaves of hydroponic P. ginseng .