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.

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.

Yellow-Cedar, Callitropsis (Chamaecyparis) nootkatensis, Secondary Metabolites, Biological Activities, and Chemical Ecology.

PubMed

Karchesy, Joseph J; Kelsey, Rick G; González-Hernández, M P

2018-05-01

Yellow-cedar, Callitropsis nootkatensis, is prevalent in coastal forests of southeast Alaska, western Canada, and inland forests along the Cascades to northern California, USA. These trees have few microbial or animal pests, attributable in part to the distinct groups of biologically active secondary metabolites their tissues store for chemical defense. Here we summarize the new yellow-cedar compounds identified and their biological activities, plus new or expanded activities for tissues, extracts, essential oils and previously known compounds since the last review more than 40 years ago. Monoterpene hydrocarbons are the most abundant compounds in foliage, while heartwood contains substantial quantities of oxygenated monoterpenes and oxygenated sesquiterpenes, with one or more tropolones. Diterpenes occur in foliage and bark, whereas condensed tannins have been isolated from inner bark. Biological activities expressed by one or more compounds in these groups include fungicide, bactericide, sporicide, acaricide, insecticide, general cytotoxicity, antioxidant and human anticancer. The diversity of organisms impacted by whole tissues, essential oils, extracts, or individual compounds now encompasses ticks, fleas, termites, ants, mosquitoes, bacteria, a water mold, fungi and browsing animals. Nootkatone, is a heartwood component with sufficient activity against arthropods to warrant research focused toward potential development as a commercial repellent and biopesticide for ticks, mosquitoes and possibly other arthropods that vector human and animal pathogens.

Statistical molecular design of balanced compound libraries for QSAR modeling.

PubMed

Linusson, A; Elofsson, M; Andersson, I E; Dahlgren, M K

2010-01-01

A fundamental step in preclinical drug development is the computation of quantitative structure-activity relationship (QSAR) models, i.e. models that link chemical features of compounds with activities towards a target macromolecule associated with the initiation or progression of a disease. QSAR models are computed by combining information on the physicochemical and structural features of a library of congeneric compounds, typically assembled from two or more building blocks, and biological data from one or more in vitro assays. Since the models provide information on features affecting the compounds' biological activity they can be used as guides for further optimization. However, in order for a QSAR model to be relevant to the targeted disease, and drug development in general, the compound library used must contain molecules with balanced variation of the features spanning the chemical space believed to be important for interaction with the biological target. In addition, the assays used must be robust and deliver high quality data that are directly related to the function of the biological target and the associated disease state. In this review, we discuss and exemplify the concept of statistical molecular design (SMD) in the selection of building blocks and final synthetic targets (i.e. compounds to synthesize) to generate information-rich, balanced libraries for biological testing and computation of QSAR models.

Discovering some novel 7-chloroquinolines carrying a biologically active benzenesulfonamide moiety as a new class of anticancer agents.

PubMed

Al-Dosari, Mohammed Salem; Ghorab, Mostafa Mohamed; Al-Said, Mansour Sulaiman; Nissan, Yassin Mohammed

2013-01-01

Based on the reported anticancer activity of quinolines, a new series of 7-chloroquinoline derivatives bearing the biologically active benzenesulfonamide moiety 2-17 and 19-25 were synthesized starting with 4,7-dichloroquinolne 1. Compound 17 was the most active compound with IC(50) value 64.41, 75.05 and 30.71 µM compared with Doxorubicin as reference drug with IC(50) values 82.53, 88.32 and 73.72 µM on breast cancer cells, skin cancer cells and neuroblastoma, respectively. All the synthesized compounds were evaluated for their in vitro anticancer activity on breast cancer cells, skin cancer cells and neuroblastoma cells. Most of the synthesized compounds showed moderate activity. In order to suggest the mechanism of action for their cytotoxic activity, molecular docking for all synthesized compounds was done on the active site of phosphoinositide kinase (PI3K) and good results were obtained.

Emergy Evaluations of the Global Biogeochemical Cycles of Six Biologically Active Elements and Two Compounds

EPA Science Inventory

Estimates of the emergy carried by the flows of biologically active elements (BAE) and compounds are needed to accurately evaluate the near and far field effects of anthropogenic wastes. The transformities and specific emergies of these elements and of their different chemical sp...

Synthesis and molecular docking of some novel anticancer sulfonamides carrying a biologically active pyrrole and pyrrolopyrimidine moieties.

PubMed

Ghorab, Mostafa M; Alsaid, Mansour S; Nissan, Yassin M

2014-01-01

Abstract: A novel series of pyrroles and pyrrolopyrimdines carrying a biologically active sulfonamide moiety have been synthesized. The structures were confirmed by elemental analyses and spectral data. All the target compounds were subjected to in vitro cytotoxic screening on breast cancer cell line (MCF-7). Most of the synthesized compounds showed good activity as cytotoxic agents with better IC50 than doxorubicin as a reference drug. In order to suggest a mechanism of action for their activity, molecular docking on the active site of human c-Src was performed for all synthesized compounds.

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

Intelligent nanomedicine integrating diagnosis and therapy

NASA Technical Reports Server (NTRS)

Li, Na (Inventor); Tan, Winny (Inventor)

2012-01-01

A method of controlling the activity of a biologically active compound. The method concerns an oligonucleotide-based compound, comprising a hairpin-forming oligonucleotide, an effector moiety physically associated with the oligonucleotide, where the effector moiety possesses a biological activity, and a regulating moiety physically associated with the oligonucleotide, where the regulating moiety controls the biological activity of the effector moiety by interacting with the effector moiety. The oligonucleotide can assume a hairpin configuration, where the effector and regulating moieties interact, or an open configuration, where the effector and regulating moieties fail to interact. Depending on the nature of the effector and regulating moieties, either configuration can result in the expression of the biological activity of the effector moiety.

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

GRIND2-based 3D-QSAR and prediction of activity spectra for symmetrical bis-pyridinium salts with promastigote antileishmanial activity.

PubMed

Diniz, Evelyn Mirella Lopes Pina; Tomich de Paula da Silva, Carlos Henrique; Gómez-Perez, Verónica; Federico, Leonardo Bruno; Campos Rosa, Joaquín María

2017-08-01

Leishmaniasis is a major group of neglected tropical diseases caused by the protozoan parasite Leishmania. About 12 million people are affected in 98 countries and 350 million people worldwide are at risk of infection. Current leishmaniasis treatments rely on a relatively small arsenal of drugs, including amphotericin B, pentamidine and others, which in general have some type of inconvenience. Recently, we have synthesized antileishmanial bis-pyridinium derivatives and symmetrical bis-pyridinium cyclophanes. These compounds are considered structural analogues of pentamidine, where the amidino moiety, protonated at physiological pH, is replaced by a positively charged nitrogen atom as a pyridinium ring. In this work, a statistically significant GRIND2-based 3D-QSAR model was built and biological activity predictions were in silico carried out allowing rationalization of the different activities recently obtained against Leishmania donovani (in L. donovani promastigotes) for a data set of 19 bis-pyridinium compounds. We will emphasize the most important structural requirements to improve the biological activity and probable interactions with the biological receptor as a guide for lead and prototype optimization. In addition, since no information about the actual biological target for this series of active compounds is provided, we have used Prediction of Activity Spectra for Biologically Active Substances to propose our compounds as potential nicotinic α6β3β4α5 receptor antagonists. This proposal is reinforced by the high structural similarity observed between our compounds and several anthelmintic drugs in current clinical use, which have the same drug action mechanism here predicted. Such new findings would be confirmed with further and additional experimental assays.

Biological Activity of Peanut (Arachis hypogaea) Phytoalexins and Selected Natural and Synthetic Stilbenoids

PubMed Central

SOBOLEV, VICTOR S.; KHAN, SHABANA I.; TABANCA, NURHAYAT; WEDGE, DAVID E.; MANLY, SUSAN P.; CUTLER, STEPHEN J.; COY, MONIQUE R.; BECNEL, JAMES J.; NEFF, SCOTT A.; GLOER, JAMES B.

2011-01-01

The peanut plant (Arachis hypogaea L.), when infected by a microbial pathogen, is capable of producing stilbene-derived compounds that are considered antifungal phytoalexins. In addition, the potential health benefits of other stilbenoids from peanuts, including resveratrol and pterostilbene, have been acknowledged by several investigators. Despite considerable progress in peanut research, relatively little is known about the biological activity of the stilbenoid phytoalexins. This study investigated the activities of some of these compounds in a broad spectrum of biological assays. Since peanut stilbenoids appear to play roles in plant defense mechanisms, they were evaluated for their effects on economically important plant pathogenic fungi of the genera Colletotrichum, Botrytis, Fusarium, and Phomopsis. We further investigated these peanut phytoalexins, together with some related natural and synthetic stilbenoids (a total of 24 compounds) in a panel of bioassays to determine their anti-inflammatory, cytotoxic, and antioxidant activities in mammalian cells. Several of these compounds were also evaluated as mammalian opioid receptor competitive antagonists. Assays for adult mosquito and larvae toxicity were also performed. The results of these studies reveal that peanut stilbenoids, as well as related natural and synthetic stilbene derivatives, display a diverse range of biological activities. PMID:21314127

Mimicking/extracting structure and functions of natural products: synthetic approaches that address unexplored needs in chemical biology.

PubMed

Hirai, Go

2015-04-01

Natural products are often attractive and challenging targets for synthetic chemists, and many have interesting biological activities. However, synthetic chemists need to be more than simply suppliers of compounds to biologists. Therefore, we have been seeking ways to actively apply organic synthetic methods to chemical biology studies of natural products and their activities. In this personal review, I would like to introduce our work on the development of new biologically active compounds inspired by, or extracted from, the structures of natural products, focusing on enhancement of functional activity and specificity and overcoming various drawbacks of the parent natural products. Copyright © 2014 The Chemical Society of Japan and Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antiplasmodial, cytotoxic activities and characterization of a new naturally occurring quinone methide pentacyclic triterpenoid derivative isolated from Salacia leptoclada Tul. (Celastraceae) originated from Madagascar

PubMed Central

Ruphin, Fatiany Pierre; Baholy, Robijaona; Emmanue, Andrianarivo; Amelie, Raharisololalao; Martin, Marie-Therese; Koto-te-Nyiwa, Ngbolua

2013-01-01

Objective To validate scientifically the traditional use of Salacia leptoclada Tul. (Celastraceae) (S. leptoclada) and to isolate and elucidate the structure of the biologically active compound. Methods Bioassay-guided fractionation of the acetonic extract of the stem barks of S. leptoclada was carried out by a combination of chromatography technique and biological experiments in viro using Plasmodium falciparum and P388 leukemia cell lines as models. The structure of the biologically active pure compound was elucidated by 1D and 2D NMR spectroscopy and mass spectrometry. Results Biological screening of S. leptoclada extracts resulted in the isolation of a pentacyclic triterpenic quinone methide. The pure compound exhibited both in vitro a cytotoxic effect on murine P388 leukemia cells with IC50 value of (0.041±0.020) µg/mL and an antiplasmodial activity against the chloroquine-resistant strain FC29 of Plasmodium falciparum with an IC50 value of (0.052±0.030) µg/mL. Despite this interesting anti-malarial property of the lead compound, the therapeutic index was weak (0.788). In the best of our knowledge, the quinone methide pentacyclic triterpenoid derivative compound is reported for the first time in S. leptoclada. Conclusions The results suggest that furthers studies involving antineoplastic activity is needed for the development of this lead compound as anticancer drug. PMID:24075342

Antiplasmodial, cytotoxic activities and characterization of a new naturally occurring quinone methide pentacyclic triterpenoid derivative isolated from Salacia leptoclada Tul. (Celastraceae) originated from Madagascar.

PubMed

Ruphin, Fatiany Pierre; Baholy, Robijaona; Emmanue, Andrianarivo; Amelie, Raharisololalao; Martin, Marie-Therese; Koto-te-Nyiwa, Ngbolua

2013-10-01

To validate scientifically the traditional use of Salacia leptoclada Tul. (Celastraceae) (S. leptoclada) and to isolate and elucidate the structure of the biologically active compound. Bioassay-guided fractionation of the acetonic extract of the stem barks of S. leptoclada was carried out by a combination of chromatography technique and biological experiments in viro using Plasmodium falciparum and P388 leukemia cell lines as models. The structure of the biologically active pure compound was elucidated by 1D and 2D NMR spectroscopy and mass spectrometry. Biological screening of S. leptoclada extracts resulted in the isolation of a pentacyclic triterpenic quinone methide. The pure compound exhibited both in vitro a cytotoxic effect on murine P388 leukemia cells with IC50 value of (0.041±0.020) μg/mL and an antiplasmodial activity against the chloroquine-resistant strain FC29 of Plasmodium falciparum with an IC50 value of (0.052±0.030) μg/mL. Despite this interesting anti-malarial property of the lead compound, the therapeutic index was weak (0.788). In the best of our knowledge, the quinone methide pentacyclic triterpenoid derivative compound is reported for the first time in S. leptoclada. The results suggest that furthers studies involving antineoplastic activity is needed for the development of this lead compound as anticancer drug. Copyright © 2013 Asian Pacific Tropical Biomedical Magazine. Published by Elsevier B.V. All rights reserved.

Biological Mimics: A New Paradigm in the Detection of Toxic Compounds

ERIC Educational Resources Information Center

Monty, Chelsea Nicole

2009-01-01

The purpose of this thesis is to introduce a new idea: using biological mimics in the detection of toxic compounds. Biological mimics imitate the active site of a given enzyme or have catalytic chemistry similar to enzymes and can be used in place of biological molecules to provide longer stability and simpler operation. In the following text the…

Design, synthesis, molecular modeling and biological evaluation of novel 2,3-dihydrophthalazine-1,4-dione derivatives as potential anticonvulsant agents

NASA Astrophysics Data System (ADS)

El-Helby, Abdel Ghany A.; Ayyad, Rezk R.; Sakr, Helmy M.; Abdelrahim, Adel S.; El-Adl, K.; Sherbiny, Farag S.; Eissa, Ibrahim H.; Khalifa, Mohamed M.

2017-02-01

In view of their expected anticonvulsant activity, some novel derivatives of 2,3-dihydrophthalazine-1,4-dione 4-22 were designed, synthesized and evaluated using pentylenetetrazole (PTZ) and picrotoxin as convulsion-inducing models. Moreover, the most active compounds were tested against electrical induced convulsion using maximal electroshock (MES) models of seizures. Most of the tested compounds showed considerable anticonvulsant activity in at least one of the anticonvulsant tests. Compounds 13 and 14g were proved to be the most potent compounds of this series with relatively low toxicity in the median lethal dose test when compared with the reference drug. Molecular modeling studies were done to verify the biological activity. The obtained results showed that the most potent compounds could be useful as a template for future design, optimization, and investigation to produce more active analogues.

Synthesis, biological activity and molecular modeling of 4-fluoro-N-[ω-(1,2,3,4-tetrahydroacridin-9-ylamino)-alkyl]-benzamide derivatives as cholinesterase inhibitors.

PubMed

Szymański, P; Markowicz, M; Bajda, M; Malawska, B; Mikiciuk-Olasik, E

2012-12-01

The aim of this study was to synthesize and determine the biological activity of new derivatives of 4-fluorobenzoic acid and tetrahydroacridine towards inhibition of cholinesterases. Compounds were synthesized in condensation reaction between 9-aminoalkyl-tetrahydroacridines and the activated 4-fluorobenzoic acid. Properties towards inhibition of acetyl- and butyrylcholinesterase were estimated according to Ellman's spectrophotometric method. Among synthesized compounds the most active were compounds 4a and 4d. These compounds, in comparison with tacrine, were characterized by the similar values of IC50. Among all obtained compounds, 4d presented the highest selectivity towards inhibition of acetylcholinesterase. Molecular modeling studies revealed that all derivatives presented similar extended conformation in the gorge of acetylcholinesterase, however, there were 2 main conformations in the active center of butyrylcholinesterase: bent and extended conformation. © Georg Thieme Verlag KG Stuttgart · New York.

Marine Rare Actinobacteria: Isolation, Characterization, and Strategies for Harnessing Bioactive Compounds

PubMed Central

Dhakal, Dipesh; Pokhrel, Anaya Raj; Shrestha, Biplav; Sohng, Jae Kyung

2017-01-01

Actinobacteria are prolific producers of thousands of biologically active natural compounds with diverse activities. More than half of these bioactive compounds have been isolated from members belonging to actinobacteria. Recently, rare actinobacteria existing at different environmental settings such as high altitudes, volcanic areas, and marine environment have attracted attention. It has been speculated that physiological or biochemical pressures under such harsh environmental conditions can lead to the production of diversified natural compounds. Hence, marine environment has been focused for the discovery of novel natural products with biological potency. Many novel and promising bioactive compounds with versatile medicinal, industrial, or agricultural uses have been isolated and characterized. The natural compounds cannot be directly used as drug or other purposes, so they are structurally modified and diversified to ameliorate their biological or chemical properties. Versatile synthetic biological tools, metabolic engineering techniques, and chemical synthesis platform can be used to assist such structural modification. This review summarizes the latest studies on marine rare actinobacteria and their natural products with focus on recent approaches for structural and functional diversification of such microbial chemicals for attaining better applications. PMID:28663748

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.

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

Generation of ligand-based pharmacophore model and virtual screening for identification of novel tubulin inhibitors with potent anticancer activity.

PubMed

Chiang, Yi-Kun; Kuo, Ching-Chuan; Wu, Yu-Shan; Chen, Chung-Tong; Coumar, Mohane Selvaraj; Wu, Jian-Sung; Hsieh, Hsing-Pang; Chang, Chi-Yen; Jseng, Huan-Yi; Wu, Ming-Hsine; Leou, Jiun-Shyang; Song, Jen-Shin; Chang, Jang-Yang; Lyu, Ping-Chiang; Chao, Yu-Sheng; Wu, Su-Ying

2009-07-23

A pharmacophore model, Hypo1, was built on the basis of 21 training-set indole compounds with varying levels of antiproliferative activity. Hypo1 possessed important chemical features required for the inhibitors and demonstrated good predictive ability for biological activity, with high correlation coefficients of 0.96 and 0.89 for the training-set and test-set compounds, respectively. Further utilization of the Hypo1 pharmacophore model to screen chemical database in silico led to the identification of four compounds with antiproliferative activity. Among these four compounds, 43 showed potent antiproliferative activity against various cancer cell lines with the strongest inhibition on the proliferation of KB cells (IC(50) = 187 nM). Further biological characterization revealed that 43 effectively inhibited tubulin polymerization and significantly induced cell cycle arrest in G(2)-M phase. In addition, 43 also showed the in vivo-like anticancer effects. To our knowledge, 43 is the most potent antiproliferative compound with antitubulin activity discovered by computer-aided drug design. The chemical novelty of 43 and its anticancer activities make this compound worthy of further lead optimization.

Benzoin Schiff Bases: Design, Synthesis, and Biological Evaluation as Potential Antitumor Agents.

PubMed

Sabbah, Dima A; Al-Tarawneh, Fatima; Talib, Wamidh H; Sweidan, Kamal; Bardaweel, Sanaa K; Al-Shalabi, Eveen; Zhong, Haizhen A; Abu Sheikha, Ghassan; Abu Khalaf, Reema; Mubarak, Mohammad S

2018-04-12

Phosphoinositide 3-kinase α (PI3Kα) is an attractive target for anticancer drug design. Target compounds were designed to probe the significance of alcohol and imine moieties tailored on a benzoin scaffold to better understand the structure activity relation (SAR) and improve their biological activity as anticancer compounds. Chemical synthesis of the targeted compounds, biological evaluation tests against human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines, as well as Glide docking studies were employed in this investigation. A new series of 1,2-diphenylimino ethanol was successfully synthesized and characterized by means of FT-IR, HRMS, NMR, and by elemental analysis. Biological screening revealed that the newly synthesized compounds inhibit PI3Kα activity in human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines. Results additionally showed that these compounds exhibit selective antiproliferative activity, induce apoptosis, and suppress the VEGF production. Compounds 2b, 2d, and 2g displayed promising inhibitory activity in HCT-116 suggesting that hydrophobic and/or hydrogen bond-acceptor mediate(s) ligand-receptor interaction on o- and m-positions. Furthermore, compounds 2g, 2i, 2j, and 2h, bearing hydrophobic moiety on m- and p-position, exerted high antiproliferative activity in T47D and MCF-7 cells, whereas compound 2e showed selectivity against T47D and MCF-7. Molecular docking studies against PI3Kα and caspase-3 demonstrated a strong correlation between the predicted binding affinity (ΔGobsd) and IC50 values of prepared compounds for the caspase-3 model, implying that the cellulous inhibitory activity was caspase-3-dependent. Moreover, Glide docking against PI3Kα identified Ser774, Lys802, E849, V851, and Asp933 as key binding residues. The series exerted a potential PI3Kα inhibitory activity in human carcinoma cell lines expressing PI3Kα. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Vitual screening and binding mode elucidation of curcumin analogues on Cyclooxygenase-2 using AYO_COX2_V1.1 protocol

NASA Astrophysics Data System (ADS)

Mulatsari, E.; Mumpuni, E.; Herfian, A.

2017-05-01

Curcumin is yellow colored phenolic compounds contained in Curcuma longa. Curcumin is known to have biological activities as anti-inflammatory, antiviral, antioxidant, and anti-infective agent [1]. Synthesis of curcumin analogue compounds has been done and some of them had biological activity like curcumin. In this research, the virtual screening of curcumin analogue compounds has been conducted. The purpose of this research was to determine the activity of these compounds as selective Cyclooxygenase-2inhibitors in in-silico. Binding mode elucidation was made by active and inactive representative compounds to see the interaction of the amino acids in the binding site of the compounds. This research used AYO_COX2_V.1.1, a structure-based virtual screening protocol (SBVS) that has been validated by Mumpuni E et al, 2014 [2]. AYO_COX2_V.1.1 protocol using a variety of integrated applications such as SPORES, PLANTS, BKchem, OpenBabel and PyMOL. The results of virtual screening conducted on 49 curcumin analogue compounds obtained 8 compounds with 4 active amino acid residues (GLY340, ILE503, PHE343, and PHE367) that were considered active as COX-2 inhibitor.

Chemistry and biology of ω-3 PUFA peroxidation-derived compounds.

PubMed

Wang, Weicang; Yang, Haixia; Johnson, David; Gensler, Catherine; Decker, Eric; Zhang, Guodong

2017-09-01

The ω-3 polyunsaturated fatty acids (PUFAs) are among the most popular dietary supplements in the US, but they are chemically unstable and highly prone to lipid peroxidation. Many studies performed in different countries demonstrate that the majority of ω-3 PUFA products on the market are oxidized, suggesting that the resulting ω-3 PUFA peroxidation-derived compounds could be widely consumed by the general public. Therefore, it is of practical importance to understand the effects of these oxidized lipid compounds on human health. In this review, we summarize and discuss the chemical structures and biological activities of ω-3 PUFA peroxidation-derived compounds, and emphasize the importance to better understand the role of lipid peroxidation in biological activities of ω-3 PUFAs. Copyright © 2016 Elsevier Inc. All rights reserved.

Biological activity of aldose reductase and lipophilicity of pyrrolyl-acetic acid derivatives

NASA Astrophysics Data System (ADS)

Kumari, A.; Kumari, R.; Kumar, R.; Gupta, M.

2011-12-01

Quantitative Structure-Activity Relationship modeling is a powerful approach for correlating an organic compound to its lipophilicity. In this paper QSAR models are established for estimation of correlation of the lipophilicity of a series of pyrrolyl-acetic acid derivatives, inhibitors of the aldose reductase enzyme, in the n-octanol-water system with biological activity of aldose reductase. Lipophilicity, expressed by the logarithm of n-octnol-water partition coefficient log P and biological activity of aldose reductase inhibitory activity by log it. Result obtained by QSAR modeling of compound series reveal a definite trend in biological activity and a further improvement in quantitative relationships are established if, beside log P, Hammett electronic constant σ and connectivity index chi-3 (3 χ) term included in the regression equation. The tri-parametric model with log P, 3 χ and σ as correlating parameters have been found to be the best which gives a variance of 87% ( R 2 = 0.8743). A compound has been found to be serious outlier and when the same has been excluded the model explains about 94% variance of the data set ( R 2 = 0.9447). The topological index (3 χ) has been found to be a good parameter for modeling the biological activity.

Synthesis, Biological Evaluation and Molecular Docking of New Benzenesulfonylhydrazone as Potential anti-Trypanosoma cruzi Agents.

PubMed

Elizondo-Jimenez, Silvia; Moreno-Herrera, Antonio; Reyes-Olivares, Rogelio; Dorantes-Gonzalez, Edith; Nogueda-Torres, Benjamín; Oliveira, Eduardo A Gamosa de; Romeiro, Nelilma C; Lima, Lidia M; Palos, Isidro; Rivera, Gildardo

2017-01-01

Chagas disease is a public health problem caused by Trypanosoma cruzi. Cruzain is a pharmacological target for designing a new drug against this parasite. Hydrazone and Nacylhydrazone derivatives have been traditionally associated as potential Cruzain inhibitors. Additionally, benzenesulfonyl derivatives show trypanocidal activity. Therefore, in this study, the combination of both structures has been taken into account for drug design. Seven benzenesulfonylhydrazone (BS-H) and seven N-propionyl benzenesulfonylhydrazone (BS-NAH) derivatives were synthetized and elucidated by infrared spectroscopy, nuclear magnetic resonance, and elemental analysis. All compounds were evaluated biologically in vitro against two strains of Trypanosoma cruzi (NINOA and INC-5), which are endemic in Mexico, and compared with the reference drugs nifurtimox and benznidazole. In order to gain insight into the putative molecular origin of the trypanocidal properties of these derivatives, docking studies were carried out with Cruzain. Compounds 4 and 6 (BS-H) and 10, 12-14 (BS-NAH) showed the best biological activity against NINOA and INC-5 strains, respectively. Compound 13 was the most potent trypanocidal compound showing a LC50 of 0.06 µM against INC-5 strain. However, compound 4 showed the best activity against both strains (LC50 <30 µM). Theoretical binding modes obtained suggested covalent binding that could explain their biological activity. Benzenesulfonyl and N-propionyl benzenesulfonyl hydrazone derivatives are good options for developing new trypanocidal agents. Particularly, compound 4 could be considered a lead compound. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

How to acquire new biological activities in old compounds by computer prediction

NASA Astrophysics Data System (ADS)

Poroikov, V. V.; Filimonov, D. A.

2002-11-01

Due to the directed way of testing chemical compounds' in drug research and development many projects fail because serious adverse effects and toxicity are discovered too late, and many existing prospective activities remain unstudied. Evaluation of the general biological potential of molecules is possible using a computer program PASS that predicts more than 780 pharmacological effects, mechanisms of action, mutagenicity, carcinogenicity, etc. on the basis of structural formulae of compounds, with average accuracy ˜85%. PASS applications to both databases of available samples included hundreds of thousands compounds, and small collections of compounds synthesized by separate medicinal chemists are described. It is shown that 880 compounds from Prestwick chemical library represent a very diverse pharmacological space. New activities can be found in existing compounds by prediction. Therefore, on this basis, the selection of compounds with required and without unwanted properties is possible. Even when PASS cannot predict very new activities, it may recognize some unwanted actions at the early stage of R&D, providing the medicinal chemist with the means to increase the efficiency of projects.

Semisynthesis, Characterization and Evaluation of New Adenosine Derivatives as Antiproliferative Agents.

PubMed

Valdés Zurita, Francisco; Brown Vega, Nelson; Gutiérrez Cabrera, Margarita

2018-05-08

We describe the semisynthesis and biological effects of adenosine derivatives, which were anticipated to function as agonists for the A₃ receptor. Molecular docking was used to select candidate compounds. Fifteen nucleoside derivatives were obtained through nucleophilic substitutions of the N ⁶-position of the nucleoside precursor 6-chloropurine riboside by amines of different origin. All compounds were purified by column chromatography and further characterized by spectroscopic and spectrometric techniques, showing moderate yield. These molecules were then evaluated for their antiproliferative activity in human gastric cancer cells expressing the A₃ receptor. We found that the compounds obtained have antiproliferative activity and that new structural modifications can enhance their biological activity. The ADME (Absorption, Distribution, Metabolism and Excretion) properties of the most active compounds were also evaluated theoretically.

Novel Penicillin-Type Analogues Bearing a Variable Substituted 2-Azetidinone Ring at Position 6: Synthesis and Biological Evaluation.

PubMed

De Rosa, Margherita; Vigliotta, Giovanni; Palma, Giuseppe; Saturnino, Carmela; Soriente, Annunziata

2015-12-10

The synthesis and the biological activity of novel semi-synthetic β-lactam compounds containing an azetidinone moiety joined to the amino-nitrogen of the (+)-6-aminopenicillanic acid (6-APA) as new antibacterial agents is reported. The synthesized compounds were screened for their in vitro antimicrobial activity against a panel of Gram positive and Gram negative pathogens and environmental bacteria. Tested compounds displayed good antimicrobial activity against all tested Gram positive bacteria and for Staphylococcus aureus and Staphylococcus epidermidis antimicrobial activity resulted higher than that of the reference antibiotic. Additionally, in vitro cytotoxic screening was also carried out indicating that the compounds do not cause a cell vitality reduction effective at concentration next to and above those shown to be antimicrobial.

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.

Fentanyl-related compounds and derivatives: current status and future prospects for pharmaceutical applications

PubMed Central

Vardanyan, Ruben S; Hruby, Victor J

2014-01-01

Fentanyl and its analogs have been mainstays for the treatment of severe to moderate pain for many years. In this review, we outline the structural and corresponding synthetic strategies that have been used to understand the structure–biological activity relationship in fentanyl-related compounds and derivatives and their biological activity profiles. We discuss how changes in the scaffold structure can change biological and pharmacological activities. Finally, recent efforts to design and synthesize novel multivalent ligands that act as mu and delta opioid receptors and NK-1 receptors are discussed. PMID:24635521

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.

Actinobacteria Isolated from an Underground Lake and Moonmilk Speleothem from the Biggest Conglomeratic Karstic Cave in Siberia as Sources of Novel Biologically Active Compounds

PubMed Central

Tokovenko, Bogdan T.; Protasov, Eugeniy S.; Gamaiunov, Stanislav V.; Rebets, Yuriy V.; Luzhetskyy, Andriy N.; Timofeyev, Maxim A.

2016-01-01

Actinobacteria isolated from unstudied ecosystems are one of the most interesting and promising sources of novel biologically active compounds. Cave ecosystems are unusual and rarely studied. Here, we report the isolation and characterization of ten new actinobacteria strains isolated from an ancient underground lake and moonmilk speleothem from the biggest conglomeratic karstic cave in Siberia with a focus on the biological activity of the obtained strains and the metabolite dereplication of one active strain. Streptomyces genera isolates from moonmilk speleothem demonstrated antibacterial and antifungal activities. Some of the strains were able to inhibit the growth of pathogenic Candida albicans. PMID:26901168

The novel 3,4-dihydropyrimidin-2(1H)-one urea derivatives of N-aryl urea: synthesis, anti-inflammatory, antibacterial and antifungal activity evaluation.

PubMed

Tale, Rajesh H; Rodge, Atish H; Hatnapure, Girish D; Keche, Ashish P

2011-08-01

A series of novel 3,4-dihydropyrimidin-2(1H)-one urea derivatives of biological interest were prepared by sequential Bigineli's reaction, reduction followed by reaction of resulting amines with different arylisocynates. All the synthesized (1-23) compounds were screened against the pro-inflammatory cytokines (TNF-α and IL-6) and antimicrobial activity (antibacterial and antifungal). Biological activity evaluation study reveled that among all the compounds screened, compounds 12 and 17 found to have promising anti-inflammatory activity (68-62% TNF-α and 92-86% IL-6 inhibitory activity at 10 μM). Interestingly compounds 3, 4, 5, 6, 15, 22 and 23 revealed promising antimicrobial activity at MIC of 10-30 μg/mL against selected pathogenic bacteria and fungi. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Study of antioxidant activity of phenolic compounds from some species of Georgian flora].

PubMed

Alaniia, M; Shalashvili, K; Sagareishvili, T; Kavtaradze, N; Sutiashvili, M

2013-09-01

The antioxidant activity of extracts obtained from different parts of Georgian flora species Hamamelis virginiana L., Astragalus caucasicus Pall., Astragalus microcephalus Willd., Vitis vinifera L., Rhododendron ponticum L., Rhododendron Ungernii Trautv., Ginkgo biloba L., Salvia officinalis L., Querqus iberica Stev., Maclura aurantiaca Nutt., Cotinus coggygria Ledeb., Fraxinus ornus L., Urtica dioica L., Rhododendron caucasicum Pall., Pueraria hirsuta Matsum., Geranium pusillum L., Astragalus Tanae Sosn., Pinus silvestris L. has been studied. Comparison with ethylentetraacetate and α-tocopherole revealed high efficacy of all extracts studied. 45 individual phenolic compounds were isolated and described by chemical examination of biologically active objects. Common sage (Salvia officinalis) extract turned out as the most active (200 %). The chemical study revealed the dominant content of condensed tannins and low molecular phenolic compounds, which may be attributed to the high antioxidant activity. Biologically active antiatherosclerotic food additive "Salbin" was developed on the basis of Common sage - Salvia officinalis L. phenolic compounds.

Antioxidant and Antiplasmodial Activities of Bergenin and 11-O-Galloylbergenin Isolated from Mallotus philippensis

PubMed Central

Khan, Hamayun; Amin, Hazrat; Ullah, Asad; Saba, Sumbal; Rafique, Jamal; Khan, Khalid; Ahmad, Nasir; Badshah, Syed Lal

2016-01-01

Two important biologically active compounds were isolated from Mallotus philippensis. The isolated compounds were characterized using spectroanalytical techniques and found to be bergenin (1) and 11-O-galloylbergenin (2). The in vitro antioxidant and antiplasmodial activities of the isolated compounds were determined. For the antioxidant potential, three standard analytical protocols, namely, DPPH radical scavenging activity (RSA), reducing power assay (RPA), and total antioxidant capacity (TAC) assay, were adopted. The results showed that compound 2 was found to be more potent antioxidant as compared to 1. Fascinatingly, compound 2 displayed better EC50 results as compared to α-tocopherol while being comparable with ascorbic acid. The antiplasmodial assay data showed that both the compound exhibited good activity against chloroquine sensitive strain of Plasmodium falciparum (D10) and IC50 values were found to be less than 8 μM. The in silico molecular docking analyses were also performed for the determination of binding affinity of the isolated compounds using P. falciparum proteins PfLDH and Pfg27. The results showed that compound 2 has high docking score and binding affinity to both protein receptors as compared to compound 1. The demonstrated biological potentials declared that compound 2 could be the better natural antioxidant and antiplasmodial candidate. PMID:26998192

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.

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.

Secondary metabolites from marine-derived microorganisms.

PubMed

Chen, Gang; Wang, Hai-Feng; Pei, Yue-Hu

2014-01-01

In the search for novel and bioactive molecules for drug discovery, marine-derived natural resources, especially marine microorganisms are becoming an important and interesting research area. This study covers the literature published after 2008 on secondary metabolites of marine-derived microorganisms. The emphasis was on new compounds with the relevant biological activities, strain information, and country of origin. New compounds without biological activity were not included.

Antioxidant Capacity of “Mexican Arnica” Heterotheca inuloides Cass Natural Products and Some Derivatives: Their Anti-Inflammatory Evaluation and Effect on C. elegans Life Span

PubMed Central

Rodríguez-Chávez, José Luis; Nieto-Camacho, Antonio; Delgado-Lamas, Guillermo

2015-01-01

It has been suggested that the accumulation of biomolecular damage caused by reactive oxygen species (ROS) contributes to aging. The antioxidant activity is related to the ability of certain compounds to protect against the potentially harmful effect of processes or reactions involving ROS. This ability is associated with the termination of free radical propagation in biological systems. From Heterotheca inuloides various compounds which have shown to possess antioxidant capacity and scavenging ROS. The aim of this study was to determine the antioxidant capacity of additional natural components isolated from H. inuloides and some semisynthetic derivatives, their anti-inflammatory activity and the effect on Caenorhabditis elegans nematode life span. Compounds showed ability to inhibit various biological processes such as lipid peroxidation, scavenge nonbiological important oxidants such as 1O2, OH∙, H2O2, and HOCl and scavenge non biological stable free radicals (DPPH). Some cadinane type compounds showed possess antioxidant, ROS scavenging capacity, anti-inflammatory activity, and effect on the C. elegans life span. Flavonoid type compounds increased the life of the nematode and quercetin was identified as the compound with the greatest activity. The modification of chemical structure led to a change in the antioxidant capacity, the anti-inflammatory activity, and the survival of the worm. PMID:25821555

Correlation between structure, retention, property, and activity of biologically relevant 1,7-bis(aminoalkyl)diazachrysene derivatives.

PubMed

Šegan, Sandra; Trifković, Jelena; Verbić, Tatjana; Opsenica, Dejan; Zlatović, Mario; Burnett, James; Šolaja, Bogdan; Milojković-Opsenica, Dušanka

2013-01-01

The physicochemical properties, retention parameters (R(M)(0)), partition coefficients (logP(OW)), and pK(a) values for a series of thirteen 1,7-bis(aminoalkyl) diazachrysene (1,7-DAAC) derivatives were determined in order to reveal the characteristics responsible for their biological behavior. The investigated compounds inhibit three unrelated pathogens (the Botulinum neurotoxin serotype A light chain (BoNT/A LC), Plasmodium falciparum malaria, and Ebola filovirus) via three different mechanisms of action. To determine the most influential factors governing the retention and activities of the investigated diazachrysenes, R(M)(0), logP(OW), and biological activity values were correlated with 2D and 3D molecular descriptors, using a partial least squares regression. The resulting quantitative structure-retention (property) relationships indicate the importance of descriptors related to the hydrophobicity of the molecules (e.g., predicted partition coefficients and hydrophobic surface area). Quantitative structure-activity relationship models for describing biological activity against the BoNT/A LC and malarial strains also include overall compound polarity, electron density distribution, and proton donor/acceptor potential. Furthermore, models for Ebola filovirus inhibition are presented qualitatively to provide insights into parameters that may contribute to the compounds' antiviral activities. Overall, the models form the basis for selecting structural features that significantly affect the compound's absorption, distribution, metabolism, excretion, and toxicity profiles. Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical Characteristics, Synthetic Methods, and Biological Potential of Quinazoline and Quinazolinone Derivatives

PubMed Central

2014-01-01

The heterocyclic fused rings quinazoline and quinazolinone have drawn a huge consideration owing to their expanded applications in the field of pharmaceutical chemistry. Quinazoline and quinazolinone are reported for their diversified biological activities and compounds with different substitutions bring together to knowledge of a target with understanding of the molecule types that might interact with the target receptors. Quinazolines and quinazolinones are considered as an important chemical for the synthesis of various physiological significance and pharmacological utilized molecules. Quinazolines and quinazolinone are a large class of biologically active compounds that exhibited broad spectrum of biological activities such as anti-HIV, anticancer, antifungal, antibacterial, antimutagenic, anticoccidial, anticonvulsant, anti-inflammatory, antidepressant, antimalarial, antioxidant, antileukemic, and antileishmanial activities and other activities. Being considered as advantaged scaffold, the alteration is made with different substituent. PMID:25692041

COMPUTER PREDICTION OF BIOLOGICAL ACTIVITY OF DIMETHYL-N-(BENZOYL)AMIDOPHOSPHATE AND DIMETHYL-N-(PHENYLSULFONYL)AMIDOPHOSPHATE, EVALUATION OF THEIR CYTOTOXIC ACTIVITY AGAINST LEUKEMIC CELLS IN VITRO.

PubMed

Grynyuk, I I; Prylutska, S V; Kariaka, N S; Sliva, T Yu; Moroz, O V; Franskevych, D V; Amirkhanov, V M; Matyshevska, O P; Slobodyanik, M S

2015-01-01

Structural analogues of β-diketones--dimethyl-N-(benzoyl)amidophosphate (HCP) and dimethyl-N-(phenylsulfonyl)amidophosphate (HSP) were synthesized and identified by the methods of IR, 1H and 31P NMR spectroscopy. Screening of biological activity and calculation of physicochemical parameters of HCP and HSP compounds were done with the use of PASS and ACD/Labs computer programs. A wide range of biological activity of synthesized compounds, antitumor activity in particular, has been found. Calculations of the bioavailability criteria indicate that the investigated compounds have no deviations from Lipinski's rules. HCP compound is characterized by a high lipophilicity at physiological pH as compared to HSP. It was found that cytotoxic effect of the studied compounds on the leukemic L1210 cells was of time- and dose-dependent character. HCP is characterized by more pronounced and early cytotoxic effects as compared to HSP. It was shown that 2.5 mM HCP increased ROS production 3 times in the early period of incubation, and decreased cell viability by 40% after 48 h, and by 66%--after 72 h. Based on the computer calculation and undertaken research, HCP was selected for target chemical modifications and enhancement of its antitumor effect.

Ferrocenyl and organic novobiocin derivatives: Synthesis and their in vitro biological activity.

PubMed

Mbaba, Mziyanda; Mabhula, Amanda N; Boel, Natasha; Edkins, Adrienne L; Isaacs, Michelle; Hoppe, Heinrich C; Khanye, Setshaba D

2017-07-01

A focused series of novobiocin derivatives containing a ferrocene unit together with their corresponding organic novobiocin analogues have been synthesized in modest to good yields. These compounds were screened for biological activity against a chloroquine-sensitive strain of Plasmodium falciparum (3D7) and human breast cancer cell line (HCC38). With the exception of compounds 5c and 5d, the general trend observed is that incorporation of the ferrocene moiety into novobiocin scaffold resulted in compounds 6a-d/6f showing enhanced activity compared to organic analogues 5a-b and 5e-f. Copyright © 2017 Elsevier Inc. All rights reserved.

Glycolipids from seaweeds and their potential biotechnological applications.

PubMed

Plouguerné, Erwan; da Gama, Bernardo A P; Pereira, Renato C; Barreto-Bergter, Eliana

2014-01-01

Marine macroalgae, or seaweeds, are a formidable source of natural compounds with diverse biological activities. In the last five decades it has been estimated that more than 3000 natural compounds were discovered from these organisms. The great majority of the published works have focused on terpenoids. In comparison, glycolipids are a neglected class of macroalgal secondary metabolites therefore remaining as a largely unknown reservoir of molecular diversity. Nevertheless, the interest regarding these compounds has been growing fast in the last decades as activities of ecological or pharmaceutical interest have been highlighted. This paper will review recent work regarding isolation and structural characterization of glycolipids from seaweeds and their prospective biological activities.

Sulfur, selenium and tellurium pseudopeptides: synthesis and biological evaluation.

PubMed

Shaaban, Saad; Sasse, Florenz; Burkholz, Torsten; Jacob, Claus

2014-07-15

A new series of sulfur, selenium and tellurium peptidomimetic compounds was prepared employing the Passerini and Ugi isocyanide based multicomponent reactions (IMCRs). These reactions were clearly superior to conventional methods traditionally used for organoselenium and organotellurium synthesis, such as classical nucleophilic substitution and coupling methods. From the biological point of view, these compounds are of considerable interest because of suspected anticancer and antimicrobial activities. While the sulfur and selenium containing compounds generally did not show either anticancer or antimicrobial activities, their tellurium based counterparts frequently exhibited antimicrobial activity and were also cytotoxic. Some of the compounds synthesized even showed selective activity against certain cancer cells in cell culture. These compounds induced a cell cycle delay in the G0/G1 phase. At closer inspection, the ER and the actin cytoskeleton appeared to be the primary cellular targets of these tellurium compounds, in line with some of our previous studies. As most of these peptidomimetic compounds also comply with Lipinski's Rule of Five, they promise good bioavailability, which needs to be studied as part of future investigations. Copyright © 2014 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.

Ficus carica L. (Moraceae): Phytochemistry, Traditional Uses and Biological Activities.

PubMed

Mawa, Shukranul; Husain, Khairana; Jantan, Ibrahim

2013-01-01

This paper describes the botanical features of Ficus carica L. (Moraceae), its wide variety of chemical constituents, its use in traditional medicine as remedies for many health problems, and its biological activities. The plant has been used traditionally to treat various ailments such as gastric problems, inflammation, and cancer. Phytochemical studies on the leaves and fruits of the plant have shown that they are rich in phenolics, organic acids, and volatile compounds. However, there is little information on the phytochemicals present in the stem and root. Reports on the biological activities of the plant are mainly on its crude extracts which have been proven to possess many biological activities. Some of the most interesting therapeutic effects include anticancer, hepatoprotective, hypoglycemic, hypolipidemic, and antimicrobial activities. Thus, studies related to identification of the bioactive compounds and correlating them to their biological activities are very useful for further research to explore the potential of F. carica as a source of therapeutic agents.

A 4-(o-chlorophenyl)-2-aminothiazole: Microwave assisted synthesis, spectral, thermal, XRD and biological studies

NASA Astrophysics Data System (ADS)

Rajmane, S. V.; Ubale, V. P.; Lawand, A. S.; Nalawade, A. M.; Karale, N. N.; More, P. G.

2013-11-01

A 4-(o-chlorophenyl)-2-aminothiazole (CPAT) has been synthesized by reacting o-chloroacetophenone, iodine and thiourea under microwave irradiation as a green chemistry approach. The reactions proceed selectively and within a couple of minutes giving high yields of the products. The compound was characterized by elemental, spectral (UV-visible, IR, NMR and GC-MS), XRD and thermal analyses. The TG curve of the compound was analyzed to calculate various kinetic parameters (n, E, Z, ΔS and ΔG) by using Coats-Redfern (C.R.), MacCallum-Tanner (M.T.) and Horowitz-Metzger (H.M.) method. The compound was tested for the evaluation of antibacterial activity against B. subtilis and E. coli and antifungal activity against A. niger and C. albicans. The compound was evaluated for their in vitro nematicidal activity on plant parasitic nematode Meloidogyne javanica and molluscicidal activity on fresh water helminthiasis vector snail Lymnea auricularia. The compound is biologically active in very low concentration. X-ray diffraction study suggests a triclinic crystal system for the compound.

Multidirectional Efficacy of Biologically Active Nitro Compounds Included in Medicines.

PubMed

Olender, Dorota; Żwawiak, Justyna; Zaprutko, Lucjusz

2018-05-29

The current concept in searching for new bioactive products, including mainly original active substances with potential application in pharmacy and medicine, is based on compounds with a previously determined structure, well-known properties, and biological activity profile. Nowadays, many commonly used drugs originated from natural sources. Moreover, some natural materials have become the source of leading structures for processing further chemical modifications. Many organic compounds with great therapeutic significance have the nitro group in their structure. Very often, nitro compounds are active substances in many well-known preparations belonging to different groups of medicines that are classified according to their pharmacological potencies. Moreover, the nitro group is part of the chemical structure of veterinary drugs. In this review, we describe many bioactive substances with the nitro group, divided into ten categories, including substances with exciting activity and that are currently undergoing clinical trials.

Evaluation of Biologically Active Compounds from Calendula officinalis Flowers using Spectrophotometry

PubMed Central

2012-01-01

Background This study aimed to quantify the active biological compounds in C. officinalis flowers. Based on the active principles and biological properties of marigolds flowers reported in the literature, we sought to obtain and characterize the molecular composition of extracts prepared using different solvents. The antioxidant capacities of extracts were assessed by using spectrophotometry to measure both absorbance of the colorimetric free radical scavenger 2,2-diphenyl-1-picrylhydrazyl (DPPH) as well as the total antioxidant potential, using the ferric reducing power (FRAP) assay. Results Spectrophotometric assays in the ultraviolet-visible (UV-VIS) region enabled identification and characterization of the full range of phenolic and flavonoids acids, and high-performance liquid chromatography (HPLC) was used to identify and quantify phenolic compounds (depending on the method of extraction). Methanol ensured more efficient extraction of flavonoids than the other solvents tested. Antioxidant activity in methanolic extracts was correlated with the polyphenol content. Conclusions The UV-VIS spectra of assimilator pigments (e.g. chlorophylls), polyphenols and flavonoids extracted from the C. officinalis flowers consisted in quantitative evaluation of compounds which absorb to wavelengths broader than 360 nm. PMID:22540963

New Bioactive Compounds from Korean Native Mushrooms

PubMed Central

Kim, Seong-Eun; Hwang, Byung Soon; Song, Ja-Gyeong; Lee, Seung Woong; Lee, In-Kyoung

2013-01-01

Mushrooms are ubiquitous in nature and have high nutritional attributes. They have demonstrated diverse biological effects and therefore have been used in treatments of various diseases, including cancer, diabetes, bacterial and viral infections, and ulcer. In particular, polysaccharides, including β-glucan, are considered as the major constituents responsible for the biological activity of mushrooms. Although an overwhelming number of reports have been published on the importance of polysaccharides as immunomodulating agents, not all of the healing properties found in these mushrooms could be fully accounted for. Recently, many research groups have begun investigations on biologically active small-molecular weight compounds in wild mushrooms. In this mini-review, both structural diversity and biological activities of novel bioactive substances from Korean native mushrooms are described. PMID:24493936

Novel Carbonyl Analogues of Tamoxifen: Design, Synthesis, and Biological Evaluation

NASA Astrophysics Data System (ADS)

Kasiotis, Konstantinos M.; Lambrinidis, George; Fokialakis, Nikolas; Tzanetou, Evangelia N.; Mikros, Emmanuel; Haroutounian, Serkos A.

2017-09-01

Aim of this work was to provide tamoxifen analogues with enhanced estrogen receptor binding affinity. Hence, several derivatives were prepared using an efficient triarylethylenes synthetic protocol. The novel compounds bioactivity was evaluated through the determination of their receptor binding affinity and their agonist/antagonist activity against breast cancer tissue using a MCF-7 cell-based assay. Phenyl esters 6a,b and 8a,b exhibited binding affinity to both ERα and ERβ higher than 4-hydroxytamoxifen while compounds 13 and 14 have shown cellular antiestrogenic activity similar to 4-hydroxytamoxifen and the known estrogen receptor inhibitor ICI182,780. Theoretical calculations and molecular modelling were applied to investigate, support and explain the biological profile of the new compounds. The relevant data indicated an agreement between calculations and demonstrated biological activity allowing to extract useful structure-activity relationships. Results herein underline that modifications of tamoxifen structure still provide molecules with substantial activity, as portrayed in the inhibition of MCF-7 cells proliferation.

Part-1: Design, synthesis and biological evaluation of novel bromo-pyrimidine analogs as tyrosine kinase inhibitors.

PubMed

Munikrishnappa, Chandrashekar Suradhenupura; Puranik, Sangamesh B; Kumar, G V Suresh; Prasad, Y Rajendra

2016-08-25

A novel series of 5-bromo-pyrimidine derivatives (5a-l, 6a-h, 9a-m and 10a-d) were synthesized through multi step reactions starting from 5-bromo-2,4-dichloro pyrimidine. The newly synthesized compounds were characterized using elemental analysis and spectral data (IR, (1)H NMR, (13)C NMR and LC-MS) analysis. The titled compounds were evaluated for their in vitro cytotoxic activity against tumor cell lines panel consisted of HCT116 (human colon cancer cell line), A549 (human lung cancer cell line), K562 (human chronic myeloid leukemia cell line), U937 (human acute monocytic myeloid leukemia cell line), and L02 (human normal cell line) by using MTT assay Mosmann's method. As most of the compounds are highly potent against K562 cells, all the synthesized compounds were evaluated for Bcr/Abl tyrosine kinase inhibitory activity by using well-established ADP-Glo assay method. Dasatinib was utilized as positive control to validate in both biological evaluations. The biological activity revealed that the compounds 5c, 5e, 6g, 9e, 9f and 10c were potent Bcr/Abl kinase inhibitors among the titled compounds. Thus these compounds may be promising lead compounds to be developed as an alternative for current Dasatinib therapy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A network-based multi-target computational estimation scheme for anticoagulant activities of compounds.

PubMed

Li, Qian; Li, Xudong; Li, Canghai; Chen, Lirong; Song, Jun; Tang, Yalin; Xu, Xiaojie

2011-03-22

Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671) between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. This article proposes a network-based multi-target computational estimation method for anticoagulant activities of compounds by combining network efficiency analysis with scoring function from molecular docking.

A Network-Based Multi-Target Computational Estimation Scheme for Anticoagulant Activities of Compounds

PubMed Central

Li, Canghai; Chen, Lirong; Song, Jun; Tang, Yalin; Xu, Xiaojie

2011-01-01

Background Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. Methodology We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671) between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. Conclusions This article proposes a network-based multi-target computational estimation method for anticoagulant activities of compounds by combining network efficiency analysis with scoring function from molecular docking. PMID:21445339

Organocatalytic atroposelective synthesis of axially chiral styrenes

NASA Astrophysics Data System (ADS)

Zheng, Sheng-Cai; Wu, San; Zhou, Qinghai; Chung, Lung Wa; Ye, Liu; Tan, Bin

2017-05-01

Axially chiral compounds are widespread in biologically active compounds and are useful chiral ligands or organocatalysts in asymmetric catalysis. It is well-known that styrenes are one of the most abundant and principal feedstocks and thus represent excellent prospective building blocks for chemical synthesis. Driven by the development of atroposelective synthesis of axially chiral styrene derivatives, we discovered herein the asymmetric organocatalytic approach via direct Michael addition reaction of substituted diones/ketone esters/malononitrile to alkynals. The axially chiral styrene compounds were produced with good chemical yields, enantioselectivities and almost complete E/Z-selectivities through a secondary amine-catalysed iminium activation strategy under mild conditions. Such structural motifs are important precursors for further transformations into biologically active compounds and synthetic useful intermediates and may have potential applications in asymmetric synthesis as olefin ligands or organocatalysts.

Endophytic Actinobacteria from the Brazilian Medicinal Plant Lychnophora ericoides Mart. and the Biological Potential of Their Secondary Metabolites.

PubMed

Conti, Raphael; Chagas, Fernanda Oliveira; Caraballo-Rodriguez, Andrés Mauricio; Melo, Weilan Gomes da Paixão; do Nascimento, Andréa Mendes; Cavalcanti, Bruno Coêlho; de Moraes, Manoel Odorico; Pessoa, Cláudia; Costa-Lotufo, Letícia Veras; Krogh, Renata; Andricopulo, Adriano Defini; Lopes, Norberto Peporine; Pupo, Mônica Tallarico

2016-06-01

Endophytic actinobacteria from the Brazilian medicinal plant Lychnophora ericoides were isolated for the first time, and the biological potential of their secondary metabolites was evaluated. A phylogenic analysis of isolated actinobacteria was accomplished with 16S rRNA gene sequencing, and the predominance of the genus Streptomyces was observed. All strains were cultured on solid rice medium, and ethanol extracts were evaluated with antimicrobial and cytotoxic assays against cancer cell lines. As a result, 92% of the extracts showed a high or moderate activity against at least one pathogenic microbial strain or cancer cell line. Based on the biological and chemical analyses of crude extracts, three endophytic strains were selected for further investigation of their chemical profiles. Sixteen compounds were isolated, and 3-hydroxy-4-methoxybenzamide (9) and 2,3-dihydro-2,2-dimethyl-4(1H)-quinazolinone (15) are reported as natural products for the first time in this study. The biological activity of the pure compounds was also assessed. Compound 15 displayed potent cytotoxic activity against all four tested cancer cell lines. Nocardamine (2) was only moderately active against two cancer cell lines but showed strong activity against Trypanosoma cruzi. Our results show that endophytic actinobacteria from L. ericoides are a promising source of bioactive compounds. © 2016 Verlag Helvetica Chimica Acta AG, Zürich.

Ligand Biological Activity Predictions Using Fingerprint-Based Artificial Neural Networks (FANN-QSAR)

PubMed Central

Myint, Kyaw Z.; Xie, Xiang-Qun

2015-01-01

This chapter focuses on the fingerprint-based artificial neural networks QSAR (FANN-QSAR) approach to predict biological activities of structurally diverse compounds. Three types of fingerprints, namely ECFP6, FP2, and MACCS, were used as inputs to train the FANN-QSAR models. The results were benchmarked against known 2D and 3D QSAR methods, and the derived models were used to predict cannabinoid (CB) ligand binding activities as a case study. In addition, the FANN-QSAR model was used as a virtual screening tool to search a large NCI compound database for lead cannabinoid compounds. We discovered several compounds with good CB2 binding affinities ranging from 6.70 nM to 3.75 μM. The studies proved that the FANN-QSAR method is a useful approach to predict bioactivities or properties of ligands and to find novel lead compounds for drug discovery research. PMID:25502380

Synthesis, molecular docking and biological evaluation as HDAC inhibitors of cyclopeptide mimetics by a tandem three-component reaction and intramolecular [3+2] cycloaddition.

PubMed

Pirali, Tracey; Faccio, Valeria; Mossetti, Riccardo; Grolla, Ambra A; Di Micco, Simone; Bifulco, Giuseppe; Genazzani, Armando A; Tron, Gian Cesare

2010-02-01

Novel macrocyclic peptide mimetics have been synthesized by exploiting a three-component reaction and an azide-alkyne [3 + 2] cycloaddition. The prepared compounds were screened as HDAC inhibitors allowing us to identify a new compound with promising biological activity. In order to rationalize the biological results, computational studies have also been performed.

Spectral Response and Diagnostics of Biological Activity of Hydroxyl-Containing Aromatic Compounds

NASA Astrophysics Data System (ADS)

Tolstorozhev, G. B.; Mayer, G. V.; Bel'kov, M. V.; Shadyro, O. I.

2016-08-01

Using IR Fourier spectra and employing quantum-chemical calculations of electronic structure, spectra, and proton-acceptor properties, synthetic derivatives of aminophenol exhibiting biological activity in the suppression of herpes, influenza, and HIV viruses have been investigated from a new perspective, with the aim of establishing the spectral response of biological activity of the molecules. It has been experimentally established that the participation of the aminophenol hydroxyl group in intramolecular hydrogen bonds is characteristic of structures with antiviral properties. A quantum-chemical calculation of the proton-acceptor ability of the investigated aminophenol derivatives has shown that biologically active structures are characterized by a high proton-acceptor ability of oxygen of the hydroxyl group. A correlation that has been obtained among the formation of an intramolecular hydrogen bond, high proton-acceptor ability, and antiviral activity of substituted aminophenols enables us to predict the pharmacological properties of new medical preparations of the given class of compounds.

Investigating biological activity spectrum for novel quinoline analogues.

PubMed

Musiol, Robert; Jampilek, Josef; Kralova, Katarina; Richardson, Des R; Kalinowski, Danuta; Podeszwa, Barbara; Finster, Jacek; Niedbala, Halina; Palka, Anna; Polanski, Jaroslaw

2007-02-01

The lack of the wide spectrum of biological data is an important obstacle preventing the efficient molecular design. Quinoline derivatives are known to exhibit a variety of biological effects. In the current publication, we tested a series of novel quinoline analogues for their photosynthesis-inhibiting activity (the inhibition of photosynthetic electron transport in spinach chloroplasts (Spinacia oleracea L.) and the reduction of chlorophyll content in Chlorella vulgaris Beij.). Moreover, antiproliferative activity was measured using SK-N-MC neuroepithelioma cell line. We described the structure-activity relationships (SAR) between the chemical structure and biological effects of the synthesized compounds. We also measured the lipophilicity of the novel compounds by means of the RP-HPLC and illustrate the relationships between the RP-HPLC retention parameter logK (the logarithm of capacity factor K) and logP data calculated by available programs.

Novel pyrrolopyrimidines and triazolopyrrolopyrimidines carrying a biologically active sulfonamide moieties as anticancer agents.

PubMed

Ghorab, Mostafa M; Alsaisd, Mansour S; Nissan, Yassin M

2015-01-01

A new series of pyrroles 5, 6, pyrrolopyrimidines 8, 11-14, 16-29, triazolo-pyrrolopyrimidines 9, 10 and 15 carrying a biologically active sulfonamide moities were synthesized using 2-amino-3-cyano-4-(4-bromophenyl)pyrrole 5 as a strategic starting material. The structures of the prepared compounds were confirmed by elemental analyses, IR, 1H-NMR and 13C-NMR data. All of the synthesized compounds showed promising anticancer activity against breast cancer cell line (MCF7) compared to doxorubicin as reference drug, especially compounds 5-17, 21-24 and 28 with better IC50 than that of doxorubicin. In order to suggest the mechanism of action of their cytotoxic activities, molecular docking on the active site of c-Src was done and good results were obtained.

A Review on the Medicinal Plant Dalbergia odorifera Species: Phytochemistry and Biological Activity

PubMed Central

2017-01-01

The crucial medicinal plant Dalbergia odorifera T. Chen species belongs to genus Dalbergia, with interesting secondary metabolites, consisting of main classes of flavonoid, phenol, and sesquiterpene derivatives, as well as several arylbenzofurans, quinones, and fatty acids. Biological studies were carried out on extracts, fractions, and compounds from this species involved in cytotoxic assays; antibacterial, antioxidative, anti-inflammatory, antithrombotic, antiplatelet, antiosteosarcoma, antiosteoporosis, antiangiogenesis, and prostaglandin biosynthetic enzyme inhibition activities; vasorelaxant activities; alpha-glucosidase inhibitory activities; and many other effects. In terms of the valuable resources for natural new drugs development, D. odorifera species are widely used as medicinal drugs in many countries for treatment of cardiovascular diseases, cancer, diabetes, blood disorders, ischemia, swelling, necrosis, or rheumatic pain. Although natural products from this plant have been increasingly playing an important role in drug discovery programs, there is no supportive evidence to provide a general insight into phytochemical studies on D. odorifera species and biological activities of extracts, fractions, and isolated compounds. To a certain extent, this review deals with an overview of almost naturally occurring compounds from this species, along with extensive coverage of their biological evaluations. PMID:29348771

Experimental and molecular modeling investigation of isopropyl 4-(biphenyl-4-Yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate

NASA Astrophysics Data System (ADS)

Yıldırım, Sema Öztürk; ćetin, Gökalp; Büyükmumcu, Zeki; Şimşek, Rahime; Şafak, Cihat; Butcher, Ray J.; Pekdur, Özlem Savaş

2018-02-01

The most important effect of 1,4-dihydropyridine (1,4-DHP) derivatives with various biological activities is to reduce the influx of extracellular Ca2+ ions. Because of this feature, many 1,4-DHP derivatives have been identified as potent calcium channel blockers and have been included in the treatment as antihypertensive agents. On the other hand, the biphenyl group is an important group in the molecule of biologically active compounds. The active compounds are obtained by introducing the biphenyl group into the structure of various compounds. In this study, the biphenyl group was introduced into the 1,4-DHP ring to reach to hexahydroquinoline (HHQ) derivative as an active calcium channel blocker compound. The structure of the compound was proved by IR, 1H-NMR, Mass spectroscopy, X-ray crystallography and elemental analysis. The cytotoxic properties of the compound has been determined, and biological activity assays continue. The crystal structure of C28H31NO3 was determined by single crystal X-ray diffraction: monoclinic, space group C c, a = 11.9713(3) Å, b = 18.7893(5) Å, c = 10.7358(3) Å, β = 102.411(4)°, Z = 4. The title molecule is twisted with the dihedral angle between two phenyl rings being 50.86(10)°. The optimized geometries of the title compound have been obtained employing DFT method. The calculated geometrical parameters were found to be in agreement with the experimental data.

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.

Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies.

PubMed

Simic, Milena; Paunovic, Nikola; Boric, Ivan; Randjelovic, Jelena; Vojnovic, Sandra; Nikodinovic-Runic, Jasmina; Pekmezovic, Marina; Savic, Vladimir

2016-01-01

A series of novel 3-substituted isocoumarins was prepared via Pd-catalysed coupling processes and screened in vitro for antifungal activity against Candida species. The study revealed antifungal potential of isocoumarins possessing the azole substituents, which, in some cases, showed biological properties equal to those of clinically used voriconazole. Selected compounds were also screened against voriconazole resistant Candida krusei 6258 and a clinical isolate Candida parapsilosis CA-27. Although the activity against these targets needs to be improved further, the results emphasise additional potential of this new class of antifungal compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

Design, synthesis and preliminary biological evaluation of indoline-2,3-dione derivatives as novel HDAC inhibitors.

PubMed

Jin, Kang; Li, Shanshan; Li, Xiaoguang; Zhang, Jian; Xu, Wenfang; Li, Xuechen

2015-08-01

Histone deacetylases (HDACs) are zinc-dependent or NAD(+) dependent enzymes and play a critical role in the process of tumor development. Herein a series of indoline-2,3-dione derivatives have been designed and synthesized as potential HDACs inhibitors. The preliminary biological evaluation showed that most compounds synthesized have exhibited moderate Hela cell nuclear extract inhibitory activities, among which compound 25a (IC50=10.13 nM) has shown the best efficacy. The anti-proliferative activities of some of these compounds were also discussed. Copyright © 2015. Published by Elsevier Ltd.

Biological Targets and Mechanisms of Action of Natural Products from Marine Cyanobacteria

PubMed Central

Salvador-Reyes, Lilibeth A.

2015-01-01

Marine cyanobacteria are an ancient group of organisms and prolific producers of bioactive secondary metabolites. These compounds are presumably optimized by evolution over billions of years to exert high affinity for their intended biological target in the ecologically relevant organism but likely also possess activity in different biological contexts such as human cells. Screening of marine cyanobacterial extracts for bioactive natural products has largely focused on cancer cell viability; however, diversification of the screening platform led to the characterization of many new bioactive compounds. Targets of compounds have oftentimes been elusive if the compounds were discovered through phenotypic assays. Over the past few years, technology has advanced to determine mechanism of action (MOA) and targets through reverse chemical genetic and proteomic approaches, which has been applied to certain cyanobacterial compounds and will be discussed in this review. Some cyanobacterial molecules are the most-potent-in-class inhibitors and therefore may become valuable tools for chemical biology to probe protein function but also be templates for novel drugs, assuming in vitro potency translates into cellular and in vivo activity. Our review will focus on compounds for which the direct targets have been deciphered or which were found to target a novel pathway, and link them to disease states where target modulation may be beneficial. PMID:25571978

Therapeutic potential and health benefits of Sargassum species

PubMed Central

Yende, Subhash R.; Harle, Uday N.; Chaugule, Bhupal B.

2014-01-01

Sargassum species are tropical and sub-tropical brown macroalgae (seaweed) of shallow marine meadow. These are nutritious and rich source of bioactive compounds such as vitamins, carotenoids, dietary fibers, proteins, and minerals. Also, many biologically active compounds like terpenoids, flavonoids, sterols, sulfated polysaccharides, polyphenols, sargaquinoic acids, sargachromenol, pheophytine were isolated from different Sargassum species. These isolated compounds exhibit diverse biological activities like analgesic, anti-inflammatory, antioxidant, neuroprotective, anti-microbial, anti-tumor, fibrinolytic, immune-modulatory, anti-coagulant, hepatoprotective, anti-viral activity etc., Hence, Sargassum species have great potential to be used in pharmaceutical and neutralceutical areas. This review paper explores the current knowledge of phytochemical, therapeutic potential, and health benefits of different species of genus Sargassum. PMID:24600190

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.

Anticancer effect and structure-activity analysis of marine products isolated from metabolites of mangrove fungi in the South China Sea.

PubMed

Tao, Li-yang; Zhang, Jian-ye; Liang, Yong-ju; Chen, Li-ming; Zhen, Li-sheng; Wang, Fang; Mi, Yan-jun; She, Zhi-gang; To, Kenneth Kin Wah; Lin, Yong-cheng; Fu, Li-wu

2010-04-01

Marine-derived fungi provide plenty of structurally unique and biologically active secondary metabolites. We screened 87 marine products from mangrove fungi in the South China Sea for anticancer activity by MTT assay. 14% of the compounds (11/86) exhibited a potent activity against cancer in vitro. Importantly, some compounds such as compounds 78 and 81 appeared to be promising for treating cancer patients with multidrug resistance, which should encourage more efforts to isolate promising candidates for further development as clinically useful chemotherapeutic drugs. Furthermore, DNA intercalation was not involved in their anticancer activities, as determined by DNA binding assay. On the other hand, the structure-activity analysis indicated that the hydroxyl group was important for their cytotoxic activity and that bulky functional groups such as phenyl rings could result in a loss of biological activity, which will direct the further development of marine product-based derivatives.

Comparative study of binding interactions between porphyrin systems and aromatic compounds of biological importance by multiple spectroscopic techniques: A review

NASA Astrophysics Data System (ADS)

Makarska-Bialokoz, Magdalena

2018-07-01

The specific spectroscopic and redox properties of porphyrins predestine them to fulfill the role of sensors during interacting with different biologically active substances. Monitoring of binding interactions in the systems porphyrin-biologically active compound is a key question not only in the field of physiological functions of living organisms, but also in environmental protection, notably in the light of the rapidly growing drug consumption and concurrently the production of drug effluents. Not always beneficial action of drugs on natural porphyrin systems induces to further studies, with commercially available porphyrins as the model systems. Therefore the binding process between several water-soluble porphyrins and a series of biologically active compounds (e.g. caffeine, guanine, theophylline, theobromine, xanthine, uric acid) has been studied in different aqueous solutions analyzing their absorption and steady-state fluorescence spectra, the porphyrin fluorescence lifetimes and their quantum yields. The magnitude of the binding and fluorescence quenching constants values for particular quenchers decreases in a series: uric acid > guanine > caffeine > theophylline > theobromine > xanthine. In all the systems studied there are characters of static quenching, as a consequence of the π-π-stacked non-covalent and non-fluorescent complexes formation between porphyrins and interacting compounds, accompanied simultaneously by the additional specific binding interactions. The porphyrin fluorescence quenching can be explain by the photoinduced intermolecular electron transfer from aromatic compound to the center of the porphyrin molecule, playing the role of the binding site. Presented results can be valuable for designing of new fluorescent porphyrin chemosensors or monitoring of drug traces in aqueous solutions. The obtained outcomes have also the toxicological and medical importance, providing insight into the interactions of the water-soluble porphyrins with biologically active substances.

Ring-substituted 4-hydroxy-1H-quinolin-2-ones: preparation and biological activity.

PubMed

Jampilek, Josef; Musiol, Robert; Pesko, Matus; Kralova, Katarina; Vejsova, Marcela; Carroll, James; Coffey, Aidan; Finster, Jacek; Tabak, Dominik; Niedbala, Halina; Kozik, Violetta; Polanski, Jaroslaw; Csollei, Jozef; Dohnal, Jiri

2009-03-13

In the study, a series of twelve ring-substituted 4-hydroxy-1H-quinolin-2-one derivatives were prepared. The procedures for synthesis of the compounds are presented. The compounds were analyzed using RP-HPLC to determine lipophilicity and tested for their photosynthesis-inhibiting activity using spinach (Spinacia oleracea L.) chloroplasts. All the synthesized compounds were also evaluated for antifungal activity using in vitro screening with eight fungal strains. For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed, as well as their structure-activity relationships (SAR).

Synthesis and biological activity of imidazopyridine anticoccidial agents: Part II.

PubMed

Scribner, Andrew; Dennis, Richard; Lee, Shuliang; Ouvry, Gilles; Perrey, David; Fisher, Michael; Wyvratt, Matthew; Leavitt, Penny; Liberator, Paul; Gurnett, Anne; Brown, Chris; Mathew, John; Thompson, Donald; Schmatz, Dennis; Biftu, Tesfaye

2008-06-01

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. Recently, we reported the synthesis and biological activity of potent imidazo[1,2-a]pyridine anticoccidial agents. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we report the synthesis and anticoccidial activity of a second set of such compounds, focusing on derivatization of the amine side chain at the imidazopyridine 7-position. 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.

Structure and Chemical Synthesis of a Biologically Active Form of Renilla (Sea Pansy) Luciferin*

PubMed Central

Hori, Kazuo; Cormier, Milton J.

1973-01-01

The structure of a biologically active form of Renilla (sea pansy) luciferin has been elucidated; this structure, confirmed by total chemical synthesis, is 3,7-dihydro-2-methyl-6-(p-hydroxyphenyl)-8-benzylimidazo [1,2-a] pyrazin-3-one. In the natural compound the methyl group at the 2 position is replaced by an unknown, more complex group. For this reason the synthetic compound is 10% as active as the natural compound in producing light with Renilla luciferase. However, the spectral properties of the two compounds are identical. In addition the rates of the luminescent reaction with both compounds are similar, and the color of the light produced is identical in each case. A compound isolated from the calcium-triggered photoprotein aequorin has been identified by Shimomura and Johnson [(1972) Biochemistry 11, 1602] to be 2-amino-3-benzyl-5-(p-hydroxyphenyl)pyrazine. This compound forms an integral part of the structure of Renilla luciferin. This, and other evidence, suggests that the structure elucidated for Renilla luciferin is a more general one associated with the luciferins of most, if not all, bioluminescent coelenterates. PMID:16592045

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].

Enzyme-assistant extraction (EAE) of bioactive components: a useful approach for recovery of industrially important metabolites from seaweeds: a review.

PubMed

Wijesinghe, W A J P; Jeon, You-Jin

2012-01-01

Over the years, the biological activities of seaweeds could have gained a considerable research interest because of their specific functional compounds, which may not be available in land plants. Thus, efforts at discovery of novel metabolites from seaweeds over the past years have yielded a considerable amount of new active compounds. In addition, studies about the extraction of active compounds from natural products have attracted special attention in the last recent years. Potent biologically active compounds of seaweeds have been demonstrated to play a significant role in prevention of certain degenerative diseases such as cancer, inflammation, arthritis, diabetes and hypertension. Therefore, seaweed derived active components, whose immense biochemical diversity looks like to become a rich source of novel chemical entities for the use as functional ingredients in many industrial applications such as functional foods, pharmaceuticals and cosmeceuticals. Thus, the interest in the extraction of active compounds from seaweeds is obvious. However, the physical and chemical barriers of the plant material become the key drawbacks of such extraction process. Therefore, enhanced release and recovery of active compounds attached to the cells have been addressed. Taken together, the aim of this communication is to discuss the potential use of enzyme treatment as a tool to improve the extraction efficiency of bioactive compounds from seaweeds. Copyright © 2011 Elsevier B.V. All rights reserved.

Development and application of a sensitive, phenotypic, high-throughput image-based assay to identify compound activity against Trypanosoma cruzi amastigotes

PubMed Central

Sykes, Melissa L.; Avery, Vicky M.

2015-01-01

We have developed a high content 384-well, image-based assay to estimate the effect of compound treatment on Trypanosoma cruzi amastigotes in 3T3 fibroblasts. In the same well, the effect of compound activity on host cells can also be determined, as an initial indicator of cytotoxicity. This assay has been used to identify active compounds from an in-house library of compounds with either known biological activity or that are FDA approved, and separately, from the Medicines for Malaria Venture Malaria Box collection. Active compounds were screened against T. cruzi trypomastigotes, utilising an assay developed with the viability dye resazurin. Twelve compounds with reconfirmed solid sample activity, with IC50 values of less than 10 μM and selectivity indices to T. cruzi amastigotes over 3T3 host cells of between >22 and 319 times were identified from these libraries. As 3T3 cells are contact inhibited, with limited proliferation in the assay, selective compounds of interest were profiled in a separate assay to estimate the viability of compound treated, replicating HEK293 cells. Selective compounds that were not previously reported in the literature were further profiled by extending the incubation time against amastigote infected 3T3 cells to determine if there were residual amastigotes post-treatment, important for the consideration of the exposure time required for further biological characterisation. The assay development process and the suitability of identified compounds as hit molecules for Chagas disease research are discussed. PMID:27120069

Development and application of a sensitive, phenotypic, high-throughput image-based assay to identify compound activity against Trypanosoma cruzi amastigotes.

PubMed

Sykes, Melissa L; Avery, Vicky M

2015-12-01

We have developed a high content 384-well, image-based assay to estimate the effect of compound treatment on Trypanosoma cruzi amastigotes in 3T3 fibroblasts. In the same well, the effect of compound activity on host cells can also be determined, as an initial indicator of cytotoxicity. This assay has been used to identify active compounds from an in-house library of compounds with either known biological activity or that are FDA approved, and separately, from the Medicines for Malaria Venture Malaria Box collection. Active compounds were screened against T. cruzi trypomastigotes, utilising an assay developed with the viability dye resazurin. Twelve compounds with reconfirmed solid sample activity, with IC50 values of less than 10 μM and selectivity indices to T. cruzi amastigotes over 3T3 host cells of between >22 and 319 times were identified from these libraries. As 3T3 cells are contact inhibited, with limited proliferation in the assay, selective compounds of interest were profiled in a separate assay to estimate the viability of compound treated, replicating HEK293 cells. Selective compounds that were not previously reported in the literature were further profiled by extending the incubation time against amastigote infected 3T3 cells to determine if there were residual amastigotes post-treatment, important for the consideration of the exposure time required for further biological characterisation. The assay development process and the suitability of identified compounds as hit molecules for Chagas disease research are discussed. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Structure-Activity Correlations with Compounds Related to Abscisic Acid 1

PubMed Central

Sondheimer, Ernest; Walton, Daniel C.

1970-01-01

Inhibition of cell expansion of excised embryonic axes of Phaseolus vulgaris was used to evaluate the growth-inhibiting activity of abscisic acid and related compounds. None of the 13 compounds tested was as active as abscisic acid. 4-Hydroxyisophorone, a substance representative of the abscisic acid ring system was essentially inactive; cis, trans-3-methylsorbic acid, a compound resembling the side chain of abscisic acid, had low activity; and cis, trans-β-ionylideneacetic acid was one-sixth as active. Loss of the ring double bond results in a drastic decrease in biological activity. Comparison of our results with those reported previously leads to the suggestion that the double bond of the cyclohexyl moiety may have an important function in determining the degree of activity of cis, trans-ionylideneacetic acids. Two modes of action are discussed. It seems possible that the ring double bond is involved in covalent bonding in binding of the abscisic acid analogue to macromolecules. This may require formation of an intermediate epoxide. It can also be argued that stereochemical differences between cyclohexane derivatives are important factors in determining the degree of biological activity. PMID:5423465

Chemical constituents and biological activities from branches of Colubrina asiatica.

PubMed

Sangsopha, Watchara; Kanokmedhakul, Kwanjai; Lekphrom, Ratsami; Kanokmedhakul, Somdej

2018-05-01

Sixteen compounds were isolated from a Thai medicinal plant, Colubrina asiatica. The isolated compounds were elucidated on the basis of spectroscopic methods (IR, 1D and 2D NMR) as six triterpene acids (1-6), five steroids (7-11), one benzoic acid derivative (12), two peptides (13 and 14), one sesquiterpenoid (15) and one jujubogenin (16). Compounds 3 and 10 showed antimalarial activity against Plasmodium falciparum. Compound 5 showed antimycobacterial activity. Moreover, compounds 3, 5, 6, 10 and 14 exhibited weak cytotoxicity against cancer cell lines. Compounds 1-15 have been isolated for the first time from this plant.

Indonesian propolis: chemical composition, biological activity and botanical origin.

PubMed

Trusheva, Boryana; Popova, Milena; Koendhori, Eko Budi; Tsvetkova, Iva; Naydenski, Christo; Bankova, Vassya

2011-03-01

From a biologically active extract of Indonesian propolis from East Java, 11 compounds were isolated and identified: four alk(en)ylresorcinols (obtained as an inseparable mixture) (1-4) were isolated for the first time from propolis, along with four prenylflavanones (6-9) and three cycloartane-type triterpenes (5, 10 and 11). The structures of the components were elucidated based on their spectral properties. All prenylflavanones demonstrated significant radical scavenging activity against diphenylpicrylhydrazyl radicals, and compound 6 showed significant antibacterial activity against Staphylococcus aureus. For the first time Macaranga tanarius L. and Mangifera indica L. are shown as plant sources of Indonesian propolis.

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.

Secondary Metabolites from Marine Microorganisms. II. Marine Fungi and Their Habitats.

PubMed

Orlova, T I; Bulgakova, V G; Polin, A N

Marine-derived fungi are of great interest as a new promising source of biologically active products such as anticancer compounds, antibiotics, inhibitors of biochemical processes. Since marine organisms inhabit biologically competitive environment with unique conditions, the chemical diversity of the secondary metabolites from marine fungi is considerably high. Recent genomic studies demonstrated that fungi can carry gene clasters encoding production of previously unknown secondary metabolites. Activation of the attenuated or silent genes would be useful either for improving activities of the known compounds or for discovery of new products.

Secondary metabolites of cyanobacteria Nostoc sp.

NASA Astrophysics Data System (ADS)

Kobayashi, Akio; Kajiyama, Shin-Ichiro

1998-03-01

Cyanobacteria attracted much attention recently because of their secondary metabolites with potent biological activities and unusual structures. This paper reviews some recent studies on the isolation, structural, elucidation and biological activities of the bioactive compounds from cyanobacteria Nostoc species.

Borreria and Spermacoce species (Rubiaceae): A review of their ethnomedicinal properties, chemical constituents, and biological activities

PubMed Central

Conserva, Lucia Maria; Ferreira, Jesu Costa

2012-01-01

Borreira and Spermacoce are genera of Rubiaceae widespread in tropical and subtropical America, Africa, Asia, and Europe. Based on its fruits morphology they are considered by many authors to be distinct genera and most others, however, prefer to combine the two taxa under the generic name Spermacoce. Whereas the discussion is still unclear, in this work they were considered as synonyms. Some species of these genera play an important role in traditional medicine in Africa, Asia, Europe, and South America. Some of these uses include the treatment of malaria, diarrheal and other digestive problems, skin diseases, fever, hemorrhage, urinary and respiratory infections, headache, inflammation of eye, and gums. To date, more than 60 compounds have been reported from Borreria and Spermacoce species including alkaloids, iridoids, flavonoids, terpenoids, and other compounds. Studies have confirmed that extracts from Borreria and Spermacoce species as well as their isolated compounds possess diverse biological activities, including anti-inflammatory, antitumor, antimicrobial, larvicidal, antioxidant, gastrointestinal, anti-ulcer, and hepatoprotective, with alkaloids and iridoids as the major active principles. This paper briefly reviews the ethnomedicinal uses, phytochemistry, and biological activities of some isolated compounds and extracts of both genera. PMID:22654404

Approaching an experimental electron density model of the biologically active trans -epoxysuccinyl amide group-Substituent effects vs. crystal packing

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

Shi, Ming W.; Stewart, Scott G.; Sobolev, Alexandre N.

The trans-epoxysuccinyl amide group as a biologically active moiety in cysteine protease inhibitors such as loxistatin acid E64c has been used as a benchmark system for theoretical studies of environmental effects on the electron density of small active ingredients in relation to their biological activity. Here, the synthesis and the electronic properties of the smallest possible active site model compound are reported to close the gap between the unknown experimental electron density of trans-epoxysuccinyl amides and the well-known function of related drugs. Intramolecular substituent effects are separated from intermolecular crystal packing effects on the electron density, which allows us tomore » predict the conditions under which an experimental electron density investigation on trans-epoxysuccinyl amides will be possible. In this context, the special importance of the carboxylic acid function in the model compound for both crystal packing and biological activity is revealed through the novel tool of model energy analysis.« less

Method for photo-altering a biological system to improve biological effect

DOEpatents

Hill, Richard A.; Doiron, Daniel R.; Crean, David H.

2000-08-01

Photodynamic therapy is a new adjunctive therapy for filtration surgery that does not use chemotherapy agents or radiation, but uses pharmacologically-active sensitizing compounds to produce a titratable, localized, transient, post operative avascular conjunctiva. A photosensitizing agent in a biological system is selectively activated by delivering the photosensitive agent to the biological system and laser activating only a spatially selected portion of the delivered photosensitive agent. The activated portion of the photosensitive agent reacts with the biological system to obtain a predetermined biological effect. As a result, an improved spatial disposition and effectuation of the biological effect by the photosensitive agent in the biological system is achieved.

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.

Analysis of additivity and synergism in the anti-plasmodial effect of purified compounds from plant extracts.

PubMed

Deharo, Eric; Ginsburg, Hagai

2011-03-15

In the search for antimalarials from ethnobotanical origin, plant extracts are chemically fractionated and biological tests guide the isolation of pure active compounds. To establish the responsibility of isolated active compound(s) to the whole antiplasmodial activity of a crude extract, the literature in this field was scanned and results were analysed quantitatively to find the contribution of the pure compound to the activity of the whole extract. It was found that, generally, the activity of isolated molecules could not account on their own for the activity of the crude extract. It is suggested that future research should take into account the "drugs beside the drug", looking for those products (otherwise discarded along the fractionation process) able to boost the activity of isolated active compounds.

Antimicrobial Compounds from Marine Invertebrates-Derived Microorganisms.

PubMed

Liu, Juan; Jung, Jee H; Liu, Yonghong

2016-01-01

It is known that marine invertebrates, including sponges, tunicates, cnidaria or mollusks, host affluent and various communities of symbiotic microorganisms. The microorganisms associated with the invertebrates metabolized various biologically active compounds, which could be an important resource for the discovery and development of potentially novel drugs. In this review, the new compounds with antimicrobial activity isolated from marine invertebrate-derived microorganisms in the last decade (2004-2014) will be presented, with focus on the relevant antimicrobial activities, origin of isolation, and information of strain species. New compounds without antimicrobial activity were not revealed.

Aqua mediated synthesis of bio-active compounds.

PubMed

Panda, Siva S

2013-05-01

Recently the aqueous medium has attracted the interest of organic chemists, and many. Moreover, in the past 20 years, the drug-discovery process has undergone extraordinary changes, and high-throughput biological screening of potential drug candidates has led to an ever-increasing demand for novel drug-like compounds. Noteworthy advantages were observed during the course of study on aqua mediated synthesis of compounds of medicinal importance. The established advantages of water as a solvent for reactions are, water is the most abundant and available resource on the planet and many biochemical processes occur in aqueous medium. This review will focus on describing new developments in the application of water in medicinal chemistry for the synthesis of bio-active compounds possessing various biological properties.

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.

Spectroscopic characteristic (FT-IR, FT-Raman, UV, 1H and 13C NMR), theoretical calculations and biological activity of alkali metal homovanillates

NASA Astrophysics Data System (ADS)

Samsonowicz, M.; Kowczyk-Sadowy, M.; Piekut, J.; Regulska, E.; Lewandowski, W.

2016-04-01

The structural and vibrational properties of lithium, sodium, potassium, rubidium and cesium homovanillates were investigated in this paper. Supplementary molecular spectroscopic methods such as: FT-IR, FT-Raman in the solid phase, UV and NMR were applied. The geometrical parameters and energies were obtained from density functional theory (DFT) B3LYP method with 6-311++G** basis set calculations. The geometry of the molecule was fully optimized, vibrational spectra were calculated and fundamental vibrations were assigned. Geometric and magnetic aromaticity indices, atomic charges, dipole moments, HOMO and LUMO energies were also calculated. The microbial activity of investigated compounds was tested against Bacillus subtilis (BS), Pseudomonas aeruginosa (PA), Escherichia coli (EC), Staphylococcus aureus (SA) and Candida albicans (CA). The relationship between the molecular structure of tested compounds and their antimicrobial activity was studied. The principal component analysis (PCA) was applied in order to attempt to distinguish the biological activities of these compounds according to selected band wavenumbers. Obtained data show that the FT-IR spectra can be a rapid and reliable analytical tool and a good source of information for the quantitative analysis of the relationship between the molecular structure of the compound and its biological activity.

Design, synthesis and biological evaluation of novel hydrogen sulfide releasing capsaicin derivatives.

PubMed

Gao, Mingxiang; Li, Jinyu; Nie, Cunbin; Song, Beibei; Yan, Lin; Qian, Hai

2018-05-15

Capsaicin (CAP), the prototypical TRPV1 agonist, is the major active component in chili peppers with health-promoting benefits. However, its use is limited by the low bioavailability and irritating quality. In this study, for improving the activity of CAP and alleviating its irritating effects, a series of H 2 S-releasing CAPs were designed and synthesized by combining capsaicin and dihydro capsaicin with various hydrogen sulfide donors. The resulting compounds were evaluated their TRPV1 agonist activity, analgesic activity, anticancer activities, H 2 S-releasing ability, and gastric mucosa irritation. Biological evaluation indicated that the most active compound B 9 , containing 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione moiety as H 2 S donor, had better analgesic activity and displayed more potent cytotoxic effects on the test cell lines than the lead compound CAP. Furthermore, the preferred compound, B 9 reduced rat gastric mucosa irritation caused by CAP. Notably, the improved properties of this derivative are associated with its H 2 S-releasing capability. Copyright © 2018 Elsevier Ltd. All rights reserved.

Synthesis and biological evaluation of sulfur-containing cinnamate and salicylate derivatives.

PubMed

Chiang, Chih-Chia; Chang, Tsu-Chung; Tsai, Hou-Jen; Hsu, Ling-Yih

2008-03-01

UV irradiation induced formation of reactive oxygen radical species and matrix metalloproteinases (MMPs) are thought to be involved in photo-damage to the skin. MMP-1 is the major collagenolytic enzyme responsible for collagen destruction in skin tissue. To develop new anti-photoaging agents, a series of 2,2'-dithiocinnamate derivatives and 2,2'-dithio or 2-thiobenzoate derivatives were designed and synthesized. The biological activities of the synthesized compounds were assayed for ABTS [2,2'-azinobis-(3-ethyl-benzo-thiazoline-6-sulfonic acid)] radical scavenging activity, MMP-1 inhibitory activity, and cytotoxicity to human dermal fibroblast cells. Compounds with potential of resistance to UV irradiation were identified. These compounds are expected to be useful for preventing photo-damage to the skin.

Synthesis, biological evaluation, and molecular modeling of cinnamic acyl sulfonamide derivatives as novel antitubulin agents.

PubMed

Luo, Yin; Qiu, Ke-Ming; Lu, Xiang; Liu, Kai; Fu, Jie; Zhu, Hai-Liang

2011-08-15

A series of novel cinnamic acyl sulfonamide derivatives (9a-16e) have been designed and synthesized and their biological activities were also evaluated as potential tubulin polymerization inhibitors. Among all the compounds, 10c showed the most potent growth inhibitory activity against B16-F10 cancer cell line in vitro, with an IC(50) value of 0.8μg/mL. Docking simulation was performed to insert compound 10c into the crystal structure of tubulin at colchicine binding site to determine the probable binding model. Based on the preliminary results, compound 10c with potent inhibitory activity in tumor growth may be a potential anticancer agent. Copyright © 2011 Elsevier Ltd. All rights reserved.

Synthesis and biological activity of N-arylpiperazine-modified analogues of KN-62, a potent antagonist of the purinergic P2X7 receptor.

PubMed

Baraldi, Pier Giovanni; del Carmen Nuñez, Maria; Morelli, Anna; Falzoni, Simonetta; Di Virgilio, Francesco; Romagnoli, Romeo

2003-04-10

The P2X(7) receptor is involved in several processes relevant to inflammation (cytokine release, NO generation, killing of intracellular pathogens, cytotoxicity); thus, it may be an appealing target for pharmacological intervention. The characterization of native and recombinant P2X(7) receptor continues to be hindered by the lack of specific and subtype-selective antagonists. However, a tyrosine derivative named KN-62 exhibits selective P2X(7) receptor-blocking properties. The present study was designed to evaluate the functional antagonistic properties of a novel series of KN-62-related compounds characterized by the presence of different phenyl-substituted piperazine moieties. Antagonistic activity of KN-62 derivatives was tested on HEK293 cells transduced with the human P2X(7) receptor and monocyte-derived human macrophages, a cell type well-known for the high level of expression of this receptor. The biological responses investigated were ATP-dependent Ca(2+) influx across the plasma membrane, ethidium bromide uptake, and secretion of the cytokine interleukin-1beta. KN-62 was characterized by the presence of a phenylpiperazine moiety, and the presence of a one-carbon linker between the piperazine nitrogen and the phenyl ring (compound 61) increases the activity, while a two-carbon linker (compound 62) decreases biological activity 10-fold. Also, the nature and the position of substituents on the phenyl ring tethered to the piperazine seemed to exert a fundamental influence on the biological activity. In the series of synthesized compounds, the presence of a fluorine in the para position gives the most potent compound (63), while the same atom in the ortho position reduces potency by 3-fold. When the p-fluorine was replaced in the same position with other halogens, such as chlorine (compound 64) or iodine (compound 65), the activity decreased dramatically. We then tested the activity of the four most potent KN-62 derivatives on ATP-stimulated secretion of IL-1beta from monocyte-derived human macrophages, a key cell type in inflammation and innate immunity. Interestingly, compound 68 and 71 caused a complete inhibition of IL-1beta release, while with KN-62, 63, and 85, there was a small residual cytokine secretion even at concentrations exceeding 100 nM. None of the compounds tested on IL-1beta release had any effect on isolated CaMII kinase activity up to 20 microM (not shown).

DFT study of quercetin activated forms involved in antiradical, antioxidant, and prooxidant biological processes.

PubMed

Fiorucci, Sébastien; Golebiowski, Jérôme; Cabrol-Bass, Daniel; Antonczak, Serge

2007-02-07

Quercetin, one of the most representative flavonoid compounds, is involved in antiradical, antioxidant, and prooxidant biological processes. Despite a constant increase of knowledge on both positive and negative activities of quercetin, it is unclear which activated form (quinone, semiquinone, or deprotonated) actually plays a role in each of these processes. Structural, electronic, and energetic characteristics of quercetin, as well as the influence of a copper ion on all of these parameters, are studied by means of quantum chemical electronic structure calculations. Introduction of thermodynamic cycles together with the role of coreactive compounds, such as reactive oxygen species, gives a glimpse of the most probable reaction schemes. Such a theoretical approach provides another hint to clarify which reaction is likely to occur within the broad range of quercetin biological activities.

Design and synthesis of novel HDAC8 inhibitory 2,5-disubstituted-1,3,4-oxadiazoles containing glycine and alanine hybrids with anti cancer activity.

PubMed

Pidugu, Vijaya Rao; Yarla, Nagendra Sastry; Pedada, Srinivasa Rao; Kalle, Arunasree M; Satya, A Krishna

2016-11-01

Oxadiazole is a heterocyclic compound containing an oxygen atom and two nitrogen atoms in a five-membered ring. Of the four oxadiazoles known, 1,3,4-oxadiazole has become an important structural motif for the development of new drugs and the compounds containing 1,3,4-oxadiazole cores have a broad spectrum of biological activity. Herein, we describe the design, synthesis and biological evaluation of a series of novel 2,5-disubstituted 1,3,4-oxadiazoles (10a-10j) as class I histone deacetylase (HDAC) inhibitors. The compounds were designed and evaluated for HDAC8 selectivity using in silico docking software (Glide) and the top 10 compounds with high dock score and obeying Lipinski's rule were synthesized organically. Further the biological HDAC inhibitory and selectivity assays and anti-proliferative assays were carried out. In in silico and in vitro studies, all compounds (10a-10j) showed significant HDAC inhibition and exhibited HDAC8 selectivity. Among all tested compounds, 10b showed substantial HDAC8 inhibitory activity and better anticancer activity which is comparable to the positive control, a FDA approved drug, vorinostat (SAHA). Structural activity relation is discussed with various substitutions in the benzene ring connected on 1,3,4-oxadizole and glycine/alanine. The study warranted further investigations to develop HDAC8-selective inhibitory molecule as a drug for neoplastic diseases. Novel 1,3,4-oxadizole substituted with glycine/alanine showed HDAC8 inhibition. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biologically important compounds in synfuels processes

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

Clark, B R; Ho, C; Griest, W H

1980-01-01

Crude products, by-products and wastes from synfuel processes contain a broad spectrum of chemical compounds - many of which are active in biological systems. Discerning which compound classes are most important is necessary in order to establish effective control over release or exposure. Polycyclic aromatic hydrocarbons (PAH), multialkylated PAH, primary aromatic amines and N-heterocyclic PAH are significant contributors to the overall mutagenic activities of a large number of materials examined. Ames test data show that the basic, primary aromatic amine fraction is the most active. PAHs, multialkylated PAHs and N-heterocyclic PAHs are all components of the neutral fraction. In nearlymore » all cases, the neutral fractions contribute the largest portion of the mutagenic activity, while the basic primary aromatic amine fractions have the highest specific activity. Neutral fractions are usually the largest (wt %) whereas the total basic fractions are small by comparison; thus, the overall greater contribution of the neutral fraction to the mutagenic activity of most samples. Biologically active constituents are isolated in preparative scale amounts from complex mixtures utilizing combinations of liquid-liquid extraction and various liquid chromatographic column-eluant combinations. Fractions are characterized using a combination of spectroscopic techniques and gas chromatography/mass spectrometry.« less

Antimicrobial and anticancer activity of some novel fluorinated thiourea derivatives carrying sulfonamide moieties: synthesis, biological evaluation and molecular docking.

PubMed

Ghorab, Mostafa M; Alsaid, Mansour S; El-Gaby, Mohamed S A; Elaasser, Mahmoud M; Nissan, Yassin M

2017-04-07

Various thiourea derivatives have been used as starting materials for compounds with better biological activities. Molecular modeling tools are used to explore their mechanism of action. A new series of thioureas were synthesized. Fluorinated pyridine derivative 4a showed the highest antimicrobial activity (with MIC values ranged from 1.95 to 15.63 µg/mL). Interestingly, thiadiazole derivative 4c and coumarin derivative 4d exhibited selective antibacterial activities against Gram positive bacteria. Fluorinated pyridine derivative 4a was the most active against HepG2 with IC50 value of 4.8 μg/mL. Molecular docking was performed on the active site of MK-2 with good results. Novel compounds were obtained with good anticancer and antibacterial activity especially fluorinated pyridine derivative 4a and molecular docking study suggest good activity as mitogen activated protein kinase-2 inhibitor. Graphical abstract Compound 4a in the active site of MK-2.

Radiosensitization of biologically active DNA in cellular extracts by oxygen. Evidence that the presence of SH-compounds is not required

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

Vanhemmen, J.J.; Meuling, W.J.A.; Bleichrodt, J.F.

1974-01-01

The radiosensitization by oxygen of biological active bacteriophage DNA in bacterial extracts was studied. The oxygen effect in such a system appeared not to be due or due only to a minor extent to the presence of endogenous sulfhydryl compounds. The components in a cell extract which enable oxygen and other sensitizers to sensitize DNA could not be destroyed by extremely high doses of gamma radiation. (Author) (GRA)

Polymer application for separation/filtration of biological active compounds

NASA Astrophysics Data System (ADS)

Tylkowski, B.; Tsibranska, I.

2017-06-01

Membrane technology is an important part of the engineer's toolbox. This is especially true for industries that process food and other products with their primary source from nature. This review is focused on ongoing development work using membrane technologies for concentration and separation of biologically active compounds, such as polyphenols and flavonoids. We provide the readers not only with the last results achieve in this field but also, we deliver detailed information about the membrane types and polymers used for their preparation.

Natural Product Potential of the Genus Nocardiopsis

PubMed Central

Ibrahim, Alyaa Hatem; Desoukey, Samar Yehia; Fouad, Mostafa A.; Kamel, Mohamed Salah; Gulder, Tobias A. M.; Abdelmohsen, Usama Ramadan

2018-01-01

Actinomycetes are a relevant source of novel bioactive compounds. One of the pharmaceutically and biotechnologically important genera that attract natural products research is the genus Nocardiopsis, mainly for its ability to produce a wide variety of secondary metabolites accounting for its wide range of biological activities. This review covers the literature from January 2015 until February 2018 making a complete survey of all the compounds that were isolated from the genus Nocardiopsis, their biological activities, and natural sources, whenever applicable. PMID:29710816

Synthesis and biological evaluation of enantiomerically pure cyclopropyl analogues of combretastatin A4.

PubMed

Ty, Nancy; Pontikis, Renée; Chabot, Guy G; Devillers, Emmanuelle; Quentin, Lionel; Bourg, Stéphane; Florent, Jean-Claude

2013-03-01

To evaluate the influence of stereochemistry on biological activities of cis-cyclopropyl combretastatin A4 (CA4) analogues, we have prepared several cyclopropyl compounds in their pure enantiomeric forms. The key reactions in our synthesis are the cyclopropanation of a (Z)-alkenylboron compound bearing a chiral auxiliary, and the cross-coupling of both enantiomeric cyclopropyl trifluoroborate salts with aryl and olefinic halides. Three pairs of cis-cyclopropyl CA4 analogues were evaluated for their potential antivascular activities. The diarylcyclopropyl compounds with SR-configuration (-)-1b, (-)-2b and the cyclopropylvinyl enantiomer (+)-3a with RR-configuration were the most potent tubulin polymerization inhibitors. A correlation was noted between anti-tubulin activity and rounding up activity of endothelial cells. The cytotoxic activity on B16 melanoma cells was in the submicromolar range for most compounds, but unlike the anti-tubulin activity, there was no difference in cytotoxic activity between racemic and enantiomerically pure forms for the three series of compounds. Molecular docking studies within the colchicine binding site of tubulin were in good agreement with the tubulin polymerization inhibitory data and confirmed the importance of the configuration of the synthesized cis-cyclopropyl CA4 analogues for potential antivascular activities. Copyright © 2013. Published by Elsevier Ltd.

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.

Biological activities and medicinal properties of Gokhru (Pedalium murex L.)

PubMed Central

Rajashekar, V; Rao, E Upender; P, Srinivas

2012-01-01

Bada Gokhru (Pedalium murex L.) is perhaps the most useful traditional medicinal plant in India. Each part of the neem tree has some medicinal property and is thus commercially exploitable. During the last five decades, apart from the chemistry of the Pedalium murex compounds, considerable progress has been achieved regarding the biological activity and medicinal applications of this plant. It is now considered as a valuable source of unique natural products for development of medicines against various diseases and also for the development of industrial products. This review gives a bird's eye view mainly on the biological activities of some of this compounds isolated, pharmacological actions of the extracts, clinical studies and plausible medicinal applications of gokharu along with their safety evaluation. PMID:23569975

Acute toxicity and chemical evaluation of coking wastewater under biological and advanced physicochemical treatment processes.

PubMed

Dehua, Ma; Cong, Liu; Xiaobiao, Zhu; Rui, Liu; Lujun, Chen

2016-09-01

This study investigated the changes of toxic compounds in coking wastewater with biological treatment (anaerobic reactor, anoxic reactor and aerobic-membrane bioreactor, A1/A2/O-MBR) and advanced physicochemical treatment (Fenton oxidation and activated carbon adsorption) stages. As the biological treatment stages preceding, the inhibition effect of coking wastewater on the luminescence of Vibrio qinghaiensis sp. Nov. Q67 decreased. Toxic units (TU) of coking wastewater were removed by A1/A2/O-MBR treatment process, however approximately 30 % TU remained in the biologically treated effluent. There is a tendency that fewer and fewer residual organic compounds could exert equal acute toxicity during the biological treatment stages. Activated carbon adsorption further removed toxic pollutants of biologically treated effluent but the Fenton effluent increased acute toxicity. The composition of coking wastewater during the treatment was evaluated using the three-dimensional fluorescence spectra, gas chromatography-mass spectrometry (GC-MS). The organic compounds with high polarity were the main cause of acute toxicity in the coking wastewater. Aromatic protein-like matters in the coking wastewater with low biodegradability and high toxicity contributed mostly to the remaining acute toxicity of the biologically treated effluents. Chlorine generated from the oxidation process was responsible for the acute toxicity increase after Fenton oxidation. Therefore, the incorporation of appropriate advanced physicochemical treatment process, e.g., activated carbon adsorption, should be implemented following biological treatment processes to meet the stricter discharge standards and be safer to the environment.

Antascomicins A, B, C, D and E. Novel FKBP12 binding compounds from a Micromonospora strain.

PubMed

Fehr, T; Sanglier, J J; Schuler, W; Gschwind, L; Ponelle, M; Schilling, W; Wioland, C

1996-03-01

5 novel ascomycin-like compounds, antascomicins A, B, C, D and E were isolated from a strain of Micromonospora. The antascomicins bind strongly to the FK506-binding protein FKBP12 and antagonize the immunosuppressive activity of FK506 and rapamycin. The strain description, fermentation, structure elucidation and biological activity of these compounds are described.

Fused heterocyclic compounds bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 1: design, synthesis and biological evaluation of novel 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives.

PubMed

Tian, Ye; Du, Deping; Rai, Diwakar; Wang, Liu; Liu, Huiqing; Zhan, Peng; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong

2014-04-01

In our continuous efforts to identify novel potent HIV-1 NNRTIs, a novel class of 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives were rationally designed, synthesized and evaluated for their anti-HIV activities in MT4 cell cultures. Biological results showed that most of the tested compounds displayed excellent activity against wild-type HIV-1 with a wide range of EC50 values from 5.98 to 0.07μM. Among the active compounds, 5a was found to be the most promising analogue with an EC50 of 0.07μM against wild-type HIV-1 and very high selectivity index (SI, 3999). Compound 5a was more effective than the reference drugs nevirapine (by 2-fold) and delavirdine (by 2-fold). In order to further confirm their binding target, an HIV-1 RT inhibitory assay was also performed. Furthermore, SAR analysis among the newly synthesized compounds was discussed and the binding mode of the active compound 5a was rationalized by molecular modeling studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

In Vitro Biologic Activities of the Antimicrobials Triclocarban, Its Analogs, and Triclosan in Bioassay Screens: Receptor-Based Bioassay Screens

PubMed Central

Ahn, Ki Chang; Zhao, Bin; Chen, Jiangang; Cherednichenko, Gennady; Sanmarti, Enio; Denison, Michael S.; Lasley, Bill; Pessah, Isaac N.; Kültz, Dietmar; Chang, Daniel P.Y.; Gee, Shirley J.; Hammock, Bruce D.

2008-01-01

Background Concerns have been raised about the biological and toxicologic effects of the antimicrobials triclocarban (TCC) and triclosan (TCS) in personal care products. Few studies have evaluated their biological activities in mammalian cells to assess their potential for adverse effects. Objectives In this study, we assessed the activity of TCC, its analogs, and TCS in in vitro nuclear-receptor–responsive and calcium signaling bioassays. Materials and methods We determined the biological activities of the compounds in in vitro, cell-based, and nuclear-receptor–responsive bioassays for receptors for aryl hydrocarbon (AhR), estrogen (ER), androgen (AR), and ryanodine (RyR1). Results Some carbanilide compounds, including TCC (1–10 μM), enhanced estradiol (E2)-dependent or testosterone-dependent activation of ER- and AR-responsive gene expression up to 2.5-fold but exhibited little or no agonistic activity alone. Some carbanilides and TCS exhibited weak agonistic and/or antagonistic activity in the AhR-responsive bioassay. TCS exhibited antagonistic activity in both ER- and AR-responsive bioassays. TCS (0.1–10 μM) significantly enhanced the binding of [3H]ryanodine to RyR1 and caused elevation of resting cytosolic [Ca2+] in primary skeletal myotubes, but carbanilides had no effect. Conclusions Carbanilides, including TCC, enhanced hormone-dependent induction of ER- and AR-dependent gene expression but had little agonist activity, suggesting a new mechanism of action of endocrine-disrupting compounds. TCS, structurally similar to noncoplanar ortho-substituted poly-chlorinated biphenyls, exhibited weak AhR activity but interacted with RyR1 and stimulated Ca2+ mobilization. These observations have potential implications for human and animal health. Further investigations are needed into the biological and toxicologic effects of TCC, its analogs, and TCS. PMID:18795164

Activity ranking of synthetic analogs targeting vascular endothelial growth factor receptor 2 by an integrated cell membrane chromatography system.

PubMed

Wang, Dongyao; Lv, Diya; Chen, Xiaofei; Liu, Yue; Ding, Xuan; Jia, Dan; Chen, Langdong; Zhu, Zhenyu; Cao, Yan; Chai, Yifeng

2015-12-01

Evaluating the biological activities of small molecules represents an important part of the drug discovery process. Cell membrane chromatography (CMC) is a well-developed biological chromatographic technique. In this study, we have developed combined SMMC-7721/CMC and HepG2/CMC with high-performance liquid chromatography and time-of-flight mass spectrometry to establish an integrated screening platform. These systems was subsequently validated and used for evaluating the activity of quinazoline compounds, which were designed and synthesized to target vascular endothelial growth factor receptor 2. The inhibitory activities of these compounds towards this receptor were also tested using a classical caliper mobility shift assay. The results revealed a significant correlation between these two methods (R(2) = 0.9565 or 0.9420) for evaluating the activities of these compounds. Compared with traditional methods of evaluating the activities analogous compounds, this integrated cell membrane chromatography screening system took less time and was more cost effective, indicating that it could be used as a practical method in drug discovery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bioremediation of trace organic compounds found in precious metals refineries' wastewaters: a review of potential options.

PubMed

Barbosa, V L; Tandlich, R; Burgess, J E

2007-07-01

Platinum group metal (PGM) refining processes produce large quantities of wastewater, which is contaminated with the compounds that make up the solvents/extractants mixtures used in the process. These compounds often include solvesso, beta-hydroxyxime, amines, amides and methyl isobutyl ketone. A process to clean up PGM refinery wastewaters so that they could be re-used in the refining process would greatly contribute to continual water storage problems and to cost reduction for the industry. Based on the concept that organic compounds that are produced biologically can be destroyed biologically, the use of biological processes for the treatment of organic compounds in other types of waste stream has been favoured in recent years, owing to their low cost and environmental acceptability. This review examines the available biotechnologies and their effectiveness for treating compounds likely to be contained in precious metal extraction process wastewaters. The processes examined include: biofilters, fluidized bed reactors, trickle-bed bioreactors, bioscrubbers, two-phase partitioning bioreactors, membrane bioreactors and activated sludge. Although all processes examined showed adequate to excellent removal of organic compounds from various gaseous and fewer liquid waste streams, there was a variation in their effectiveness. Variations in performance of laboratory-scale biological processes are probably due to the inherent change in the microbial population composition due to selection pressure, environmental conditions and the time allowed for adaptation to the organic compounds. However, if these factors are disregarded, it can be established that activated sludge and membrane bioreactors are the most promising processes for use in the treatment of PGM refinery wastewaters.

Synthesis of 4-aminophenyl substituted indole derivatives for the instrumental analysis and molecular docking evaluation studies

NASA Astrophysics Data System (ADS)

Singh, Navneet; Kumar, Keshav

2017-07-01

The Indole has been known to maintain celebrity status since so many decades and has been a centre point at the spectrum of pharmacological research. The present work stimulates an idea of generating a pool of library of lead compounds. The data collected can be used for the mapping of biologically active compounds. The reported derivatives of 4-aminophenyl substituted Indole were prepared by the methods of Fischer Indole synthesis and Vilsemeier reaction followed by screening for instrumental analysis and molecular docking studies. The synthesized compounds 4-(1-(2-phenylhydrazono)ethyl)aniline, 1, 4-(1H-indol-2-yl)aniline, 2 and 2-(4-aminophenyl)-1H-indole-3-carbaldehyde, 3 were found to have remarkable yield and instrumental data analysis and also showed remarkable docked characteristic. The molecular docking studies revealed that ligand (amino acids) of comp. 1, 2 and 3 had been docked successfully on the binding site of the 3JUS protein selected from PDB with H bonding. The molecular docking data showed that compound 1, would possess remarkable biological activity and compd. 2 and 3 would possess mild to moderate biological activity. Thus this research work paves the way to synthesize new derivatives and thus to develop new compounds in future with accurate prediction.

Relationships Between Bioactive Compound Content and
the Antiplatelet and Antioxidant Activities of Six Allium Vegetable Species

PubMed Central

Beretta, Hebe Vanesa; Bannoud, Florencia; Insani, Marina; Berli, Federico; Hirschegger, Pablo; Galmarini, Claudio Rómulo

2017-01-01

Summary Allium sp. vegetables are widely consumed for their characteristic flavour. Additionally, their consumption may provide protection against cardiovascular disease due to their antiplatelet and antioxidant activities. Although antiplatelet and antioxidant activities in Allium sp. are generally recognised, comparative studies of antiplatelet and antioxidant potency among the main Allium vegetable species are lacking. Also, the relationship between organosulfur and phenolic compounds and these biological activities has not been well established. In this study, the in vitro antiplatelet and antioxidant activities of the most widely consumed Allium species are characterised and compared. The species total organosulfur and phenolic content, and the HPLC profiles of 11 phenolic compounds were characterised and used to investigate the relationship between these compounds and antiplatelet and antioxidant activities. Furthermore, antiplatelet activities in chives and shallot have been characterised for the first time. Our results revealed that the strongest antiplatelet agents were garlic and shallot, whereas chives had the highest antioxidant activity. Leek and bunching onion had the weakest both biological activities. Significantly positive correlations were found between the in vitro antiplatelet activity and total organosulfur (R=0.74) and phenolic (TP) content (R=0.73), as well as between the antioxidant activity and TP (R=0.91) and total organosulfur content (R=0.67). Six individual phenolic compounds were associated with the antioxidant activity, with catechin, epigallocatechin and epicatechin gallate having the strongest correlation values (R>0.80). Overall, our results suggest that both organosulfur and phenolic compounds contribute similarly to Allium antiplatelet activity, whereas phenolics, as a whole, are largely responsible for antioxidant activity, with broad variation observed among the contributions of individual phenolic compounds. PMID:28867958

QSAR studies of macrocyclic diterpenes with P-glycoprotein inhibitory activity.

PubMed

Sousa, Inês J; Ferreira, Maria-José U; Molnár, Joseph; Fernandes, Miguel X

2013-02-14

Multidrug resistance (MDR) represents a major limitation for cancer chemotherapy. There are several mechanisms of MDR but the most important is associated with P-glycoprotein (P-gp) overexpression. The development of modulators of P-gp that are able to re-establish drug sensitivity of resistant cells has been considered a promising approach for overcoming MDR. Macrocyclic lathyrane and jatrophane-type diterpenes from Euphorbia species were found to be strong MDR reversing agents. In this study we applied quantitative structure-activity relationship (QSAR) methodology in order to identify the most relevant molecular features of macrocyclic diterpenes with P-gp inhibitory activity and to determine which structural modifications can be performed to improve their activity. Using experimental biological data at two concentrations (4 and 40 μg/ml), we developed a QSAR model for a set of 51 bioactive diterpenic compounds which includes lathyrane and jatrophane-type diterpenes and another model just for jatrophanes. The cross-validation correlation values for all diterpenes QSAR models developed for biological activities at compound concentrations of 4 and 40 μg/ml were 0.758 and 0.729, respectively. Regarding the prediction ability, we get R²(pred) values of 0.765 and 0.534 for biological activities at compound concentrations of 4 and 40 μg/ml, respectively. Applying the cross-validation test to jatrophanes QSAR models, we obtained 0.680 and 0.787 for biological activities at compound concentrations of 4 and 40 μg/ml concentrations, respectively. For the same concentrations, the obtained R²(pred) values for jatrophanes models were 0.541 and 0.534, respectively. The obtained models were statistically valid and showed high prediction ability. Copyright © 2012 Elsevier B.V. All rights reserved.

Multiple biological activities and molecular docking studies of newly synthesized 3-(pyridin-4-yl)-1H-pyrazole-5-carboxamide chalcone hybrids.

PubMed

Sribalan, Rajendran; Banuppriya, Govindharasu; Kirubavathi, Maruthan; Jayachitra, A; Padmini, Vediappen

2016-12-01

A series of fifteen new chemical entities, 3-(pyridin-4-yl)-1H-pyrazole-5-carboxamide chalcones (6a-o), were synthesized as new hybrids with enriched biological activities compared to their parent molecules. The compounds were characterized by 1 H NMR, 13 C NMR, Mass and IR spectral studies. Their antibacterial, anti-inflammatory and antioxidant activities have been evaluated. These compounds showed moderate to good antibacterial, anti-inflammatory and antioxidant activities. The molecular docking analysis was performed with cyclooxygenase enzyme to ascertain the probable binding model. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthesis and biological applications of phosphinates and derivatives.

PubMed

Virieux, David; Volle, Jean-Noël; Bakalara, Norbert; Pirat, Jean-Luc

2015-01-01

This review first outlines general considerations on phosphinic acids and derivatives as bioisosteric groups. The next sections present key aspects of phosphinic acid-based molecules and include a brief description of the biological pathways involved for their activities. The synthetic aspects and the biological activities of such compounds reported in the literature between 2008 and 2013 are also described.

Chemical constituents and biological research on plants in the genus Curcuma.

PubMed

Sun, Wen; Wang, Sheng; Zhao, Wenwen; Wu, Chuanhong; Guo, Shuhui; Gao, Hongwei; Tao, Hongxun; Lu, Jinjian; Wang, Yitao; Chen, Xiuping

2017-05-03

Curcuma, a valuable genus in the family Zingiberaceae, includes approximately 110 species. These plants are native to Southeast Asia and are extensively cultivated in India, China, Sri Lanka, Indonesia, Peru, Australia, and the West Indies. The plants have long been used in folk medicine to treat stomach ailments, stimulate digestion, and protect the digestive organs, including the intestines, stomach, and liver. In recent years, substantial progress has been achieved in investigations regarding the chemical and pharmacological properties, as well as in clinical trials of certain Curcuma species. This review comprehensively summarizes the current knowledge on the chemistry and briefly discusses the biological activities of Curcuma species. A total of 720 compounds, including 102 diphenylalkanoids, 19 phenylpropene derivatives, 529 terpenoids, 15 flavonoids, 7 steroids, 3 alkaloids, and 44 compounds of other types isolated or identified from 32 species, have been phytochemically investigated. The biological activities of plant extracts and pure compounds are classified into 15 groups in detail, with emphasis on anti-inflammatory and antitumor activities.

Biological Activities of Oleanolic Acid Derivatives from Calendula officinalis Seeds.

PubMed

Zaki, Ahmed; Ashour, Ahmed; Mira, Amira; Kishikawa, Asuka; Nakagawa, Toshinori; Zhu, Qinchang; Shimizu, Kuniyoshi

2016-05-01

Phytochemical examination of butanol fraction of Calendula officinalis seeds led to the isolation of two compounds identified as 28-O-β-D-glucopyranosyl-oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS1) and oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS2). Biological evaluation was carried out for these two compounds such as melanin biosynthesis inhibitory, hyaluronic acid production activities, anti obesity using lipase inhibition and adipocyte differentiation as well as evaluation of the protective effect against hydrogen peroxide induced neurotoxicity in neuro-2A cells. The results showed that, compound CS2 has a melanin biosynthesis stimulatory activity; however, compound CS1 has a potent stimulatory effect for the production of hyaluronic acid on normal human dermal fibroblast from adult (NHDF-Ad). Both compounds did not show any inhibitory effect on both lipase and adipocyte differentiation. Compound CS2 could protect neuro-2A cells and increased cell viability against H2 O2 . These activities (melanin biosynthesis stimulatory and protective effect against H2 O2 of CS2 and hyaluronic acid productive activities of these triterpene derivatives) have been reported for the first time. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Chemical Composition and Biological Activity of Extracts Obtained by Supercritical Extraction and Ethanolic Extraction of Brown, Green and Red Propolis Derived from Different Geographic Regions in Brazil

PubMed Central

Machado, Bruna Aparecida Souza; Silva, Rejane Pina Dantas; Barreto, Gabriele de Abreu; Costa, Samantha Serra; da Silva, Danielle Figuerêdo; Brandão, Hugo Neves; da Rocha, José Luiz Carneiro; Dellagostin, Odir Antônio; Henriques, João Antônio Pegas; Umsza-Guez, Marcelo Andres; Padilha, Francine Ferreira

2016-01-01

The variations in the chemical composition, and consequently, on the biological activity of the propolis, are associated with its type and geographic origin. Considering this fact, this study evaluated propolis extracts obtained by supercritical extraction (SCO2) and ethanolic extraction (EtOH), in eight samples of different types of propolis (red, green and brown), collected from different regions in Brazil. The content of phenolic compounds, flavonoids, in vitro antioxidant activity (DPPH and ABTS), Artepillin C, p-coumaric acid and antimicrobial activity against two bacteria were determined for all extracts. For the EtOH extracts, the anti-proliferative activity regarding the cell lines of B16F10, were also evaluated. Amongst the samples evaluated, the red propolis from the Brazilian Northeast (states of Sergipe and Alagoas) showed the higher biological potential, as well as the larger content of antioxidant compounds. The best results were shown for the extracts obtained through the conventional extraction method (EtOH). However, the highest concentrations of Artepillin C and p-coumaric acid were identified in the extracts from SCO2, indicating a higher selectivity for the extraction of these compounds. It was verified that the composition and biological activity of the Brazilian propolis vary significantly, depending on the type of sample and geographical area of collection. PMID:26745799

Isolation and biological evaluation of jatrophane diterpenoids from Euphorbia dendroides.

PubMed

Aljancić, Ivana S; Pesić, Milica; Milosavljević, Slobodan M; Todorović, Nina M; Jadranin, Milka; Milosavljević, Goran; Povrenović, Dragan; Banković, Jasna; Tanić, Nikola; Marković, Ivanka D; Ruzdijić, Sabera; Vajs, Vlatka E; Tesević, Vele V

2011-07-22

From the Montenegrin spurge Euphorbia dendroides, seven new diterpenoids [jatrophanes (1-6) and a tigliane (7)] were isolated and their structures elucidated by spectroscopic techniques. The biological activity of the new compounds was studied against four human cancer cell lines. The most effective jatrophane-type compound (2) and its structurally closely related derivative (1) were evaluated for their interactions with paclitaxel and doxorubicin using a multi-drug-resistant cancer cell line. Both compounds exerted a strong reversal potential resulting from inhibition of P-glycoprotein transport.

Adamantoylated biologically active small peptides and glycopeptides structurally related to the bacterial peptidoglycan.

PubMed

Frkanec, Ruža; Vranešić, Branka; Tomić, Srdjanka

2013-01-01

A large number of novel synthetic compounds representing smaller parts of original peptidoglycan molecules have been synthesized and found to possess versatile biological activity, particularly immunomodulating properties. A series of compounds containing the adamantyl residues coupled to peptides and glycopeptides characteristic for bacterial peptidoglycan was described. The new adamantylpeptides and adamantylglycopeptides were prepared starting from N-protected racemic adamantylglycine and dipeptide L-Ala-D-isoglutamine. The adamantyl glycopeptides were obtained by coupling the adamantyltripeptides with alpha-D-mannose moiety through spacer molecule of fixed chirality. Since the starting material was D,L-(adamantyl-glycine) the condensation products with the dipeptide were mixtures of diastereoisomers. The obtained diastereoisomers were separated, characterized, and tested for immunostimulating activity. An HPLC method for purity testing was developed and adapted for the particular compounds.

Predicted Biological Activity of Purchasable Chemical Space

PubMed Central

2017-01-01

Whereas 400 million distinct compounds are now purchasable within the span of a few weeks, the biological activities of most are unknown. To facilitate access to new chemistry for biology, we have combined the Similarity Ensemble Approach (SEA) with the maximum Tanimoto similarity to the nearest bioactive to predict activity for every commercially available molecule in ZINC. This method, which we label SEA+TC, outperforms both SEA and a naïve-Bayesian classifier via predictive performance on a 5-fold cross-validation of ChEMBL’s bioactivity data set (version 21). Using this method, predictions for over 40% of compounds (>160 million) have either high significance (pSEA ≥ 40), high similarity (ECFP4MaxTc ≥ 0.4), or both, for one or more of 1382 targets well described by ligands in the literature. Using a further 1347 less-well-described targets, we predict activities for an additional 11 million compounds. To gauge whether these predictions are sensible, we investigate 75 predictions for 50 drugs lacking a binding affinity annotation in ChEMBL. The 535 million predictions for over 171 million compounds at 2629 targets are linked to purchasing information and evidence to support each prediction and are freely available via https://zinc15.docking.org and https://files.docking.org. PMID:29193970

Recent advance in oxazole-based medicinal chemistry.

PubMed

Zhang, Hui-Zhen; Zhao, Zhi-Long; Zhou, Cheng-He

2018-01-20

Oxazole compounds containing nitrogen and oxygen atoms in the five-membered aromatic ring are readily able to bind with a variety of enzymes and receptors in biological systems via diverse non-covalent interactions, and thus display versatile biological activities. The related researches in oxazole-based derivatives including oxazoles, isoxazoles, oxazolines, oxadiazoles, oxazolidones, benzoxazoles and so on, as medicinal drugs have been an extremely active topic, and numerous excellent achievements have been acquired. Noticeably, a large number of oxazole compounds as clinical drugs or candidates have been frequently employed for the treatment of various types of diseases, which have shown their large development value and wide potential as medicinal agents. This work systematically reviewed the recent researches and developments of the whole range of oxazole compounds as medicinal drugs, including antibacterial, antifungal, antiviral, antitubercular, anticancer, anti-inflammatory and analgesic, antidiabetic, antiparasitic, anti-obesitic, anti-neuropathic, antioxidative as well as other biological activities. The perspectives of the foreseeable future in the research and development of oxazole-based compounds as medicinal drugs are also presented. It is hoped that this review will serve as a stimulant for new thoughts in the quest for rational designs of more active and less toxic oxazole medicinal drugs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Enzymatic tailoring of oleuropein from Olea europaea leaves and product identification by HRMS/MS spectrometry.

PubMed

Nikolaivits, Efstratios; Termentzi, Aikaterini; Skaltsounis, Alexios-Leandros; Fokialakis, Nikolas; Topakas, Evangelos

2017-07-10

Oleuropein, a bioactive compound found in all parts of olive tree, especially in leaves and branches, presents numerous health promoting properties that increase research and market interest the last few years. In addition, oleuropein degradation products, such as hydroxytyrosol, elenolic acid, and the aglycones also exhibit biological activities with different properties compared to the starting compound. Under this view, a commercial lipase preparation Lipolase 100L and a thermophilic β-glucosidase from Myceliophthora thermophila were used for the regioselective hydrolysis of oleuropein towards the production of the corresponding biologically active compounds. The enzymatic degradation products of oleuropein, such as hydroxytyrosol, elenolic acid and its glucoside, and oleuropein aglycones were identified by LC-HRMS/MS and NMR spectroscopy. The latter, was found as a mix of diastereomers of the monoaldehydic form of oleuropein aglycone, identified as (5S, 8R, 9S)-, (5S, 8S, 9S)- and (5S, 8R, 9R). The high substrate specificity exhibited by both lipase and β-glucosidase allows the successful tailoring of oleuropein towards the production of different biologically active compounds with significant potential in the cosmeceutical and food industry. Copyright © 2017 Elsevier B.V. All rights reserved.

Propolis Diterpenes as a Remarkable Bio-Source for Drug Discovery Development: A Review.

PubMed

Aminimoghadamfarouj, Noushin; Nematollahi, Alireza

2017-06-17

Propolis is one of the complex, but valuable, bio-sources for discovering therapeutic compounds. Diterpenes are organic compounds composed of four isoprene units and are known for their biological and pharmacological characteristics, such as antibacterial, anticancer, and anti-inflammatory activities. Recently, advancements have been made in the development of antibacterial and anticancer leads from propolis-isolated diterpenes, and scrutiny of these compounds is being pursued. Thus, this review covers the progress in this arena, with a focus on the chemistry and biological activities of propolis diterpenes. It is anticipated that important information, in a comprehensive and concise manner, will be delivered here for better understanding of natural product drug discovery research.

Propolis Diterpenes as a Remarkable Bio-Source for Drug Discovery Development: A Review

PubMed Central

Aminimoghadamfarouj, Noushin; Nematollahi, Alireza

2017-01-01

Propolis is one of the complex, but valuable, bio-sources for discovering therapeutic compounds. Diterpenes are organic compounds composed of four isoprene units and are known for their biological and pharmacological characteristics, such as antibacterial, anticancer, and anti-inflammatory activities. Recently, advancements have been made in the development of antibacterial and anticancer leads from propolis-isolated diterpenes, and scrutiny of these compounds is being pursued. Thus, this review covers the progress in this arena, with a focus on the chemistry and biological activities of propolis diterpenes. It is anticipated that important information, in a comprehensive and concise manner, will be delivered here for better understanding of natural product drug discovery research. PMID:28629133

Golden Needle Mushroom: A Culinary Medicine with Evidenced-Based Biological Activities and Health Promoting Properties

PubMed Central

Tang, Calyn; Hoo, Pearl Ching-Xin; Tan, Loh Teng-Hern; Pusparajah, Priyia; Khan, Tahir Mehmood; Lee, Learn-Han; Goh, Bey-Hing; Chan, Kok-Gan

2016-01-01

Flammulina velutipes (enoki, velvet shank, golden needle mushroom or winter mushroom), one of the main edible mushrooms on the market, has long been recognized for its nutritional value and delicious taste. In recent decades, research has expanded beyond detailing its nutritional composition and delved into the biological activities and potential health benefits of its constituents. Many bioactive constituents from a range of families have been isolated from different parts of the mushroom, including carbohydrates, protein, lipids, glycoproteins, phenols, and sesquiterpenes. These compounds have been demonstrated to exhibit various biological activities, such as antitumour and anticancer activities, anti-atherosclerotic and thrombosis inhibition activity, antihypertensive and cholesterol lowering effects, anti-aging and antioxidant properties, ability to aid with restoring memory and overcoming learning deficits, anti-inflammatory, immunomodulatory, anti-bacterial, ribosome inactivation and melanosis inhibition. This review aims to consolidate the information concerning the phytochemistry and biological activities of various compounds isolated from F. velutipes to demonstrate that this mushroom is not only a great source of nutrients but also possesses tremendous potential in pharmaceutical drug development. PMID:28003804

Cuticular hydrocarbons as sex pheromone of the bee Colletes cunicularius and the key to its mimicry by the sexually deceptive orchid, Ophrys exaltata.

PubMed

Mant, Jim; Brändli, Christoph; Vereecken, Nicolas J; Schulz, Claudia M; Francke, Wittko; Schiestl, Florian P

2005-08-01

Male Colletes cunicularius bees pollinate the orchid, Ophrys exaltata, after being sexually deceived by the orchid's odor-mimicry of the female bee's sex pheromone. We detected biologically active volatiles of C. cunicularius by using gas chromatographic-electroantennographic detection (GC-EAD) with simultaneous flame ionization detection. After identification of the target compounds by coupled gas chromatography mass spectrometry (GC-MS), we performed behavioral tests using synthetic blends of the active components. We detected 22 EAD active compounds in cuticular extracts of C. cunicularius females. Blends of straight chain, odd-numbered alkanes and (Z)-7-alkenes with 21-29 carbon atoms constituted the major biologically active compounds. Alkenes were the key compounds releasing mating behavior, especially those with (Z)-7 unsaturation. Comparison of patterns of bee volatiles with those of O. exaltata subsp. archipelagi revealed that all EAD-active compounds were also found in extracts of orchid labella. Previous studies of the mating behavior in C. cunicularius showed linalool to be an important attractant for patrolling males. We confirmed this with synthetic linalool but found that it rarely elicited copulatory behavior, in accordance with previous studies. A blend of active cuticular compounds with linalool elicited both attraction and copulation behavior in patrolling males. Thus, linalool appears to function as a long-range attractant, whereas cuticular hydrocarbons are necessary for inducing short-range mating behavior.

Natural Organohalogens: A New Frontier for Medicinal Agents?

ERIC Educational Resources Information Center

Gribble, Gordon W.

2004-01-01

Newly discovered biogenic organo halogens with an emphasis on the biologically active examples from marine organisms, bacteria, terrestrial plants and higher life forms, including humans, are focused. Organohalogen compounds represent a valuable and expanding class of natural products, in many cases boasting exceptional biological activity.

Design and synthesis of new potent PTP1B inhibitors with the skeleton of 2-substituted imino-3-substituted-5-heteroarylidene-1,3-thiazolidine-4-one: Part I.

PubMed

Meng, Ge; Zheng, Meilin; Wang, Mei; Tong, Jing; Ge, Weijuan; Zhang, Jiehe; Zheng, Aqun; Li, Jingya; Gao, Lixin; Li, Jia

2016-10-21

A new series of 2-substituted imino-3-substituted-5- heteroarylidene-1,3-thiazolidine-4-ones as the potent bidentate PTP1B inhibitors were designed and synthesized in this paper. All of the new compounds were characterized and identified by spectra analysis. The biological screening test against PTP1B showed that some of these compounds have the positive inhibitory activity against PTP1B. The activity of the compounds with 5-substituted pyrrole on 5-postion of 1,3-thiazolidine-4-one are more potent than that of those compounds with 5-substituted pyridine group. Compound 14b, 14h and 14i showed IC50 values of 8.66 μM, 6.83 μM and 6.09 μM against PTP1B, respectively. Docking analysis of these active compounds with PTP1B showed the possible interaction modes of these biheterocyclic compounds with the active sites of PTP1B. The inhibition tests against oncogenetic CDC25B were also conducted on this set of compounds to evaluate the selectivity and possible anti-neoplastic activity. Compound 14b also showed the lowest IC50 of 1.66 μM against CDC25B among all the possible inhibitors, including 14g, 14h, 14i and 15c. Some pharmacological parameters including VolSurf, steric and electric descriptors of all the compounds were calculated to give some hints about the relative relationship with the biological activity. The result of this study might give some light on designing the possible anti-cancer drugs targeting at phosphatases. The most active compound 14i might be used as the lead compound for further structure modification of the new low molecular weight PTP1B inhibitors with the N-containing heterocyclic skeleton. Copyright © 2016. Published by Elsevier Masson SAS.

Comparative study of binding interactions between porphyrin systems and aromatic compounds of biological importance by multiple spectroscopic techniques: A review.

PubMed

Makarska-Bialokoz, Magdalena

2018-07-05

The specific spectroscopic and redox properties of porphyrins predestine them to fulfill the role of sensors during interacting with different biologically active substances. Monitoring of binding interactions in the systems porphyrin-biologically active compound is a key question not only in the field of physiological functions of living organisms, but also in environmental protection, notably in the light of the rapidly growing drug consumption and concurrently the production of drug effluents. Not always beneficial action of drugs on natural porphyrin systems induces to further studies, with commercially available porphyrins as the model systems. Therefore the binding process between several water-soluble porphyrins and a series of biologically active compounds (e.g. caffeine, guanine, theophylline, theobromine, xanthine, uric acid) has been studied in different aqueous solutions analyzing their absorption and steady-state fluorescence spectra, the porphyrin fluorescence lifetimes and their quantum yields. The magnitude of the binding and fluorescence quenching constants values for particular quenchers decreases in a series: uric acid > guanine > caffeine > theophylline > theobromine > xanthine. In all the systems studied there are characters of static quenching, as a consequence of the π-π-stacked non-covalent and non-fluorescent complexes formation between porphyrins and interacting compounds, accompanied simultaneously by the additional specific binding interactions. The porphyrin fluorescence quenching can be explain by the photoinduced intermolecular electron transfer from aromatic compound to the center of the porphyrin molecule, playing the role of the binding site. Presented results can be valuable for designing of new fluorescent porphyrin chemosensors or monitoring of drug traces in aqueous solutions. The obtained outcomes have also the toxicological and medical importance, providing insight into the interactions of the water-soluble porphyrins with biologically active substances. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Arylazolyl(azinyl)thioacetanilides. Part 16: Structure-based bioisosterism design, synthesis and biological evaluation of novel pyrimidinylthioacetanilides as potent HIV-1 inhibitors.

PubMed

Li, Xiao; Lu, Xueyi; Chen, Wenmin; Liu, Huiqing; Zhan, Peng; Pannecouque, Christophe; Balzarini, Jan; De Clercq, Erik; Liu, Xinyong

2014-10-01

A series of novel pyrimidinylthioacetanilides were designed, synthesized, and evaluated for their biological activity as potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Most of the tested compounds were proved to be effective in inhibiting HIV-1 (IIIB) replication with EC50 ranging from 0.15 μM to 24.2 μM, thereinto compound 15 was the most active lead with favorable inhibitory activity against HIV-1 (IIIB) (EC50=0.15 μM, SI=684). Besides, compound 6 displayed moderate inhibition against the double-mutated HIV-1 strain (K103N/Y181C) (EC50=3.9 μM). Preliminary structure-activity relationships (SARs), structure-cytotoxicity relationships (SCRs) data, and molecular modeling studies were discussed as well, which may provide valuable insights for further optimizations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Helleborus purpurascens-Amino Acid and Peptide Analysis Linked to the Chemical and Antiproliferative Properties of the Extracted Compounds.

PubMed

Segneanu, Adina-Elena; Grozescu, Ioan; Cziple, Florentina; Berki, Daniel; Damian, Daniel; Niculite, Cristina Mariana; Florea, Alexandru; Leabu, Mircea

2015-12-11

There is a strong drive worldwide to discover and exploit the therapeutic potential of a large variety of plants. In this work, an alcoholic extract of Helleborus purpurascens (family Ranunculaceae) was investigated for the identification of amino acids and peptides with putative antiproliferative effects. In our work, a separation strategy was developed using solvents of different polarity in order to obtain active compounds. Biochemical components were characterized through spectroscopic (mass spectroscopy) and chromatographic techniques (RP-HPLC and GC-MS). The biological activity of the obtained fractions was investigated in terms of their antiproliferative effects on HeLa cells. Through this study, we report an efficient separation of bioactive compounds (amino acids and peptides) from a plant extract dependent on solvent polarity, affording fractions with unaffected antiproliferative activities. Moreover, the two biologically tested fractions exerted a major antiproliferative effect, thereby suggesting potential anticancer therapeutic activity.

Synthesis of Novel Aza-aromatic Curcuminoids with Improved Biological Activities towards Various Cancer Cell Lines.

PubMed

Theppawong, Atiruj; Van de Walle, Tim; Grootaert, Charlotte; Bultinck, Margot; Desmet, Tom; Van Camp, John; D'hooghe, Matthias

2018-05-01

Curcumin, a natural compound extracted from the rhizomes of Curcuma longa , displays pronounced anticancer properties but lacks good bioavailability and stability. In a previous study, we initiated structure modification of the curcumin scaffold by imination of the labile β-diketone moiety to produce novel β-enaminone derivatives. These compounds showed promising properties for elaborate follow-up studies. In this work, we focused on another class of nitrogen-containing curcuminoids with a similar objective: to address the bioavailability and stability issues and to improve the biological activity of curcumin. This paper thus reports on the synthesis of new pyridine-, indole-, and pyrrole-based curcumin analogues (aza-aromatic curcuminoids) and discusses their water solubility, antioxidant activity, and antiproliferative properties. In addition, multivariate statistics, including hierarchical clustering analysis and principal component analysis, were performed on a broad set of nitrogen-containing curcuminoids. Compared to their respective mother structures, that is, curcumin and bisdemethoxycurcumin, all compounds, and especially the pyridin-3-yl β-enaminone analogues, showed better water solubility profiles. Interestingly, the pyridine-, indole-, and pyrrole-based curcumin derivatives demonstrated improved biological effects in terms of mitochondrial activity impairment and protein content, in addition to comparable or decreased antioxidant properties. Overall, the biologically active N -alkyl β-enaminone aza-aromatic curcuminoids were shown to offer a desirable balance between good solubility and significant bioactivity.

A Review of the Composition of the Essential Oils and Biological Activities of Angelica Species.

PubMed

Sowndhararajan, Kandasamy; Deepa, Ponnuvel; Kim, Minju; Park, Se Jin; Kim, Songmun

2017-09-20

A number of Angelica species have been used in traditional systems of medicine to treat many ailments. Especially, essential oils (EOs) from the Angelica species have been used for the treatment of various health problems, including malaria, gynecological diseases, fever, anemia, and arthritis. EOs are complex mixtures of low molecular weight compounds, especially terpenoids and their oxygenated compounds. These components deliver specific fragrance and biological properties to essential oils. In this review, we summarized the chemical composition and biological activities of EOs from different species of Angelica . For this purpose, a literature search was carried out to obtain information about the EOs of Angelica species and their bioactivities from electronic databases such as PubMed, Science Direct, Wiley, Springer, ACS, Google, and other journal publications. There has been a lot of variation in the EO composition among different Angelica species. EOs from Angelica species were reported for different kinds of biological activities, such as antioxidant, anti-inflammatory, antimicrobial, immunotoxic, and insecticidal activities. The present review is an attempt to consolidate the available data for different Angelica species on the basis of major constituents in the EOs and their biological activities.

Synthesis, biological evaluation and molecular modeling studies of imidazo[1,2-a]pyridines derivatives as protein kinase inhibitors.

PubMed

Lawson, Marie; Rodrigo, Jordi; Baratte, Blandine; Robert, Thomas; Delehouzé, Claire; Lozach, Olivier; Ruchaud, Sandrine; Bach, Stéphane; Brion, Jean-Daniel; Alami, Mouad; Hamze, Abdallah

2016-11-10

We report here the synthesis, the biological evaluation and the molecular modeling studies of new imidazo[1,2-a]pyridines derivatives designed as potent kinase inhibitors. This collection was obtained from 2-aminopyridines and 2-bromoacetophenone which afforded final compound in only one step. The bioactivity of this family of new compounds was tested using protein kinase and ATP competition assays. The structure-activity relationship (SAR) revealed that six compounds inhibit DYRK1A and CLK1 at a micromolar range. Docking studies provided possible explanations that correlate with the SAR data. The most active compound 4c inhibits CLK1 (IC50 of 0.7 μM) and DYRK1A (IC50 of 2.6 μM). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Photochemical tools to study dynamic biological processes

PubMed Central

Specht, Alexandre; Bolze, Frédéric; Omran, Ziad; Nicoud, Jean-François; Goeldner, Maurice

2009-01-01

Light-responsive biologically active compounds offer the possibility to study the dynamics of biological processes. Phototriggers and photoswitches have been designed, providing the capability to rapidly cause the initiation of wide range of dynamic biological phenomena. We will discuss, in this article, recent developments in the field of light-triggered chemical tools, specially how two-photon excitation, “caged” fluorophores, and the photoregulation of protein activities in combination with time-resolved x-ray techniques should break new grounds in the understanding of dynamic biological processes. PMID:20119482

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.

Synthesis and biological activity of chimeric structures derived from the cytotoxic natural compounds dolastatin 10 and dolastatin 15.

PubMed

Poncet, J; Busquet, M; Roux, F; Pierré, A; Atassi, G; Jouin, P

1998-04-23

The natural cytotoxic compounds dolastatins 10 and 15 exhibit great similarities in structure and in their biological activity profiles. Two compounds (1 and 2) formed by interchanging the dolaisoleuine residue of dolastatin 10 and the MeVal-Pro dipeptide of dolastatin 15 were synthesized in order to evaluate the possible equivalence of these units. These compounds can be considered as chimeras of dolastatins 10 and 15 formed by the N-terminal part of the former and the C-terminal part of the latter and vice versa. Both analogues exhibited a marked decrease in their cytotoxic activity but showed similar differential cytotoxicity with regard to the cell lines assayed compared with the parent compounds. HT-29 cell line was the least sensitive one. However, this activity was in the nanomolar level and close to that of vincristine. The differences in their effect on tubulin polymerization were less pronounced. We confirmed the already known crucial role of the Dil residue in this assay. The nonequivalence of the Dil unit and the MeVal-Pro dipeptide probably reflects modification in the relative positions of the N-dimethylamino and the phenyl moieties.

Characterization and structure elucidation of antibacterial compound of Streptomyces sp. ECR77 isolated from east coast of India.

PubMed

Thirumurugan, D; Vijayakumar, R

2015-05-01

Forty marine actinobacteria were isolated from the sediments of east coast (Bay of Bengal) region of Tamilnadu, India. Morphologically distinct colonies were primarily tested against fish pathogenic bacteria such as Vibrio cholerae, V. parahaemolyticus, V. alginolyticus, Pseudomonas fluorescens and Aeromonas hydrophila by cross-streak plate method. The secondary metabolites produced by the highly potential strain cultured on starch casein broth were extracted separately with various solvents such as alcohol, ethyl acetate, methanol, petroleum ether and chloroform. The antibacterial assay of the bioactive compounds was tested against the fish pathogenic bacteria by well diffusion method. Of the various solvents used, the ethyl acetate extract of the isolate had good antibacterial activity. The potential strain was identified as Streptomyces labedae by phenotypic, 16S rRNA gene sequence and phylogenetic analysis. Purification of the biologically active compounds by column chromatography led to isolation of 27 fractions. The biologically active fraction was re-chromatographed on a silica gel column to obtain a single active compound, namely N-isopentyltridecanamide. The structure of the compounds was elucidated on the basis of ultra violet, Fourier transform infrared and nuclear magnetic resonance spectra.

Biological evaluation and molecular docking of some chromenyl-derivatives as potential antimicrobial agents.

PubMed

Ionuţ, Ioana; Vodnar, Dan Cristian; Oniga, Ilioara; Oniga, Ovidiu; Tiperciuc, Brînduşa; Tamaian, Radu

2016-01-01

Various thiosemicarbazones (TSCs) and their heterocyclic thiadiazolines (TDZ) possess important biological effects. In addition, chromenyl derivatives exhibit a wide range of pharmacological activities. Based on these findings and as a continuation of our research on nitrogen and sulfur containing compounds, we investigated a series of previously reported chromenyl-TSCs (1a-j) and chromenyl-TDZs (2a-j) for their in vitro antimicrobial activities against two bacterial and four fungal strains. MIC and MBC/MFC (µg/mL) values of these compounds were evaluated and compared to those of Spectinomycin, Moxifloxacin and Fluconazole, used as reference drugs. For a better understanding of the drug-receptor interactions, all the compounds were further subjected to molecular docking against four targets that were chosen based on the specific mechanism of action of the reference drugs used in the antimicrobial screening. All compounds tested showed equal or higher antibacterial/antifungal activities relative to the used reference drugs. In silico studies (molecular docking) revealed that all the investigated compounds showed good binding energies towards four receptor protein targets and supported their antimicrobial properties.

New steroids from Anemarrhena asphodeloides rhizome and their α-glucosidase inhibitory activity.

PubMed

Khang, Pham Van; Phuong, Dao Mai; Ma, Lei

2017-05-01

Two new steroids were isolated from acid hydrolysis residue of the rhizomes of Anemarrhena asphodeloides. Their structures were identified on the basis of several spectroscopic analysis approaches including 1D, 2D-NMR techniques, and MS data, and by the comparison of spectral data of the known compounds. The biological activities of these two isolated compounds were explored on α-glucosidase. Compound 1 displayed 4.7 folds inhibitory activity against α-glucosidase compared with the positive control acarbose.

[Review in the studies on tannins activity of cancer prevention and anticancer].

PubMed

Li, Haixia; Wang, Zhao; Liu, Yanze

2003-06-01

This paper reviewed the biological activities of tannins in cancer prevention and anticancer, and mainly discussed related mechanisms. The results suggest that tannins, whether total tannins or pure tannin compound, have remarkable activity in cancer prevention and anticancer. It has wealthy foreground for developing new cancer prevention agents and/or new anticancer drugs screening among tannin compounds.

Biological evaluation, docking and molecular dynamic simulation of some novel diaryl urea derivatives bearing quinoxalindione moiety

PubMed Central

Sadeghian-Rizi, Sedighe; Khodarahmi, Ghadamali Ali; Sakhteman, Amirhossein; Jahanian-Najafabadi, Ali; Rostami, Mahboubeh; Mirzaei, Mahmoud; Hassanzadeh, Farshid

2017-01-01

In this study a series of diarylurea derivatives containing quinoxalindione group were biologically evaluated for their cytotoxic activities using MTT assay against MCF-7 and HepG2 cell lines. Antibacterial activities of these compounds were also evaluated by Microplate Alamar Blue Assay (MABA) against three Gram-negative (Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi), three Gram-positive (Staphylococcus aureus, Bacillus subtilis and Listeria monocitogenes) and one yeast-like fungus (Candida albicans) strain. Furthermore, molecular docking was carried out to study the binding pattern of the compounds to the active site of B-RAF kinase (PDB code: 1UWH). Molecular dynamics simulation was performed on the best ligand (16e) to investigate the ligand binding dynamics in the physiological environment. Cytotoxic evaluation revealed the most prominent cytotoxicity for 6 compounds with IC50 values of 10-18 μM against two mentioned cell lines. None of the synthesized compounds showed significant antimicrobial activity. The obtained results of the molecular docking study showed that all compounds fitted in the binding site of enzyme with binding energy range of -11.22 to -12.69 kcal/mol vs sorafenib binding energy -11.74 kcal/mol as the lead compound. Molecular dynamic simulation indicated that the binding of ligand (16e) was stable in the active site of B-RAF during the simulation. PMID:29204178

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.

Bioavailability of antioxidants in extruded products prepared from purple potato and dry pea flours

USDA-ARS?s Scientific Manuscript database

Measuring antioxidant activity using biological relevant assay is unique to understand the role of phytochemicals in vivo than common chemical assays. Cellular antioxidant activity assay could provide more biological relevant information on bioactive compounds in the raw as well as processed food pr...

Elevated temperature altered photosynthetic products in wheat seedlings and organic compounds and biological activity in rhizopshere soil under cadmium stress.

PubMed

Jia, Xia; Zhao, YongHua; Wang, WenKe; He, Yunhua

2015-09-23

The objective of this study was to investigate the effects of slightly elevated atmospheric temperature in the spring on photosynthetic products in wheat seedlings and on organic compounds and biological activity in rhizosphere soil under cadmium (Cd) stress. Elevated temperature was associated with increased soluble sugars, reducing sugars, starch, and total sugars, and with decreased amino acids in wheat seedlings under Cd stress. Elevated temperature improved total soluble sugars, free amino acids, soluble phenolic acids, and organic acids in rhizosphere soil under Cd stress. The activity of amylase, phenol oxidase, invertase, β-glucosidase, and l-asparaginase in rhizosphere soil was significantly improved by elevated temperature under Cd stress; while cellulase, neutral phosphatase, and urease activity significantly decreased. Elevated temperature significantly improved bacteria, fungi, actinomycetes, and total microorganisms abundance and fluorescein diacetate activity under Cd stress. In conclusion, slightly elevated atmospheric temperature in the spring improved the carbohydrate levels in wheat seedlings and organic compounds and biological activity in rhizosphere soil under Cd stress in the short term. In addition, elevated atmospheric temperature in the spring stimulated available Cd by affecting pH, DOC, phenolic acids, and organic acids in rhizosphere soil, which resulted in the improvement of the Cd uptake by wheat seedlings.

Elevated temperature altered photosynthetic products in wheat seedlings and organic compounds and biological activity in rhizopshere soil under cadmium stress

PubMed Central

Jia, Xia; Zhao, YongHua; Wang, WenKe; He, Yunhua

2015-01-01

The objective of this study was to investigate the effects of slightly elevated atmospheric temperature in the spring on photosynthetic products in wheat seedlings and on organic compounds and biological activity in rhizosphere soil under cadmium (Cd) stress. Elevated temperature was associated with increased soluble sugars, reducing sugars, starch, and total sugars, and with decreased amino acids in wheat seedlings under Cd stress. Elevated temperature improved total soluble sugars, free amino acids, soluble phenolic acids, and organic acids in rhizosphere soil under Cd stress. The activity of amylase, phenol oxidase, invertase, β-glucosidase, and l-asparaginase in rhizosphere soil was significantly improved by elevated temperature under Cd stress; while cellulase, neutral phosphatase, and urease activity significantly decreased. Elevated temperature significantly improved bacteria, fungi, actinomycetes, and total microorganisms abundance and fluorescein diacetate activity under Cd stress. In conclusion, slightly elevated atmospheric temperature in the spring improved the carbohydrate levels in wheat seedlings and organic compounds and biological activity in rhizosphere soil under Cd stress in the short term. In addition, elevated atmospheric temperature in the spring stimulated available Cd by affecting pH, DOC, phenolic acids, and organic acids in rhizosphere soil, which resulted in the improvement of the Cd uptake by wheat seedlings. PMID:26395070

Elevated temperature altered photosynthetic products in wheat seedlings and organic compounds and biological activity in rhizopshere soil under cadmium stress

NASA Astrophysics Data System (ADS)

Jia, Xia; Zhao, Yonghua; Wang, Wenke; He, Yunhua

2015-09-01

The objective of this study was to investigate the effects of slightly elevated atmospheric temperature in the spring on photosynthetic products in wheat seedlings and on organic compounds and biological activity in rhizosphere soil under cadmium (Cd) stress. Elevated temperature was associated with increased soluble sugars, reducing sugars, starch, and total sugars, and with decreased amino acids in wheat seedlings under Cd stress. Elevated temperature improved total soluble sugars, free amino acids, soluble phenolic acids, and organic acids in rhizosphere soil under Cd stress. The activity of amylase, phenol oxidase, invertase, β-glucosidase, and L-asparaginase in rhizosphere soil was significantly improved by elevated temperature under Cd stress; while cellulase, neutral phosphatase, and urease activity significantly decreased. Elevated temperature significantly improved bacteria, fungi, actinomycetes, and total microorganisms abundance and fluorescein diacetate activity under Cd stress. In conclusion, slightly elevated atmospheric temperature in the spring improved the carbohydrate levels in wheat seedlings and organic compounds and biological activity in rhizosphere soil under Cd stress in the short term. In addition, elevated atmospheric temperature in the spring stimulated available Cd by affecting pH, DOC, phenolic acids, and organic acids in rhizosphere soil, which resulted in the improvement of the Cd uptake by wheat seedlings.

Role of physicochemical properties in the activation of peroxisome proliferator-activated receptor δ.

PubMed

Maltarollo, Vinícius G; Homem-de-Mello, Paula; Honorio, Káthia M

2011-10-01

Current researches on treatments for metabolic diseases involve a class of biological receptors called peroxisome proliferator-activated receptors (PPARs), which control the metabolism of carbohydrates and lipids. A subclass of these receptors, PPARδ, regulates several metabolic processes, and the substances that activate them are being studied as new drug candidates for the treatment of diabetes mellitus and metabolic syndrome. In this study, several PPARδ agonists with experimental biological activity were selected for a structural and chemical study. Electronic, stereochemical, lipophilic and topological descriptors were calculated for the selected compounds using various theoretical methods, such as density functional theory (DFT). Fisher's weight and principal components analysis (PCA) methods were employed to select the most relevant variables for this study. The partial least squares (PLS) method was used to construct the multivariate statistical model, and the best model obtained had 4 PCs, q ( 2 ) = 0.80 and r ( 2 ) = 0.90, indicating a good internal consistency. The prediction residues calculated for the compounds in the test set had low values, indicating the good predictive capability of our PLS model. The model obtained in this study is reliable and can be used to predict the biological activity of new untested compounds. Docking studies have also confirmed the importance of the molecular descriptors selected for this system.

Biological activity of neosergeolide and isobrucein B (and two semi-synthetic derivatives) isolated from the Amazonian medicinal plant Picrolemma sprucei (Simaroubaceae).

PubMed

Silva, Ellen C C; Cavalcanti, Bruno C; Amorim, Rodrigo C N; Lucena, Jorcilene F; Quadros, Dulcimar S; Tadei, Wanderli P; Montenegro, Raquel C; Costa-Lotufo, Letícia V; Pessoa, Cláudia; Moraes, Manoel O; Nunomura, Rita C S; Nunomura, Sergio M; Melo, Marcia R S; Andrade-Neto, Valter F de; Silva, Luiz Francisco R; Vieira, Pedro Paulo R; Pohlit, Adrian M

2009-02-01

In the present study, in vitro techniques were used to investigate a range of biological activities of known natural quassinoids isobrucein B (1) and neosergeolide (2), known semi-synthetic derivative 1,12-diacetylisobrucein B (3), and a new semi-synthetic derivative, 12-acetylneosergeolide (4). These compounds were evaluated for general toxicity toward the brine shrimp species Artemia franciscana, cytotoxicity toward human tumour cells, larvicidal activity toward the dengue fever mosquito vector Aedes aegypti, haemolytic activity in mouse erythrocytes and antimalarial activity against the human malaria parasite Plasmodium falciparum. Compounds 1 and 2 exhibited the greatest cytotoxicity against all the tumor cells tested (IC50 = 5-27 microg/L) and against multidrug-resistant P. falciparum K1 strain (IC50 = 1.0-4.0 g/L) and 3 was only cytotoxic toward the leukaemia HL-60 strain (IC50 = 11.8 microg/L). Quassinoids 1 and 2 (LC50 = 3.2-4.4 mg/L) displayed greater lethality than derivative 4 (LC50 = 75.0 mg/L) toward A. aegypti larvae, while derivative 3 was inactive. These results suggest a novel application for these natural quassinoids as larvicides. The toxicity toward A. franciscana could be correlated with the activity in several biological models, a finding that is in agreement with the literature. Importantly, none of the studied compounds exhibited in vitro haemolytic activity, suggesting specificity of the observed cytotoxic effects. This study reveals the biological potential of quassinoids 1 and 2 and to a lesser extent their semi-synthetic derivatives for their in vitro antimalarial and cytotoxic activities.

Synthesis and Biological Evaluation of 3-Benzylidene-4-chromanone Derivatives as Free Radical Scavengers and α-Glucosidase Inhibitors.

PubMed

Takao, Koichi; Yamashita, Marimo; Yashiro, Aruki; Sugita, Yoshiaki

2016-01-01

A series of 3-benzylidene-4-chromanone derivatives (3-20) were synthesized and the structure-activity relationships for antioxidant and α-glucosidase inhibitory activities were evaluated. Among synthesized compounds, compounds 5, 13, 18, which contain catechol moiety, showed the potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity (5: EC50 13 µM; 13: EC50 14 µM; 18: EC50 13 µM). The compounds 12, 14, 18 showed higher α-glucosidase inhibitory activity (12: IC50 15 µM; 14: IC50 25 µM; 18: IC50 28 µM). The compound 18 showed both of potent DPPH radical scavenging and α-glucosidase inhibitory activities. These data suggest that 3-benzylidene-4-chromanone derivatives, such as compound 18, may serve as the lead compound for the development of novel α-glucosidase inhibitors with antioxidant activity.

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.

Transformation of Contaminant Candidate List (CCL3) compounds during ozonation and advanced oxidation processes in drinking water: Assessment of biological effects.

PubMed

Mestankova, Hana; Parker, Austa M; Bramaz, Nadine; Canonica, Silvio; Schirmer, Kristin; von Gunten, Urs; Linden, Karl G

2016-04-15

The removal of emerging contaminants during water treatment is a current issue and various technologies are being explored. These include UV- and ozone-based advanced oxidation processes (AOPs). In this study, AOPs were explored for their degradation capabilities of 25 chemical contaminants on the US Environmental Protection Agency's Contaminant Candidate List 3 (CCL3) in drinking water. Twenty-three of these were found to be amenable to hydroxyl radical-based treatment, with second-order rate constants for their reactions with hydroxyl radicals (OH) in the range of 3-8 × 10(9) M(-1) s(-1). The development of biological activity of the contaminants, focusing on mutagenicity and estrogenicity, was followed in parallel with their degradation using the Ames and YES bioassays to detect potential changes in biological effects during oxidative treatment. The majority of treatment cases resulted in a loss of biological activity upon oxidation of the parent compounds without generation of any form of estrogenicity or mutagenicity. However, an increase in mutagenic activity was detected by oxidative transformation of the following CCL3 parent compounds: nitrobenzene (OH, UV photolysis), quinoline (OH, ozone), methamidophos (OH), N-nitrosopyrolidine (OH), N-nitrosodi-n-propylamine (OH), aniline (UV photolysis), and N-nitrosodiphenylamine (UV photolysis). Only one case of formation of estrogenic activity was observed, namely, for the oxidation of quinoline by OH. Overall, this study provides fundamental and practical information on AOP-based treatment of specific compounds of concern and represents a framework for evaluating the performance of transformation-based treatment processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Natural Products from the Lithistida: A Review of the Literature since 2000

PubMed Central

Winder, Priscilla L.; Pomponi, Shirley A.; Wright, Amy E.

2011-01-01

Lithistid sponges are known to produce a diverse array of compounds ranging from polyketides, cyclic and linear peptides, alkaloids, pigments, lipids, and sterols. A majority of these structurally complex compounds have very potent and interesting biological activities. It has been a decade since a thorough review has been published that summarizes the literature on the natural products reported from this amazing sponge order. This review provides an update on the current taxonomic classification of the Lithistida, describes structures and biological activities of 131 new natural products, and discusses highlights from the total syntheses of 16 compounds from marine sponges of the Order Lithistida providing a compilation of the literature since the last review published in 2002. PMID:22363244

Biological Activities of Extracts from Loquat (Eriobotrya japonica Lindl.): A Review

PubMed Central

Liu, Yilong; Zhang, Wenna; Xu, Changjie; Li, Xian

2016-01-01

Loquat (Eriobotrya japonica Lindl.) is a subtropical fruit tree with high medicinal value native to China. Different organs of loquat have been used historically as folk medicines and this has been recorded in Chinese history for thousands of years. Research shows that loquat extracts contain many antioxidants, and different extracts exhibit bioactivity capable of counteracting inflammation, diabetes, cancer, bacterial infection, aging, pain, allergy and other health issues. Bioactive compounds such as phenolics and terpenoids have been isolated and characterized to provide a better understanding of the chemical mechanisms underlying the biological activities of loquat extracts. As the identification of compounds progresses, studies investigating the in vivo metabolism, bioavailability, and structure–activity relationships, as well as potential toxicity of loquat extracts in animal or cell models are receiving more attention. In addition, genetic studies and breeding of loquat germplasms for high contents of health-benefiting compounds may provide new insight for the loquat industry and research. This review is focused on the main medicinal properties reported and the possible pharmaceutically active compounds identified in different loquat extracts. PMID:27929430

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.

Recent developments in therapeutic applications of Cyanobacteria.

PubMed

Raja, Rathinam; Hemaiswarya, Shanmugam; Ganesan, Venkatesan; Carvalho, Isabel S

2016-05-01

The cyanobacteria (blue-green algae) are photosynthetic prokaryotes having applications in human health with numerous biological activities and as a dietary supplement. It is used as a food supplement because of its richness in nutrients and digestibility. Many cyanobacteria (Microcystis sp, Anabaena sp, Nostoc sp, Oscillatoria sp., etc.) produce a great variety of secondary metabolites with potent biological activities. Cyanobacteria produce biologically active and chemically diverse compounds belonging to cyclic peptides, lipopeptides, fatty acid amides, alkaloids and saccharides. More than 50% of the marine cyanobacteria are potentially exploitable for extracting bioactive substances which are effective in killing cancer cells by inducing apoptotic death. Their role as anti-viral, anti-tumor, antimicrobial, anti-HIV and a food additive have also been well established. However, such products are at different stages of clinical trials and only a few compounds have reached to the market.

Marine natural flavonoids: chemistry and biological activities.

PubMed

Martins, Beatriz T; Correia da Silva, Marta; Pinto, Madalena; Cidade, Honorina; Kijjoa, Anake

2018-05-04

As more than 70% of the world's surface is covered by oceans, marine organisms offer a rich and unlimited resource of structurally diverse bioactive compounds. These organisms have developed unique properties and bioactive compounds that are, in majority of them, unparalleled by their terrestrial counterparts due to the different surrounding ecological systems. Marine flavonoids have been extensively studied in the last decades due to a growing interest concerning their promising biological/pharmacological activities. The most common classes of marine flavonoids are flavones and flavonols, which are mostly isolated from marine plants. Although most of flavonoids are hydroxylated and methoxylated, some marine flavonoids possess an unusual substitution pattern, not commonly found in terrestrial organisms, namely the presence of sulphate, chlorine, and amino groups. This review presents, for the first time in a systematic way, the structure, natural occurrence, and biological activities of marine flavonoids.

Biological activities of xanthatin from Xanthium strumarium leaves.

PubMed

Nibret, Endalkachew; Youns, Mahamoud; Krauth-Siegel, R Luise; Wink, Michael

2011-12-01

The objective of the present work was to evaluate the biological activities of the major bioactive compound, xanthatin, and other compounds from Xanthium strumarium (Asteraceae) leaves. Inhibition of bloodstream forms of Trypanosoma brucei brucei and leukaemia HL-60 cell proliferation was assessed using resazurin as a vital stain. Xanthatin was found to be the major and most active compound against T. b. brucei with an IC(50) value of 2.63 µg/mL and a selectivity index of 20. The possible mode of action of xanthatin was further evaluated. Xanthatin showed antiinflammatory activity by inhibiting both PGE(2) synthesis (24% inhibition) and 5-lipoxygenase activity (92% inhibition) at concentrations of 100 µg/mL and 97 µg/mL, respectively. Xanthatin exhibited weak irreversible inhibition of parasite specific trypanothione reductase. Unlike xanthatin, diminazene aceturate and ethidium bromide showed strong DNA intercalation with IC(50) values of 26.04 µg/mL and 44.70 µg/mL, respectively. Substantial induction of caspase 3/7 activity in MIA PaCa-2 cells was observed after 6 h of treatment with 100 µg/mL of xanthatin. All these data taken together suggest that xanthatin exerts its biological activity by inducing apoptosis and inhibiting both PGE(2) synthesis and 5-lipoxygenase activity thereby avoiding unwanted inflammation commonly observed in diseases such as trypanosomiasis. Copyright © 2011 John Wiley & Sons, Ltd.

[Quod medicina aliis, aliis est acre venenum**--venoms as a source of anticancer agents].

PubMed

Kucińska, Małgorzata; Ruciński, Piotr; Murias, Marek

2013-01-01

Natural product derived from plants and animals were used in folk medicine for centuries. The venoms produced by animals for hunting of self-defence are rich in bioactive compounds with broad spectrum of biological activity. The papers presents the most promising compounds isolated from venoms of snakes, scorpions and toads. For these compounds both: mechanism of anticancer activity as well as possibilities of clinical use are presented.

High-throughput screen of drug repurposing library identifies inhibitors of Sarcocystis neurona growth.

PubMed

Bowden, Gregory D; Land, Kirkwood M; O'Connor, Roberta M; Fritz, Heather M

2018-04-01

The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60-70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S. neurona activity. Our screen identified 18 compounds with confirmed inhibitory activity against S. neurona growth, including compounds active in the nM concentration range. Many identified inhibitory compounds have well-defined mechanisms of action, making them useful tools to study parasite biology in addition to being potential therapeutic agents. In comparing the activity of inhibitory compounds identified by our screen to that of other screens against other apicomplexan parasites, we found that most compounds (15/18; 83%) have activity against one or more related apicomplexans. Interestingly, nearly half (44%; 8/18) of the inhibitory compounds have reported activity against dopamine receptors. We also found that dantrolene, a compound already formulated for horses with a peak plasma concentration of 37.8 ± 12.8 ng/ml after 500 mg dose, inhibits S. neurona parasites at low concentrations (0.065 μM [0.036-0.12; 95% CI] or 21.9 ng/ml [12.1-40.3; 95% CI]). These studies demonstrate the use of a new tool for discovering new chemotherapeutic agents for EPM and potentially providing new reagents to elucidate biologic pathways required for successful S. neurona infection. Copyright © 2018. Published by Elsevier Ltd.

A Non-Biological Method for Screening Active Components against Influenza Virus from Traditional Chinese Medicine by Coupling a LC Column with Oseltamivir Molecularly Imprinted Polymers

PubMed Central

Yang, Ya-Jun; Li, Jian-Yong; Liu, Xi-Wang; Zhang, Ji-Yu; Liu, Yu-Rong; Li, Bing

2013-01-01

To develop a non-biological method for screening active components against influenza virus from traditional Chinese medicine (TCM) extraction, a liquid chromatography (LC) column prepared with oseltamivir molecularly imprinted polymer (OSMIP) was employed with LC-mass spectrometry (LC-MS). From chloroform extracts of compound TCM liquid preparation, we observed an affinitive component m/z 249, which was identified to be matrine following analysis of phytochemical literatures, OSMIP-LC column on-line of control compounds and MS/MS off-line. The results showed that matrine had similar bioactivities with OS against avian influenza virus H9N2 in vitro for both alleviating cytopathic effect and hemagglutination inhibition and that the stereostructures of these two compounds are similar while their two-dimensional structures were different. In addition, our results suggested that the bioactivities of those affinitive compounds were correlated with their chromatographic behaviors, in which less difference of the chromatographic behaviors might have more similar bioactivities. This indicates that matrine is a potential candidate drug to prevent or cure influenza for human or animal. In conclusion, the present study showed that molecularly imprinted polymers can be used as a non-biological method for screening active components against influenza virus from TCM. PMID:24386385

Acetylated Triterpene Glycosides and Their Biological Activity from Holothuroidea Reported in the Past Six Decades

PubMed Central

Bahrami, Yadollah; Franco, Christopher M. M.

2016-01-01

Sea cucumbers have been valued for many centuries as a tonic and functional food, dietary delicacies and important ingredients of traditional medicine in many Asian countries. An assortment of bioactive compounds has been described in sea cucumbers. The most important and abundant secondary metabolites from sea cucumbers are triterpene glycosides (saponins). Due to the wide range of their potential biological activities, these natural compounds have gained attention and this has led to their emergence as high value compounds with extended application in nutraceutical, cosmeceutical, medicinal and pharmaceutical products. They are characterized by bearing a wide spectrum of structures, such as sulfated, non-sulfated and acetylated glycosides. Over 700 triterpene glycosides have been reported from the Holothuroidea in which more than 145 are decorated with an acetoxy group having 38 different aglycones. The majority of sea cucumber triterpene glycosides are of the holostane type containing a C18 (20) lactone group and either Δ7(8) or Δ9(11) double bond in their genins. The acetoxy group is mainly connected to the C-16, C-22, C-23 and/or C-25 of their aglycone. Apparently, the presence of an acetoxy group, particularly at C-16 of the aglycone, plays a significant role in the bioactivity; including induction of caspase, apoptosis, cytotoxicity, anticancer, antifungal and antibacterial activities of these compounds. This manuscript highlights the structure of acetylated saponins, their biological activity, and their structure-activity relationships. PMID:27527190

Novel coumarin derivatives bearing N-benzyl pyridinium moiety: potent and dual binding site acetylcholinesterase inhibitors.

PubMed

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

2012-12-15

A novel series of coumarin derivatives linked to benzyl pyridinium group were synthesized and biologically evaluated as inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The enzyme inhibitory activity of synthesized compounds was measured using colorimetric Ellman's method. It was revealed that compounds 3e, 3h, 3l, 3r and 3s have shown higher activity compared with donepezil hydrochloride as standard drug. Most of the compounds in these series had nanomolar range IC(50) in which compound 3r (IC(50) = 0.11 nM) was the most active compound against acetylcholinesterase enzyme. Copyright © 2012 Elsevier Ltd. All rights reserved.

Synthetic and Medicinal Prospective of Structurally Modified Curcumins.

PubMed

Kumar, Bhupinder; Singh, Virender; Shankar, Ravi; Kumar, Kapil; Rawal, Ravindra K

2017-01-01

Curcumin, a natural yellow phenolic compound, is present in various types of herbs, particularly in Turmeric, Curcuma longa Linn. (Zingiberaceae family) rhizomes. Curcumin is a polyphenolic natural compound with diverse and attractive biological activities. In the last decade curcumine and its various synthetic analogues have been prepared and evaluated for various pharmacological activities that prove it as a lead molecule against several biological targets. It is a natural antioxidant and exhibited many pharmacological activities such as anti-inflammatory, anti-microbial, anticancer, anti-Alzheimer in both preclinical and clinical studies. Moreover, Curcumin and its analogues have anti-tubercular, cardioprotective, anti-diabetic, hepatoprotective, neuroprotective, nephroprotective, antirheumatic and anti-viral activities. The substitutions of 1,6-heptadiene linkage moiety via carbonyl group sustituion and addition of heterocyclic linker; isoxazole, 1H-pyrazole, cyclopentanone, piperidin-4-one, N-methylpiperidin-4-one enhance biological activities. The structure activity relationship of various curcumin analogues is studied for medicinal purposes and it reveals that monocarbonyl linkage analogues have anticancer properties. The current review gives an insight of the history, chemistry, analogues and most interesting in vitro and in vivo studies on the biological effects of Curcumin and its analogues.

Synthesis, antitubercular and anticancer activities of substituted furyl-quinazolin-3(4H)-ones.

PubMed

Raghavendra, Nulgulmnalli M; Thampi, Parameshwaran; Gurubasavarajaswamy, Purvarga M; Sriram, Dharmarajan

2007-12-01

Some novel substituted-3-{[(1E)-(substituted-2-furyl)-methylene]amino}quinazolin-4(3H)-one (5, 6, 7) a-f were synthesized by a multi-step process. These synthesized compounds are characterized by various spectroscopic techniques and evaluated for their antitubercular and anticancer activities. Biological activity indicated that some of the title compounds are potent antitubercular and anticancer agents.

Tramesan, a novel polysaccharide from Trametes versicolor. Structural characterization and biological effects

PubMed Central

Sveronis, Aris; Cescutti, Paola; Rizzo, Roberto

2017-01-01

Mushrooms represent a formidable source of bioactive compounds. Some of these may be considered as biological response modifiers; these include compounds with a specific biological function: antibiotics (e.g. plectasin), immune system stimulator (e,g, lentinan), antitumor agents (e.g. krestin, PSK) and hypolipidemic agents (e.g. lovastatin) inter alia. In this study, we focused on the Chinese medicinal mushroom “yun zhi”, Trametes versicolor, traditionally used for (cit.) “replenish essence and qi (vital energy)”. Previous studies indicated the potential activity of extracts from culture filtrate of asexual mycelia of T. versicolor in controlling the growth and secondary metabolism (e.g. mycotoxins) of plant pathogenic fungi. The quest of active principles produced by T. versicolor, allowed us characterising an exo-polysaccharide released in its culture filtrate and naming it Tramesan. Herein we evaluate the biological activity of Tramesan in different organisms: plants, mammals and plant pathogenic fungi. We suggest that the bioactivity of Tramesan relies mostly on its ability to act as pro antioxidant molecule regardless the biological system on which it was applied. PMID:28829786

Tramesan, a novel polysaccharide from Trametes versicolor. Structural characterization and biological effects.

PubMed

Scarpari, Marzia; Reverberi, Massimo; Parroni, Alessia; Scala, Valeria; Fanelli, Corrado; Pietricola, Chiara; Zjalic, Slaven; Maresca, Vittoria; Tafuri, Agostino; Ricciardi, Maria R; Licchetta, Roberto; Mirabilii, Simone; Sveronis, Aris; Cescutti, Paola; Rizzo, Roberto

2017-01-01

Mushrooms represent a formidable source of bioactive compounds. Some of these may be considered as biological response modifiers; these include compounds with a specific biological function: antibiotics (e.g. plectasin), immune system stimulator (e,g, lentinan), antitumor agents (e.g. krestin, PSK) and hypolipidemic agents (e.g. lovastatin) inter alia. In this study, we focused on the Chinese medicinal mushroom "yun zhi", Trametes versicolor, traditionally used for (cit.) "replenish essence and qi (vital energy)". Previous studies indicated the potential activity of extracts from culture filtrate of asexual mycelia of T. versicolor in controlling the growth and secondary metabolism (e.g. mycotoxins) of plant pathogenic fungi. The quest of active principles produced by T. versicolor, allowed us characterising an exo-polysaccharide released in its culture filtrate and naming it Tramesan. Herein we evaluate the biological activity of Tramesan in different organisms: plants, mammals and plant pathogenic fungi. We suggest that the bioactivity of Tramesan relies mostly on its ability to act as pro antioxidant molecule regardless the biological system on which it was applied.

Synthesis, biological evaluation and structure-activity correlation study of a series of imidazol-based compounds as Candida albicans inhibitors.

PubMed

Moraca, Francesca; De Vita, Daniela; Pandolfi, Fabiana; Di Santo, Roberto; Costi, Roberta; Cirilli, Roberto; D'Auria, Felicia Diodata; Panella, Simona; Palamara, Anna Teresa; Simonetti, Giovanna; Botta, Maurizio; Scipione, Luigi

2014-08-18

A new series of 2-(1H-imidazol-1-yl)-1-phenylethanol derivatives was synthesized. The antifungal activity was evaluated in vitro against different fungal species. The biological results show that the most active compounds possess an antifungal activity comparable or higher than Fluconazole against Candida albicans, non-albicans Candida species, Cryptococcus neoformans and dermathophytes. Because of their racemic nature, the most active compounds 5f and 6c were tested as pure enantiomers. For 6c the (R)-enantiomer resulted more active than the (S)-one, otherwise for 5f the (S)-enantiomer resulted the most active. To rationalize the experimental data, a ligand-based computational study was carried out; the results of the modelling study show that (S)-5f and (R)-6c perfectly align to the ligand-based model, showing the same relative configuration. Preliminary studies on the human lung adenocarcinoma epithelial cells (A549) have shown that 6c, 5e and 5f possess a low cytotoxicity. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Bioactive compounds in bee propolis for drug discovery

NASA Astrophysics Data System (ADS)

Kumazawa, Shigenori

2018-02-01

Propolis is a natural resinous product collected by honeybees. It has been used in folk medicine since ancient times because of its numerous biological properties such as antioxidant, antimicrobial, anti-cancer, and anti-inflammatory activities. Studies of the chemical composition of propolis have demonstrated that its compositional variability depends on the source plant. We have studied the chemistry and biological activities of various types of propolis from Apis mellifera. The studies of propolis collected in Brazil, Japan, Korea, the Solomon Island and Senegal are summarized. Brazilian green propolis contained high levels of artepillin C (3,5-diprenyl-4-hydroxycinnamic acid), which has a potent apoptosis-inducing agent as well as an angiogenesis inhibitor. The several phenolic compounds with potent antibacterial activity in Brazilian red propolis were found. The propolis from Okinawa, Japan, contained some prenylflavonoids with antioxidant and antimicrobial activities. The propolis from the Solomon Islands and Hawaii have the same compounds as Okinawan propolis. The propolis from Jeju Island, Korea had the promotion effect on nerve growth factor (NGF) secretion in human glioblastoma T98G cells. The compounds isolated from Senegalese propolis showed high anti-inflammatory activity due to their inhibition of the liposaccharide (LPS)-induced expression of inducible NO synthase (iNOS).

Some biologically active oxovanadium(IV) complexes of triazole derived Schiff bases: their synthesis, characterization and biological properties.

PubMed

Chohan, Zahid H; Sumrra, Sajjad H

2010-10-01

A series of biologically active oxovanadium(IV) complexes of triazole derived Schiff bases L(1)-L(5) have been synthesized and characterized by their physical, analytical, and spectral data. The synthesized ligands potentially act as bidentate, in which the oxygen of furfural and nitrogen of azomethine coordinate with the oxovanadium atom to give a stoichiometry of vanadyl complexes 1:2 (M:L) in a square-pyramidal geometry. In vitro antibacterial and antifungal activities on different species of pathogenic bacteria (E. coli, S. flexneri, P. aeruginosa, S. typhi, S. aureus, and B. subtilis) and fungi (T. longifusus, C. albicans, A. flavus, M. canis, F. solani, and C. glabrata) have been studied. All compounds showed moderate to significant antibacterial activity against one or more bacterial strains and good antifungal activity against most of the fungal strains. The brine shrimp bioassay was also carried out to check the cytotoxicity of coordinated and uncoordinated synthesized compounds.

Advances in the Study of the Structures and Bioactivities of Metabolites Isolated from Mangrove-Derived Fungi in the South China Sea

PubMed Central

Wang, Xin; Mao, Zhi-Gang; Song, Bing-Bing; Chen, Chun-Hua; Xiao, Wei-Wei; Hu, Bin; Wang, Ji-Wen; Jiang, Xiao-Bing; Zhu, Yong-Hong; Wang, Hai-Jun

2013-01-01

Many metabolites with novel structures and biological activities have been isolated from the mangrove fungi in the South China Sea, such as anthracenediones, xyloketals, sesquiterpenoids, chromones, lactones, coumarins and isocoumarin derivatives, xanthones, and peroxides. Some compounds have anticancer, antibacterial, antifungal and antiviral properties, but the biosynthesis of these compounds is still limited. This review summarizes the advances in the study of secondary metabolites from the mangrove-derived fungi in the South China Sea, and their biological activities reported between 2008 and mid-2013. PMID:24084782

Novel antiprotozoal products: imidazole and benzimidazole N-oxide derivatives and related compounds.

PubMed

Aguirre, Gabriela; Boiani, Mariana; Cerecetto, Hugo; Gerpe, Alejandra; González, Mercedes; Sainz, Yolanda Fernández; Denicola, Ana; De Ocáriz, Carmen Ochoa; Nogal, Juan José; Montero, David; Escario, José Antonio

2004-05-01

The syntheses and biological evaluation of the first anti-protozoa imidazole N-oxide and benzimidazole N-oxide and their derivatives are reported. They were tested in vitro against two different protozoa, Trypanosoma cruzi and Trichomonas vaginalis. Derivative 7c, ethyl-1-(i-butyloxycarbonyloxy)-6-nitrobenzimid-azole-2-carboxylate, displayed activity on both protozoa. Lipophilicity and redox potential were experimentally determined in order to study the relationship with activity of the compounds. These properties are well related with the observed bioactivity. Imidazole and benzimidazole N-oxide derivatives are becoming leaders for further chemical modifications and advanced biological studies.

Synthesis and Biological Evaluation of Neopeltolide and Analogs

PubMed Central

Cui, Yubo; Balachandran, Raghavan

2012-01-01

The synthesis of neopeltolide analogs that contain variations in the oxazole-containing side chain and in the macrolide core are reported along with the GI50 values for these compounds against MCF7, HCT-116, and p53 knockout HCT-116 cell lines. Although biological activity is sensitive to changes in the macrocycle and the side chain, several analogs displayed GI50 values of <25 nM. Neopeltolide and several of the more potent analogs were significantly less potent against p53 knockout cells, suggesting that p53 plays an auxiliary role in the activity of these compounds. PMID:22329423

Design, synthesis and biological evaluation of novel pyrazolo-pyrimidinones as DPP-IV inhibitors in diabetes.

PubMed

Sagar, Sneha R; Agarwal, Jessica K; Pandya, Dhaivat H; Dash, Ranjeet Prasad; Nivsarkar, Manish; Vasu, Kamala K

2015-10-15

We report the design, synthesis, biological activity and docking studies of series of novel pyrazolo[3,4-d]pyrimidinones as DPP-IV inhibitors in diabetes. Molecules were synthesized and evaluated for their DPP-IV inhibition activity. Compounds 5e, 5k, 5o and 6a were found to be potent inhibitors of DPP-IV enzyme. Amongst all the synthesized compounds, 6-methyl-5-(4-methylpyridin-2-yl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one (5k) was found to be the most active based on in vitro DPP-IV studies and also exhibited promising in vivo blood glucose lowering activity in male Wistar rats. Copyright © 2015. Published by Elsevier Ltd.

Novel ciprofloxacin hybrids using biology oriented drug synthesis (BIODS) approach: Anticancer activity, effects on cell cycle profile, caspase-3 mediated apoptosis, topoisomerase II inhibition, and antibacterial activity.

PubMed

Kassab, Asmaa E; Gedawy, Ehab M

2018-04-25

As we are interested in synthetizing biologically active leads with dual anticancer and antibacterial activity, we adopted biology oriented drug synthesis (BIODS) strategy to synthesize a series of novel ciprofloxacin (CP) hybrids. The National Cancer Institute (USA) selected seventeen newly synthesized compounds for anticancer evaluation against 59 different human tumor cell lines. Five compounds 3e, 3f, 3h, 3o and 3p were further studied through determination of IC 50 values against the most sensitive cancer cell lines. In vitro results showed that the five compounds exhibited potent anticancer activity against test cell lines in nanomolar to micromolar range, with IC 50 values between 0.72 and 4.92 μM, which was 9 to1.5 folds more potent than doxorubicin. In this study, two promising potent anticancer CP hybrids, 3f and 3o, were identified. The anti-proliferative activity of these compounds appears to correlate well with their ability to inhibit Topo II (IC 50  = 0.58 and 0.86 μM). It is worth mentioning that compound 3f was 6 folds more potent than doxorubicin, 5 folds more potent than amsacrine and 1.5 folds more potent than etoposide. At the same time, compound 3o showed 4 folds more inhibitory activity against Topo II than doxorubicin, 3 folds more potent than amsacrine and almost equipotent activity to etoposide. Activation of damage response pathway of the DNA leads to cell cycle arrest at G2/M phase, accumulation of cells in pre-G1 phase and annexin-V and propidium iodide staining, indicating that cell death proceeds through an apoptotic mechanism. Moreover, compounds 3f and 3o showed potent pro-apoptotic effect through induction of the intrinsic mitochondrial pathway of apoptosis. This mechanistic pathway was confirmed by a significant increase in the level of active caspase-3 compared to control. This observation may indicate that both CP hybrids can chelate with zinc, a powerful inhibitor of procaspase-3 enzymatic activity, so procaspase-3 may process itself to the active form. The synthesized CP derivatives were tested for their in vitro antibacterial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa strains. The results proved that all of the test compounds have shown good to excellent antibacterial activity, as compared to its parent molecule ciprofloxacin. Compounds 2, 3b, 3k, 3l, 3m, 3p, 5a, 5b, 5d and 5e exhibited equipotent or comparable activity to ciprofloxacin against the test strains. Compounds 3p and 5a were more potent than ciprofloxacin against Pseudomonas aeruginosa, a common organism causing infections in granulocytopenic cancer patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemical composition, in vitro antitumor and pro-oxidant activities of Glandora rosmarinifolia (Boraginaceae) essential oil.

PubMed

Poma, Paola; Labbozzetta, Manuela; Notarbartolo, Monica; Bruno, Maurizio; Maggio, Antonella; Rosselli, Sergio; Sajeva, Maurizio; Zito, Pietro

2018-01-01

The biological properties of essential oils have been demonstrated in the treatment of several diseases and to enhance the bioavailability of other drugs. In natural habitats the essential oils compounds may play important roles in the protection of the plants as antibacterials, antivirals, antifungals, insecticides and also against herbivores by reducing their appetite for such plants or by repelling undesirable others. We analyzed by gas-chromatography mass spectrometry the chemical composition of the essential oil of aerial parts of Glandora rosmarinifolia (Ten.) D.C. Thomas obtained by hydrodistillation and verified some biological activities on a panel of hepatocellular carcinoma cell lines (HA22T/VGH, HepG2, Hep3B) and triple negative breast cancer cell lines (SUM 149, MDA-MB-231). In the essential oil we detected 35 compounds. The results of the biological assays indicate that essential oil of G. rosmarinifolia induces cell growth inhibition at concentration-dependent way in all cell line models. This oil does not seem to possess antioxidant activity, while the cytotoxicity of G. rosmarinifolia essential oil appeared to involve, at least in part, a pro-oxidant mechanism. Our results show for the first time the antitumoral and pro-oxidant activities of G. rosmarinifolia essential oil and suggest that it may represent a resource of pharmacologically active compounds.

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.

Novel CYP17 inhibitors: synthesis, biological evaluation, structure-activity relationships and modelling of methoxy- and hydroxy-substituted methyleneimidazolyl biphenyls.

PubMed

Hille, Ulrike E; Hu, Qingzhong; Vock, Carsten; Negri, Matthias; Bartels, Marc; Müller-Vieira, Ursula; Lauterbach, Thomas; Hartmann, Rolf W

2009-07-01

Recently, the steroidal CYP17 inhibitor Abiraterone entered phase II clinical trial for the treatment of androgen-dependent prostate cancer. As 17alpha-hydroxylase-17,20-lyase (CYP17) catalyzes the last step in androgen biosynthesis, inhibition of this target should affect not only testicular but also adrenal androgen formation. Therefore CYP17 inhibitors should be advantageous over existing therapies, for example with GnRH analogues. However, steroidal drugs are known for side effects which are due to affinities for steroid receptors. Therefore we decided to synthesize non-steroidal compounds mimicking the natural CYP17 substrates pregnenolone and progesterone. The synthesis and biological evaluation of a series of 15 novel and highly active non-steroidal CYP17 inhibitors are reported. The compounds were prepared via Suzuki-cross-coupling, Grignard reaction and CDI-assisted S(N)t-reaction with imidazole and their inhibitory activity was examined with recombinant human CYP17 expressed in Escherichia coli. Promising compounds were further tested for their selectivity against the hepatic enzyme CYP3A4 and the glucocorticoid-forming enzyme CYP11B1. All compounds turned out to be potent CYP17 inhibitors. The most active compounds 7 and 8 were much more active than Ketoconazole showing activity comparable to Abiraterone (IC(50) values of 90 and 52nM vs. 72nM). Most compounds also showed higher selectivities than Ketoconazole, but turned out to be less selective than Abiraterone. Docking studies using our CYP17 protein model were performed with selected compounds to study the interactions between the inhibitors and the amino acid residues of the active site.

Can Invalid Bioactives Undermine Natural Product-Based Drug Discovery?

PubMed Central

2015-01-01

High-throughput biology has contributed a wealth of data on chemicals, including natural products (NPs). Recently, attention was drawn to certain, predominantly synthetic, compounds that are responsible for disproportionate percentages of hits but are false actives. Spurious bioassay interference led to their designation as pan-assay interference compounds (PAINS). NPs lack comparable scrutiny, which this study aims to rectify. Systematic mining of 80+ years of the phytochemistry and biology literature, using the NAPRALERT database, revealed that only 39 compounds represent the NPs most reported by occurrence, activity, and distinct activity. Over 50% are not explained by phenomena known for synthetic libraries, and all had manifold ascribed bioactivities, designating them as invalid metabolic panaceas (IMPs). Cumulative distributions of ∼200,000 NPs uncovered that NP research follows power-law characteristics typical for behavioral phenomena. Projection into occurrence–bioactivity–effort space produces the hyperbolic black hole of NPs, where IMPs populate the high-effort base. PMID:26505758

Bioactive terpenes from marine-derived fungi.

PubMed

Elissawy, Ahmed M; El-Shazly, Mohamed; Ebada, Sherif S; Singab, AbdelNasser B; Proksch, Peter

2015-04-03

Marine-derived fungi continue to be a prolific source of secondary metabolites showing diverse bioactivities. Terpenoids from marine-derived fungi exhibit wide structural diversity including numerous compounds with pronounced biological activities. In this review, we survey the last five years' reports on terpenoidal metabolites from marine-derived fungi with particular attention on those showing marked biological activities.

Carboxylic acid isosteres improve the activity of ring-fused 2-pyridones that inhibit pilus biogenesis in E. coli

PubMed Central

Åberg, Veronica; Das, Pralay; Chorell, Erik; Hedenström, Mattias; Pinkner, Jerome S.; Hultgren, Scott J.; Almqvist, Fredrik

2009-01-01

Ring-fused 2-pyridones, termed pilicides, are small synthetic compounds that inhibit pilus assembly in uropathogenic E. coli. Their biological activity is clearly dependent upon a carboxylic acid functionality. Here we present the synthesis and biological evaluation of carboxylic acid isosteres, including e.g. tetrazoles, acyl sulfonamides and hydroxamic acids, of two lead 2-pyridones. Two independent biological evaluations show that acyl sulfonamides and tetrazoles significantly improve pilicide activity against uropathogenic E. coli. PMID:18499455

Essential Oils’ Chemical Characterization and Investigation of Some Biological Activities: A Critical Review

PubMed Central

Dhifi, Wissal; Bellili, Sana; Jazi, Sabrine; Bahloul, Nada; Mnif, Wissem

2016-01-01

This review covers literature data summarizing, on one hand, the chemistry of essential oils and, on the other hand, their most important activities. Essential oils, which are complex mixtures of volatile compounds particularly abundant in aromatic plants, are mainly composed of terpenes biogenerated by the mevalonate pathway. These volatile molecules include monoterpenes (hydrocarbon and oxygenated monoterpens), and also sesquiterpenes (hydrocarbon and oxygenated sesquiterpens). Furthermore, they contain phenolic compounds, which are derived via the shikimate pathway. Thanks to their chemical composition, essential oils possess numerous biological activities (antioxidant, anti-inflammatory, antimicrobial, etc…) of great interest in food and cosmetic industries, as well as in the human health field. PMID:28930135

Synthesis and structure-activity relationships of carbohydrazides and 1,3,4-oxadiazole derivatives bearing imidazolidine moiety against the yellow fever and dengue vector, Aedes aegypti

USDA-ARS?s Scientific Manuscript database

BACKGROUND: 1,3,4-oxadiazole and imidazolidine rings are important heterocyclic compounds exhibiting a variety of biological activities. In this study, novel compounds with oxadiazole and imidazolidine rings were synthesized from 3-(methylsulfonyl)-2-oxoimidazolidine-1-carbonyl chloride and screened...

Anticancer activity of seaweeds.

PubMed

Gutiérrez-Rodríguez, Anllely G; Juárez-Portilla, Claudia; Olivares-Bañuelos, Tatiana; Zepeda, Rossana C

2018-02-01

Cancer is a major health problem worldwide and still lacks fully effective treatments. Therefore, alternative therapies, using natural products, have been proposed. Marine algae are an important component of the marine environment, with high biodiversity, and contain a huge number of functional compounds, including terpenes, polyphenols, phlorotannins, and polysaccharides, among others. These compounds have complex structures that have shown several biological activities, including anticancer activity, using in vitro and in vivo models. Moreover, seaweed-derived compounds target important molecules that regulate cancer processes. Here, we review our current understanding of the anticancer activity of seaweeds. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

[Cyclic phosphatidic acids and their analogues--unique lipid mediators].

PubMed

Grzelczyk, Anna; Koziołkiewicz, Maria

2012-01-01

Lysophosphatidic acid (1-acyl-2-sn-glycerol-3-phosphate; LPA) and its naturally occurring analog, cyclic phosphatidic acid (1-acyl-sn-glycerol-2,3-cyclic phosphate; cPA) belong to a group of bioactive glycerophospholipids, which attract attention of many scientists because of their biological functions. Among these two compounds LPA is known better; information about unique biological properties of cPA appeared for the first time in the 90's. The synthesis of various, chemically modified analogues of cPA was performed to highlight mechanisms of the compound actions. Both native cPA and its derivatives emerge into the limelight because of their anti-cancer activities. Knowledge about pathways of biosynthesis and biodegradation of LPA and cPA as well as understanding of mechanisms of their action are increasing gradually. Previous studies have shown that both the metabolism and signaling cascades of these compounds have numerous common points. What is even more interesting, LPA and cPA seem to induce opposite biological activities.

Synthesis and antitumour activity of 4-aminoquinazoline derivatives

NASA Astrophysics Data System (ADS)

Lipunova, G. N.; Nosova, E. V.; Charushin, V. N.; Chupakhin, O. N.

2016-07-01

Pieces of data on the synthesis and antitumour activity of 4-aminoquinazolines are summarized and analyzed. Key methods for the synthesis of these compounds are considered, primarily cyclocondensation of carboxylic acid derivatives, as well as the oxidation of quinazolines and the cyclization of disubstituted thioureas. Improvements of synthetic schemes for erlotinib, gefitinib and lapatinib, which are the best-known pharmaceuticals based on compounds of the title class, are also considered. Synthetic strategies and biological activities for new 4-aminoquinazoline derivatives that are EGFR-tyrosine kinase inhibitors, multiactive compounds, and labelled compounds for use as positron emission tomography (PET) imaging agents are discussed. The bibliography includes 263 references.

Structure-activity relationship of antiparasitic and cytotoxic indoloquinoline alkaloids, and their tricyclic and bicyclic analogues.

PubMed

Van Baelen, Gitte; Hostyn, Steven; Dhooghe, Liene; Tapolcsányi, Pál; Mátyus, Péter; Lemière, Guy; Dommisse, Roger; Kaiser, Marcel; Brun, Reto; Cos, Paul; Maes, Louis; Hajós, György; Riedl, Zsuzsanna; Nagy, Ildikó; Maes, Bert U W; Pieters, Luc

2009-10-15

Based on the indoloquinoline alkaloids cryptolepine (1), neocryptolepine (2), isocryptolepine (3) and isoneocryptolepine (4), used as lead compounds for new antimalarial agents, a series of tricyclic and bicyclic analogues, including carbolines, azaindoles, pyrroloquinolines and pyrroloisoquinolines was synthesized and biologically evaluated. None of the bicyclic compounds was significantly active against the chloroquine-resistant strain Plasmodium falciparum K1, in contrast to the tricyclic derivatives. The tricyclic compound 2-methyl-2H-pyrido[3,4-b]indole (9), or 2-methyl-beta-carboline, showed the best in vitro activity, with an IC(50) value of 0.45 microM against P. falciparum K1, without apparent cytotoxicity against L6 cells (SI>1000). However, this compound was not active in the Plasmodium berghei mouse model. Structure-activity relationships are discussed and compared with related naturally occurring compounds.

Bioturbo similarity searching: combining chemical and biological similarity to discover structurally diverse bioactive molecules.

PubMed

Wassermann, Anne Mai; Lounkine, Eugen; Glick, Meir

2013-03-25

Virtual screening using bioactivity profiles has become an integral part of currently applied hit finding methods in pharmaceutical industry. However, a significant drawback of this approach is that it is only applicable to compounds that have been biologically tested in the past and have sufficient activity annotations for meaningful profile comparisons. Although bioactivity data generated in pharmaceutical institutions are growing on an unprecedented scale, the number of biologically annotated compounds still covers only a minuscule fraction of chemical space. For a newly synthesized compound or an isolated natural product to be biologically characterized across multiple assays, it may take a considerable amount of time. Consequently, this chemical matter will not be included in virtual screening campaigns based on bioactivity profiles. To overcome this problem, we herein introduce bioturbo similarity searching that uses chemical similarity to map molecules without biological annotations into bioactivity space and then searches for biologically similar compounds in this reference system. In benchmark calculations on primary screening data, we demonstrate that our approach generally achieves higher hit rates and identifies structurally more diverse compounds than approaches using chemical information only. Furthermore, our method is able to discover hits with novel modes of inhibition that traditional 2D and 3D similarity approaches are unlikely to discover. Test calculations on a set of natural products reveal the practical utility of the approach for identifying novel and synthetically more accessible chemical matter.

Nitrogen-Containing Constituents of Black Cohosh: Chemistry, Structure Elucidation, and Biological Activities

PubMed Central

Lankin, David C.; Cisowska, Tamara; Chen, Shao-Nong; Pauli, Guido F.; van Breemen, Richard B.

2016-01-01

The roots/rhizomes of black cohosh (Actaea racemosa L. syn. Cimicifuga racemosa [L]. Nutt., Ranunculaceae) have been used traditionally by Native Americans to treat colds, rheumatism, and a variety of conditions related to women’s health. In recent years black cohosh preparations have become popular dietary supplements among women seeking alternative treatments for menopausal complaints. The popularity of the plant has led to extensive phytochemical and biological investigations, including several clinical trials. Most of the phytochemical and biological research has focused on two abundant classes of compounds: the triterpene glycosides and phenolic acids. A third group of phytoconstituents that has received far less attention consists of the alkaloids and related compounds that contain nitrogen. This chapter summarizes the current state of knowledge of the chemistry and biological activities associated with this group of constituents and provides some perspective on their significance for future research on this interesting plant. PMID:27795590

Anti AIDS drug design with the help of neural networks

NASA Astrophysics Data System (ADS)

Tetko, I. V.; Tanchuk, V. Yu.; Luik, A. I.

1995-04-01

Artificial neural networks were used to analyze and predict the human immunodefiency virus type 1 reverse transcriptase inhibitors. Training and control set included 44 molecules (most of them are well-known substances such as AZT, TIBO, dde, etc.) The biological activities of molecules were taken from literature and rated for two classes: active and inactive compounds according to their values. We used topological indices as molecular parameters. Four most informative parameters (out of 46) were chosen using cluster analysis and original input parameters' estimation procedure and were used to predict activities of both control and new (synthesized in our institute) molecules. We applied pruning network algorithm and network ensembles to obtain the final classifier and avoid chance correlation. The increasing of neural network generalization of the data from the control set was observed, when using the aforementioned methods. The prognosis of new molecules revealed one molecule as possibly active. It was confirmed by further biological tests. The compound was as active as AZT and in order less toxic. The active compound is currently being evaluated in pre clinical trials as possible drug for anti-AIDS therapy.

QSAR modelling using combined simple competitive learning networks and RBF neural networks.

PubMed

Sheikhpour, R; Sarram, M A; Rezaeian, M; Sheikhpour, E

2018-04-01

The aim of this study was to propose a QSAR modelling approach based on the combination of simple competitive learning (SCL) networks with radial basis function (RBF) neural networks for predicting the biological activity of chemical compounds. The proposed QSAR method consisted of two phases. In the first phase, an SCL network was applied to determine the centres of an RBF neural network. In the second phase, the RBF neural network was used to predict the biological activity of various phenols and Rho kinase (ROCK) inhibitors. The predictive ability of the proposed QSAR models was evaluated and compared with other QSAR models using external validation. The results of this study showed that the proposed QSAR modelling approach leads to better performances than other models in predicting the biological activity of chemical compounds. This indicated the efficiency of simple competitive learning networks in determining the centres of RBF neural networks.

Key aspects of the Novartis compound collection enhancement project for the compilation of a comprehensive chemogenomics drug discovery screening collection.

PubMed

Jacoby, Edgar; Schuffenhauer, Ansgar; Popov, Maxim; Azzaoui, Kamal; Havill, Benjamin; Schopfer, Ulrich; Engeloch, Caroline; Stanek, Jaroslav; Acklin, Pierre; Rigollier, Pascal; Stoll, Friederike; Koch, Guido; Meier, Peter; Orain, David; Giger, Rudolph; Hinrichs, Jürgen; Malagu, Karine; Zimmermann, Jürg; Roth, Hans-Joerg

2005-01-01

The NIBR (Novartis Institutes for BioMedical Research) compound collection enrichment and enhancement project integrates corporate internal combinatorial compound synthesis and external compound acquisition activities in order to build up a comprehensive screening collection for a modern drug discovery organization. The main purpose of the screening collection is to supply the Novartis drug discovery pipeline with hit-to-lead compounds for today's and the future's portfolio of drug discovery programs, and to provide tool compounds for the chemogenomics investigation of novel biological pathways and circuits. As such, it integrates designed focused and diversity-based compound sets from the synthetic and natural paradigms able to cope with druggable and currently deemed undruggable targets and molecular interaction modes. Herein, we will summarize together with new trends published in the literature, scientific challenges faced and key approaches taken at NIBR to match the chemical and biological spaces.

Synthesis, characterization and biological studies of substituted quinozoline-4-(3H)-ones containing diazepine moiety.

PubMed

Narayana Rao, D V; Raghavendra Guru Prasad, A; Spoorthy, Y N; Pariplavi, M; Ravindranath, L K

2014-01-01

The synthesis and characterization of new series of 1,4-benzodiazepine derivatives have been presented. The structures were confirmed by elemental analyses, IR spectral, (1)H NMR spectral and mass spectral data. All the compounds were screened for in vitro antimicrobial and anthelmintic activities. The antibacterial activity was tested against Staphylococcus aureus (Gram positive), Bacillus cereus (Gram positive), Escherichia coli (Gram negative) and Pseudomonas aeruginosa (Gram negative). The antifungal activity was tested against Aspergillus niger and Candida albicans. All the compounds showed considerable antimicrobial activity against the microorganism studied. The significant anthelmintic activity of all novel compounds was demonstrated against Pheretima posthuma. Based on the nature of substituent present, the structure-activity correlation of novel compounds was discussed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

In Vitro Phytotoxicity and Antioxidant Activity of Selected Flavonoids

PubMed Central

De Martino, Laura; Mencherini, Teresa; Mancini, Emilia; Aquino, Rita Patrizia; De Almeida, Luiz Fernando Rolim; De Feo, Vincenzo

2012-01-01

The knowledge of flavonoids involved in plant-plant interactions and their mechanisms of action are poor and, moreover, the structural characteristics required for these biological activities are scarcely known. The objective of this work was to study the possible in vitro phytotoxic effects of 27 flavonoids on the germination and early radical growth of Raphanus sativus L. and Lepidium sativum L., with the aim to evaluate the possible structure/activity relationship. Moreover, the antioxidant activity of the same compounds was also evaluated. Generally, in response to various tested flavonoids, germination was only slightly affected, whereas significant differences were observed in the activity of the various tested flavonoids against radical elongation. DPPH test confirms the antioxidant activity of luteolin, quercetin, catechol, morin, and catechin. The biological activity recorded is discussed in relation to the structure of compounds and their capability to interact with cell structures and physiology. No correlation was found between phytotoxic and antioxidant activities. PMID:22754304

From Chemistry to Behavior. Molecular Structure and Bioactivity of Repellents against Ixodes ricinus Ticks

PubMed Central

Fabbro, Simone Del; Nazzi, Francesco

2013-01-01

Tick-borne zoonoses are considered as emerging diseases. Tick repellents represent an effective tool for reducing the risk of tick bite and pathogens transmission. Previous work demonstrated the repellent activity of the phenylpropanoid eugenol against Ixodes ricinus; here we investigate the relationship between molecular structure and repellency in a group of substances related to that compound. We report the biological activity of 18 compounds varying for the presence/number of several moieties, including hydroxyl and methoxy groups and carbon side-chain. Each compound was tested at different doses with a bioassay designed to measure repellency against individual tick nymphs. Both vapor pressure and chemical features of the tested compounds appeared to be related to repellency. In particular, the hydroxyl and methoxy groups as well as the side-chain on the benzene ring seem to play a role. These results are discussed in light of available data on chemical perception in ticks. In the course of the study new repellent compounds were identified; the biological activity of some of them (at least as effective as the “gold standard” repellent DEET) appears to be very promising from a practical point of view. PMID:23805329

Synthesis and biological evaluation of 3-thiazolocoumarinyl Schiff-base derivatives as cholinesterase inhibitors.

PubMed

Raza, Rabia; Saeed, Aamer; Arif, Mubeen; Mahmood, Shamsul; Muddassar, Muhammad; Raza, Ahsan; Iqbal, Jamshed

2012-10-01

On the basis of the observed biological activity of the coumarins, a new set of 3-thiazolocoumarinyl Schiff-base derivatives with chlorine, hydroxy and methoxy functional group substitutions were designed and synthesized. These compounds were tested against acetylcholinesterase from Electrophorus electricus and butyrylcholinesterase from horse serum and their structure-activity relationship was established. Studies revealed them as the potential inhibitors of cholinesterase (acetylcholinesterase and butyrylcholinesterase). The 3f was found to be most potent against acetylcholinesterase with K(i) value of 1.05 ± 0.3 μM and 3l showed excellent inhibitory action against butyrylcholinesterase with K(i) value of 0.041 ± 0.002 μM. The synthesized compounds were also docked into the active sites of the homology models of acetylcholinesterase and butyrylcholinesterase to predict the binding modes of these compounds. It was predicted that most of the compounds have similar binding modes with reasonable binding affinities. Our docking studies have also shown that these synthesized compounds have better interaction patterns with butyrylcholinesterase over acetylcholinesterase. The main objective of the study was to develop new potent and selective compounds, which might be further optimized to prevent the progression of the Alzheimer's disease and could provide symptomatic treatment. © 2012 John Wiley & Sons A/S.

Synthesis, biological evaluation and molecular modelling of diversely functionalized heterocyclic derivatives as inhibitors of acetylcholinesterase/butyrylcholinesterase and modulators of Ca2+ channels and nicotinic receptors.

PubMed

Marco, José L; de los Ríos, Cristóbal; García, Antonio G; Villarroya, Mercedes; Carreiras, M Carmo; Martins, Carla; Eleutério, Ana; Morreale, Antonio; Orozco, M; Luque, F Javier

2004-05-01

The synthesis and the biological activity of compounds 5-40 as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as modulators of voltage-dependent Ca(2+) channels and nicotinic receptors, are described. These molecules are tacrine analogues, which have been prepared from polyfunctionalized 6-amino-5-cyano-4H-pyrans, 6-amino-5-cyano-pyridines and 5-amino-2-aryl-3-cyano-1,3-oxazoles via Friedländer reaction with selected cycloalkanones. These compounds are moderate acetylcholinesterase and butyrylcholinesterase inhibitors, the BuChE/AChE selectivity of the most active molecules ranges from 10.0 (compound 29) to 76.9 (compound 16). Interestingly, the 'oxazolo-tacrine' derivatives are devoid of any activity. All compounds showed an important inhibitory effect on the nicotinic acetylcholine receptor. Most of them also blocked L-type Ca(2+) channels, and three of them, 64, 19 and 67, the non-L type of Ca(2+) channels. Molecular modelling studies suggest that these compounds might bind at the peripheral binding site of AChE, which opens the possibility to design inhibitors able to bind at both, the catalytic and peripheral binding sites of the enzyme.

4'-alpha-C-Branched N,O-nucleosides: synthesis and biological properties.

PubMed

Chiacchio, Ugo; Genovese, Filippo; Iannazzo, Daniela; Piperno, Anna; Quadrelli, Paolo; Antonino, Corsaro; Romeo, Roberto; Valveri, Vincenza; Mastino, Antonio

2004-07-15

The synthesis of 4'-alpha-C-branched N,O-nucleosides has been described, based on the 1,3-dipolar cycloaddition of nitrones with vinyl acetate followed by coupling with silylated nucleobases, The obtained compounds have been evaluated for their activity against HSV-1, HSV-2, HTLV-1. Cytotoxicity and apoptotic activity have been also investigated: compound 10c shows moderate apoptotic activity in Molt-3 cells.

Structure-Based Design: Synthesis, X-ray Crystallography, and Biological Evaluation of N-Substituted-4-Hydroxy-2-Quinolone-3-Carboxamides as Potential Cytotoxic Agents.

PubMed

Sabbah, Dima A; Hishmah, Bayan; Sweidan, Kamal; Bardaweel, Sanaa; AlDamen, Murad; Zhong, Haizhen A; Abu Khalaf, Reema; Hasan Ibrahim, Ameerah; Al-Qirim, Tariq; Abu Sheikha, Ghassan; Mubarak, Mohammad S

2018-01-01

Oncogenic potential of phosphatidylinositol 3-kinase (PI3Kα) has been highlighted as a therapeutic target for anticancer drug design. Target compounds were designed to address the effect of different substitution patterns at the N atom of the carboxamide moiety on the bioactivity of this series. Synthesis of the targeted compounds, crystallography, biological evaluation tests against human colon carcinoma (HCT-116), and Glide docking studies. A new series of N-substituted- 4-hydroxy-2-quinolone-3-carboxamides was prepared and characterized by means of FT-IR, 1H and 13C NMR, and elemental analysis. In addition, the identity of the core nucleus 5 was successfully characterized with the aid of X-ray crystallography. Biological activity of prepared compounds was investigated in vitro against human colon carcinoma (HCT-116) cell line. Results revealed that these compounds inhibit cell proliferation and induce apoptosis through an increase in caspase-3 activity and a decrease in DNA cellular content. Compounds 7, 14, and 17 which have H-bond acceptor moiety on p-position displayed promising PI3Kα inhibitory activity. On the other hand, derivatives tailored with bulky and hydrophobic motifs (16 and 18) on o- and m-positions exhibited moderate activity. Molecular docking studies against PI3Kα and caspase-3 showed an agreement between the predicted binding affinity (ΔGobsd) and IC50 values of the derivatives for the caspase-3 model. Furthermore, Glide docking studies against PI3Kα demonstrated that the newly synthesized compounds accommodate PI3Kα kinase catalytic domain and form H-bonding with key binding residues. The series exhibited a potential PI3Kα inhibitory activity in HCT-116 cell line. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Computer-aided discovery of biological activity spectra for anti-aging and anti-cancer olive oil oleuropeins.

PubMed

Corominas-Faja, Bruna; Santangelo, Elvira; Cuyàs, Elisabet; Micol, Vicente; Joven, Jorge; Ariza, Xavier; Segura-Carretero, Antonio; García, Jordi; Menendez, Javier A

2014-09-01

Aging is associated with common conditions, including cancer, diabetes, cardiovascular disease, and Alzheimer's disease. The type of multi-targeted pharmacological approach necessary to address a complex multifaceted disease such as aging might take advantage of pleiotropic natural polyphenols affecting a wide variety of biological processes. We have recently postulated that the secoiridoids oleuropein aglycone (OA) and decarboxymethyl oleuropein aglycone (DOA), two complex polyphenols present in health-promoting extra virgin olive oil (EVOO), might constitute a new family of plant-produced gerosuppressant agents. This paper describes an analysis of the biological activity spectra (BAS) of OA and DOA using PASS (Prediction of Activity Spectra for Substances) software. PASS can predict thousands of biological activities, as the BAS of a compound is an intrinsic property that is largely dependent on the compound's structure and reflects pharmacological effects, physiological and biochemical mechanisms of action, and specific toxicities. Using Pharmaexpert, a tool that analyzes the PASS-predicted BAS of substances based on thousands of "mechanism-effect" and "effect-mechanism" relationships, we illuminate hypothesis-generating pharmacological effects, mechanisms of action, and targets that might underlie the anti-aging/anti-cancer activities of the gerosuppressant EVOO oleuropeins.

Aqueous phase synthesis, crystal structure and biological study of isoxazole extensions of pyrazole-4-carbaldehyde derivatives

NASA Astrophysics Data System (ADS)

Wazalwar, Sachin S.; Banpurkar, Anita R.; Perdih, Franc

2017-12-01

A series of novel isoxazol derivatives was synthesized by green route in aqueous phase at room temperature by the reaction of 3-methyl-4H-isoxazol-5-one with 3-(substituted phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde by one-pot Knoevenagel condensation method using sodium benzoate as a catalyst. Compounds were characterized on the basis of IR, 1H NMR, mass spectroscopy and melting point determination. Crystal structures of five compounds were determined by X-ray diffraction. The compounds formed were screened for antibacterial and antifungal activity. Some compounds showed activity close to ampicillin against E. coli, S. aureus, and S. pyogenus. Two compounds showed antifungal activity against C. albicans close to standard greseofulvin.

Relationship between electronic properties and drug activity of seven quinoxaline compounds: A DFT study

NASA Astrophysics Data System (ADS)

Behzadi, Hadi; Roonasi, Payman; Assle taghipour, Khatoon; van der Spoel, David; Manzetti, Sergio

2015-07-01

The quantum chemical calculations at the DFT/B3LYP level of theory were carried out on seven quinoxaline compounds, which have been synthesized as anti-Mycobacterium tuberculosis agents. Three conformers were optimized for each compound and the lowest energy structure was found and used in further calculations. The electronic properties including EHOMO, ELUMO and related parameters as well as electron density around oxygen and nitrogen atoms were calculated for each compound. The relationship between the calculated electronic parameters and biological activity of the studied compounds were investigated. Six similar quinoxaline derivatives with possible more drug activity were suggested based on the calculated electronic descriptors. A mechanism was proposed and discussed based on the calculated electronic parameters and bond dissociation energies.

Synthesis and biological evaluation of 2-heteroarylthioalkanoic acid analogues of clofibric acid as peroxisome proliferator-activated receptor alpha agonists.

PubMed

Giampietro, Letizia; Ammazzalorso, Alessandra; Giancristofaro, Antonella; Lannutti, Fabio; Bettoni, Giancarlo; De Filippis, Barbara; Fantacuzzi, Marialuigia; Maccallini, Cristina; Petruzzelli, Michele; Morgano, Annalisa; Moschetta, Antonio; Amoroso, Rosa

2009-10-22

A series of 2-heteroarylthioalkanoic acids were synthesized through systematic structural modifications of clofibric acid and evaluated for human peroxisome proliferator-activated receptor alpha (PPARalpha) transactivation activity, with the aim of obtaining new hypolipidemic compounds. Some thiophene and benzothiazole derivatives showing a good activation of the receptor alpha were screened for activity against the PPARgamma isoform. The gene induction of selected compounds was also investigated in the human hepatoma cell line.

Chemical characterisation of Nigerian red propolis and its biological activity against Trypanosoma Brucei.

PubMed

Omar, Ruwida M K; Igoli, John; Gray, Alexander I; Ebiloma, Godwin Unekwuojo; Clements, Carol; Fearnley, James; Ebel, Ru Angeli Edrada; Zhang, Tong; De Koning, Harry P; Watson, David G

2016-01-01

A previous study showed the unique character of Nigerian red propolis from Rivers State, Nigeria (RSN), with regards to chemical composition and activity against Trypanosoma brucei in comparison with other African propolis. To carry out fractionation and biological testing of Nigerian propolis in order to isolate compounds with anti-trypanosomal activity. To compare the composition of the RSN propolis with the composition of Brazilian red propolis. Profiling was carried out using HPLC-UV-ELSD and HPLC-Orbitrap-FTMS on extracts of two samples collected from RSN with data extraction using MZmine software. Isolation was carried out by normal phase and reversed phase MPLC. Elucidation of the compounds with a purity > 95% was performed by 1D/2D NMR HRMS and HRLC-MS(n) . Ten phenolic compounds were isolated or in the case of liquiritigenin partially purified. Data for nine of these correlated with literature reports of known compounds i.e. one isoflavanone, calycosin (1); two flavanones, liquiritigenin (2) and pinocembrin (5); an isoflavan, vestitol (3); a pterocarpan, medicarpin (4); two prenylflavanones, 8-prenylnaringenin (7) and 6-prenylnaringenin (8); and two geranyl flavonoids, propolin D (9) and macarangin (10). The tenth was elucidated as a previously undescribed dihydrobenzofuran (6). The isolated compounds were tested against Trypanosoma brucei and displayed moderate to high activity. Some of the compounds tested had similar activity against wild type T. brucei and two strains displaying pentamidine resistance. Nigerian propolis from RSN has some similarities with Brazilian red propolis. The propolis displayed anti-trypanosomal activity at a potentially useful level. Copyright © 2015 John Wiley & Sons, Ltd.

Synthesis of Some New Quinazolinone Derivatives and Evaluation of Their Antimicrobial Activities

PubMed Central

Khodarahmi, Ghadamali; Jafari, Elham; Hakimelahi, Gholamhossein; Abedi, Daryoush; Rahmani Khajouei, Marzieh; Hassanzadeh, Farshid

2012-01-01

Wide range of quinazolinone biological properties including: antibacterial, anticancer, and anti-inflammatory activities encouraged us to synthesis some fused quinazolinone derivatives. Anthranilic acid was condensed with chloro acylchloride followed by dehydration to form the benzoxazinone intermediate; subsequent addition of an amine provided the fused quinazolinones. Deoxyvasicinone which was previously synthesized by a multi step complex reactions was prepared in three steps using the following procedure: Log P values of the compounds were measured using the shake flask method in octanol/water solvent system. The synthesized compounds were evaluated against six strains of bacteria (three Gram-positive and three Gram-negative) and three strains of fungi. Overall results of antimicrobial tests showed that the compounds had better bacteriostatic activity against Gram-negative bacteria. The obtained results of MBC revealed that these compounds had more significant bacteriostatic than bactericidal activities. Almost all of the screened compounds showed good activity against C. albicans and A. niger. The obtained results of MFC indicated that these compounds had more significant fungistatic than fungicidal activities. PMID:24250506

Bioassay Directed Isolation and Biological Evaluation of Compounds Isolated from Rubus fairholmianus Gard.

PubMed Central

Plackal George, Blassan; Thangaraj, Parimelazhagan; Sulaiman, Cheruthazhakkatt; Piramanayagam, Shanmughavel; Ramaswamy, Sathish Kumar

2014-01-01

The in vitro and in silico analysis of Rubus fairholmianus acetone extract for antioxidant, antiproliferative, and anti-inflammatory activity led to the isolation of six compounds. Amongst all the six isolated compounds tested, 1-(2-hydroxyphenyl)-4-methylpentan-1-one (compound 1) and 2-[(3-methylbutoxy) carbonyl] benzoic acid (compound 2) were found to be more active in inhibiting BRCA and COX target proteins, which also showed the better results for DPPH and ABTS radical scavenging assays. The promising results of this investigation emphasize the importance of using R. fairholmianus in the treatment of radical generated disorders mainly cancer and other inflammatory diseases. PMID:25254204

Isolation, identification, synthesis and biological activity of volatile compounds from the heads of Atta ants

Treesearch

R. G. Riley; R. M. Silverstein; John C. Moser

1974-01-01

S-(+)-4-methyl-3-hetanone has been identified as the principal alarm pheromone of Atta texana and Atta cephalotes. Both enantiomers of 4-methyl-3-heptanone have been synthesized and their biological activities have been compared on both species of ants. Comparison of the geometric averages of responnse rations, at...

Mannich bases in medicinal chemistry and drug design.

PubMed

Roman, Gheorghe

2015-01-07

The biological activity of Mannich bases, a structurally heterogeneous class of chemical compounds that are generated from various substrates through the introduction of an aminomethyl function by means of the Mannich reaction, is surveyed, with emphasis on the relationship between structure and biological activity. The review covers extensively the literature reports that have disclosed Mannich bases as anticancer and cytotoxic agents, or compounds with potential antibacterial and antifungal activity in the last decade. The most relevant studies on the activity of Mannich bases as antimycobacterial agents, antimalarials, or antiviral candidates have been included as well. The review contains also a thorough coverage of anticonvulsant, anti-inflammatory, analgesic and antioxidant activities of Mannich bases. In addition, several minor biological activities of Mannich bases, such as their ability to regulate blood pressure or inhibit platelet aggregation, their antiparasitic and anti-ulcer effects, as well as their use as agents for the treatment of mental disorders have been presented. The review gives in the end a brief overview of the potential of Mannich bases as inhibitors of various enzymes or ligands for several receptors. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Identification of Compounds with Anti-Proliferative Activity against Trypanosoma brucei brucei Strain 427 by a Whole Cell Viability Based HTS Campaign

PubMed Central

Kaiser, Marcel; Chatelain, Eric; Moawad, Sarah R.; Ganame, Danny; Ioset, Jean-Robert; Avery, Vicky M.

2012-01-01

Human African Trypanosomiasis (HAT) is caused by two trypanosome sub-species, Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Drugs available for the treatment of HAT have significant issues related to difficult administration regimes and limited efficacy across species and disease stages. Hence, there is considerable need to find new alternative and less toxic drugs. An approach to identify starting points for new drug candidates is high throughput screening (HTS) of large compound library collections. We describe the application of an Alamar Blue based, 384-well HTS assay to screen a library of 87,296 compounds against the related trypanosome subspecies, Trypanosoma brucei brucei bloodstream form lister 427. Primary hits identified against T.b. brucei were retested and the IC50 value compounds were estimated for T.b. brucei and a mammalian cell line HEK293, to determine a selectivity index for each compound. The screening campaign identified 205 compounds with greater than 10 times selectivity against T.b. brucei. Cluster analysis of these compounds, taking into account chemical and structural properties required for drug-like compounds, afforded a panel of eight compounds for further biological analysis. These compounds had IC50 values ranging from 0.22 µM to 4 µM with associated selectivity indices ranging from 19 to greater than 345. Further testing against T.b. rhodesiense led to the selection of 6 compounds from 5 new chemical classes with activity against the causative species of HAT, which can be considered potential candidates for HAT early drug discovery. Structure activity relationship (SAR) mining revealed components of those hit compound structures that may be important for biological activity. Four of these compounds have undergone further testing to 1) determine whether they are cidal or static in vitro at the minimum inhibitory concentration (MIC), and 2) estimate the time to kill. PMID:23209849

Propolis volatile compounds: chemical diversity and biological activity: a review

PubMed Central

2014-01-01

Propolis is a sticky material collected by bees from plants, and used in the hive as building material and defensive substance. It has been popular as a remedy in Europe since ancient times. Nowadays, propolis use in over-the-counter preparations, “bio”-cosmetics and functional foods, etc., increases. Volatile compounds are found in low concentrations in propolis, but their aroma and significant biological activity make them important for propolis characterisation. Propolis is a plant-derived product: its chemical composition depends on the local flora at the site of collection, thus it offers a significant chemical diversity. The role of propolis volatiles in identification of its plant origin is discussed. The available data about chemical composition of propolis volatiles from different geographic regions are reviewed, demonstrating significant chemical variability. The contribution of volatiles and their constituents to the biological activities of propolis is considered. Future perspectives in research on propolis volatiles are outlined, especially in studying activities other than antimicrobial. PMID:24812573

Savinin, a lignan from Pterocarpus santalinus inhibits tumor necrosis factor-alpha production and T cell proliferation.

PubMed

Cho, J Y; Park, J; Kim, P S; Yoo, E S; Baik, K U; Park, M H

2001-02-01

Two lignans were isolated from the heartwood of Pterocarpus santalinus by activity-guided fractionation and investigated for their biological properties and molecular mechanism of action. On the basis of their spectroscopic data, these compounds were identified as savinin (1) and calocedrin (2), dibenzyl butyrolactone-type lignan compounds having an alpha-arylidene gamma-lactone structure. These lignans significantly inhibited tumor necrosis factor (TNF)-a production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and T cell proliferation elicited by concanavalin (Con A), without displaying cytotoxicity. The molecular inhibitory mechanism of compound 1 was confirmed to be mediated by the non-polar butyrolactone ring, according to a structure-relationship study with structurally related and unrelated compounds, such as arctigenin (a dibenzyl butyrolactone type lignan), eudesmin (a furofuran type lignan), isolariciresinol (a dibenzylbutane type lignan), and cynaropicrin (a sesquiterpene lactone). The results suggest that savinin may act as an active principle in the reported biological activities of P. santalinus, such as antiinflammatory effect, by mediation of the butyrolactone ring as a valuable pharmacophore.

Haberlea rhodopensis: pharmaceutical and medical potential as a food additive.

PubMed

Todorova, Roumiana; Atanasov, Atanas T

2016-01-01

This review discusses the potential of Haberlea rhodopensis as a food additive. The following are described: plant distribution, reproduction, cultivation, propagation and resurrection properties; extraction, isolation and screening of biologically active compounds; metabolite changes during dehydration; phytotherapy-related properties such as antioxidant potential and free radical-scavenging activities, antioxidant skin effect, antibacterial activity, cytotoxic activity and cancer-modulating effect, radioprotective effect, chemoprotective effect, immunologic effect; present use in homoeopathy and cosmetics, pharmacological and economical importance; perspectives based on the ethnobotanical data for medicinal, cosmetic or ritual attributes. H. rhodopensis showed unique medical and pharmaceutical potential, related to antioxidant, antimicrobial, antimutagenic, anticancer, radioprotective, chemoprotective and immunological properties. H. rhodopensis extracts lack any cytotoxic activity and could be used in phytotherapy. The metabolic profiling of H. rhodopensis extracts revealed the presence of biologically active compounds, possessing antiradical and other physiological activities, useful for design of in vitro synthesised analogues and drugs.

New quaternary ammonium camphor derivatives and their antiviral activity, genotoxic effects and cytotoxicity.

PubMed

Sokolova, Anastasiya S; Yarovaya, Capital O Cyrilliclga I; Shernyukov, Capital A Cyrillicndrey V; Pokrovsky, Capital Em Cyrillicichail A; Pokrovsky, Capital A Cyrillicndrey G; Lavrinenko, Valentina A; Zarubaev, Vladimir V; Tretiak, Tatiana S; Anfimov, Pavel M; Kiselev, Oleg I; Beklemishev, Anatoly B; Salakhutdinov, Nariman F

2013-11-01

The synthesis and biological evaluation of a novel series of dimeric camphor derivatives are described. The resulting compounds were studied for their antiviral activity, cyto- and genotoxicity. Compounds 3a and 3d in which the quaternary nitrogen atoms are separated by the C5H10 and С9H18 aliphatic chain, exhibited the highest efficiency as an agent inhibiting the reproduction of the influenza virus A(H1N1)pdm09. The cytotoxicity data of compounds 3 and 4 revealed their moderate activity against malignant cell lines; compound 3f had the highest activity for the CEM-13 cells. These results show close agreement with the data of independent studies on toxicity of these compounds, in particular that the toxicity of compounds strongly depends on spacer length. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of biological and chemical oxidation on the removal of estrogenic compounds (NP and BPA) from wastewater: an integrated assessment procedure.

PubMed

Bertanza, Giorgio; Pedrazzani, Roberta; Dal Grande, Mario; Papa, Matteo; Zambarda, Valerio; Montani, Claudia; Steimberg, Nathalie; Mazzoleni, Giovanna; Di Lorenzo, Diego

2011-04-01

A major source of the wide presence of EDCs (Endocrine Disrupting Compounds) in water bodies is represented by direct/indirect discharge of sewage. Recent scientific literature reports data about their trace concentration in water, sediments and aquatic organisms, as well as removal efficiencies of different wastewater treatment schemes. Despite the availability of a huge amount of data, some doubts still persist due to the difficulty in evaluating synergistic effects of trace pollutants in complex matrices. In this paper, an integrated assessment procedure was used, based on chemical and biological analyses, in order to compare the performance of two full scale biological wastewater treatment plants (either equipped with conventional settling tanks or with an ultrafiltration membrane unit) and tertiary ozonation (pilot scale). Nonylphenol and bisphenol A were chosen as model EDCs, together with the parent compounds mono- and di-ethoxylated nonylphenol (quantified by means of GC-MS). Water estrogenic activity was evaluated by applying the human breast cancer MCF-7 based reporter gene assay. Process parameters (e.g., sludge age, temperature) and conventional pollutants (e.g., COD, suspended solids) were also measured during monitoring campaigns. Conventional activated sludge achieved satisfactory removal of both analytes and estrogenicity. A further reduction of biological activity was exerted by MBR (Membrane Biological Reactor) as well as ozonation; the latter contributed also to decrease EDC concentrations. Copyright © 2011 Elsevier Ltd. All rights reserved.

Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 4: design, synthesis and biological evaluation of novel imidazo[1,2-a]pyrazines.

PubMed

Huang, Boshi; Liang, Xin; Li, Cuicui; Chen, Wenmin; Liu, Tao; Li, Xiao; Sun, Yueyue; Fu, Lu; Liu, Huiqing; De Clercq, Erik; Pannecouque, Christophe; Zhan, Peng; Liu, Xinyong

2015-03-26

Through a structure-guided core-refining approach, a series of novel imidazo[1,2-a]pyrazine derivatives were designed, synthesized and evaluated as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Biological results of antiviral assay in MT-4 cell cultures showed that 12 target compounds displayed moderate activities against wild-type (wt) HIV-1 strain (IIIB) with EC50 values ranging from 0.26 μM to 19 μM. Among them, 4a and 5a were found to be the two most active analogues possessing EC50 values of 0.26 μM and 0.32 μM respectively, comparable to delavirdine (DLV, EC50 = 0.54 μM) and nevirapine (NVP, EC50 = 0.31 μM) in a cell-based assay. Additionally, 9 compounds showed RT inhibitory activity superior to that of NVP. Moreover, some predicted drug-like properties of representative compounds 4a and 5a, as well as the structure-activity relationship (SAR) analysis were discussed in detail. The binding mode of compound 4a was investigated by molecular simulation studies. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Syntheses, Characterization, Resolution, and Biological Studies of Coordination Compounds of Aspartic Acid and Glycine

PubMed Central

Akinkunmi, Ezekiel; Ojo, Isaac; Adebajo, Clement; Isabirye, David

2017-01-01

Enantiomerically enriched coordination compounds of aspartic acid and racemic mixtures of coordination compounds of glycine metal-ligand ratio 1 : 3 were synthesized and characterized using infrared and UV-Vis spectrophotometric techniques and magnetic susceptibility measurements. Five of the complexes were resolved using (+)-cis-dichlorobis(ethylenediamine)cobalt(III) chloride, (+)-bis(glycinato)(1,10-phenanthroline)cobalt(III) chloride, and (+)-tris(1,10-phenanthroline)nickel(II) chloride as resolving agents. The antimicrobial and cytotoxic activities of these complexes were then determined. The results obtained indicated that aspartic acid and glycine coordinated in a bidentate fashion. The enantiomeric purity of the compounds was in the range of 22.10–32.10%, with (+)-cis-dichlorobis(ethylenediamine)cobalt(III) complex as the more efficient resolving agent. The resolved complexes exhibited better activity in some cases compared to the parent complexes for both biological activities. It was therefore inferred that although the increase in the lipophilicity of the complexes may assist in the permeability of the complexes through the cell membrane of the pathogens, the enantiomeric purity of the complexes is also of importance in their activity as antimicrobial and cytotoxic agents. PMID:28293149

Monoalkylated barbiturate derivatives: X-ray crystal structure, theoretical studies, and biological activities

NASA Astrophysics Data System (ADS)

Barakat, Assem; Al-Majid, Abdullah Mohammed; Soliman, Saied M.; Islam, Mohammad Shahidul; Ghawas, Hussain Mansur; Yousuf, Sammer; Choudhary, M. Iqbal; Wadood, Abdul

2017-08-01

Barbiturate derivatives are privileged structures with a broad range of pharmaceutical applications. We prepared a series of 5-monoalkylated barbiturate derivatives (3a-l) and evaluated, in vitro, their antioxidant (DPPH assay), and α-glucosidase inhibitory activities. Compounds 3a-l were synthesized via Michael addition. The structure of compound 3k was determined using X-ray single-crystal diffraction, and geometric parameters were calculated using density functional theory at the B3LYP/6-311G(d,p) level of theory. Further, the structural analysis of 3k were also investigated. Biological studies revealed that compounds 3b (IC50 = 133.1 ± 3.2 μM), 3d (IC50 = 305 ± 7.7 μM), and 3e (IC50 = 184 ± 2.3 μM) have potent α-glucosidase enzyme inhibitors and showed greater activity than the standard drug acarbose (IC50 = 841 ± 1.73 μM). Compounds 3a-3i were found to show weak antioxidant activity against 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals (IC50 = 91 ± 0.75 to 122 ± 1.0 μM) when tested against a standard antioxidant, gallic acid (IC50 = 23 ± 0.43 μM).

C-Aryl glucoside SGLT2 inhibitors containing a biphenyl motif as potential anti-diabetic agents.

PubMed

Ding, Yuyang; Mao, Liufeng; Xu, Dengfeng; Xie, Hui; Yang, Ling; Xu, Hongjiang; Geng, Wenjun; Gao, Yong; Xia, Chunguang; Zhang, Xiquan; Meng, Qingyi; Wu, Donghai; Zhao, Junling; Hu, Wenhui

2015-07-15

A series of highly active C-aryl glucoside SGLT2 inhibitors containing a biphenyl motif were designed and synthesized for biological evaluation. Among the compounds tested, compound 16l demonstrated high inhibitory activity against SGLT2 (IC50=1.9 nM) with an excellent pharmacokinetic profile. Further study indicated that the in vivo efficacy of compound 16l was comparable to that of dapagliflozin, suggesting that further development would be worthwhile. Copyright © 2015 Elsevier Ltd. All rights reserved.

Target specific compound identification using a support vector machine.

PubMed

Plewczynski, Dariusz; von Grotthuss, Marcin; Spieser, Stephane A H; Rychlewski, Leszek; Wyrwicz, Lucjan S; Ginalski, Krzysztof; Koch, Uwe

2007-03-01

In many cases at the beginning of an HTS-campaign, some information about active molecules is already available. Often known active compounds (such as substrate analogues, natural products, inhibitors of a related protein or ligands published by a pharmaceutical company) are identified in low-throughput validation studies of the biochemical target. In this study we evaluate the effectiveness of a support vector machine applied for those compounds and used to classify a collection with unknown activity. This approach was aimed at reducing the number of compounds to be tested against the given target. Our method predicts the biological activity of chemical compounds based on only the atom pairs (AP) two dimensional topological descriptors. The supervised support vector machine (SVM) method herein is trained on compounds from the MDL drug data report (MDDR) known to be active for specific protein target. For detailed analysis, five different biological targets were selected including cyclooxygenase-2, dihydrofolate reductase, thrombin, HIV-reverse transcriptase and antagonists of the estrogen receptor. The accuracy of compound identification was estimated using the recall and precision values. The sensitivities for all protein targets exceeded 80% and the classification performance reached 100% for selected targets. In another application of the method, we addressed the absence of an initial set of active compounds for a selected protein target at the beginning of an HTS-campaign. In such a case, virtual high-throughput screening (vHTS) is usually applied by using a flexible docking procedure. However, the vHTS experiment typically contains a large percentage of false positives that should be verified by costly and time-consuming experimental follow-up assays. The subsequent use of our machine learning method was found to improve the speed (since the docking procedure was not required for all compounds from the database) and also the accuracy of the HTS hit lists (the enrichment factor).

Improved anticancer and antiparasitic activity of new lawsone Mannich bases.

PubMed

Mahal, Katharina; Ahmad, Aamir; Schmitt, Florian; Lockhauserbäumer, Julia; Starz, Kathrin; Pradhan, Rohan; Padhye, Subhash; Sarkar, Fazlul H; Koko, Waleed S; Schobert, Rainer; Ersfeld, Klaus; Biersack, Bernhard

2017-01-27

Substituted lawsone Mannich bases 2a-e, 3a-e and 4a-e were prepared and tested for their biological activities. The new fatty alkyl substituted compounds 2a-c exhibited strong and selective growth inhibitory activities in the low one-digit micromolar and sub-micromolar range against a panel of human cancer cell lines associated with ROS formation. In addition, compounds 2a-c revealed sub-micromolar anti-trypanosomal activities against parasitic Trypanosoma brucei brucei cells via deformation of the microtubule cytoskeleton. The N-hexadecyl compound 2c was also highly active against locally isolated Entamoeba histolytica parasite samples exceeding the activity of metronidazole. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Synthesis and Biological Evaluation of New Hydrazone Derivatives of Quinoline and Their Cu(II) and Zn(II) Complexes against Mycobacterium tuberculosis

PubMed Central

Mandewale, Mustapha C.; Thorat, Bapu; Shelke, Dnyaneshwar; Yamgar, Ramesh

2015-01-01

A new series of quinoline hydrazone derivatives and their metal complexes have been synthesized and their biological properties have been evaluated against Mycobacterium tuberculosis (H37 RV strain). Most of the newly synthesized compounds displayed 100% inhibitory activity at a concentration of 6.25–25 μg/mL, against Mycobacterium tuberculosis. Fluorescence properties of all the synthesized compounds have been studied. PMID:26759537

Plantago maxima leaves extract inhibits adipogenic action of a high-fat diet in female Wistar rats.

PubMed

Tinkov, Alexey A; Nemereshina, Olga N; Popova, Elizaveta V; Polyakova, Valentina S; Gritsenko, Viktor A; Nikonorov, Alexandr A

2014-04-01

The primary objective of this study is to investigate the content of biologically active compounds producing an antioxidant effect in Plantago maxima and their influence on main mechanisms of dietary obesity development. Biologically active compounds in P. maxima were tested using paper chromatography. In in vivo experiment, high-fat-fed Wistar rats obtained P. maxima water extract for 3 months. Morphometric parameters, weight gain, serum adipokines, and cytokines, as well as oxidative stress biomarkers in rats’ tissues were evaluated. Gut microflora was also examined. Plantago maxima leaves used in the experiment contained significant amount of flavonoids, iridoids, phenol carboxylic acids, and tannins and ascorbic acid. Our in vivo experiment data demonstrate that P. maxima water extract prevents excessive adiposity in a diet-induced model. P. maxima consumption reduced serum leptin (twofold), macrophage chemoattractant protein-1 (sevenfold), tumornecrosis factor-α (25%), and interleukine-6 (26%) levels. P. maxima water extract decreased adipose tissue oxidative stress biomarkers in rats fed a high-fat diet. In addition, increased bacterial growth in the diet-induced obesity model was reversed by the P. maxima extract treatment. Plantago maxima water extract possessed antiadipogenic, antidiabetic, antiinflammatory, antioxidant activity, and normalized gut microflora in a rat model of diet-induced excessive adiposity due to a high content of biologically active compounds.

Synthesis, biological activity and dyeing performance of some novel azo disperse dyes incorporating pyrazolo[1,5-a]pyrimidines for dyeing of polyester fabrics

NASA Astrophysics Data System (ADS)

Sayed, Ahmed Z.; Aboul-Fetouh, Mahmoud S.; Nassar, Hesham S.

2012-02-01

Several novel pyrazolopyrimidine azo compounds were achieved from diazotization of 4-aminoacetanilide and coupling with malononitrile and then refluxed with hydrazine hydrate to furnish 3,5-diamino-4-(4-acetamidophenylazo)-1H-pyrazole. The later compound was diazotized and coupled with substituted α-cyanocinnamate, α-cyanocinnamonitrile, 2-cyano-3-ethoxyacrylic acid ethyl ester, chalcones and ethylacetoacetate to produce novel dyestuffs. Structures of the dyes were fully characterized by using FT-IR, 1H NMR, mass spectroscopy and elemental analysis. The dyes were applied to polyester fiber, affording satisfactory results and showed biological activity towards various microorganisms.

Bioactive Natural Products of Marine Sponges from the Genus Hyrtios.

PubMed

Shady, Nourhan Hisham; El-Hossary, Ebaa M; Fouad, Mostafa A; Gulder, Tobias A M; Kamel, Mohamed Salah; Abdelmohsen, Usama Ramadan

2017-05-11

Marine sponges are known as a rich source for novel bioactive compounds with valuable pharmacological potential. One of the most predominant sponge genera is Hyrtios , reported to have various species such as Hyrtios erectus , Hyrtios reticulatus , Hyrtios gumminae , Hyrtios communis , and Hyrtios tubulatus and a number of undescribed species. Members of the genus Hyrtios are a rich source of natural products with diverse and valuable biological activities, represented by different chemical classes including alkaloids, sesterterpenes and sesquiterpenes. This review covers the literature until June 2016, providing a complete survey of all compounds isolated from the genus Hyrtios with their corresponding biological activities whenever applicable.

Modulation of Immune Function by Polyphenols: Possible Contribution of Epigenetic Factors

PubMed Central

Cuevas, Alejandro; Saavedra, Nicolás; Salazar, Luis A.; Abdalla, Dulcineia S. P.

2013-01-01

Several biological activities have been described for polyphenolic compounds, including a modulator effect on the immune system. The effects of these biologically active compounds on the immune system are associated to processes as differentiation and activation of immune cells. Among the mechanisms associated to immune regulation are epigenetic modifications as DNA methylation of regulatory sequences, histone modifications and posttranscriptional repression by microRNAs that influences the gene expression of key players involved in the immune response. Considering that polyphenols are able to regulate the immune function and has been also demonstrated an effect on epigenetic mechanisms, it is possible to hypothesize that there exists a mediator role of epigenetic mechanisms in the modulation of the immune response by polyphenols. PMID:23812304

Synthesis of the biologically active natural product cyclodepsipeptides apratoxin A and its analogues.

PubMed

Doi, Takayuki

2014-01-01

This paper describes the synthetic studies conducted on a marine natural product, cyclodepsipeptide apratoxin A. Total synthesis of the oxazoline analogue of apratoxin A was achieved. The conversion of oxazoline to thioamide, as well as thioamide formation from a serine-derived compound, were both unsuccessful. However, thiazoline formation from a cysteine-derived compound led to the total synthesis of apratoxin A. An in vivo study on synthetic apratoxin A revealed that it has potent antitumor activity, but with significant toxicity. Solid-phase synthesis of apratoxin A was accomplished using a preformed thiazoline derivative as a coupling unit. This method was used to synthesize several azido-containing analogues as precursors of molecular probes, and these analogues exhibited potent biological activity.

Phytochemical components and biological activities of Silene arenarioides Desf.

PubMed

Golea, Lynda; Benkhaled, Mohammed; Lavaud, Catherine; Long, Christophe; Haba, Hamada

2017-12-01

In this study, six known compounds 1-6 were isolated from the aerial parts of Silene arenarioides Desf. using different chromatographic methods. The structures of these compounds were identified as maltol glycoside (1), soyacerebroside I (2), chrysin (3), apigenin (4), quercetin (5) and stigmasterol glucoside (6). The compounds (1) and (2) are reported for the first time from this genus. The isolated compounds were determined using NMR techniques ( 1 H NMR, 13 C NMR, COSY, HSQC and HMBC) and mass spectroscopy (ESI-MS). The antibacterial and antioxidant activities of extracts and of compound (1) have been evaluated. The antioxidant activity was performed by DPPH radical scavenging method, which showed that methanol extract possesses a good antioxidant activity with value of IC 50  = 8.064 ± 0.005 μg/mL.

[Chemical constituents of Rauvolfia verticillata].

PubMed

Hong, Bo; Li, Wen-Jing; Zhao, Chun-Jie

2012-06-01

The study on the Rauvolfia verticillata (Lour.) Baill., which belongs to Apocynaceae, was carried out to look for its chemical constituents and pharmacological activity. The isolation and purification were performed by chromatography on silica gel, Sephadex LH-20 and ODS (octadecyl silane) open column. The structures of obtained compounds were elucidated on the basis of physicochemical properties and spectral analysis. Three indole alkaloids and one acridone alkaloid were isolated from chloroform layer extract and identified as ajmalicine B (1), sandwicine (2), raunescine (3) and 7-hydroxynoracronycine (4) separately. Ajmalicine B (1) is a new compound belonging to indole alkaloid. Compound 4 as an acridone alkaloid was a new type compound isolated from Rauvolfia genus for the first time. We also did some biological activity research on the new type compound (4) to explore other pharmacological activities in addition to antihypertensive activity.

Synthesis and Biological Activity of Azine Heterocycle Functionalized Quaternary Phosphonium salts

NASA Astrophysics Data System (ADS)

Akshay Ravindra, Patil; Karpagam, S.

2017-11-01

Various azine heterocycles (pyrazine, quinoxaline and quinoline) possessing phosphonium salts (3a-3c) were prepared as cationic biocides. The structural characterization of the phosphonium compounds was confirmed by FTIR, NMR and HR-Mass spectroscopy. These compounds has shown excellent bactericidal activity against two Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis) and two Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae). Quinoline functionalized phosphonium has shown more antibacterial activity than pyrazine and quinoxaline.

[Biological activity of selenorganic compounds at heavy metal salts intoxication].

PubMed

Rusetskaya, N Y; Borodulin, V B

2015-01-01

Possible mechanisms of the antitoxic action of organoselenium compounds in heavy metal poisoning have been considered. Heavy metal toxicity associated with intensification of free radical oxidation, suppression of the antioxidant system, damage to macromolecules, mitochondria and the genetic material can cause apoptotic cell death or the development of carcinogenesis. Organic selenium compounds are effective antioxidants during heavy metal poisoning; they exhibit higher bioavailability in mammals than inorganic ones and they are able to activate antioxidant defense, bind heavy metal ions and reactive oxygen species formed during metal-induced oxidative stress. One of promising organoselenium compounds is diacetophenonyl selenide (DAPS-25), which is characterized by antioxidant and antitoxic activity, under conditions including heavy metal intoxication.

Synthesis and biological properties of new 5-nitroindazole derivatives.

PubMed

Arán, Vicente J; Ochoa, Carmen; Boiani, Lucía; Buccino, Pablo; Cerecetto, Hugo; Gerpe, Alejandra; González, Mercedes; Montero, David; Nogal, Juan José; Gómez-Barrio, Alicia; Azqueta, Amaya; López de Ceráin, Adela; Piro, Oscar E; Castellano, Eduardo E

2005-05-02

A series of new 3-alkoxy- or 3-hydroxy-1-[omega-(dialkylamino)alkyl]-5-nitroindazoles have been synthesized and their trichomonacidal, antichagasic and antineoplastic properties studied. Five derivatives (5, 6, 8, 9 and 17) showed remarkable trichomonacidal activity against Trichomonas vaginalis at 10 microg/mL concentration. Three compounds (8, 10, 11) exhibited interesting antichagasic activity and these same compounds moderate antineoplastic activity against TK-10 and HT-29 cell lines. Unspecific cytotoxicity against macrophages has also been evaluated and only compounds 9, 10 and 11 resulted cytotoxic at the higher dose evaluated (100 microg/mL), loosing cytotoxicity at lower doses. QSAR studies have been carried out. X-ray crystallographic study of compound 8 has been performed.

Identification of Novel Activators of Constitutive Androstane Receptor from FDA-approved Drugs by Integrated Computational and Biological Approaches

PubMed Central

Lynch, Caitlin; Pan, Yongmei; Li, Linhao; Ferguson, Stephen S.; Xia, Menghang; Swaan, Peter W.; Wang, Hongbing

2012-01-01

Purpose The constitutive androstane receptor (CAR, NR1I3) is a xenobiotic sensor governing the transcription of numerous hepatic genes associated with drug metabolism and clearance. Recent evidence suggests that CAR also modulates energy homeostasis and cancer development. Thus, identification of novel human (h) CAR activators is of both clinical importance and scientific interest. Methods Docking and ligand-based structure-activity models were used for virtual screening of a database containing over 2000 FDA-approved drugs. Identified lead compounds were evaluated in cell-based reporter assays to determine hCAR activation. Potential activators were further tested in human primary hepatocytes (HPHs) for the expression of the prototypical hCAR target gene CYP2B6. Results Nineteen lead compounds with optimal modeling parameters were selected for biological evaluation. Seven of the 19 leads exhibited moderate to potent activation of hCAR. Five out of the seven compounds translocated hCAR from the cytoplasm to the nucleus of HPHs in a concentration-dependent manner. These compounds also induce the expression of CYP2B6 in HPHs with rank-order of efficacies closely resembling that of hCAR activation. Conclusion These results indicate that our strategically integrated approaches are effective in the identification of novel hCAR modulators, which may function as valuable research tools or potential therapeutic molecules. PMID:23090669

Synthesis of 1-Substituted Carbazolyl-1,2,3,4-tetrahydro- and Carbazolyl-3,4-dihydro-β-carboline Analogs as Potential Antitumor Agents

PubMed Central

Shen, Ya-Ching; Chang, Yao-To; Lin, Chun-Ling; Liaw, Chia-Ching; Kuo, Yao Haur; Tu, Lan-Chun; Yeh, Sheau Farn; Chern, Ji-Wang

2011-01-01

A series of 1-substituted carbazolyl-1,2,3,4-tetrahydro- and carbazolyl-3,4-dihydro-β-carboline analogs have been synthesized and evaluated for antitumor activity against human tumor cells including KB, DLD, NCI-H661, Hepa, and HepG2/A2 cell lines. Among these, compounds 2, 6, 7, and 9 exhibited the most potent and selective activity against the tested tumor cells. As for inhibition of topoisomerase II, compounds 1–14 and 18 showed better activity than etoposide. Among them, compounds 3, 4, 7, 9, and 10 exhibited potent activity. The structure and activity relationship (SAR) study revealed correlation between carbon numbers of the side chain and biological activities. The molecular complex with DNA for compound 2 was proposed. PMID:21566798

Synthesis and biological evaluation of novel flavone/triazole/benzimidazole hybrids and flavone/isoxazole-annulated heterocycles as antiproliferative and antimycobacterial agents.

PubMed

Rao, Yerrabelly Jayaprakash; Sowjanya, Thummala; Thirupathi, Gogula; Murthy, Nandula Yadagiri Sreenivasa; Kotapalli, Sudha Sravanti

2018-06-04

A series of new flavone/isoxazole fused heterocycles 5a-f and flavone/1,2,3-triazole/benzimidazole hybrid heterocycles compounds 7a-t were synthesized via an intramolecular cyclization and Cu(I)-catalyzed click 1,3-dipolar cycloaddition. The products were evaluated for their antiproliferative activity against human breast cancer cell line (MCF-7) using sulforhodamine B assay (SRB) and antimycobacterial activity using turbidometric assay. The majority of the tested compounds exhibited antiproliferative activity and antimycobacterial activity. Compounds 7l, 7q and 7r showed moderate antiproliferative activity with IC50 values 17.9, 14.2, 19.1 [Formula: see text], respectively, and compound 5a showed moderate antimycobacterial activity with 41.7% of inhibition at 30 [Formula: see text] concentration.

Synthesis, molecular docking, DFT calculations and cytotoxicity activity of benzo[g]quinazoline derivatives in choline chloride-urea

NASA Astrophysics Data System (ADS)

Lakshmanan, Sivalingam; Govindaraj, Dharman; Ramalakshmi, Narayanan; Antony, S. Arul

2017-12-01

Green and highly efficient one-pot three component approach for the synthesis of benzo[g]quinazoline derivatives (6a-g) using Choline chloride-urea (DES). Synthesized compounds 6b and 6g showed the most potent biological activity against A549 lung cancer cell line. Docking simulation was performed to position compounds 6b and 6g showed the greater affinity for anaplastic lymphoma kinase (ALK) receptor. Quantum chemical studies were carried out on these compounds to understand the structural features essential for activity using DFT/6-31G level of theory.

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.

Synthesis, biophysical properties and biological activity of second generation antisense oligonucleotides containing chiral phosphorothioate linkages

PubMed Central

Wan, W. Brad; Migawa, Michael T.; Vasquez, Guillermo; Murray, Heather M.; Nichols, Josh G.; Gaus, Hans; Berdeja, Andres; Lee, Sam; Hart, Christopher E.; Lima, Walt F.; Swayze, Eric E.; Seth, Punit P.

2014-01-01

Bicyclic oxazaphospholidine monomers were used to prepare a series of phosphorothioate (PS)-modified gapmer antisense oligonucleotides (ASOs) with control of the chirality of each of the PS linkages within the 10-base gap. The stereoselectivity was determined to be 98% for each coupling. The objective of this work was to study how PS chirality influences biophysical and biological properties of the ASO including binding affinity (Tm), nuclease stability, activity in vitro and in vivo, RNase H activation and cleavage patterns (both human and E. coli) in a gapmer context. Compounds that had nine or more Sp-linkages in the gap were found to be poorly active in vitro, while compounds with uniform Rp-gaps exhibited activity very similar to that of the stereo-random parent ASOs. Conversely, when tested in vivo, the full Rp-gap compound was found to be quickly metabolized resulting in low activity. A total of 31 ASOs were prepared with control of the PS chirally of each linkage within the gap in an attempt to identify favorable Rp/Sp positions. We conclude that a mix of Rp and Sp is required to achieve a balance between good activity and nuclease stability. PMID:25398895

Parsley: a review of ethnopharmacology, phytochemistry and biological activities.

PubMed

Farzaei, Mohammad Hosein; Abbasabadi, Zahra; Ardekani, Mohammad Reza Shams; Rahimi, Roja; Farzaei, Fatemeh

2013-12-01

To summarize comprehensive information concerning ethnomedicinal uses, phytochemistry, and pharmacological activities of parsley. Databases including PubMed, Scopus, Google Scholar, and Web of Science were searched for studies focusing on the ethnomedicinal use, phytochemical compounds and biological and pharmacological activities of parsley. Data were collected from 1966 to 2013. The search terms were: "Parsley" or "Petroselinum crispum" or "Petroselinum hortence". Parsley has been used as carminative, gastro tonic, diuretic, antiseptic of urinary tract, anti-urolithiasis, anti-dote and anti-inflammatory and for the treatment of amenorrhea, dysmenorrhea, gastrointestinal disorder, hypertension, cardiac disease, urinary disease, otitis, sniffle, diabetes and also various dermal disease in traditional and folklore medicines. Phenolic compounds and flavonoids particularly apigenin, apiin and 6"-Acetylapiin; essential oil mainly myristicin and apiol; and also coumarins are the active compounds identified in Petroselinum crispum. Wide range of pharmacological activity including antioxidant, hepatoprotective, brain protective, anti-diabetic, analgesic, spasmolytic, immunosuppressant, anti-platelet, gastroprotective, cytoprotective, laxative, estrogenic, diuretic, hypotensive, antibacterial and antifungal activities have been exhibited for this plant in modern medicine. It is expectant that this study resulted in improvement the tendencies toward Petroselinum crispum as a useful and important medicinal plant with wide range of proven medicinal activity.

Screening the efficient biological prospects of triazole allied mixed ligand metal complexes

NASA Astrophysics Data System (ADS)

Utthra, Ponnukalai Ponya; Kumaravel, Ganesan; Raman, Natarajan

2017-12-01

Triazole appended mixed ligand complexes (1-8) of the general formula [ML (bpy/phen)2]Cl2, where M = Cu(II), Co(II), Ni(II) and Zn(II), L = triazole appended Schiff base (E)sbnd N-(4-nitrobenzylidene)-1H-1,2,4-triazol-3-amine and bpy/phen = 2,2‧-bipyridine/1,10-phenanthroline, have been synthesized. The design and synthesis of this elaborate ligand has been performed with the aim of increasing stability and conjugation of 1,2,4 triazole, whose Schiff base derivatives are known as biologically active compounds thereby exploring their DNA binding affinity and other biological applications. The compounds have been comprehensively characterized by elemental analysis, spectroscopic methods (IR, UV-Vis, EPR, 1H and 13C NMR spectroscopy), ESI mass spectrometry and magnetic susceptibility measurements. The complexes were found to exhibit octahedral geometry. The complexes 1-8 were subjected to DNA binding techniques evaluated using UV-Vis absorption, CV, CD, Fluorescence spectroscopy and hydrodynamic measurements. Complex 5 showed a Kb value of 3.9 × 105 M-1. The DNA damaging efficacy for the complexes was observed to be high compared to the ligand. The antimicrobial screening of the compounds against bacterial and fungal strains indicates that the complexes possess excellent antimicrobial activity than the ligand. The overall biological activity of the complexes with phen as a co-ligand possessed superior potential than the ligand.

Pharmaceutically active secondary metabolites of marine actinobacteria.

PubMed

Manivasagan, Panchanathan; Venkatesan, Jayachandran; Sivakumar, Kannan; Kim, Se-Kwon

2014-04-01

Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinobacteria from terrestrial sources have been studied and screened since the 1950s, for many important antibiotics, anticancer, antitumor and immunosuppressive agents. However, frequent rediscovery of the same compounds from the terrestrial actinobacteria has made them less attractive for screening programs in the recent years. At the same time, actinobacteria isolated from the marine environment have currently received considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. They are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic, cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral, antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the current status of research on marine actinobacteria yielding pharmaceutically active secondary metabolites. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens. With the increasing advancement in science and technology, there would be a greater demand for new bioactive compounds synthesized by actinobacteria from various marine sources in future. Copyright © 2013 Elsevier GmbH. All rights reserved.

Algae as promising organisms for environment and health

PubMed Central

2011-01-01

Algae, like other plants, produce a variety of remarkable compounds collectively referred to as secondary metabolites. They are synthesized by these organisms at the end of the growth phase and/or due to metabolic alterations induced by environmental stress conditions. Carotenoids, phenolic compounds, phycobiliprotein pigments, polysaccharides and unsaturated fatty acids are same of the algal natural products, which were reported to have variable biological activities, including antioxidant activity, anticancer activity, antimicroabial activity against bacteria-virus-algae-fungi, organic fertilizer and bioremediation potentials. PMID:21862867

The Difference a Single Atom Can Make: Synthesis and Design at the Chemistry–Biology Interface

PubMed Central

2017-01-01

A Perspective of work in our laboratory on the examination of biologically active compounds, especially natural products, is presented. In the context of individual programs and along with a summary of our work, selected cases are presented that illustrate the impact single atom changes can have on the biological properties of the compounds. The examples were chosen to highlight single heavy atom changes that improve activity, rather than those that involve informative alterations that reduce or abolish activity. The examples were also chosen to illustrate that the impact of such single-atom changes can originate from steric, electronic, conformational, or H-bonding effects, from changes in functional reactivity, from fundamental intermolecular interactions with a biological target, from introduction of a new or altered functionalization site, or from features as simple as improvements in stability or physical properties. Nearly all the examples highlighted represent not only unusual instances of productive deep-seated natural product modifications and were introduced through total synthesis but are also remarkable in that they are derived from only a single heavy atom change in the structure. PMID:28945374

Design and synthesis of some new 2,3'-bipyridine-5-carbonitriles as potential anti-inflammatory/antimicrobial agents.

PubMed

Elzahhar, Perihan A; Elkazaz, Salwa; Soliman, Raafat; El-Tombary, Alaa A; Shaltout, Hossam A; El-Ashmawy, Ibrahim M; Abdel Wahab, Abeer E; El-Hawash, Soad A

2017-08-01

Inflammation may cause accumulation of fluid in the injured area, which may promote bacterial growth. Other reports disclosed that non-steroidal anti-inflammatory drugs may enhance progression of bacterial infection. This work describes synthesis of new series of 2,3'-bipyridine-5-carbonitriles as structural analogs of etoricoxib, linked at position-6 to variously substituted thio or oxo moieties. Biological screening results revealed that compounds 2b, 4b, 7e and 8 showed significant acute and chronic AI activities and broad spectrum of antimicrobial activity. In addition, similarity ensemble approach was applied to predict potential biological targets of the tested compounds. Then, pharmacophore modeling study was employed to determine the most important structural parameters controlling bioactivity. Moreover, title compounds showed physicochemical properties within those considered adequate for drug candidates. This study explored the potential of such series of compounds as structural leads for further modification to develop a new class of dual AI-antimicrobial agents.

Synthesis and biological evaluation of pyrimidine bridged combretastatin derivatives as potential anticancer agents and mechanistic studies.

PubMed

Kumar, Bhupinder; Sharma, Praveen; Gupta, Vivek Prakash; Khullar, Madhu; Singh, Sandeep; Dogra, Nilambra; Kumar, Vinod

2018-08-01

A number of pyrimidine bridged combretastatin derivatives were designed, synthesized and evaluated for anticancer activities against breast cancer (MCF-7) and lung cancer (A549) cell lines using MTT assays. Most of the synthesized compounds displayed good anticancer activity with IC 50 values in low micro-molar range. Compounds 4a and 4p were found most potent in the series with IC 50 values of 4.67 µM & 3.38 µM and 4.63 µM & 3.71 µM against MCF7 and A549 cancer cell lines, respectively. Biological evaluation of these compounds showed that selective cancer cell toxicity (in vitro using human lung and breast cancer cell lines) might be due to the inhibition of antioxidant enzymes instigating elevated ROS levels which triggers intrinsic apoptotic pathways. These compounds were found nontoxic to the normal human primary cells. Compound 4a, was found to be competitive inhibitor of colchicine and in the tubulin binding assay it showed tubulin polymerization inhibition potential comparable to colchicine. The molecular modeling studies also showed that the synthesized compounds fit well in the colchicine-binding pocket. Copyright © 2018 Elsevier Inc. All rights reserved.

Synthesis, Structural Studies and Biological Evaluation of Connections of Thiosemicarbazide, 1,2,4-Triazole and 1,3,4-Thiadiazole with Palmitic Acid.

PubMed

Jóźwiak, Michał; Stępień, Karolina; Wrzosek, Małgorzata; Olejarz, Wioletta; Kubiak-Tomaszewska, Grażyna; Filipowska, Anna; Filipowski, Wojciech; Struga, Marta

2018-04-03

Thirty new derivatives of palmitic acid were efficiently synthesized. All obtained compounds can be divided into three groups of derivatives: Thiosemicarbazides (compounds 1 - 10 ), 1,2,4-triazoles (compounds 1a - 10a ) and 1,3,4-thiadiazoles (compounds 1b - 10b ) moieties. ¹H-NMR, 13 C-NMR and MS methods were used to confirm the structure of derivatives. All obtained compounds were tested in vitro against a number of microorganisms, including Gram-positive cocci, Gram-negative rods and Candida albicans . Compounds 4 , 5 , 6 , 8 showed significant inhibition against C. albicans . The range of MIC values was 50-1.56 μg/mL. The halogen atom, especially at the 3rd position of the phenyl group was significantly important for antifungal activity. The biological activity against Candida albicans and selected molecular descriptors were used as a basis for QSAR models, that have been determined by means of multiple linear regression. The models have been validated by means of the Leave-One-Out Cross Validation. The obtained QSAR models were characterized by high determination coefficients and good prediction power.

Changes in hormone and stress-inducing activities of municipal wastewater in a conventional activated sludge wastewater treatment plant.

PubMed

Wojnarowicz, Pola; Yang, Wenbo; Zhou, Hongde; Parker, Wayne J; Helbing, Caren C

2014-12-01

Conventional municipal wastewater treatment plants do not efficiently remove contaminants of emerging concern, and so are primary sources for contaminant release into the aquatic environment. Although these contaminants are present in effluents at ng-μg/L concentrations (i.e. microcontaminants), many compounds can act as endocrine disrupting compounds or stress-inducing agents at these levels. Chemical fate analyses indicate that additional levels of wastewater treatment reduce but do not always completely remove all microcontaminants. The removal of microcontaminants from wastewater does not necessarily correspond to a reduction in biological activity, as contaminant metabolites or byproducts may still be biologically active. To evaluate the efficacy of conventional municipal wastewater treatment plants to remove biological activity, we examined the performance of a full scale conventional activated sludge municipal wastewater treatment plant located in Guelph, Ontario, Canada. We assessed reductions in levels of conventional wastewater parameters and thyroid hormone disrupting and stress-inducing activities in wastewater at three phases along the treatment train using a C-fin assay. Wastewater treatment was effective at reducing total suspended solids, chemical and biochemical oxygen demand, and stress-inducing bioactivity. However, only minimal reduction was observed in thyroid hormone disrupting activities. The present study underscores the importance of examining multiple chemical and biological endpoints in evaluating and monitoring the effectiveness of wastewater treatment for removal of microcontaminants. Copyright © 2014 Elsevier Ltd. All rights reserved.

Astaxanthin: Sources, Extraction, Stability, Biological Activities and Its Commercial Applications—A Review

PubMed Central

Ambati, Ranga Rao; Siew Moi, Phang; Ravi, Sarada; Aswathanarayana, Ravishankar Gokare

2014-01-01

There is currently much interest in biological active compounds derived from natural resources, especially compounds that can efficiently act on molecular targets, which are involved in various diseases. Astaxanthin (3,3′-dihydroxy-β, β′-carotene-4,4′-dione) is a xanthophyll carotenoid, contained in Haematococcus pluvialis, Chlorella zofingiensis, Chlorococcum, and Phaffia rhodozyma. It accumulates up to 3.8% on the dry weight basis in H. pluvialis. Our recent published data on astaxanthin extraction, analysis, stability studies, and its biological activities results were added to this review paper. Based on our results and current literature, astaxanthin showed potential biological activity in in vitro and in vivo models. These studies emphasize the influence of astaxanthin and its beneficial effects on the metabolism in animals and humans. Bioavailability of astaxanthin in animals was enhanced after feeding Haematococcus biomass as a source of astaxanthin. Astaxanthin, used as a nutritional supplement, antioxidant and anticancer agent, prevents diabetes, cardiovascular diseases, and neurodegenerative disorders, and also stimulates immunization. Astaxanthin products are used for commercial applications in the dosage forms as tablets, capsules, syrups, oils, soft gels, creams, biomass and granulated powders. Astaxanthin patent applications are available in food, feed and nutraceutical applications. The current review provides up-to-date information on astaxanthin sources, extraction, analysis, stability, biological activities, health benefits and special attention paid to its commercial applications. PMID:24402174

Divergent Synthesis and Real-Time Biological Annotation of Optically Active Tetrahydrocyclopenta[c]pyranone Derivatives

PubMed Central

2016-01-01

Sp3-rich compounds are underrepresented in libraries for probe- and drug-discovery, despite their promise of extending the range of accessible molecular shapes beyond planar geometries. With this in mind, a collection of single-enantiomer bicyclic, fused cyclopentenones underpinned by a complexity-generating Pauson–Khand cyclization was synthesized. A fingerprint of biological actions of these compounds was determined immediately after synthesis using real-time annotation−a process relying on multiplexed measurements of alterations in cell morphological features. PMID:27978655

Synthesis and biological evaluation of novel dioxa-bicycle C-aryl glucosides as SGLT2 inhibitors.

PubMed

Yan, Qi; Ding, Ning; Li, Yingxia

2016-02-08

A series of novel C-aryl glucosides containing dioxa-bicycle were synthesized and evaluated for inhibition activity against hSGLT2. Among the compounds tested, compound 6a showed moderate SGLT2 inhibition activities at 700 nM. The results could benefit the discovery of new SGLT2 inhibitors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Investigation of biological effects of some Mannich Bases containing Bis-1,2,4- Triazole.

PubMed

Parlak, A E; Celik, S; Karatepe, M; Turkoglu, S; Alayunt, N O; Dastan, S D; Ulas, M; Sandal, S; Tekin, S; Koparir, M

2016-06-30

In this study, the effects of Mannich bases containing bis-1,2,4-triazole on the levels of in vivo malondialdehyde (MDA) and antioxidant vitamins (A, E, C) were examined in serum, livers and kidneys of rats. DA and vitamin (A, E, C) levels were determined by high performance liquid chromatography (HPLC). Antioxidant effect was investigated by determining the MDA levels in Saccharomyces cerevisiae cells as in vitro. Furthermore, the antitumor effects of compounds were investigated against MCF-7 human breast cancer cells. Interrelations of results among control and compound groups were evaluated using SPSS statistical software package. As a result, some of the compounds showed effective biological activity when compared to control conditions. The test compounds used in this study may be effective for utilization in the selection and design of model compounds for further studies.

Biological activities of Agave by-products and their possible applications in food and pharmaceuticals.

PubMed

López-Romero, Julio Cesar; Ayala-Zavala, Jesús Fernando; González-Aguilar, Gustavo Adolfo; Peña-Ramos, Etna Aida; González-Ríos, Humberto

2018-05-01

Agave leaves are considered a by-product of alcoholic beverage production (tequila, mezcal and bacanora) because they are discarded during the production process, despite accounting for approximately 50% of the total plant weight. These by-products constitute a potential source of Agave extracts rich in bioactive compounds, such as saponins, phenolic compounds and terpenes, and possess different biological effects, as demonstrated by in vitro and in vivo tests (e.g. antimicrobial, antifungal, antioxidant, anti-inflammatory, antihypertensive, immunomodulatory, antiparasitic and anticancer activity). Despite their positive results in biological assays, Agave extracts have not been widely evaluated in food systems and pharmaceutical areas, and these fields represent a potential route to improve the usage of Agave plants as food additives and agents for treating medical diseases. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Enhanced Production of Anthraquinones and Phenolic Compounds and Biological Activities in the Cell Suspension Cultures of Polygonum multiflorum

PubMed Central

Thiruvengadam, Muthu; Rekha, Kaliyaperumal; Rajakumar, Govindasamy; Lee, Taek-Jun; Kim, Seung-Hyun; Chung, Ill-Min

2016-01-01

Anthraquinones (AQs) and phenolic compounds are important phytochemicals that are biosynthesized in cell suspension cultures of Polygonum multiflorum. We wanted to optimize the effects of plant growth regulators (PGRs), media, sucrose, l-glutamine, jasmonic acid (JA), and salicylic acid (SA) for the production of phytochemicals and biomass accumulation in a cell suspension culture of P. multiflorum. The medium containing Murashige and Skoog (MS) salts and 4% sucrose supplemented with 1 mg/L 2,4-dichlorophenoxyacetic acid, 0.5 mg/L thidiazuron, and 100 µM l-glutamine at 28 days of cell suspension culture was suitable for biomass accumulation and AQ production. Maximum biomass accumulation (12.5 and 12.35 g fresh mass (FM); 3 and 2.93 g dry mass (DM)) and AQ production (emodin 295.20 and 282 mg/g DM; physcion 421.55 and 410.25 mg/g DM) were observed using 100 µM JA and SA, respectively. JA- and SA-elicited cell cultures showed several-fold higher biomass accumulation and AQ production than the control cell cultures. Furthermore, the cell suspension cultures effectively produced 23 phenolic compounds, such as flavonols and hydroxycinnamic and hydroxybenzoic acid derivatives. PGR-, JA-, and SA-elicited cell cultures produced a higher amount of AQs and phenolic compounds. Because of these metabolic changes, the antioxidant, antimicrobial, and anticancer activities were high in the PGR-, JA-, and SA-elicited cell cultures. The results showed that the elicitors (JA and SA) induced the enhancement of biomass accumulation and phytochemical (AQs and phenolic compounds) production as well as biological activities in the cell suspension cultures of P. multiflorum. This optimized protocol can be developed for large-scale biomass accumulation and production of phytochemicals (AQs and phenolic compounds) from cell suspension cultures, and the phytochemicals can be used for various biological activities. PMID:27854330

A pharmacological screen for compounds that rescue the developmental lethality of a Drosophila ATM mutant.

PubMed

Rimkus, Stacey A; Wassarman, David A

2018-01-01

Ataxia-telangiectasia (A-T) is a neurodegenerative disease caused by mutation of the A-T mutated (ATM) gene. ATM encodes a protein kinase that is activated by DNA damage and phosphorylates many proteins, including those involved in DNA repair, cell cycle control, and apoptosis. Characteristic biological and molecular functions of ATM observed in mammals are conserved in Drosophila melanogaster. As an example, conditional loss-of-function ATM alleles in flies cause progressive neurodegeneration through activation of the innate immune response. However, unlike in mammals, null alleles of ATM in flies cause lethality during development. With the goals of understanding biological and molecular roles of ATM in a whole animal and identifying candidate therapeutics for A-T, we performed a screen of 2400 compounds, including FDA-approved drugs, natural products, and bioactive compounds, for modifiers of the developmental lethality caused by a temperature-sensitive ATM allele (ATM8) that has reduced kinase activity at non-permissive temperatures. Ten compounds reproducibly suppressed the developmental lethality of ATM8 flies, including Ronnel, which is an organophosphate. Ronnel and other suppressor compounds are known to cause mitochondrial dysfunction or to inhibit the enzyme acetylcholinesterase, which controls the levels of the neurotransmitter acetylcholine, suggesting that detrimental consequences of reduced ATM kinase activity can be rescued by inhibiting the function of mitochondria or increasing acetylcholine levels. We carried out further studies of Ronnel because, unlike the other compounds that suppressed the developmental lethality of homozygous ATM8 flies, Ronnel was toxic to the development of heterozygous ATM8 flies. Ronnel did not affect the innate immune response of ATM8 flies, and it further increased the already high levels of DNA damage in brains of ATM8 flies, but its effects were not harmful to the lifespan of rescued ATM8 flies. These results provide new leads for understanding the biological and molecular roles of ATM and for the treatment of A-T.

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 and structure-activity relationships of constrained heterocyclic analogues of combretastatin A4.

PubMed

Arthuis, Martin; Pontikis, Renée; Chabot, Guy G; Seguin, Johanne; Quentin, Lionel; Bourg, Stéphane; Morin-Allory, Luc; Florent, Jean-Claude

2011-09-05

A series of combretastatin A4 (CA4) analogues with a lactam or lactone ring fused to the trimethoxyphenyl or the B-phenyl moiety were synthesized in an efficient and stereoselective manner by using a domino Heck-Suzuki-Miyaura coupling reaction. The vascular-disrupting potential of these conformationally restricted CA4 analogues was assessed by various in vitro assays: inhibition of tubulin polymerization, modification of endothelial cell morphology, and disruption of endothelial cell cords. Compounds were also evaluated for their growth inhibitory effects against murine and human tumor cells. B-ring-constrained derivatives that contain an oxindole ring (in contrast to compounds with a benzofuranone ring) as well as analogues bearing a six-membered lactone core fused to the trimethoxyphenyl ring are endowed with significant biological activity. The most potent compound of this series (oxindole 9 b) is of particular interest, as it combines chemical stability and a biological activity profile characteristic of a vascular-disrupting agent. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and biological evaluation of some N-(3-(1H-tetrazol-5-yl) phenyl)acetamide derivatives as novel non-carboxylic PTP1B inhibitors designed through bioisosteric modulation.

PubMed

Maheshwari, Neelesh; Karthikeyan, Chandrabose; Bhadada, Shraddha V; Sahi, Chandan; Verma, Amit K; Hari Narayana Moorthy, N S; Trivedi, Piyush

2018-06-08

Described herein is the synthesis and biological evaluation of a series of non-carboxylic inhibitors of Protein Tyrosine Phosphatase 1B designed using bioisosteric replacement strategy. Six N-(3-(1H-tetrazol-5-yl)phenyl)acetamide derivatives designed employing the aforementioned strategy were synthesized and screened for PTP1B inhibitory activity. Among the synthesized compounds, compound NM-03 exhibited the most potent inhibitory activity with IC 50 value of 4.48 µM. Docking studies with NM-03 revealed the key interactions with desired amino acids in the binding site of PTP1B. Furthermore, compound NM-03 also elicited good in vivo activity. Taken together, the results of this study establish N-(3-(1H-tetrazole-5-yl)phenyl)-2-(benzo[d]oxazol-2-ylthio)acetamide (NM-03) as a valuable lead molecule with great potential for PTP1B inhibitor development targeting diabetes. Copyright © 2018 Elsevier Inc. All rights reserved.

Oxaphosphinanes: new therapeutic perspectives for glioblastoma.

PubMed

Clarion, Ludovic; Jacquard, Carine; Sainte-Catherine, Odile; Loiseau, Séverine; Filippini, Damien; Hirlemann, Marie-Hélène; Volle, Jean-Noël; Virieux, David; Lecouvey, Marc; Pirat, Jean-Luc; Bakalara, Norbert

2012-03-08

This paper reports the design and the synthesis of a new family of compounds, the phostines, belonging to the [1,2]oxaphosphinane family. Twenty-six compounds have been screened for their antiproliferative activity against a large panel of NCI cancer cell lines. Because of its easy synthesis and low EC(50) value (500 nM against the C6 rat glioma cell line), compound 3.1a was selected for further biological study. Moreover, the specific biological effect of 3.1a on the glioblastoma phylogenetic cluster from the NCI is dependent on its stereochemistry. Within that cluster, 3.1a has a higher antiproliferative activity than Temozolomide and is more potent than paclitaxel for the SF295 and SNB75 cell lines. In constrast with paclitaxel and vincristine, 3.1a is devoid of astrocyte toxicity. The original activity spectrum of 3.1a on the NCI cancer cell line panel allows the development of this family for use in association with existing drugs, opening new therapeutic perspectives.

The isolation and characterization of actinobacteria from dominant benthic macroinvertebrates endemic to Lake Baikal.

PubMed

Axenov-Gribanov, Denis; Rebets, Yuriy; Tokovenko, Bogdan; Voytsekhovskaya, Irina; Timofeyev, Maxim; Luzhetskyy, Andriy

2016-03-01

The high demand for new antibacterials fosters the isolation of new biologically active compounds producing actinobacteria. Here, we report the isolation and initial characterization of cultured actinobacteria from dominant benthic organisms' communities of Lake Baikal. Twenty-five distinct strains were obtained from 5 species of Baikal endemic macroinvertebrates of amphipods, freshwater sponges, turbellaria worms, and insects (caddisfly larvae). The 16S ribosomal RNA (rRNA)-based phylogenic analysis of obtained strains showed their affiliation to Streptomyces, Nocardia, Pseudonocardia, Micromonospora, Aeromicrobium, and Agromyces genera, revealing the diversity of actinobacteria associated with the benthic organisms of Lake Baikal. The biological activity assays showed that 24 out of 25 strains are producing compounds active against at least one of the test cultures used, including Gram-negative bacteria and Candida albicans. Complete dereplication of secondary metabolite profiles of two isolated strains led to identification of only few known compounds, while the majority of detected metabolites are not listed in existing antibiotic databases.

Synthesis, biological evaluation and molecular docking of novel 5-phenyl-1H-pyrazol derivatives as potential BRAF(V600E) inhibitors.

PubMed

Dong, Jing-Jun; Li, Qing-Shan; Wang, Shu-Fu; Li, Cui-Yun; Zhao, Xin; Qiu, Han-Yue; Zhao, Meng-Yue; Zhu, Hai-Liang

2013-10-07

The RAF-MEK-ERK cascade appears to be intimately involved in the regulation of cell cycle progression and apoptosis. The BRAF(V600E) mutant results in constitutive activation of the ERK pathway, which can lead to cellular growth dysregulation. A series of 5-phenyl-1H-pyrazol derivatives (3a-5e) have been designed and synthesized, and their biological activities were evaluated as potential BRAF(V600E) inhibitors. All the compounds were reported for the first time except 3e, and compound 1-(4-bromo-2-hydroxybenzyl)-3-phenyl-1-(5-phenyl-1H-pyrazol-3-yl)urea (5c) displayed the most potent inhibitory activity (BRAF(V600E) IC50 = 0.19 μM). Antiproliferative assay results indicated that compound 5c possessed high antiproliferative activity against cell lines WM266.4 and A375 in vitro, with IC50 values of 1.50 and 1.32 μM, respectively, which were comparable with the positive control vemurafenib. Docking simulations showed that compound 5c binds tightly to the BRAF(V600E) active site and acts as BRAF(V600E) inhibitor. A 3D-QSAR model was also built to provide more pharmacophore understanding towards designing new agents with more potent BRAF(V600E) inhibitory activity.

Effect of Citrus Flavonoids, Naringin and Naringenin, on Metabolic Syndrome and Their Mechanisms of Action12

PubMed Central

Alam, M. Ashraful; Subhan, Nusrat; Rahman, M. Mahbubur; Uddin, Shaikh J.; Reza, Hasan M.; Sarker, Satyajit D.

2014-01-01

Flavonoids are important natural compounds with diverse biologic activities. Citrus flavonoids constitute an important series of flavonoids. Naringin and its aglycone naringenin belong to this series of flavonoids and were found to display strong anti-inflammatory and antioxidant activities. Several lines of investigation suggest that naringin supplementation is beneficial for the treatment of obesity, diabetes, hypertension, and metabolic syndrome. A number of molecular mechanisms underlying its beneficial activities have been elucidated. However, their effect on obesity and metabolic disorder remains to be fully established. Moreover, the therapeutic uses of these flavonoids are significantly limited by the lack of adequate clinical evidence. This review aims to explore the biologic activities of these compounds, particularly on lipid metabolism in obesity, oxidative stress, and inflammation in context of metabolic syndrome. PMID:25022990

Antioxidant, anti-inflammatory and anticancer activities of the medicinal halophyte Reaumuria vermiculata

PubMed Central

Karker, Manel; Falleh, Hanen; Msaada, Kamel; Smaoui, Abderrazak; Abdelly, Chedly; Legault, Jean; Ksouri, Riadh

2016-01-01

Reaumuria vermiculata is a xero-halophytic specie widely distributed in the south of Tunisia. In the current study, antioxidant, anti-inflammatory and anticancer activities of Reaumuria vermiculata shoot extracts as well as its phenolic compounds were investigated in different solvent extracts (hexane, dichloromethane, methanol and water). Results showed a strong antioxidant activity, using the ORAC method and a cell based-assay, in methanol extract as well as an important phenolic composition (117.12 mg GAE/g). Hexane and dichloromethane proved an interesting anticancer activity against A-549 lung carcinoma cells, with IC50 values of 17 and 23 µg/ml, respectively. Besides, dichloromethane extract displayed the utmost anti-inflammatory activity, inhibiting NO release over 100 % at 80 µg/ml in LPS-stimulated RAW 264.7. Taken together, these finding suggest that R. vermiculata exhibited an interesting biological activities which may be related to the phenolic composition of this plant. Moreover, the identification of phenolic compounds in R. vermiculata dichloromethane extract using RP-HPLC revealed that myricetin was the major molecule. These results allow us to propose R. vermiculata as a valuable source for bioactive and natural compounds exhibiting interesting biological capacities. PMID:27298615

Biologically active perspective synthesis of heteroannulated 8-nitroquinolines with green chemistry approach.

PubMed

Arasakumar, Thangaraj; Mathusalini, Sadasivam; Gopalan, Subashini; Shyamsivappan, Selvaraj; Ata, Athar; Mohan, Palathurai Subramaniam

2017-04-01

A new class of pyrazolo[4,3-c]quinoline (5a-i, 7a-b) and pyrano[3,2-c]quinoline (9a-i) derivatives were designed and synthesized in moderate to good yields by microwave conditions. To enhance the yield of pyrano[3,2-c]quinoline derivatives, multicomponent one-pot synthesis has been developed. The synthesized compounds were identified by spectral and elemental analyses. Compounds 9a and 9i showed good antibacterial activity against Gram-positive and Gram-negative bacterial strains. All of the new compounds exhibited weak to moderate antioxidant activity, compound 9d exerted significant antioxidant power. The cytotoxicity of these compounds were also evaluated against MCF-7 (breast) and A549 (Lung) cancer cell lines. Most of the compounds displayed moderate to good cytotoxic activity against these cell lines. Compound 9i was found to be significantly active in this assay and also induced cell death by apoptosis. Molecular docking studies were carried out using EGFR inhibitor in order to determine the molecular interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dapson in heterocyclic chemistry, part VIII: synthesis, molecular docking and anticancer activity of some novel sulfonylbiscompounds carrying biologically active 1,3-dihydropyridine, chromene and chromenopyridine moieties.

PubMed

Al-Said, Mansour S; Ghorab, Mostafa M; Nissan, Yassin M

2012-07-02

Several new sulfonebiscompounds having a biologically active 1,2-dihydropyridine-2-one 3-19, acrylamide 20, chromene 21, 22 and chromenopyridine 23, 24 moieties were synthesized and evaluated as potential anticancer agents. The structures of the products were confirmed via elemental analyses and spectral data. The screening tests showed that many of the biscompounds obtained exhibited good anticancer activity against human breast cell line (MCF7) comparable to doxorubicin which was used as reference drug. Compounds 11, 17 and 24 showed IC50 values 35.40 μM, 29.86 μM and 30.99 μM, respectively. In order to elucidate the mechanism of action of the synthesized compounds as anticancer agents, docking on the active site of farnesyltransferase and arginine methyltransferase was also performed and good results were obtained.

Synthesis and Free Radical Scavenging Activity of New Hydroxybenzylidene Hydrazines.

PubMed

Sersen, Frantisek; Gregan, Fridrich; Kotora, Peter; Kmetova, Jarmila; Filo, Juraj; Loos, Dusan; Gregan, Juraj

2017-05-29

Hydroxybenzylidene hydrazines exhibit a wide spectrum of biological activities. Here, we report synthesis and free radical scavenging activity of nine new N-(hydroxybenzylidene)-N'-[2,6-dinitro-4-(trifluoromethyl)]phenylhydrazines. The chemical structures of these compounds were confirmed by 1H-NMR, 13C-NMR, 19F-NMR, IR spectroscopy, LC-MS, and elemental analysis. The prepared compounds were tested for their activity to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), galvinoxyl radical (GOR), and 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulphonic acid (ABTS) radicals. The free radical scavenging activity expressed as SC50 values of these compounds varied in a wide range, from a strong to no radical scavenging effect. The most effective radical scavengers were hydroxybenzylidene hydrazines containing three hydroxyl groups in the benzylidene part of their molecules. The prepared compounds were also tested for their activity to inhibit photosynthetic electron transport in spinach chloroplasts. IC50 values of these compounds varied in wide range, from an intermediate to no inhibitory effect.

The Mulberry (Morus alba L.) Fruit-A Review of Characteristic Components and Health Benefits.

PubMed

Yuan, Qingxia; Zhao, Longyan

2017-12-06

Mulberry (Morus alba L.) fruit has a high yield in one fruiting season in many countries, especially in Asia, and a long history of use as an edible fruit and traditional medicine. A great diversity of nutritive compounds such as fatty acids, amino acids, vitamins, minerals, and bioactive compounds, including anthocyanins, rutin, quercetin, chlorogenic acid, and polysaccharides have been found in mulberry fruit depending on the cultivars and maturity stages. Furthermore, the extracts and active components of mulberry fruit have demonstrated numerous biological activities, including antioxidant, neuroprotective, antiatherosclerosis, immunomodulative, antitumor, antihyperglycemic, and hypolipidemic activities in in vitro and in vivo studies, and they have received increasing interest from researchers and pharmaceutical companies. Although some mechanistic studies further substantiate these potential health benefits of mulberry fruit, a need exists to make a better understanding of the roles of these compounds in traditional medicine and the diet. This review provides recent findings regarding the chemical constituents and biological activities of mulberry fruit, which may be useful for stimulating deep research of mulberry fruit and for predicting their uses as important and safe contributors to benefit human health.

Metabolic profile and biological activities of Lavandula pedunculata subsp. lusitanica (Chaytor) Franco: studies on the essential oil and polar extracts.

PubMed

Costa, Patrícia; Gonçalves, Sandra; Valentão, Patrícia; Andrade, Paula B; Almeida, Carlos; Nogueira, José M F; Romano, Anabela

2013-12-01

We investigated the metabolic profile and biological activities of the essential oil and polar extracts of Lavandula pedunculata subsp. lusitanica (Chaytor) Franco collected in south Portugal. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that oxygen-containing monoterpenes was the principal group of compounds identified in the essential oil. Camphor (40.6%) and fenchone (38.0%) were found as the major constituents. High-performance liquid chromatography with diode array detection (HPLC-DAD) analysis allowed the identification of hydroxycinnamic acids (3-O-caffeoylquinic, 4-O-caffeoylquinic, 5-O-caffeoylquinic and rosmarinic acids) and flavones (luteolin and apigenin) in the polar extracts, with rosmarinic acid being the main compound in most of them. The bioactive compounds from L. pedunculata polar extracts were the most efficient free-radical scavengers, Fe(2+) chelators and inhibitors of malondialdehyde production, while the essential oil was the most active against acetylcholinesterase. Our results reveal that the subspecies of L. pedunculata studied is a potential source of active metabolites with a positive effect on human health. Copyright © 2013 Elsevier Ltd. All rights reserved.

Concise Synthesis and Biological Evaluation of 2-Aroyl-5-Amino Benzo[b]thiophene Derivatives As a Novel Class of Potent Antimitotic Agents

PubMed Central

Romagnoli, Romeo; Baraldi, Pier Giovanni; Lopez-Cara, Carlota; Preti, Delia; Tabrizi, Mojgan Aghazadeh; Balzarini, Jan; Bassetto, Marcella; Brancale, Andrea; Fu, Xian-Hua; Gao, Yang; Li, Jun; Zhang, Su-Zhan; Hamel, Ernest; Bortolozzi, Roberta; Basso, Giuseppe; Viola, Giampietro

2014-01-01

The biological importance of microtubules make them an interesting target for the synthesis of antitumor agents. The 2-(3′,4′,5′-trimethoxybenzoyl)-5-aminobenzo[b]thiophene moiety was identified as a novel scaffold for the preparation of potent inhibitors of microtubule polymerization acting through the colchicine site of tubulin. The position of the methoxy group on the benzo[b]thiophene was important for maximal antiproliferative activity. Structure–activity relationship analysis established that the best activities were obtained with amino and methoxy groups placed at the C-5 and C-7 positions, respectively. Compounds 3c–e showed more potent inhibition of tubulin polymerization than combretastatin A-4 and strong binding to the colchicine site. These compounds also demonstrated substantial antiproliferative activity, with IC50 values ranging from 2.6 to 18 nM in a variety of cancer cell lines. Importantly, compound 3c (50 mg/kg), significantly inhibited the growth of the human osteosarcoma MNNG/HOS xenograft in nude mice. PMID:24164557

Effect-based assessment of persistent organic pollutant and pesticide dumpsite using mammalian CALUX reporter cell lines.

PubMed

Pieterse, B; Rijk, I J C; Simon, E; van Vugt-Lussenburg, B M A; Fokke, B F H; van der Wijk, M; Besselink, H; Weber, R; van der Burg, B

2015-10-01

A combined chemical and biological analysis of samples from a major obsolete pesticide and persistent organic pollutant (POP) dumpsite in Northern Tajikistan was carried out. The chemical analytical screening focused on a range of prioritized compounds and compounds known to be present locally. Since chemical analytics does not allow measurements of hazards in complex mixtures, we tested the use of a novel effect-based approach using a panel of quantitative high-throughput CALUX reporter assays measuring distinct biological effects relevant in hazard assessment. Assays were included for assessing effects related to estrogen, androgen, and progestin signaling, aryl hydrocarbon receptor-mediated signaling, AP1 signaling, genotoxicity, oxidative stress, chemical hypoxia, and ER stress. With this panel of assays, we first quantified the biological activities of the individual chemicals measured in chemical analytics. Next, we calculated the expected sum activity by these chemicals in the samples of the pesticide dump site and compared the results with the measured CALUX bioactivity of the total extracts of these samples. The results showed that particularly endocrine disruption-related effects were common among the samples. This was consistent with the toxicological profiles of the individual chemicals that dominated these samples. However, large discrepancies between chemical and biological analysis were found in a sample from a burn place present in this site, with biological activities that could not be explained by chemical analysis. This is likely to be caused by toxic combustion products or by spills of compounds that were not targeted in the chemical analysis.

Review on fate and mechanism of removal of pharmaceutical pollutants from wastewater using biological approach.

PubMed

Tiwari, Bhagyashree; Sellamuthu, Balasubramanian; Ouarda, Yassine; Drogui, Patrick; Tyagi, Rajeshwar D; Buelna, Gerardo

2017-01-01

Due to research advancement and discoveries in the field of medical science, maintains and provides better human health and safer life, which lead to high demand for production of pharmaceutical compounds with a concomitant increase in population. These pharmaceutical (biologically active) compounds were not fully metabolized by the body and excreted out in wastewater. This micro-pollutant remains unchanged during wastewater treatment plant operation and enters into the receiving environment via the discharge of treated water. Persistence of pharmaceutical compounds in both surface and ground waters becomes a major concern due to their potential eco-toxicity. Pharmaceuticals (emerging micro-pollutants) deteriorate the water quality and impart a toxic effect on living organisms. Therefore, from last two decades, plenty of studies were conducted on the occurrence, impact, and removal of pharmaceutical residues from the environment. This review provides an overview on the fate and removal of pharmaceutical compounds via biological treatment process. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthesis and biological evaluation of manzamine analogues.

PubMed

Winkler, Jeffrey D; Londregan, Allyn T; Ragains, Justin R; Hamann, Mark T

2006-07-20

[Structure: see text] The synthesis and biological evaluation of a series of analogues of manzamine A, representing partial structures of the pentacyclic ABCDE diamine core, is described. All new compounds were screened against Plasmodium falciparum and demonstrated attenuated antimalarial activity relative to that of manzamine A.

Use of Primary Human Cell Systems for Creating Predictive Toxicology Profiles

EPA Science Inventory

Use of cellular regulatory networks to detect and distinguish effects of compounds with a broad range of on- and off-target mechanisms and biological processes provides an opportunity to understand toxicity mechanisms of action. Here we use the Biologically Multiplexed Activity P...

Valuable natural products from marine and freshwater macroalgae obtained from supercritical fluid extracts.

PubMed

Messyasz, Beata; Michalak, Izabela; Łęska, Bogusława; Schroeder, Grzegorz; Górka, Bogusława; Korzeniowska, Karolina; Lipok, Jacek; Wieczorek, Piotr; Rój, Edward; Wilk, Radosław; Dobrzyńska-Inger, Agnieszka; Górecki, Henryk; Chojnacka, Katarzyna

2018-01-01

The biologically active compounds (fatty acids, pigments, phenolics, and flavonoid content) were studied in supercritical fluid extracts from the biomass of marine ( Ulva clathrata , Cladophora glomerata , Polysiphonia fucoides , and their multi-species mixture) and freshwater ( C. glomerata ) macroalgae. Different extraction techniques were used in order to compare differences in the biologically active compound composition of the macroalgal extracts. The results indicated that the saturated and unsaturated fatty acids ranged from C9:0 to C22:0. The analysis of differences in the composition of unsaturated to saturated fatty acids in extracts showed that palmitic acid (C16:0) and oleic acid (C18:1, n-9) reached the highest value not only in marine monospecies and multi-species biomass but also in the freshwater macroalga C. glomerata . When comparing the similarity between the concentration of fatty acids and the ratio of the concentration of unsaturated fatty acids to saturated in macroalgal extracts, we found small but not statistically significant variations in values between years (up to 10%). This is acceptable for applications as a stable raw material for industrial purposes. Significantly higher values of fatty acids, carotenoids, and chlorophylls were obtained in the case of SC-CO 2 extraction. The active ingredients of polyphenols, possessing antioxidant activity ranged from approximately 2-4%. Moreover, flavonoids represented less than 10% of the total content of polyphenolic compounds. The extraction efficiency of polyphenols was higher from a mixture of marine algae for the ultrasound-assisted extraction compared to freshwater. All these findings show that marine and freshwater macroalgae, as a raw material, have the optimal biologically active compounds composition for cosmetics.

Novel urea and bis-urea primaquine derivatives with hydroxyphenyl or halogenphenyl substituents: Synthesis and biological evaluation.

PubMed

Perković, I; Antunović, M; Marijanović, I; Pavić, K; Ester, K; Kralj, M; Vlainić, J; Kosalec, I; Schols, D; Hadjipavlou-Litina, D; Pontiki, E; Zorc, B

2016-11-29

A series of novel compounds 3a-j and 6a-j with primaquine and hydroxyl or halogen substituted benzene moieties bridged by urea or bis-urea functionalities were designed, synthesized and evaluated for biological activity. The title compounds were prepared using benzotriazole as the synthon, through several synthetic steps. 3-[3,5-Bis(trifluoromethyl)phenyl]-1-{4-[(6-methoxyquinolin-8-yl)amino]pentyl}urea (3j) was the most active urea and 1-[({4-[(6-methoxyquinolin-8-yl)amino]pentyl}carbamoyl)amino]-3-[3-(trifluoromethyl)phenyl]urea (6h) the most active bis-urea derivative in antiproliferative screening in vitro against eight tested cancer cell lines. Urea derivatives 3a-g with hydroxy group or one halogen atom showed moderate antiproliferative effects against all the tested cell lines, but stronger activity against breast carcinoma MCF-7 cell line, while trifluoromethyl derivatives 3h-j showed antiproliferative effects against all the tested cell lines in low micromolar range. Finally, bis-ureas with hydroxy and fluoro substituents 6a-d showed extreme selectivity and chloro or bromo derivatives 6e-g high selectivity against MCF-7 cells (IC 50 0.1-2.6 μM). p-Fluoro derivative 6d, namely 3-(4-fluorophenyl)-1-[({4-[(6-methoxyquinolin-8-yl)amino]pentyl}carbamoyl)amino]urea, is the most promising compound. Further biological experiments showed that 6d affected cell cycle and induced cell death of MCF-7 cell line. Due to its high activity against MCF-7 cell line (IC 50 0.31 μM), extreme selectivity and full agreement with the Lipinski's and Gelovani's rules for prospective small molecular drugs, 6d may be considered as a lead compound in development of breast carcinoma drugs. Urea 3b and almost all bis-ureas showed high antioxidant activity in DPPH assay, but urea derivatives were more active in lipid peroxidation test. Only few compounds exhibited weak inhibition of soybean lipoxygenase. Compound 3j exhibited the strongest antimicrobial activity in susceptibility assay in vitro (MIC = 1.6-12.5 μg ml -1 ). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Exploring Marine Cyanobacteria for Lead Compounds of Pharmaceutical Importance

PubMed Central

Uzair, Bushra; Tabassum, Sobia; Rasheed, Madiha; Rehman, Saima Firdous

2012-01-01

The Ocean, which is called the “mother of origin of life,” is also the source of structurally unique natural products that are mainly accumulated in living organisms. Cyanobacteria are photosynthetic prokaryotes used as food by humans. They are excellent source of vitamins and proteins vital for life. Several of these compounds show pharmacological activities and are helpful for the invention and discovery of bioactive compounds, primarily for deadly diseases like cancer, acquired immunodeficiency syndrome (AIDS), arthritis, and so forth, while other compounds have been developed as analgesics or to treat inflammation, and so forth. They produce a large variety of bioactive compounds, including substances with anticancer and antiviral activity, UV protectants, specific inhibitors of enzymes, and potent hepatotoxins and neurotoxins. Many cyanobacteria produce compounds with potent biological activities. This paper aims to showcase the structural diversity of marine cyanobacterial secondary metabolites with a comprehensive coverage of alkaloids and other applications of cyanobacteria. PMID:22545008

Novel coumarins and related copper complexes with biological activity: DNA binding, molecular docking and in vitro antiproliferative activity.

PubMed

Pivetta, Tiziana; Valletta, Elisa; Ferino, Giulio; Isaia, Francesco; Pani, Alessandra; Vascellari, Sarah; Castellano, Carlo; Demartin, Francesco; Cabiddu, Maria Grazia; Cadoni, Enzo

2017-12-01

Coumarins show biological activity and are widely exploited for their therapeutic effects. Although a great number of coumarins substituted by heterocyclic moieties have been prepared, few studies have been carried out on coumarins containing pyridine heterocycle, which is known to modulate their physiological activities. We prepared and characterized three novel 3-(pyridin-2-yl)coumarins and their corresponding copper(II) complexes. We extended our investigations also to three known similar coumarins, since no data about their biochemical activity was previously been reported. The antiproliferative activity of the studied compounds was tested against human derived tumor cell lines and one human normal cell line. The DNA binding constants were determined and docking studies with DNA carried out. Selected Quantitative Structure-Activity Relationship (QSAR) descriptors were calculated in order to relate a set of structural and topological descriptors of the studied compounds to their DNA interaction and cytotoxic activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Synthesis and biological evaluation of kresoxim-methyl analogues as novel inhibitors of hypoxia-inducible factor (HIF)-1 accumulation in cancer cells.

PubMed

Lee, Sanghyuck; Kwon, Oh Seok; Lee, Chang-Soo; Won, Misun; Ban, Hyun Seung; Ra, Choon Sup

2017-07-01

We designed and synthesized strobilurin analogues as hypoxia-inducible factor (HIF) inhibitors based on the molecular structure of kresoxim-methyl. Biological evaluation in human colorectal cancer HCT116 cells showed that most of the synthesized kresoxim-methyl analogues possessed moderate to potent inhibitory activity against hypoxia-induced HIF-1 transcriptional activation. Three candidates, compounds 11b, 11c, and 11d were identified as potent inhibitors against HIF-1 activation with IC 50 values of 0.60-0.94µM. Under hypoxic condition, compounds 11b, 11c, and 11d increased the intracellular oxygen contents, thereby attenuating the hypoxia-induced accumulation of HIF-1α protein. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biologically Active Metabolites Synthesized by Microalgae

PubMed Central

Costa, Jorge Alberto Vieira

2015-01-01

Microalgae are microorganisms that have different morphological, physiological, and genetic traits that confer the ability to produce different biologically active metabolites. Microalgal biotechnology has become a subject of study for various fields, due to the varied bioproducts that can be obtained from these microorganisms. When microalgal cultivation processes are better understood, microalgae can become an environmentally friendly and economically viable source of compounds of interest, because production can be optimized in a controlled culture. The bioactive compounds derived from microalgae have anti-inflammatory, antimicrobial, and antioxidant activities, among others. Furthermore, these microorganisms have the ability to promote health and reduce the risk of the development of degenerative diseases. In this context, the aim of this review is to discuss bioactive metabolites produced by microalgae for possible applications in the life sciences. PMID:26339647

Development and Mining of a Volatile Organic Compound Database

PubMed Central

Abdullah, Azian Azamimi; Ono, Naoaki; Sugiura, Tadao; Morita, Aki Hirai; Katsuragi, Tetsuo; Muto, Ai; Nishioka, Takaaki; Kanaya, Shigehiko

2015-01-01

Volatile organic compounds (VOCs) are small molecules that exhibit high vapor pressure under ambient conditions and have low boiling points. Although VOCs contribute only a small proportion of the total metabolites produced by living organisms, they play an important role in chemical ecology specifically in the biological interactions between organisms and ecosystems. VOCs are also important in the health care field as they are presently used as a biomarker to detect various human diseases. Information on VOCs is scattered in the literature until now; however, there is still no available database describing VOCs and their biological activities. To attain this purpose, we have developed KNApSAcK Metabolite Ecology Database, which contains the information on the relationships between VOCs and their emitting organisms. The KNApSAcK Metabolite Ecology is also linked with the KNApSAcK Core and KNApSAcK Metabolite Activity Database to provide further information on the metabolites and their biological activities. The VOC database can be accessed online. PMID:26495281

HDAC inhibitors: a 2013-2017 patent survey.

PubMed

Faria Freitas, Micaela; Cuendet, Muriel; Bertrand, Philippe

2018-04-19

Zinc-dependent histone deacetylases (HDAC) inhibitors represent an important class of biologically active compounds with four of them approved by the FDA. A wide range of molecules has been reported for applications in several human diseases.Area covered: This review covers recent efforts in the synthesis and applications of HDAC inhibitors from 2013-2017.Expert opinion: HDAC inhibitors represent an important class of biologically active compounds for single or combination therapies. The current synthetic methodologies are oriented towards selective HDAC isoforms to achieve better therapeutic effects. Among the recent patents available, most of them focus on HDAC6 selective inhibitors. Beside this search for isoform selectivity, the quest for zinc binding groups with better pharmacokinetic properties and high potency against HDACs only motivates medicinal chemists, as well as the design of inhibitors targeting HDACs and at the same time another biological target. If the major applications are for anticancer activity, one can note the emerging applications in neurological or metabolic disorders or for the stimulation of the immune system.

Design, synthesis, and biological evaluation of 6-methoxy-2-arylquinolines as potential P-glycoprotein inhibitors.

PubMed

Aboutorabzadeh, Sayyed Mohammad; Mosaffa, Fatemeh; Hadizadeh, Farzin; Ghodsi, Razieh

2018-01-01

In the present study, a new series of 6-methoxy-2-arylquinoline analogues was designed and synthesized as P-glycoprotein (P-gp) inhibitors using quinine and flavones as the lead compounds. The cytotoxic activity of the synthesized compounds was evaluated against two human cancer cell lines including EPG85-257RDB, multidrug-resistant gastric carcinoma cells (P-gp-positive gastric carcinoma cell line), and EPG85-257P, drug-sensitive gastric carcinoma cells. Compounds showing low to moderate toxicity in the MTT test were selected to investigate their P-gp inhibition activity. Moreover, trying to explain the results of biological experiments, docking studies of the selected compounds into the homology-modeled human P-gp, were carried out. The physicochemical and ADME properties of the compounds as drug candidate were also predicted. Most of our compounds exhibited negligible or much lower cytotoxic effect in both cancer cells. Among the series, 5a and 5b, alcoholic quinoline derivatives were found to inhibit the efflux of rhodamine 123 at the concentration of 10 μM significantly. Among the tested quinolines, 5a and 5b showed the most potent P-gp inhibitory activity in the series and were 1.3-fold and 2.1-fold stronger than verapamil, respectively. SAR data revealed that hydroxyl methyl in position 4 of quinolines has a key role in P-gp efflux inhibition of our compounds. ADME studies suggested that all of the compounds included in this study may have a good human intestinal absorption.

Design, synthesis and biological screening of some pyridinylpyrazole and pyridinylisoxazole derivatives as potential anti-inflammatory, analgesic, antipyretic and antimicrobial agents.

PubMed

El-Hawash, Soad A M; Soliman, Raafat; Youssef, Amal M; Ragab, Hanan M A; Elzahhar, Perihan A S; El-Ashmawey, Ibrahim M; Abdel Wahab, Abeer E; Shaat, Iman A

2014-05-01

A series of substituted pyridinylpyrazole (or isoxazole) derivatives were synthesized and evaluated for their anti-inflammatory (AI) activity using formalin-induced paw edema bioassays. Their inhibitory activities of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) were also determined. The analgesic activity of the same compounds was evaluated using rat-tail withdrawal technique. Their antipyretic activity was also evaluated. The results revealed that compounds 4a,b, 6a, 8a, 14c and 15a exhibited significant AI and analgesic activities. Compounds 5a, 6a and 8a displayed good antipyretic activity. Compounds 14c and 15a showed good COX-2 inhibitory activity and weak inhibition of COX-1. Additionally, the most active compounds were shown to have a large safety margin (ALD50 >300-400 mg / Kg) and minimal ulcerogenic potentialities when administered orally at a dose of 300 mg/Kg. Docking studies for 14c and 15a with COX-2 showed good binding profile. Antimicrobial evaluation proved that most of the compounds exhibited distinctive activity against the gram negative bacteria, P. aeruginosa and E coli.

Novel non-trimethoxylphenyl piperlongumine derivatives selectively kill cancer cells.

PubMed

Zhang, Youjun; Ma, Hao; Wu, Yuelin; Wu, Zhongli; Yao, Zhengguang; Zhang, Wannian; Zhuang, Chunlin; Miao, Zhenyuan

2017-06-01

Piperlongumine (PL) is a natural alkaloid with broad biological activities. Twelve analogues have been designed and synthesized with non-substituted benzyl rings or heterocycles in this work. Most of the compounds showed better anticancer activities than the parent PL without apparent toxicity in normal cells. Elevation of cellular ROS levels was one of the main anticancer mechanisms of these compounds. Cell apoptosis and cell cycle arrest for the best compound ZM90 were evaluated and similar mechanism of action with PL was demonstrated. The SAR was also characterized, providing worthy directions for further optimization of PL compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dihydroagarofuranoid Sesquiterpenes as Acetylcholinesterase Inhibitors from Celastraceae Plants: Maytenus disticha and Euonymus japonicus.

PubMed

Alarcón, Julio; Cespedes, Carlos L; Muñoz, Evelyn; Balbontin, Cristian; Valdes, Francisco; Gutierrez, Margarita; Astudillo, Luis; Seigler, David S

2015-12-02

Natural cholinesterase inhibitors have been found in many biological sources. Nine compounds with agarofuran (epoxyeudesmane) skeletons were isolated from seeds and aerial parts of Maytenus disticha and Euonymus japonicus. The identification and structural elucidation of compounds were based on spectroscopic data analyses. All compounds had inhibitory acetylcholinesterase (AChE) activity. These natural compounds, which possessed mixed or uncompetitive mechanisms of inhibitory activity against AChE, may be considered as models for the design and development of new naturally occurring drugs for management strategies for neurodegenerative diseases. This is the first report of these chemical structures for seeds of M. disticha.

Study Approach of Antioxidant Properties in Foods: Update and Considerations.

PubMed

Durazzo, Alessandra

2017-02-28

The assessment of interactions between natural antioxidants and other food matrix components represents the main step in the investigation of total antioxidant properties, in terms of potential health benefits. The diversity of chemical structures of natural compounds, besides their possible interactions, as well as the biological role and different modes of action makes it difficult to assess a single and reliable procedure for the evaluation of antioxidant activity. Today, much attention is given to the distinction between extractable and non-extractable antioxidants as a key tool in the description of the nutritional and healthy properties of food matrices. The starting point for the investigation of antioxidant effects of food extracts is the analysis of antioxidant properties of pure compounds and their interactions. Another complementary approach could be represented by the study of how different biologically active compound-rich extracts contribute to the total antioxidant capacity.

Study Approach of Antioxidant Properties in Foods: Update and Considerations

PubMed Central

Durazzo, Alessandra

2017-01-01

The assessment of interactions between natural antioxidants and other food matrix components represents the main step in the investigation of total antioxidant properties, in terms of potential health benefits. The diversity of chemical structures of natural compounds, besides their possible interactions, as well as the biological role and different modes of action makes it difficult to assess a single and reliable procedure for the evaluation of antioxidant activity. Today, much attention is given to the distinction between extractable and non-extractable antioxidants as a key tool in the description of the nutritional and healthy properties of food matrices. The starting point for the investigation of antioxidant effects of food extracts is the analysis of antioxidant properties of pure compounds and their interactions. Another complementary approach could be represented by the study of how different biologically active compound-rich extracts contribute to the total antioxidant capacity. PMID:28264480

Analysis of defense signals in Arabidopsis thaliana leaves by ultra-performance liquid chromatography/tandem mass spectrometry: jasmonates, salicylic acid, abscisic acid.

PubMed

Stingl, Nadja; Krischke, Markus; Fekete, Agnes; Mueller, Martin J

2013-01-01

Defense signaling compounds and phytohormones play an essential role in the regulation of plant responses to various environmental abiotic and biotic stresses. Among the most severe stresses are herbivory, pathogen infection, and drought stress. The major hormones involved in the regulation of these responses are 12-oxo-phytodienoic acid (OPDA), the pro-hormone jasmonic acid (JA) and its biologically active isoleucine conjugate (JA-Ile), salicylic acid (SA), and abscisic acid (ABA). These signaling compounds are present and biologically active at very low concentrations from ng/g to μg/g dry weight. Accurate and sensitive quantification of these signals has made a significant contribution to the understanding of plant stress responses. Ultra-performance liquid chromatography (UPLC) coupled with a tandem quadrupole mass spectrometer (MS/MS) has become an essential technique for the analysis and quantification of these compounds.

Photoelectron spectra and biological activity of cinnamic acid derivatives revisited

NASA Astrophysics Data System (ADS)

Novak, Igor; Klasinc, Leo; McGlynn, Sean P.

2018-01-01

The electronic structures of several derivatives of cinnamic acid have been studied by UV photoelectron spectroscopy (UPS) and Green's function quantum chemical calculations. The spectra reveal the presence of dimers in the gas phase for p-coumaric and ferulic acids. The electronic structure analysis has been related to the biological properties of these compounds through the analysis of some structure-activity relationships (SAR).

The synthesis and biological activity of 4-[bis(2-chloroethyl)amino]-DL-, L, and D-phenylalanine amides and peptides

NASA Astrophysics Data System (ADS)

Krasnov, Victor P.; Zhdanova, E. A.; Smirnova, L. I.

1995-11-01

The review is devoted to the synthesis and biological properties of the amides and peptides containing the stereoisomers of 4-[bis(2-chloroethyl)amino]phenylalanine. The approaches to the selection of the structures of the compounds indicated, ensuring an increase in the selectivity of their antitumour activity, are examined. The bibliography includes 131 references.

Biological activity of some derivatives of β-cyclodextrin.

PubMed

Batalova, T A; Dorovskich, V A; Kurochkina, G I; Grachev, M K; Plastinin, M L; Sergievich, A A

2011-10-01

New compounds of β-cyclodextrin containing covalently bound (conjugated) residues of acetylsalicylic and 1-(4-isobutylphenyl)-propionic acids were synthesized in the reaction of chlorides of the corresponding acids with β-cyclodextrin. We studied antiplatelet and antiphlogistic properties of these substances. It was shown that new compounds are comparable and in some cases are superior to the reference drugs acetylsalicylic acid and ibuprofen by anti-inflammatory and antiaggregant activities.

Synthesis, anti-inflammatory, bactericidal activities and docking studies of novel 1,2,3-triazoles derived from ibuprofen using click chemistry.

PubMed

Angajala, Kishore Kumar; Vianala, Sunitha; Macha, Ramesh; Raghavender, M; Thupurani, Murali Krishna; Pathi, P J

2016-01-01

Nonsteroidal anti-inflammatory drugs are of vast therapeutic benefit in the treatment of different types of inflammatory conditions. 1,2,3-Triazoles and their derivatives have a wide range of applications as anti-bacterial, anti-fungal, anti-tubercular, cytostatic, anti-HIV, anti-allergic, anti-neoplastic and anti-inflammatory (AI) agents. Considering the individual biological and medicinal importance of ibuprofen and 1,2,3-triazoles, we wanted to explore novel chemical entities based on ibuprofen and triazole moieties towards their biological significance. Click chemistry has utilized as an ideal strategy to prepare novel ibuprofen-based 1,4-disubstituted 1,2,3-triazole containing molecules. These compounds were screened for their in vivo AI activity, among all the synthesized analogues 13o was shown potent effect than the reference AI drug ibuprofen at the same concentration (10 mg/kg body weight). Compounds 13l, 13g, 13c, 13k, 13i, 13n, 13m and 13j were shown significant AI activity. These triazole analogues were also screened for their bactericidal profile. Compounds 13c, 13i, 13l and 13o exhibited considerable bactericidal activity against gram positive and gram negative strains. In addition to this, molecular docking studies were also carried out into cyclooxygenase-2 active site to predict the affinity and orientation of these novel compounds (13a-q). In summary, we have designed and synthesized 1,2,3-triazole analogues of ibuprofen in good yields using Click chemistry approach. AI and bactericidal activities of these compounds were evaluated and shown remarkable results.

Derivatives of diphosphonic acids: synthesis and biological activity

NASA Astrophysics Data System (ADS)

Zolotukhina, M. M.; Krutikov, V. I.; Lavrent'ev, A. N.

1993-07-01

The scientific-technical and patent literature on the synthesis of derivatives of diphosphonic acids is surveyed. Various methods of synthesis of diphosphonate, phosphonylphosphinyl, and phosphonophosphate compounds are described. The principal aspects of the use of the above compounds in medicine, biochemistry, and agriculture are examined. The bibliography includes 174 references.

FATE OF PAH COMPOUNDS IN TWO SOIL TYPES: INFLUENCE OF VOLATILIZATION, ABIOTIC LOSS, AND BIOLOGICAL ACTIVITY

EPA Science Inventory

The fate of 14 polycyclic aromatic hydrocarbon (PAH) compounds was evaluated with regard to interphase transfer potential and mechanisms of treatment in soil under unsaturated conditions. Volatilization and abiotic and biotic fate of the PAHs were determined using two soils not p...

Inquiry-Based Instruction of Compound Microscopy Using Simulated Paleobiogeography

ERIC Educational Resources Information Center

Hodgson, Jay Y. S.; Mateer, Scott C.

2015-01-01

The compound microscope is an important tool in biology, and mastering it requires repetition. Unfortunately, introductory activities for students can be formulaic, and consequently, students are often unengaged and fail to develop the required experience to become proficient in microscopy. To engage students, increase repetition, and develop…

The activation of fibroblast growth factors by heparin: synthesis, structure, and biological activity of heparin-like oligosaccharides.

PubMed

de Paz, J L; Angulo, J; Lassaletta, J M; Nieto, P M; Redondo-Horcajo, M; Lozano, R M; Giménez-Gallego, G; Martín-Lomas, M

2001-09-03

An effective strategy has been designed for the synthesis of oligosaccharides of different sizes structurally related to the regular region of heparin; this is illustrated by the preparation of hexasaccharide 1 and octasaccharide 2. This synthetic strategy provides the oligosaccharide sequence containing a D-glucosamine unit at the nonreducing end that is not available either by enzymatic or chemical degradation of heparin. It may permit, after slight modifications, the preparation of oligosaccharide fragments with different charge distribution as well. NMR spectroscopy and molecular dynamics simulations have shown that the overall structure of 1 in solution is a stable right-hand helix with four residues per turn. Hexasaccharide 1 and, most likely, octasaccharide 2 are, therefore, chemically well-defined structural models of naturally occurring heparin-like oligosaccharides for use in binding and biological activity studies. Both compounds 1 and 2 induce the mitogenic activity of acid fibroblast growth factor (FGF1), with the half-maximum activating concentration of 2 being equivalent to that of heparin. Sedimentation equilibrium analysis with compound 2 suggests that heparin-induced FGF1 dimerization is not an absolute requirement for biological activity.

Potential amoebicidal activity of hydrazone derivatives: synthesis, characterization, electrochemical behavior, theoretical study and evaluation of the biological activity.

PubMed

Toledano-Magaña, Yanis; García-Ramos, Juan Carlos; Navarro-Olivarria, Marisol; Flores-Alamo, Marcos; Manzanera-Estrada, Mayra; Ortiz-Frade, Luis; Galindo-Murillo, Rodrigo; Ruiz-Azuara, Lena; Meléndrez-Luevano, Ruth Ma; Cabrera-Vivas, Blanca M

2015-05-29

Four new hydrazones were synthesized by the condensation of the selected hydrazine and the appropriate nitrobenzaldehyde. A complete characterization was done employing 1H- and 13C-NMR, electrochemical techniques and theoretical studies. After the characterization and electrochemical analysis of each compound, amoebicidal activity was tested in vitro against the HM1:IMSS strain of Entamoeba histolytica. The results showed the influence of the nitrobenzene group and the hydrazone linkage on the amoebicidal activity. meta-Nitro substituted compound 2 presents a promising amoebicidal activity with an IC50 = 0.84 μM, which represents a 7-fold increase in cell growth inhibition potency with respect to metronidazole (IC50 = 6.3 μM). Compounds 1, 3, and 4 show decreased amoebicidal activity, with IC50 values of 7, 75 and 23 µM, respectively, as a function of the nitro group position on the aromatic ring. The observed differences in the biological activity could be explained not only by the redox potential of the molecules, but also by their capacity to participate in the formation of intra- and intermolecular hydrogen bonds. Redox potentials as well as the amoebicidal activity can be described with parameters obtained from the DFT analysis.

Diversity of Secondary Metabolites from Marine Bacillus Species: Chemistry and Biological Activity

PubMed Central

Mondol, Muhammad Abdul Mojid; Shin, Hee Jae; Islam, Mohammad Tofazzal

2013-01-01

Marine Bacillus species produce versatile secondary metabolites including lipopeptides, polypeptides, macrolactones, fatty acids, polyketides, and isocoumarins. These structurally diverse compounds exhibit a wide range of biological activities, such as antimicrobial, anticancer, and antialgal activities. Some marine Bacillus strains can detoxify heavy metals through reduction processes and have the ability to produce carotenoids. The present article reviews the chemistry and biological activities of secondary metabolites from marine isolates. Side by side, the potential for application of these novel natural products from marine Bacillus strains as drugs, pesticides, carotenoids, and tools for the bioremediation of heavy metal toxicity are also discussed. PMID:23941823

Spectroscopic, thermal, catalytic and biological studies of Cu(II) azo dye complexes

NASA Astrophysics Data System (ADS)

El-Sonbati, A. Z.; Diab, M. A.; El-Bindary, A. A.; Shoair, A. F.; Hussein, M. A.; El-Boz, R. A.

2017-08-01

New complexes of copper(II) with azo compounds of 5-amino-2-(aryl diazenyl)phenol (HLn) are prepared and investigated by elemental analyses, molar conductance, IR, 1H NMR, UV-Visible, mass, ESR spectra, magnetic susceptibility measurements and thermal analyses. The complexes have a square planar structure and general formula [Cu(Ln)(OAc)]H2O. Study the catalytic activities of Cu(II) complexes toward oxidation of benzyl alcohol derivatives to carbonyl compounds were tested using H2O2 as the oxidant. The intrinsic binding constants (Kb) of the ligands (HLn) and Cu(II) complexes (1-4) with CT-DNA are determined. The formed compounds have been tested for biological activity of antioxidants, antibacterial against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria and yeast Candida albicans. Antibiotic (Ampicillin) and antifungal against (Colitrimazole) and cytotoxic compounds HL1, HL2, HL3 and complex (1) showed moderate to good activity against S. aureus, E. coli and Candida albicans, and also to be moderate on antioxidants and toxic substances. Molecular docking is used to predict the binding between the ligands with the receptor of breast cancer (2a91).

3-Acetyl-8-methoxy-2[H]-chromen-2-one derived Schiff bases as potent antiproliferative agents: Insight into the influence of 4(N)-substituents on the in vitro biological activity

NASA Astrophysics Data System (ADS)

Kalaiarasi, G.; Rex Jeya Rajkumar, S.; Aswini, G.; Dharani, S.; Fronczek, Frank R.; Prabhakaran, R.

2018-07-01

A series of 3-acetyl-8-methoxycoumarin appended thiosemicarbazones (1-4) was prepared from the reaction of 3-acetyl-8-methoxycoumarin with 4(N)-substituted thiosemicarbazides in a view of ascertaining their biological properties with the change of N-terminal substitution in the thiosemicarbazide moiety. Comprehensive characterization was brought about by various spectral and analytical methods. The molecular structures of all the compounds were determined by single crystal X-ray diffraction analysis. Binding studies with Calf thymus DNA (CT-DNA) and proteins such as Bovine Serum Albumin (BSA) and Human Serum Albumin (HSA) indicated an intercalative mode of binding with DNA and static quenching mechanism with proteins. The compounds cleaved plasmid DNA (pBR322) and acted well as free radical scavengers. A good spectrum of antimicrobial activity was observed against four bacterial and five fungal pathogens. The compounds exhibited profound antiproliferative activity on MCF-7 (human breast cancer) and A549 (human lung carcinoma) cell lines. Assay on human normal keratinocyte cell line HaCaT showed that the compounds were non-toxic to normal cells.

Carboxylesterase inhibitors

PubMed Central

Hatfield, M. Jason; Potter, Philip M.

2011-01-01

Introduction Carboxylesterases play major roles in the hydrolysis of numerous therapeutically active compounds. This is, in part, due to the prevalence of the ester moiety in these small molecules. However, the impact these enzymes may play on drug stability and pharmacokinetics is rarely considered prior to molecule development. Therefore, the application of selective inhibitors of this class of proteins may have utility in modulating the metabolism, distribution and toxicity of agents that are subjected to enzyme hydrolysis. Areas covered This review details the development of all such compounds dating back to 1986, but principally focuses on the very recent identification of selective human carboxylesterases inhibitors. Expert opinion The implementation of carboxylesterase inhibitors may significantly revolutionize drug discovery. Such molecules may allow for improved efficacy of compounds inactivated by this class of enzymes and/or reduce the toxicity of agents that are activated by these proteins. Furthermore, since lack of carboxylesterase activity appears to have no obvious biological consequence, these compounds could be applied in combination with virtually any esterified drug. Therefore, inhibitors of these proteins may have utility in altering drug hydrolysis and distribution in vivo. The characteristics, chemical and biological properties, and potential uses of such agents, are discussed here. PMID:21609191

The nematode Caenorhabditis elegans as a tool to predict chemical activity on mammalian development and identify mechanisms influencing toxicological outcome.

PubMed

Harlow, Philippa H; Perry, Simon J; Widdison, Stephanie; Daniels, Shannon; Bondo, Eddie; Lamberth, Clemens; Currie, Richard A; Flemming, Anthony J

2016-03-18

To determine whether a C. elegans bioassay could predict mammalian developmental activity, we selected diverse compounds known and known not to elicit such activity and measured their effect on C. elegans egg viability. 89% of compounds that reduced C. elegans egg viability also had mammalian developmental activity. Conversely only 25% of compounds found not to reduce egg viability in C. elegans were also inactive in mammals. We conclude that the C. elegans egg viability assay is an accurate positive predictor, but an inaccurate negative predictor, of mammalian developmental activity. We then evaluated C. elegans as a tool to identify mechanisms affecting toxicological outcomes among related compounds. The difference in developmental activity of structurally related fungicides in C. elegans correlated with their rate of metabolism. Knockdown of the cytochrome P450s cyp-35A3 and cyp-35A4 increased the toxicity to C. elegans of the least developmentally active compounds to the level of the most developmentally active. This indicated that these P450s were involved in the greater rate of metabolism of the less toxic of these compounds. We conclude that C. elegans based approaches can predict mammalian developmental activity and can yield plausible hypotheses for factors affecting the biological potency of compounds in mammals.

Design, synthesis and biological activity of 6-substituted carbamoyl benzimidazoles as new nonpeptidic angiotensin II AT₁ receptor antagonists.

PubMed

Zhang, Jun; Wang, Jin-Liang; Zhou, Zhi-Ming; Li, Zhi-Huai; Xue, Wei-Zhe; Xu, Di; Hao, Li-Ping; Han, Xiao-Feng; Fei, Fan; Liu, Ting; Liang, Ai-Hua

2012-07-15

A series of 6-substituted carbamoyl benzimidazoles were designed and synthesised as new nonpeptidic angiotensin II AT(1) receptor antagonists. The preliminary pharmacological evaluation revealed a nanomolar AT(1) receptor binding affinity for all compounds in the series, and a potent antagonistic activity in an isolated rabbit aortic strip functional assay for compounds 6f, 6g, 6h and 6k was also demonstrated. Furthermore, evaluation in spontaneous hypertensive rats and a preliminary toxicity evaluation showed that compound 6g is an orally active AT(1) receptor antagonist with low toxicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Synthesis and characterization of curcumin-sulfonamide hybrids: Biological evaluation and molecular docking studies

NASA Astrophysics Data System (ADS)

Banuppriya, Govindharasu; Sribalan, Rajendran; Padmini, Vediappen

2018-03-01

Curcumin-sulfonamide hybrids (4a-e) were synthesized and their in vitro antioxidant, anti-inflammatory and anticancer activities were studied. The synthesized compounds showed a very good potent activity towards antioxidant and anti-inflammatory studies rather than its parent as well as standard. These compounds have exhibited an excellent toxicity effect to the cancer cell lines such as A549 and AGS. The compounds 4a and 4c have showed good anticancer activity than curcumin. The molecular docking studies were also performed against various Epidermal Growth Factor Receptor (EGFR) enzymes. The DFT calculations were also done in order to support the docking results.

Synthesis, molecular docking, and biological evaluation of some novel hydrazones and pyrazole derivatives as anti-inflammatory agents.

PubMed

Mohammed, Khaled O; Nissan, Yassin M

2014-10-01

2-Hydrazinyl-N-(4-sulfamoylphenyl)acetamide 3 was the key intermediate for the synthesis of novel hydrazones 4-10 and pyrazole derivatives 11-17. All compounds were tested for their in vivo anti-inflammatory activity and their ability to inhibit the production of PGE(2) in serum samples of rats. IC(50) values for the most active compounds for inhibition of COX-1 and COX-2 enzymes were determined in vitro, and they were also tested for their ulcerogenic effect. Molecular docking was performed on the active site of COX-2 to predict their mode of binding to the amino acids. Most of the synthesized compounds showed good anti-inflammatory activity especially compounds 3, 4, 8, 9, 15, and 17 which showed better activity than diclofenac as the reference drug. Compounds 3, 8, 9, 13, and 15-17 were less ulcerogenic than indomethacine as the reference drug. Most of the synthesized compounds interacted with Tyr 385 and Ser 530 in molecular docking study with additional hydrogen bond for compound 17. Compound 17 showed good selectivity index value of 11.1 for COX-1/COX-2 inhibition in vitro. © 2014 John Wiley & Sons A/S.

Dioxin-like biological activity of organic extracts from sediments and fish livers sampled along the Israeli Mediterranean and Red Sea coasts.

PubMed

Yudkovski, Yana; Herut, Barak; Shefer, Edna; Tom, Moshe

2015-09-15

This study provides, for the first time, a baseline evaluation of dioxin-like biological activity in sediments and fish sampled in- and adjacent to anchorages along the Mediterranean and Red Sea coasts of Israel. It indicates the effect of past pollution, still present in the sediments of older Israeli harbors, with putative contribution of still existing sources of pollution. A commercial reporter gene bioassay was used to evaluate the biological activity of dioxin-like compounds extracted from the samples. HRGC/HRMS analysis of several samples contributed a profile of dioxin-like compounds in sediments and fish. The results point out 1,2,3,4,6,7,8-HeptaCDD, 2,3,4,6,7,8-HexaCDF, 1,2,3,4,6,7,8-HeptaCDF, РСВ-126 and РСВ-118 as major contributors to the dioxin-like activity in sediments. It indicates polychlorinated biphenyls non-selective absorption in fish livers, in contrary to a biased accumulation of poorly chlorinated and more potent dibenzodioxins and dibenzofurans. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cytotoxic grifolin derivatives isolated from the wild mushroom Boletus pseudocalopus (Basidiomycetes).

PubMed

Song, Junsik; Manir, Md Maniruzzaman; Moon, Surk-Sik

2009-09-01

Activity-guided purification of a MeOH extract of the Korean wild mushroom Boletus pseudocalopus afforded three new grifolin derivatives, 1-3, along with four known phenolic compounds 4-7. Their structures were established by a combination of 1H- and 13C-NMR, NOESY, and extensive two-dimensional NMR spectroscopic experiments such as gCOSY, gHSQC, gHMBC, and ROESY. The major metabolites 4 and 5 were subjected to reduction to provide the side chain-reduced compounds 8 and 9 for biological testing. All of the compounds except compound 6 showed anticancer activities in the range of IC(50) 3.5-11.0 microg/ml against human lung carcinoma A549 and mouse melanoma B16F1 cell lines. In addition, all compounds showed moderate radical-scavenging activities determined by DPPH assay.

Biological evaluation of certain substituted hydantoins and benzalhydantoins against microbes

NASA Astrophysics Data System (ADS)

Hidayat, Ika-Wiani; Thu, Yee Yee; Black, David St. C.; Read, Roger W.

2016-02-01

Twenty-three synthetic (thio)hydantoins and benzalhydantoins were evaluated for antimicrobial activity against Candida albicans, Malassezia furfur, Escherichia coli and Staphylococcus aureus, by the paper disc diffusion method. 3-n-butyl-4'-nitrobenzalhydantoin showed very high activity against E. coli and high selectivity with respect to the other microorganisms, while 3-n-butyl-2'-bromo-4',5'-dimethoxybenzal hydantoin demonstrated very high selectivity in its activity against M. furfur and S. aureus. These compounds show the most promise as drug lead compounds.

Studies on novel 2-imidazolidinones and tetrahydropyrimidin-2(1H)-ones as potential TACE inhibitors: design, synthesis, molecular modeling, and preliminary biological evaluation.

PubMed

DasGupta, Shirshendu; Murumkar, Prashant R; Giridhar, Rajani; Yadav, Mange Ram

2009-05-15

Compounds belonging to the class of 2-imidazolidinones and tetrahydropyrimidin-2(1H)-ones were synthesized and evaluated for their TACE inhibitory activity. Most of the compounds showed very good TACE inhibitory activity. Docking study clearly indicates importance of the P1' group of the inhibitor for the TACE inhibitory activity. This work proves that these two classes of molecules could be used as potential leads for the development of TACE inhibitors.

Sesquiterpene Lactones from Artemisia Genus: Biological Activities and Methods of Analysis

PubMed Central

Miron, Anca; Corciova, Andreia

2015-01-01

Sesquiterpene lactones are a large group of natural compounds, found primarily in plants of Asteraceae family, with over 5000 structures reported to date. Within this family, genus Artemisia is very well represented, having approximately 500 species characterized by the presence of eudesmanolides and guaianolides, especially highly oxygenated ones, and rarely of germacranolides. Sesquiterpene lactones exhibit a wide range of biological activities, such as antitumor, anti-inflammatory, analgesic, antiulcer, antibacterial, antifungal, antiviral, antiparasitic, and insect deterrent. Many of the biological activities are attributed to the α-methylene-γ-lactone group in their molecule which reacts through a Michael-addition with free sulfhydryl or amino groups in proteins and alkylates them. Due to the fact that most sesquiterpene lactones are thermolabile, less volatile compounds, they present no specific chromophores in the molecule and are sensitive to acidic and basic mediums, and their identification and quantification represent a difficult task for the analyst. Another problematic aspect is represented by the complexity of vegetal samples, which may contain compounds that can interfere with the analysis. Therefore, this paper proposes an overview of the methods used for the identification and quantification of sesquiterpene lactones found in Artemisia genus, as well as the optimal conditions for their extraction and separation. PMID:26495156

Bayesian screening for active compounds in high-dimensional chemical spaces combining property descriptors and molecular fingerprints.

PubMed

Vogt, Martin; Bajorath, Jürgen

2008-01-01

Bayesian classifiers are increasingly being used to distinguish active from inactive compounds and search large databases for novel active molecules. We introduce an approach to directly combine the contributions of property descriptors and molecular fingerprints in the search for active compounds that is based on a Bayesian framework. Conventionally, property descriptors and fingerprints are used as alternative features for virtual screening methods. Following the approach introduced here, probability distributions of descriptor values and fingerprint bit settings are calculated for active and database molecules and the divergence between the resulting combined distributions is determined as a measure of biological activity. In test calculations on a large number of compound activity classes, this methodology was found to consistently perform better than similarity searching using fingerprints and multiple reference compounds or Bayesian screening calculations using probability distributions calculated only from property descriptors. These findings demonstrate that there is considerable synergy between different types of property descriptors and fingerprints in recognizing diverse structure-activity relationships, at least in the context of Bayesian modeling.

Design of novel potent antihyperlipidemic agents with antioxidant/anti-inflammatory properties: exploiting phenothiazine's strong antioxidant activity.

PubMed

Matralis, Alexios N; Kourounakis, Angeliki P

2014-03-27

Because atherosclerosis is an inflammatory process involving a series of pathological events such as dyslipidemia, oxidative stress, and blood clotting mechanisms, we hereby report the synthesis and evaluation of novel compounds in which antioxidant, anti-inflammatory, and squalene synthase (SQS) inhibitory/hypolipidemic activities are combined in simple molecules through design. The coupling of two different pharmacophores afforded compounds 1-12, whose biological profile was markedly improved compared to those of parent lead structures (i.e., the hypolipidemic 2-hydroxy-2-aryl-(benzo)oxa(or thia)zine and the antioxidant phenothiazine). Most derivatives strongly inhibited in vitro microsomal lipid and LDL peroxidation, exhibiting potent free-radical scavenging activity. They further significantly inhibited SQS activity and showed remarkable antidyslipidemic activity in vivo in animal models of acute and high-fat-induced hyperlipidemia. Finally, several compounds showed anti-inflammatory activity in vitro, inhibiting cycloxygenase (COX-1/2) activity. The multimodal properties of the new compounds and especially their combined antioxidant/SQS/COX inhibitory activity render them interesting lead compounds for further evaluation against atherosclerosis.

Anticancer activity of ferrocenylthiosemicarbazones.

PubMed

Sandra, Cortez-Maya; Elena, Klimova; Marcos, Flores-Alamo; Elena, Martínez-Klimova; Arturo, Ramírez-Ramírez; Teresa, Ramírez Apan; Marcos, Martínez-García

2014-03-01

Aliphatic and aromatic ferrocenylthiosemicarbazones were synthesized. The characterization of the new ferrocenylthiosemicarbazones was done by IR, (1)H-NMR and (13)C-NMR spectroscopy, elemental analysis and X-ray diffraction studies. The biological activity of the obtained compounds was assessed in terms of anticancer activity. Their activity against U251 (human glyoblastoma), PC-3 (human prostatic adenocarcinoma), K562 (human chronic myelogenous leukemia), HCT-15 (human colorectal adenocarcinoma), MCF-7 (human mammary adenocarcinoma) and SKLU-1 (human lung adenocarcinoma) cell lines was studied and compared with cisplatin. All tested compounds showed good activity and the aryl-chloro substituted ferrocenylthiosemicarbazones showed the best anticancer activity.

Synthesis of biologically active N-methyl derivatives of amidines and cyclized five-membered products of amidines with oxalyl chloride.

PubMed

Sondhi, Sham M; Dinodia, Monica; Jain, Shubhi; Kumar, Ashok

2008-12-01

A series of substituted N-methylisonicotinamidine (2a-f), N-methylpyrazine-2-carboxamidine (2g-i) derivatives were synthesized by reaction of amidine derivatives (1a-i) with methyl iodide in presence of triethylamine. Five-membered condensed dihydroimidazolylbenzenesulfonamide derivatives (3a-i) were obtained by the reaction of amidine derivatives (1a-i) with acylating agent oxalyl chloride. All the compounds, i.e. 2a-i and 3a-i were purified by crystallization. Structures of all the synthesized compounds are supported by correct IR, (1)H NMR, mass spectral and analytical data. Anti-inflammatory activity evaluation was carried out using carrageenan-induced paw oedema assay and compounds 2e, 3a and 3d exhibited good anti-inflammatory activity (44%, 31% and 37% activity at 50 mg/kg p.o., respectively). Analgesic activity evaluation was carried out using acetic acid writhing assay and compounds 2a and 3f gave 75% activity each at 100 mg/kg p.o.; on the other hand compounds 3a and 3d exhibited 60% analgesic activity each at 50 mg/kg p.o. Compounds 3a and 3d exhibited good anti-inflammatory and analgesic activities.

Immunotoxicity of perfluorooctanoic acid and perfluorooctane sulfonate and the role of peroxisome proliferator-activated receptor alpha

EPA Science Inventory

Peroxisome proliferators, including perfluorooctanoic acid (PFOA), are environmentally widespread and persistent and multiple toxicities have been reported in experimental animals and humans. These compounds trigger biological activity via activation of the alpha isotype of pero...

Predicting activity approach based on new atoms similarity kernel function.

PubMed

Abu El-Atta, Ahmed H; Moussa, M I; Hassanien, Aboul Ella

2015-07-01

Drug design is a high cost and long term process. To reduce time and costs for drugs discoveries, new techniques are needed. Chemoinformatics field implements the informational techniques and computer science like machine learning and graph theory to discover the chemical compounds properties, such as toxicity or biological activity. This is done through analyzing their molecular structure (molecular graph). To overcome this problem there is an increasing need for algorithms to analyze and classify graph data to predict the activity of molecules. Kernels methods provide a powerful framework which combines machine learning with graph theory techniques. These kernels methods have led to impressive performance results in many several chemoinformatics problems like biological activity prediction. This paper presents a new approach based on kernel functions to solve activity prediction problem for chemical compounds. First we encode all atoms depending on their neighbors then we use these codes to find a relationship between those atoms each other. Then we use relation between different atoms to find similarity between chemical compounds. The proposed approach was compared with many other classification methods and the results show competitive accuracy with these methods. Copyright © 2015 Elsevier Inc. All rights reserved.

Synthesis, characterization and toxicity studies of pyridinecarboxaldehydes and L-tryptophan derived Schiff bases and corresponding copper (II) complexes.

PubMed

Malakyan, Margarita; Babayan, Nelly; Grigoryan, Ruzanna; Sarkisyan, Natalya; Tonoyan, Vahan; Tadevosyan, Davit; Matosyan, Vladimir; Aroutiounian, Rouben; Arakelyan, Arsen

2016-01-01

Schiff bases and their metal-complexes are versatile compounds exhibiting a broad range of biological activities and thus actively used in the drug development process. The aim of the present study was the synthesis and characterization of new Schiff bases and their copper (II) complexes, derived from L-tryptophan and isomeric (2-; 3-; 4-) pyridinecarboxaldehydes, as well as the assessment of their toxicity in vitro . The optimal conditions of the Schiff base synthesis resulting in up to 75-85% yield of target products were identified. The structure-activity relationship analysis indicated that the location of the carboxaldehyde group at 2-, 3- or 4-position with regard to nitrogen of the pyridine ring in aldehyde component of the L-tryptophan derivative Schiff bases and corresponding copper complexes essentially change the biological activity of the compounds. The carboxaldehyde group at 2- and 4-positions leads to the higher cytotoxic activity, than that of at 3-position, and the presence of the copper in the complexes increases the cytotoxicity. Based on toxicity classification data, the compounds with non-toxic profile were identified, which can be used as new entities in the drug development process using Schiff base scaffold.

Synthesis, characterization and toxicity studies of pyridinecarboxaldehydes and L-tryptophan derived Schiff bases and corresponding copper (II) complexes

PubMed Central

Malakyan, Margarita; Babayan, Nelly; Grigoryan, Ruzanna; Sarkisyan, Natalya; Tonoyan, Vahan; Tadevosyan, Davit; Matosyan, Vladimir; Aroutiounian, Rouben; Arakelyan, Arsen

2016-01-01

Schiff bases and their metal-complexes are versatile compounds exhibiting a broad range of biological activities and thus actively used in the drug development process. The aim of the present study was the synthesis and characterization of new Schiff bases and their copper (II) complexes, derived from L-tryptophan and isomeric (2-; 3-; 4-) pyridinecarboxaldehydes, as well as the assessment of their toxicity in vitro. The optimal conditions of the Schiff base synthesis resulting in up to 75-85% yield of target products were identified. The structure-activity relationship analysis indicated that the location of the carboxaldehyde group at 2-, 3- or 4-position with regard to nitrogen of the pyridine ring in aldehyde component of the L-tryptophan derivative Schiff bases and corresponding copper complexes essentially change the biological activity of the compounds. The carboxaldehyde group at 2- and 4-positions leads to the higher cytotoxic activity, than that of at 3-position, and the presence of the copper in the complexes increases the cytotoxicity. Based on toxicity classification data, the compounds with non-toxic profile were identified, which can be used as new entities in the drug development process using Schiff base scaffold. PMID:28344771

Information processing through a bio-based redox capacitor: signatures for redox-cycling.

PubMed

Liu, Yi; Kim, Eunkyoung; White, Ian M; Bentley, William E; Payne, Gregory F

2014-08-01

Redox-cycling compounds can significantly impact biological systems and can be responsible for activities that range from pathogen virulence and contaminant toxicities, to therapeutic drug mechanisms. Current methods to identify redox-cycling activities rely on the generation of reactive oxygen species (ROS), and employ enzymatic or chemical methods to detect ROS. Here, we couple the speed and sensitivity of electrochemistry with the molecular-electronic properties of a bio-based redox-capacitor to generate signatures of redox-cycling. The redox capacitor film is electrochemically-fabricated at the electrode surface and is composed of a polysaccharide hydrogel with grafted catechol moieties. This capacitor film is redox-active but non-conducting and can engage diffusible compounds in either oxidative or reductive redox-cycling. Using standard electrochemical mediators ferrocene dimethanol (Fc) and Ru(NH3)6Cl3 (Ru(3+)) as model redox-cyclers, we observed signal amplifications and rectifications that serve as signatures of redox-cycling. Three bio-relevant compounds were then probed for these signatures: (i) ascorbate, a redox-active compound that does not redox-cycle; (ii) pyocyanin, a virulence factor well-known for its reductive redox-cycling; and (iii) acetaminophen, an analgesic that oxidatively redox-cycles but also undergoes conjugation reactions. These studies demonstrate that the redox-capacitor can enlist the capabilities of electrochemistry to generate rapid and sensitive signatures of biologically-relevant chemical activities (i.e., redox-cycling). Published by Elsevier B.V.

The Design and Development of Potent Small Molecules as Anticancer Agents Targeting EGFR TK and Tubulin Polymerization

PubMed Central

Ihmaid, Saleh; Ahmed, Hany E. A.; Zayed, Mohamed F.

2018-01-01

Some novel anthranilate diamides derivatives 4a–e, 6a–c and 9a–d were designed and synthesized to be evaluated for their in vitro anticancer activity. Structures of all newly synthesized compounds were confirmed by infra-red (IR), high-resolution mass (HR-MS) spectra, 1H nuclear magnetic resonance (NMR) and 13C nuclear magnetic resonance (NMR) analyses. Cytotoxic screening was performed according to (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium (MTT) assay method using erlotinib as a reference drug against two different types of breast cancer cells. The molecular docking study was performed for representative compounds against two targets, epidermal growth factor receptor (EGFR) and tubulin in colchicine binding site to assess their binding affinities in order to rationalize their anticancer activity in a qualitative way. The data obtained from the molecular modeling was correlated with that obtained from the biological screening. These data showed considerable anticancer activity for these newly synthesized compounds. Biological data for most of the anthranilate diamide showed excellent activity with nanomolar or sub nanomolar half maximal inhibitory concentration (IC50) values against tumor cells. EGFR tyrosine kinase (TK) inhibition assay, tubulin inhibition assay and apoptosis analysis were performed for selected compounds to get more details about their mechanism of action. Extensive structure activity relationship (SAR) analyses were also carried out. PMID:29385728

Synthesis, spectroscopic characterization, crystal structure, DNA interaction study and invitro biological screenings of 4-(5-chloro-2-hydroxyphenylamino)-4-oxobut-2-enoic acid

NASA Astrophysics Data System (ADS)

Sirajuddin, Muhammad; Nooruddin; Ali, Saqib; McKee, Vickie; Khan, Shahan Zeb; Malook, Khan

2015-01-01

The titled compound, 4-(5-chloro-2-hydroxyphenylamino)-4-oxobut-2-enoic acid was synthesized and characterized by various techniques like elemental analyses, FT-IR, NMR (1H, and 13C) and single crystal X-ray structural analysis. The appearance of the OH peak of the carboxylic acid in the FT-IR and NMR spectra conform the formation of the compound. A good agreement was found between the calculated values of C, H, N and found values in elemental analysis that show the purity of the compound. Protons H2 and H3 are in cis conformation with each other as conformed both from 1H NMR as well as from single crystal X-ray analysis. The molecular structure of the title compound, C10H10NO3Cl, is stabilized by short intramolecular Osbnd H- - -O hydrogen bonds within the molecule. In the crystal structure, intermolecular Nsbnd H- - -O hydrogen bonds link molecules into zigzag chains resulting in a dendrimer like structure. The title compound was screened for biological activities like interaction with DNA, cytotoxicity, antitumor and antioxidant activities. DNA interaction study reveals that the binding mode of interaction of the compound with SS-DNA is intercalative as it results in hypochromism along with significant red shift of 5 nm. It was also found to be effective antioxidant of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and show almost comparable antioxidant activity to that of the standard and known antioxidant, ascorbic acid, at higher concentration. The antitumor activity data of the compound shows that it can be used as potent antitumor agent.

Influence of operating parameters on the biodegradation of steroid estrogens and nonylphenolic compounds during biological wastewater treatment processes.

PubMed

Koh, Yoong K K; Chiu, Tze Y; Boobis, Alan R; Scrimshaw, Mark D; Bagnall, John P; Soares, Ana; Pollard, Simon; Cartmell, Elise; Lester, John N

2009-09-01

This study investigated operational factors influencing the removal of steroid estrogens and nonylphenolic compounds in two sewage treatment works, one a nitrifying/denitrifying activated sludge plant and the other a nitrifying/denitrifying activated sludge plant with phosphorus removal. Removal efficiencies of >90% for steroid estrogens and for longer chain nonylphenol ethoxylates (NP4-12EO) were observed at both works, which had equal sludge ages of 13 days. However, the biological activity in terms of milligrams of estrogen removed per day per tonne of biomass was found to be 50-60% more efficient in the nitrifying/denitrifying activated sludge works compared to the works which additionallyincorporated phosphorusremoval. A temperature reduction of 6 degrees C had no impact on the removal of free estrogens, but removal of the conjugated estrone-3-sulfate was reduced by 20%. The apparent biomass sorption (LogKp) values were greater in the nitrifying/denitrifying works than those in the nitrifying/denitrifying works with phosphorus removal for both steroid estrogens and honylphenolic compounds possibly indicating a different cell surface structure and therefore microbial population. The difference in biological activity (mg tonne(-1) d(-1)) identified in this study, of up to seven times, suggests thatthere is the potential for enhancing the removal of estrogens and nonylphenols if more detailed knowledge of the factors responsible for these differences can be identified and maximized, thus potentially improving the quality of receiving waters.

Biological Evaluation of Endophytic Fungus Chaetomium sp. NF15 of Justicia adhatoda L.: A Potential Candidate for Drug Discovery

PubMed Central

Fatima, Nighat; Mukhtar, Usman; Ihsan-Ul-Haq; Ahmed Qazi, Muneer; Jadoon, Muniba; Ahmed, Safia

2016-01-01

Background The endophytes of medicinal plants, such as Justicia adhatoda L., represent a promising and largely underexplored domain that is considered as a repository of biologically active compounds. Objectives The aim of present study was isolation, identification, and biological evaluation of endophytic fungi associated with the J. adhatoda L. plant for the production of antimicrobial, antioxidant, and cytotoxic compounds Materials and Methods Endophytic fungi associated with the J. adhatoda L. plant were isolated from healthy plant parts and taxonomically characterized through morphological, microscopic, and 18S rDNA sequencing methods. The screening for bioactive metabolite production was achieved using ethyl acetate extracts, followed by the optimization of different parameters for maximum production of bioactive metabolites. Crude and partially purified extracts were used to determine the antimicrobial, antioxidant, and cytotoxic potential Results Out of six endophytic fungal isolates, Chaetomium sp. NF15 showed the most promising biological activity and was selected for detailed study. The crude ethyl acetate extract of NF15 isolate after cultivation under optimized culture conditions showed promising antimicrobial activity, with significant inhibition of the clinical isolates of Staphylococcus aureus (87%, n=42), Pseudomonas aeruginosa (> 85%, n = 41), and Candida albicans (62%, n = 24). Conclusions The present study confirms the notion of selecting endophytic fungi of medicinal plant Justicia for the bioassay-guided isolation of its bioactive compounds, and demonstrates that endophytic fungus Chaetomium sp. NF15 could be a potential source of bioactive metabolites PMID:27635208

EDCs, estrogenicity and genotoxicity reduction in a mixed (domestic + textile) secondary effluent by means of ozonation: a full-scale experience.

PubMed

Bertanza, G; Papa, M; Pedrazzani, R; Repice, C; Mazzoleni, G; Steimberg, N; Feretti, D; Ceretti, E; Zerbini, I

2013-08-01

WWTP (wastewater treatment plant) effluents are considered to be a major source for the release in the aquatic environment of EDCs (Endocrine-Disrupting Compounds), a group of anthropogenic substances able to alter the normal function of the endocrine system. The application of conventional processes (e.g. activated sludge with biological nitrogen removal) does not provide complete elimination of all these micropollutants and, consequently, an advanced treatment should be implemented. This experimental work was conducted on the tertiary ozonation stage of a 140,000 p.e. activated sludge WWTP, treating a mixed domestic and textile wastewater: an integrated monitoring, including both chemical (nonylphenol, together with the parent compounds mono- and di-ethoxylated, and bisphenol A were chosen as model EDCs) and biological (estrogenic and genotoxic activities) analyses, was carried out. Removal efficiencies of measured EDCs varied from 20% to 70%, depending on flow conditions (ozone dosage being 0.5 gO3/gTOC). Biological tests, furthermore, displayed that the oxidation stage did not significantly reduce (only by 20%) the estrogenicity of the effluent and revealed the presence and/or formation of genotoxic compounds. These results highlight the importance of the application of an integrated (biological+chemical) analytical procedure for a global evaluation of treatment suitability; poor performances recorded in this study have been attributed to the presence of a significant industrial component in the influent wastewater. Copyright © 2013 Elsevier B.V. All rights reserved.

Computer-assisted determination of minimum energy conformations. 7: A pharmacophore model of the active region of the alpha2-adrenoceptor

NASA Astrophysics Data System (ADS)

Ashman, William P.; Mickiewicz, A. P.; Nelson, Todd M.

1992-09-01

Molecular modeling and computational chemistry techniques are used to analyze compounds in developing pharmacophores of biological receptors to use as templates in structure activity relationship studies and to design new chemicals having physiological activity of interest. In this study, the results of x-ray crystal analyses and PM3 semi-empirical molecular orbital conformational analyses are used to determine the three-dimensional representations of selected adrenergic compounds known to be agonists with the alpha2-adrenoceptor in achieving optimized geometries and electrostatic parameters. The alpha2-adrenergic agonists interact with the adrenergic system receptors to produce various increases or decreases in hemodynamic responses (i.e., hypertension, hypotension, and bradycardia) and sedation. A pharmacophore model of the active region of the alpha2-adrenoceptor is described based on the superimposition of common structural, electrostatic, and physicochemical features of the compounds. Using the model to predict compound adrenergic activity and to design alpha2-adrenergic compounds is discussed.

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.

Structural analysis and antimicrobial activity of 2[1H]-pyrimidinethione/selenone derivatives

NASA Astrophysics Data System (ADS)

Żesławska, Ewa; Korona-Głowniak, Izabela; Szczesio, Małgorzata; Olczak, Andrzej; Żylewska, Alicja; Tejchman, Waldemar; Malm, Anna

2017-08-01

Four new crystal structures of sulfur and selenium analogues of 2[1H]-pyrimidinone derivatives were determined with the use of X-ray diffraction method. The molecular geometry and intermolecular interactions of the investigated molecules were analyzed in order to find the structural features and geometrical parameters, which can be responsible for antimicrobial activities. The influence of chalcogen substituents (sulfur and selenium) on the crystal packing was also studied. The main differences in the molecular structures exist in mutual arrangement of two aromatic rings. The intermolecular interactions in all investigated compounds are similar. Furthermore, the in vitro antibacterial and antifungal activities for these compounds were evaluated. Preliminary investigations have identified two highly potent antibacterial compounds containing selenium atom, which display selectivity towards staphylococci and micrococci. This selectivity was not observed for a control compound used as a drug, namely vancomycin. These compounds possess also good antifungal activity. This is the first report of biological activities of 2[1H]-pyrimidineselenone derivatives.

Modifications of the chemical structure of phenolics differentially affect physiological activities in pulvinar cells of Mimosa pudica L. II. Influence of various molecular properties in relation to membrane transport.

PubMed

Rocher, Françoise; Roblin, Gabriel; Chollet, Jean-François

2017-03-01

Early prediction of compound absorption by cells is of considerable importance in the building of an integrated scheme describing the impact of a compound on intracellular biological processes. In this scope, we study the structure-activity relationships of several benzoic acid-related phenolics which are involved in many plant biological phenomena (growth, flowering, allelopathy, defense processes). Using the partial least squares (PLS) regression method, the impact of molecular descriptors that have been shown to play an important role concerning the uptake of pharmacologically active compounds by animal cells was analyzed in terms of the modification of membrane potential, variations in proton flux, and inhibition of the osmocontractile reaction of pulvinar cells of Mimosa pudica leaves. The hydrogen bond donors (HBD) and hydrogen bond acceptors (HBA), polar surface area (PSA), halogen ratio (Hal ratio), number of rotatable bonds (FRB), molar volume (MV), molecular weight (MW), and molar refractivity (MR) were considered in addition to two physicochemical properties (logD and the amount of non-dissociated form in relation to pKa). HBD + HBA and PSA predominantly impacted the three biological processes compared to the other descriptors. The coefficient of determination in the quantitative structure-activity relationship (QSAR) models indicated that a major part of the observed seismonasty inhibition and proton flux modification can be explained by the impact of these descriptors, whereas this was not the case for membrane potential variations. These results indicate that the transmembrane transport of the compounds is a predominant component. An increasing number of implicated descriptors as the biological processes become more complex may reflect their impacts on an increasing number of sites in the cell. The determination of the most efficient effectors may lead to a practical use to improve drugs in the control of microbial attacks on plants.

Progress in the field of physiologically active lanosterol compounds

NASA Astrophysics Data System (ADS)

Reshetova, I. G.; Tkhaper, R. K.; Kamernitskii, Alexey V.

1992-08-01

This review correlates the studies (up to 1991) on the isolation, structural determination, biological activity, and synthesis of physiologically active polyoxidised lanosterol derivatives of vegetable (inotodiol, ganoderic acids) and animal (seychellogenin) origin. The cytotoxic, cardiovascular, and other forms of activity of compounds of this type are of considerable interest in relation to their medical use. It is noted that the functionalised side chain (in an open form or containing lactones, lactols, etc.) is generally responsible for the activity exhibited by lanosterol derivatives. Two basic approaches to the derivation of these structures are defined: either by complete reconstruction of the side chain of lanosterol (degradation and rebuilding with oxygen-containing residues) or by progressive functionalisation of the Δ24-side chain of lanosterol. The synthesis of the known anticancer compound "inotodiol", seychellogenins, ganoderic acids, and other compounds are described. The bibliography includes 105 references.

Biotransformation and sorption of trace organic compounds in biological nutrient removal treatment systems.

PubMed

Lakshminarasimman, Narasimman; Quiñones, Oscar; Vanderford, Brett J; Campo-Moreno, Pablo; Dickenson, Eric V; McAvoy, Drew C

2018-05-28

This study determined biotransformation rates (k bio ) and sorption-distribution coefficients (K d ) for a select group of trace organic compounds (TOrCs) in anaerobic, anoxic, and aerobic activated sludge collected from two different biological nutrient removal (BNR) treatment systems located in Nevada (NV) and Ohio (OH) in the United States (US). The NV and OH facilities operated at solids retention times (SRTs) of 8 and 23 days, respectively. Using microwave-assisted extraction, the biotransformation rates of the chosen TOrCs were measured in the total mixed liquor. Sulfamethoxazole, trimethoprim, and atenolol biotransformed in all three redox regimes irrespective of the activated sludge source. The biotransformation of N, N-diethyl-3-methylbenzamide (DEET), triclosan, and benzotriazole was observed in aerobic activated sludge from both treatment plants; however, anoxic biotransformation of these three compounds was seen only in anoxic activated sludge from NV. Carbamazepine was recalcitrant in all three redox regimes and both sources of activated sludge. Atenolol and DEET had greater biotransformation rates in activated sludge with a higher SRT (23 days), while trimethoprim had a higher biotransformation rate in activated sludge with a lower SRT (8 days). The remaining compounds did not show any dependence on SRT. Lyophilized, heat inactivated sludge solids were used to determine the sorption-distribution coefficients. Triclosan was the most sorptive compound followed by carbamazepine, sulfamethoxazole, DEET, and benzotriazole. The sorption-distribution coefficients were similar across redox conditions and sludge sources. The biotransformation rates and sorption-distribution coefficients determined in this study can be used to improve fate prediction of the target TOrCs in BNR treatment systems. Copyright © 2018. Published by Elsevier B.V.

Polyphenolic profile and biological activity of Chinese hawthorn (Crataegus pinnatifida BUNGE) fruits.

PubMed

Jurikova, Tunde; Sochor, Jiri; Rop, Otakar; Mlcek, Jiri; Balla, Stefan; Szekeres, Ladislav; Adam, Vojtech; Kizek, Rene

2012-12-06

Chinese hawthorn (Crataegus pinnatifida Bge.) fruits are rich in polyphenols (e.g., epicatechin, procyanidin B2, procyanidin B5, procyanidin C1, hyperoside, isoquercitrin and chlorogenic acid)--active compounds that exert beneficial effects. This review summarizes all information available on polyphenolic content and methods for their quantification in Chinese hawthorn berries and the relationships between individual polyphenolic compounds as well. The influence of species or cultivars, the locality of cultivation, the stage of maturity, and extract preparation conditions on the polyphenolic content were discussed as well. Currently, only fruits of C. pinnatifida and C. pinnatifida var. major are included in the Chinese Pharmacopoeia. Recent trials have demonstrated the efficacy of Chinese hawthorn fruit in lowering blood cholesterol and the risk of cardiovascular diseases. The fruit has also demonstrated anti-inflammatory and anti-tumour activities. This review deals mainly with the biological activity of the fruit related to its antioxidant properties.

Computer-aided identification, synthesis, and biological evaluation of novel inhibitors for botulinum neurotoxin serotype A

DOE PAGES

Teng, Y. G.; Berger, W. T.; Nesbitt, N. M.; ...

2015-07-27

Botulinum neurotoxins (BoNTs) are among the most potent biological toxin known to humans, and are classified as Category A bioterrorism agents by the Centers for Disease Control and prevention (CDC). There are seven known BoNT serotypes (A-G) which have been thus far identified in literature. BoNTs have been shown to block neurotransmitter release by cleaving proteins of the soluble NSF attachment protein receptor (SNARE) complex. Disruption of the SNARE complex precludes motor neuron failure which ultimately results in flaccid paralysis in humans and animals. Currently, there are no effective therapeutic treatments against the neurotoxin light chain (LC) after translocation intomore » the cytosols of motor neurons. In this work, high-throughput virtual screening was employed to screen a library of commercially available compounds from ZINC database against BoNT/A-LC. Among the hit compounds from the in-silico screening, two lead compounds were identified and found to have potent inhibitory activity against BoNT/A-LC in vitro, as well as in Neuro-2a cells. A few analogues of the lead compounds were synthesized and their potency examined. One of these analogues showed an enhanced activity than the lead compounds« less

Aromatic compounds produced by Periconia atropurpurea, an endophytic fungus associated with Xylopia aromatica.

PubMed

Teles, Helder Lopes; Sordi, Renata; Silva, Geraldo Humberto; Castro-Gamboa, Ian; Bolzani, Vanderlan da Silva; Pfenning, Ludwig Heinrich; de Abreu, Lucas Magalhães; Costa-Neto, Claudio Miguel; Young, Maria Claudia Marx; Araújo, Angela Regina

2006-12-01

6,8-Dimethoxy-3-(2'-oxo-propyl)-coumarin (1) and 2,4-dihydroxy-6-[(1'E,3'E)-penta-1',3'-dienyl]-benzaldehyde (2), in addition to the known compound periconicin B (3), were isolated from the ethyl acetate extract of Periconia atropurpurea, an endophytic fungus obtained from the leaves of Xylopia aromatica, a native plant of the Brazilian Cerrado. Their chemical structures were assigned based on analyses of MS, 1D and 2D-NMR spectroscopic experiments. Biological analyses were performed using two mammalian cell lines, human cervix carcinoma (HeLa) and Chinese hamster ovary (CHO). The results showed that compound 1 had no effect when compared to the control group, which was treated with the vehicle (DMSO). Compound 2 was able to induce a slight increase in cell proliferation of HeLa (37% of increase) and CHO (38% of increase) cell lines. Analysis of compound 3 showed that it has potent cytotoxic activity against both cell lines, with an IC50 of 8.0 microM. Biological analyses using the phytopathogenic fungi Cladosporium sphaerospermum and C. cladosporioides revealed that also 2 showed potent antifungal activity compared to nystatin.

Synthesis of galactosyl compounds for targeted gene delivery.

PubMed

Ren, T; Zhang, G; Liu, D

2001-11-01

Cell-specific DNA delivery offers a great potential for targeted gene therapy. Toward this end, we have synthesized a series of compounds carrying galactose residues as a targeting ligand for asialoglycoprotein receptors of hepatocytes and primary amine groups as a functional domain for DNA binding. Biological activity of these galactosyl compounds in DNA delivery was evaluated in HepG2 and BL-6 cells and compared with respect to the number of galactose residues as well as primary amine groups in each molecule. Transfection experiments using a firefly luciferase gene as a reporter revealed that compounds with multivalent binding properties were more active in DNA delivery. An optimal transfection activity in HepG2 cells requires seven primary amine groups and a minimum of two galactose residues in each molecule. The transfection activity of compounds carrying multi-galactose residues can be inhibited by asialofetuin, a natural substrate for asialoglycoprotein receptors of hepatocytes, suggesting that gene transfer by these galactosyl compounds is asialoglycoprotein receptor-mediated. These results provide direct evidence in support of our new strategy for the use of small and synthetic compounds for cell specific and targeted gene delivery.

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.

Synthesis, characterization, stereochemistry and biological investigation of certain N-dichloroacetyl-bis(2-chlorophenyl)piperidin-4-ones

NASA Astrophysics Data System (ADS)

Kayalvizhi, R.; Ponnuswamy, S.; Gomathi, K.; Ezhilarasi, K. S.; Usha, G.

2018-02-01

A new series of N-dichloroacetyl-bis(2-chlorophenyl)piperidin-4-ones 4-6 has been synthesized and characterized using IR, 1H, 13C, DEPT and 2D (COSY and HSQC) NMR spectral techniques. The NMR spectral data indicate that the N-acylpiperidin-4-ones 4-6 prefer to exist in an equilibrium between the twist boat conformations with coplanar orientation of Nsbnd Cdbnd O moiety. Furthermore, the antibacterial and antifungal studies have been carried out for compounds 1-6 and the results show that they possess significant activity towards the bacterial organisms Staphylococcus aureus and Salmoneela paratyphi and better activity against the remaining bacterial organisms. All the compounds 1-6 possess moderate antifungal activity. The compounds 4-6 have been docked with the structure of MRSA and the results demonstrate that the compounds 4-6 have similar docking score and glide energy when compared to each other and thus having equal binding affinity. The antioxidant studies show greater activity for compound 4 and poor activity for compounds 5 &6 when compared to the standard drug.

Phenolic compounds and biological effects of edible Rumex scutatus and Pseudosempervivum sempervivum: potential sources of natural agents with health benefits.

PubMed

Savran, Ahmet; Zengin, Gokhan; Aktumsek, Abdurrahman; Mocan, Andrei; Glamoćlija, Jasmina; Ćirić, Ana; Soković, Marina

2016-07-13

The present study outlines a chemical characterization and further effects beneficial to health of edible Rumex scutatus and Pseudosempervivum sempervivum, in addition to presenting the antioxidant, enzyme inhibitory effects and antimicrobial properties of different extracts. The phenolic compounds composition of the extracts was assessed by RP-HPLC-DAD, outlining benzoic acid and rutin as major constituents in P. sempervivum and rutin and hesperidin in R. scutatus. Moreover, further biological effects were tested on key enzymes involved in diabetes mellitus, Alzheimer's disease and skin melanogenesis revealing an important tyrosinase inhibitory effect of Pseudosempervivum water extract. Moreover, both species possessed antimicrobial properties towards bacteria and fungi relevant to public health. Accordingly, we find that R. scutatus and P. sempervivum can be considered as novel functional foods because they are rich sources of biologically active compounds that provide health benefits.

Antioxidant and biological properties of bioactive phenolic compounds from Quercus suber L.

PubMed

Fernandes, Ana; Fernandes, Iva; Cruz, Luís; Mateus, Nuno; Cabral, Miguel; de Freitas, Victor

2009-12-09

Phenolic compounds, namely, hydrolyzable tannins and low molecular weight phenolic compounds, were isolated and purified from Portuguese cork from Quercus suber L. Some of these compounds were studied to evaluate their antioxidant activity, including free-radical scavenging capacity (DPPH method) and reducing capacity (FRAP method). All compounds tested showed significant antioxidant activity, namely, antiradical and reducing properties. The antiradical capacity seemed to increase with the presence of galloyl groups. Regarding the reducing capacity, this structure-activity relationship was not so clear. These compounds were also studied to evaluate the growth inhibitory effect on the estrogen responsive human breast cancer cell line (ER+) MCF-7 and two other colon cancer cell lines (Caco-2 and HT-29). Generally, all the compounds tested exhibited, after a continuous exposure during a 48 h period, a dose-dependent growth inhibitory effect. Relative inhibitory activity was primarily related to the number of phenolic hydroxyl groups (galloyl and HHDP moieties) found in the active structures, with more groups generally conferring increased effects, except for HHDP-di-galloyl-glucose. Mongolicain B showed a greater potential to inhibit the growth of the three cell lines tested, identical to the effect observed with castalagin. Since these compounds are structurally related with each other, this activity might be based within the C-glycosidic ellagitannin moiety.

Antioxidant, anti-glycation and anti-inflammatory activities of phenolic constituents from Cordia sinensis.

PubMed

Al-Musayeib, Nawal; Perveen, Shagufta; Fatima, Itrat; Nasir, Muhammad; Hussain, Ajaz

2011-12-08

Nine compounds have been isolated from the ethyl acetate soluble fraction of C. sinensis, namely protocatechuic acid (1), trans-caffeic acid (2), methyl rosmarinate (3), rosmarinic acid (4), kaempferide-3-O-β-D-glucopyranoside (5), kaempferol-3-O-β-D-glucopyranoside (6), quercetin-3-O-β-D-glucopyranoside (7), kaempferide-3-O-α-L-rhamnopyranosyl (1→6)-β-D-glucopyranoside (8) and kaempferol-3-O-α-L-rhamno-pyranosyl (1→6)-β-D-glucopyranoside (9), all reported for the first time from this species. The structures of these compounds were deduced on the basis of spectroscopic studies, including 1D and 2D NMR techniques. Compounds 1-9 were investigated for biological activity and showed significant anti-inflammatory activity in the carrageen induced rat paw edema test. The antioxidant activities of isolated compounds 1-9 were evaluated by the DPPH radical scavenging test, and compounds 1, 2, 4 and 7-9 exhibited marked scavenging activity compared to the standard BHA. These compounds were further studied for their anti-glycation properties and some compounds showed significant anti-glycation inhibitory activity. The purity of compounds 2-5, 8 and 9 was confirmed by HPLC. The implications of these results for the chemotaxonomic studies of the genus Cordia have also been discussed.

Novel and rare prenyllipids - Occurrence and biological activity.

PubMed

Szymańska, Renata; Kruk, Jerzy

2018-01-01

The data presented indicate that there is a variety of unique prenyllipids, often of very limited taxonomic distribution, whose origin, biosynthesis, metabolism and biological function deserves to be elucidated. These compounds include tocoenols, tocochromanol esters, tocochromanol acids, plastoquinones and ubiquinones. Additionally, based on the available data, it can be assumed that there are still unrecognized prenyllipids, like prenylquinols fatty acid esters of the hydroquinone ring, including prenylquinol phosphates, and others, whose biological function might be of great importance. Our knowledge of these compounds is not only important from the scientific point of view, but may also be of practical significance to medicine, pharmacy or cosmetics. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Mannich-Benzimidazole Derivatives as Antioxidant and Anticholinesterase Inhibitors: Synthesis, Biological Evaluations, and Molecular Docking Study.

PubMed

Alpan, Ayşe Selcen; Sarıkaya, Görkem; Çoban, Güneş; Parlar, Sülünay; Armagan, Güliz; Alptüzün, Vildan

2017-07-01

A series of Mannich bases of benzimidazole derivatives having a phenolic group were designed to assess their anticholinesterase and antioxidant activities. The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities were evaluated in vitro by using Ellman's method. According to the activity results, all of the compounds exhibited moderate to good AChE inhibitory activity (except for 2a), with IC 50 values ranging from 0.93 to 10.85 μM, and generally displayed moderate BuChE inhibitory activity. Also, most of the compounds were selective against BuChE. Compound 4b was the most active molecule on the AChE enzyme and also selective. In addition, we investigated the antioxidant effects of the synthesized compounds against FeCl 2 /ascorbic acid-induced oxidative stress in the rat brain in vitro, and the activity results showed that most of the compounds are effective as radical scavengers. Molecular docking studies and molecular dynamics simulations were also carried out. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical Properties of Caffeic and Ferulic Acids in Biological System: Implications in Cancer Therapy. A Review.

PubMed

Damasceno, Sarah S; Dantas, Bruna B; Ribeiro-Filho, Jaime; Antônio M Araújo, Demetrius; Galberto M da Costa, José

2017-01-01

The antioxidant properties of caffeic and ferulic acids in biological systems have been extensively demonstrated. As antioxidants, these compounds prevent the production of reactive oxygen species (ROS), which cause cell lesions that are associated with the development of several diseases, including cancer. Recent findings suggest that the chemoprotective action of these phenolic acids occurs through the following mechanisms: regulation of gene expression, chelation and / or reduction of transition metals, formation of covalent adducts and direct toxicity. The biological efficacy of these promising chemoprotective agents is strongly related with their chemical structure. Therefore, in this study, we discuss the structural characteristics of ferulic and caffeic acids that are responsible for their biological activities, as well as the mechanisms of action involved with the anti-cancer activity. Several reports indicated that the antioxidant effect of these phenylpropanoids results from reactions with free radicals with formation of stable products in the cells. The chelating effect of these compounds was also reported as an important protective mechanism against oxidative. Finally, the lipophilicity of these agents facilitates their entry into the cells, and thus, contributes to the anticancer activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Myricetin: A Dietary Molecule with Diverse Biological Activities

PubMed Central

Semwal, Deepak Kumar; Semwal, Ruchi Badoni; Combrinck, Sandra; Viljoen, Alvaro

2016-01-01

Myricetin is a common plant-derived flavonoid and is well recognised for its nutraceuticals value. It is one of the key ingredients of various foods and beverages. The compound exhibits a wide range of activities that include strong anti-oxidant, anticancer, antidiabetic and anti-inflammatory activities. It displays several activities that are related to the central nervous system and numerous studies have suggested that the compound may be beneficial to protect against diseases such as Parkinson’s and Alzheimer’s. The use of myricetin as a preserving agent to extend the shelf life of foods containing oils and fats is attributed to the compound’s ability to protect lipids against oxidation. A detailed search of existing literature revealed that there is currently no comprehensive review available on this important molecule. Hence, the present work includes the history, synthesis, pharmaceutical applications and toxicity studies of myricetin. This report also highlights structure-activity relationships and mechanisms of action for various biological activities. PMID:26891321

Antimicrobial and Probiotic Properties of Yeasts: From Fundamental to Novel Applications

PubMed Central

Hatoum, Rima; Labrie, Steve; Fliss, Ismail

2012-01-01

The yeasts constitute a large and heterogeneous group of microorganisms that are currently attracting increased attention from scientists and industry. Numerous and diverse biological activities make them promising candidates for a wide range of applications not limited to the food sector. In addition to their major contribution to flavor development in fermented foods, their antagonistic activities toward undesirable bacteria, and fungi are now widely known. These activities are associated with their competitiveness for nutrients, acidification of their growth medium, their tolerance of high concentrations of ethanol, and release of antimicrobial compounds such as antifungal killer toxins or “mycocins” and antibacterial compounds. While the design of foods containing probiotics (microorganisms that confer health benefits) has focused primarily on Lactobacillus and Bifidobacterium, the yeast Saccharomyces cerevisiae var. boulardii has long been known effective for treating gastroenteritis. In this review, the antimicrobial activities of yeasts are examined. Mechanisms underlying this antagonistic activity as well as recent applications of these biologically active yeasts in both the medical and veterinary sectors are described. PMID:23267352

Therapeutic Uses and Pharmacological Properties of Garlic, Shallot, and Their Biologically Active Compounds

PubMed Central

Mikaili, Peyman; Maadirad, Surush; Moloudizargari, Milad; Aghajanshakeri, Shahin; Sarahroodi, Shadi

2013-01-01

Objective(s): Garlic (Allium sativum L. family Liliaceae) is well known in Iran and its leaves, flowers, and cloves have been used in traditional medicine for a long time. Research in recent decades has shown widespread pharmacological effects of A. sativum and its organosulfur compounds especially Allicin. Studies carried out on the chemical composition of the plant show that the most important constituents of this plant are organosulfur compounds such as allicin, diallyl disulphide, S-allylcysteine, and diallyl trisulfide. Allicin represents one of the most studied among these naturally occurring compounds. In addition to A. sativum, these compounds are also present in A. hirtifolium (shallot) and have been used to treat various diseases. This article reviews the pharmacological effects and traditional uses of A. sativum, A. hirtifolium, and their active constituents to show whether or not they can be further used as potential natural sources for the development of novel drugs. Materials and Methods: For this purpose, the authors went through a vast number of sources and articles and all needed data was gathered. The findings were reviewed and classified on the basis of relevance to the topic and a summary of all effects were reported as tables. Conclusion: Garlic and shallots are safe and rich sources of biologically active compounds with low toxicity. Further studies are needed to confirm the safety and quality of the plants to be used by clinicians as therapeutic agents. PMID:24379960

Influence of plant origin natural α-pinene with different enantiomeric composition on bacteria, yeasts and fungi.

PubMed

Ložienė, Kristina; Švedienė, Jurgita; Paškevičius, Algimantas; Raudonienė, Vita; Sytar, Oksana; Kosyan, Anatoliy

2018-04-22

Although the nature-identical chemical compounds are cheaper, they not always repeat biological activity of plant origin natural chemical compounds, often react allergies and resistance of microorganisms. The aim of this study was to investigate effects of Juniperus communis origin α-pinene with different enantiomeric composition on bacteria, yeasts and fungi. Results showed that different enantiomeric composition of α-pinene have different activities on microorganisms: essential oil with (1S)-(-) ≈ (1R)-(+) enantiomeric composition of α-pinene influenced on some microorganisms stronger than essential oil with (1S)-(-) < (1R)-(+) enantiomeric composition of α-pinene; the pure natural α-pinene with enantiomeric composition S < R more strongly inhibited growth of investigated bacteria and Candida yeasts, α-pinene with enantiomeric composition S ≈ R - growth of Trichophyton and Aspergillus. (1S)-(-) and (1R)-(+) enantiomeric forms of α-pinene can have also different synergistic effects with other compounds of essential oil. The results of study showed that the same amount of α-pinene with different enantiomeric composition can have diverse antimicrobial potential due different specific interactions with other chemical compounds of essential oil. Therefore, it is very important to determine and present the enantiomeric composition of those plant origin compounds, which are characterized by enantiomerisation, during the course of research of biological activities of natural plant products (essential oils and other) and their isolated compounds. Copyright © 2018 Elsevier B.V. All rights reserved.

FR258900, a novel glycogen phosphorylase inhibitor isolated from Fungus No. 138354. I. Taxonomy, fermentation, isolation and biological activities.

PubMed

Furukawa, Shigetada; Tsurumi, Yasuhisa; Murakami, Kana; Nakanishi, Tomoko; Ohsumi, Keisuke; Hashimoto, Michizane; Nishikawa, Motoaki; Takase, Shigehiro; Nakayama, Osamu; Hino, Motohiro

2005-08-01

FR258900 is a novel glycogen synthesis activator produced by Fungus No. 138354. This compound was isolated from the culture broth by solvent extraction and reverse-phase column chromatography. FR258900 stimulated glycogen synthesis and glycogen synthase activity in primary rat hepatocytes. FR258900 exhibited a potent inhibitory effect on the activity of liver glycogen phosphorylase, suggesting that this compound may activate hepatic glycogen synthesis via glycogen phosphorylase inhibition. Thus, this glycogen phosphorylase inhibitor may be useful in the treatment of postprandial hyperglycemia in type 2 diabetes.

Indolo[3,2-c]cinnolines with antiproliferative, antifungal, and antibacterial activity.

PubMed

Barraja, P; Diana, P; Lauria, A; Passannanti, A; Almerico, A M; Minnei, C; Longu, S; Congiu, D; Musiu, C; La Colla, P

1999-08-01

A series of indolo[3,2-c]cinnoline derivatives was prepared and tested to evaluate their biological activity. Most of them inhibited the proliferation of leukemia, lymphoma and solid tumor-derived cell lines at micromolar concentrations, whereas none of the compounds were active against HIV-1. With the exception of 7g, all title compounds showed antibacterial activity against gram-positive bacteria, being up to 200 times more potent than the reference drug streptomycin. Some of the indolo[3,2-c]cinnolines were also endowed with good antifungal activity, particularly against Criptococcus neoformans.

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...

Adjudin - A Male Contraceptive with Other Biological Activities

PubMed Central

Cheng, Yan-Ho; Xia, Weiliang; Wong, Elissa W.P.; Xie, Qian R.; Shao, Jiaxiang; Liu, Tengyuan; Quan, Yizhou; Zhang, Tingting; Yang, Xiao; Geng, Keyi; Silvestrini, Bruno; Cheng, Chuen-Yan

2018-01-01

Background Adjudin has been explored as a male contraceptive for the last 15 years since its initial synthesis in the late 1990s. More than 50 papers have been published and listed in PubMed in which its mechanism that induces exfoliation of germ cells from the seminiferous epithelium, such as its effects on actin microfilaments at the apical ES (ectoplasmic specialization, a testis-specific actin-rich anchoring junction) has been delineated. Objective Recent studies have demonstrated that, besides its activity to induce germ cell exfoliation from the seminiferous epithelium to cause reversible infertility in male rodents, adjudin possesses other biological activities, which include anti-cancer, anti-inflammation in the brain, and anti-ototoxicity induced by gentamicin in rodents. Results of these findings likely spark the interest of investigators to explore other medical use of this and other indazole-based compounds, possibly mediated by the signaling pathway(s) in the mitochondria of mammalian cells following treatment with adjudin. In this review, we carefully evaluate these recent findings. Methods Papers published and listed at www.pubmed.org and patents pertinent to adjudin and its related compounds were searched. Findings were reviewed and critically evaluated, and summarized herein. Results Adjudin is a novel compound that possesses anti-spermatogenetic activity. Furthermore, it possesses anti-cancer, anti-inflammation, anti-neurodegeneration, and anti-ototoxicity activities based on studies using different in vitro and in vivo models. Conclusion: Studies on adjudin should be expanded to better understand its biological activities so that it can become a useful drug for treatment of other ailments besides serving as a male contraceptive. PMID:26510796

Adjudin--A Male Contraceptive with Other Biological Activities.

PubMed

Cheng, Yan-Ho; Xia, Weiliang; Wong, Elissa W P; Xie, Qian R; Shao, Jiaxiang; Liu, Tengyuan; Quan, Yizhou; Zhang, Tingting; Yang, Xiao; Geng, Keyi; Silvestrini, Bruno; Cheng, Chuen-Yan

2015-01-01

Adjudin has been explored as a male contraceptive for the last 15 years since its initial synthesis in the late 1990s. More than 50 papers have been published and listed in PubMed in which its mechanism that induces exfoliation of germ cells from the seminiferous epithelium, such as its effects on actin microfilaments at the apical ES (ectoplasmic specialization, a testis-specific actin-rich anchoring junction) has been delineated. Recent studies have demonstrated that, besides its activity to induce germ cell exfoliation from the seminiferous epithelium to cause reversible infertility in male rodents, adjudin possesses other biological activities, which include anti-cancer, anti-inflammation in the brain, and anti-ototoxicity induced by gentamicin in rodents. Results of these findings likely spark the interest of investigators to explore other medical use of this and other indazole-based compounds, possibly mediated by the signaling pathway(s) in the mitochondria of mammalian cells following treatment with adjudin. In this review, we carefully evaluate these recent findings. Papers published and listed at www.pubmed.org and patents pertinent to adjudin and its related compounds were searched. Findings were reviewed and critically evaluated, and summarized herein. Adjudin is a novel compound that possesses anti-spermatogenetic activity. Furthermore, it possesses anti-cancer, anti-inflammation, anti-neurodegeneration, and anti-ototoxicity activities based on studies using different in vitro and in vivo models. Studies on adjudin should be expanded to better understand its biological activities so that it can become a useful drug for treatment of other ailments besides serving as a male contraceptive.

Hit identification of IKKβ natural product inhibitor.

PubMed

Leung, Chung-Hang; Chan, Daniel Shiu-Hin; Li, Ying-Wei; Fong, Wang-Fun; Ma, Dik-Lung

2013-01-07

The nuclear factor-κB (NF-κB) proteins are a small group of heterodimeric transcription factors that play an important role in regulating the inflammatory, immune, and apoptotic responses. NF-κB activity is suppressed by association with the inhibitor IκB. Aberrant NF-κB signaling activity has been associated with the development of cancer, chronic inflammatory diseases and auto-immune diseases. The IKK protein complex is comprised of IKKα, IKKβ and NEMO subunits, with IKKβ thought to play the dominant role in modulating NF-κB activity. Therefore, the discovery of new IKKβ inhibitors may offer new therapeutic options for the treatment of cancer and inflammatory diseases. A structure-based molecular docking approach has been employed to discover novel IKKβ inhibitors from a natural product library of over 90,000 compounds. Preliminary screening of the 12 highest-scoring compounds using a luciferase reporter assay identified 4 promising candidates for further biological study. Among these, the benzoic acid derivative (1) showed the most promising activity at inhibiting IKKβ phosphorylation and TNF-α-induced NF-κB signaling in vitro. In this study, we have successfully identified a benzoic acid derivative (1) as a novel IKKβ inhibitor via high-throughput molecular docking. Compound 1 was able to inhibit IKKβ phosphorylation activity in vitro, and block IκBα protein degradation and subsequent NF-κB activation in human cells. Further in silico optimization of the compound is currently being conducted in order to generate more potent analogues for biological tests.

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.

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.

Rapid Scanning Structure-Activity Relationships in Combinatorial Data Sets: Identification of Activity Switches

PubMed Central

Medina-Franco, José L.; Edwards, Bruce S.; Pinilla, Clemencia; Appel, Jon R.; Giulianotti, Marc A.; Santos, Radleigh G.; Yongye, Austin B.; Sklar, Larry A.; Houghten, Richard A.

2013-01-01

We present a general approach to describe the structure-activity relationships (SAR) of combinatorial data sets with activity for two biological endpoints with emphasis on the rapid identification of substitutions that have a large impact on activity and selectivity. The approach uses Dual-Activity Difference (DAD) maps that represent a visual and quantitative analysis of all pairwise comparisons of one, two, or more substitutions around a molecular template. Scanning the SAR of data sets using DAD maps allows the visual and quantitative identification of activity switches defined as specific substitutions that have an opposite effect on the activity of the compounds against two targets. The approach also rapidly identifies single- and double-target R-cliffs, i.e., compounds where a single or double substitution around the central scaffold dramatically modifies the activity for one or two targets, respectively. The approach introduced in this report can be applied to any analogue series with two biological activity endpoints. To illustrate the approach, we discuss the SAR of 106 pyrrolidine bis-diketopiperazines tested against two formylpeptide receptors obtained from positional scanning deconvolution methods of mixture-based libraries. PMID:23705689

[Synthesis and biological activity of 1,4-benzoquinone-guanylhydrazone-thiosemicarbazone analogs. 1. Substitution at the S atom].

PubMed

Schulze, W; Gutsche, W; Wohlrabe, K; Fleck, W; Tresselt, D

1985-08-01

The synthesis of S-substituted derivatives of 1,4-benzoquinone-guanylhydrazone-thiosemicarbazone is described. The obtained 1,4-benzoquinone-guanylhydrazone-S-alkyl (resp. aralkyl)-isothiosemicarbazones, in comparison with the unsubstituted standard compound, showed a significantly decreased biological activity against the murine leukemias L 1210 and P 388 as well as against the growth of several kinds of bacteria. Therefore the S-substitution seems not to be useful for reaching a maximum activity.

Advanced biological activated carbon filter for removing pharmaceutically active compounds from treated wastewater.

PubMed

Sbardella, Luca; Comas, Joaquim; Fenu, Alessio; Rodriguez-Roda, Ignasi; Weemaes, Marjoleine

2018-04-28

Through their release of effluents, conventional wastewater treatment plants (WWTPs) represent a major pollution point sources for pharmaceutically active compounds (PhACs) in water bodies. The combination of a biological activated carbon (BAC) filter coupled with an ultrafiltration (UF) unit was evaluated as an advanced treatment for PhACs removal at pilot scale. The BAC-UF pilot plant was monitored for one year. The biological activity of the biofilm that developed on the granular activated carbon (GAC) particles and the contribution of this biofilm to the overall removal of PhACs were evaluated. Two different phases were observed during the long-term monitoring of PhACs removal. During the first 9200 bed volumes (BV; i.e., before GAC saturation), 89, 78, 83 and 79% of beta-blockers, psychiatric drugs, antibiotics and a mix of other therapeutic groups were removed, respectively. The second phase was characterized by deterioration of the overall performances during the period between 9200 and 13,800 BV. To quantify the respective contribution of adsorption and biodegradation, a lab-scale setup was operated for four months and highlighted the essential role played by GAC in biofiltration units. Physical adsorption was indeed the main removal mechanism. Nevertheless, a significant contribution due to biological activity was detected for some PhACs. The biofilm contributed to the removal of 22, 25, 30, 32 and 35% of ciprofloxacin, bezafibrate, ofloxacin, azithromycin and sulfamethoxazole, respectively. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

2-Aryl benzimidazoles: Synthesis, In vitro α-amylase inhibitory activity, and molecular docking study.

PubMed

Adegboye, Akande Akinsola; Khan, Khalid Mohammed; Salar, Uzma; Aboaba, Sherifat Adeyinka; Kanwal; Chigurupati, Sridevi; Fatima, Itrat; Taha, Mohammad; Wadood, Abdul; Mohammad, Jahidul Isalm; Khan, Huma; Perveen, Shahnaz

2018-04-25

Despite of many diverse biological activities exhibited by benzimidazole scaffold, it is rarely explored for the α-amylase inhibitory activity. For that purpose, 2-aryl benzimidazole derivatives 1-45 were synthesized and screened for in vitro α-amylase inhibitory activity. Structures of all synthetic compounds were deduced by various spectroscopic techniques. All compounds revealed inhibition potential with IC 50 values of 1.48 ± 0.38-2.99 ± 0.14 μM, when compared to the standard acarbose (IC 50  = 1.46 ± 0.26 μM). Limited SAR suggested that the variation in the inhibitory activities of the compounds are the result of different substitutions on aryl ring. In order to rationalize the binding interactions of most active compounds with the active site of α-amylase enzyme, in silico study was conducted. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Bioactive carbohydrates and recently discovered analogues as chemotherapeutics.

PubMed

Wrodnigg, Tanja M; Sprenger, Friedrich K Fitz

2004-05-01

Infectious diseases such as tuberculosis, malaria, the "simple flu" or HIV and HBV, are killing more than 50,000 people a day according to estimations by the World Health Organisation (WHO). Consequently, the development of biologically active agents in general, such as antibiotics and chemotherapeutics, is of great importance. Hand in hand with the understanding of the mechanisms of biological agents, structures carrying sugar moieties have become increasingly important during the last decades. This review will cover the most recent developments in the field of new antibiotics and synthetic agents containing carbohydrates which are active against tuberculosis and malaria. In addition, compounds having antiviral, antibacterial and anticancer properties will be examined. Compounds such as aminoglycosides, iminosugars, carbacycles, nucleosides, and other selected substance classes will be considered.

Design, synthesis and biological evaluation of non-peptide PAR1 thrombin receptor antagonists based on small bifunctional templates: arginine and phenylalanine side chain groups are keys for receptor activity.

PubMed

Androutsou, Maria-Eleni; Saifeddine, Mahmoud; Hollenberg, Morley D; Matsoukas, John; Agelis, George

2010-04-01

In the present study, we report the synthesis and biological evaluation of a series of new non-peptide PAR(1) mimetic receptor antagonists, based on conformational analysis of the S(42)FLLR(46) tethered ligand (TL) sequence of PAR(1). These compounds incorporate the key pharmacophore groups in the TL sequence, guanidyl, amino and phenyl, which are essential for triggering receptor activity. Compounds 5 and 15 (50-100 microM) inhibited both TFLLR-amide (10 microM) and thrombin-mediated (0.5 and 1 U/ml; 5 and 10 microM) calcium signaling in a cultured human HEK cell assay.

[The release of biologically active compounds from peat peloids].

PubMed

Babaskin, D V

2011-01-01

This work had the objective to study kinetics of the release of flavonoides from peat peloid compositions containing extracts of medicinal herbs in model systems.The key parameters of the process are defined. The rate of liberation of flavonoides is shown to depend on their initial concentration in the compositions being used. The influence of the flavonoide composition of the tested extracts and dimethylsulfoxide on the release of biologically active compounds contained in the starting material in the model environment is estimated. The possibility of the layer-by-layer deposition of the compositions and peat peloids in order to increase the efficacy of flavonoide release from the starting composition and to ensure more rational utilization of the extracts of medicinal plants is demonstrated.

Molecular locks and keys: the role of small molecules in phytohormone research

PubMed Central

Fonseca, Sandra; Rosado, Abel; Vaughan-Hirsch, John; Bishopp, Anthony; Chini, Andrea

2014-01-01

Plant adaptation, growth and development rely on the integration of many environmental and endogenous signals that collectively determine the overall plant phenotypic plasticity. Plant signaling molecules, also known as phytohormones, are fundamental to this process. These molecules act at low concentrations and regulate multiple aspects of plant fitness and development via complex signaling networks. By its nature, phytohormone research lies at the interface between chemistry and biology. Classically, the scientific community has always used synthetic phytohormones and analogs to study hormone functions and responses. However, recent advances in synthetic and combinational chemistry, have allowed a new field, plant chemical biology, to emerge and this has provided a powerful tool with which to study phytohormone function. Plant chemical biology is helping to address some of the most enduring questions in phytohormone research such as: Are there still undiscovered plant hormones? How can we identify novel signaling molecules? How can plants activate specific hormone responses in a tissue-specific manner? How can we modulate hormone responses in one developmental context without inducing detrimental effects on other processes? The chemical genomics approaches rely on the identification of small molecules modulating different biological processes and have recently identified active forms of plant hormones and molecules regulating many aspects of hormone synthesis, transport and response. We envision that the field of chemical genomics will continue to provide novel molecules able to elucidate specific aspects of hormone-mediated mechanisms. In addition, compounds blocking specific responses could uncover how complex biological responses are regulated. As we gain information about such compounds we can design small alterations to the chemical structure to further alter specificity, enhance affinity or modulate the activity of these compounds. PMID:25566283

Medicinal uses, phytochemistry and pharmacology of Pongamia pinnata (L.) Pierre: a review.

PubMed

Al Muqarrabun, L M R; Ahmat, N; Ruzaina, S A S; Ismail, N H; Sahidin, I

2013-11-25

Pongamia pinnata (L.) Pierre is one of the many plants with diverse medicinal properties where all its parts have been used as traditional medicine in the treatment and prevention of several kinds of ailments in many countries such as for treatment of piles, skin diseases, and wounds. This review discusses the current knowledge of traditional uses, phytochemistry, biological activities, and toxicity of this species in order to reveal its therapeutic and gaps requiring future research opportunities. This review is based on literature study on scientific journals and books from library and electronic sources such as ScienceDirect, PubMed, ACS, etc. Several different classes of flavonoid derivatives, such as flavones, flavans, and chalcones, and several types of compounds including terpenes, steroid, and fatty acids have been isolated from all parts of this plant. The pharmacological studies revealed that various types of preparations, extracts, and single compounds of this species exhibited a broad spectrum of biological activities such as antioxidant, antimicrobial, anti-inflammatory, and anti-diabetic activities. The results of several toxicity studies indicated that extracts and single compounds isolated from this species did not show any significant toxicity and did not cause abnormality on some rats' organs. Thus, this plant has a potential to be used as an effective therapeutic remedy due to its low toxicity towards mammalian cells. However, further study on chemical constituents and their mechanisms in exhibiting certain biological activities are needed to understand the full phytochemical profile and the complex pharmacological effects of this plant. In addition, further study on the toxicity of the other compounds isolated from this plant required to be assessed to ensure their eligibility to be used as sources of drugs. © 2013 Elsevier Ireland Ltd. All rights reserved.

Arylazolylthioacetanilide. Part 11: design, synthesis and biological evaluation of 1,2,4-triazole thioacetanilide derivatives as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.

PubMed

Li, Zhenyu; Cao, Yuan; Zhan, Peng; Pannecouque, Christophe; Balzarini, Jan; Clercq, Erik De; Shen, Yuemao; Liu, Xinyong

2013-11-01

A series of novel 1,2,4-triazole thioacetanilide derivatives has been designed, synthesized and evaluated for their anti-HIV activities in MT-4 cells. Half of these compounds showed moderate to potent activities against wild-type HIV-1 with an EC50 ranging from 38.0 μM to 4.08 µM. Among them, 2-(4-(2-fluorobenzyl)-5-isopropyl-4H-1,2,4-triazol- 3-ylthio)-N-(2-nitrophenyl)acetamide 7d was identified as the most promising compound (EC50 = 4.26 µM, SI = 49). However, no compound was active against HIV-2. The preliminary structure-activity relationships among the newly synthesized congeners are discussed.

The antioxidant effect of derivatives pyroglutamic lactam

NASA Astrophysics Data System (ADS)

Rohadi, Atisya; Lazim, Azwani Mat; Hasbullah, Siti Aishah

2013-11-01

Diphenylpicrylhydrazyl (DPPH) is widely used for quickly accessing the ability of polyphenols to transfer labile H atoms to radicals. The antioxidant activity of all the synthesized compounds was screened by DPPH method. Compound (4) showed 54% antioxidant potential while all other compounds were found to have moderate to have moderate to mild antioxidant activity ranging from 47-52%. Pyroglutamic lactams have been synthesized stereoselectively in racemic form from levulinic acid as bifunctional adduct using convertible isocyanide in one-pot Ugi 4-center-3-component condensation reaction (U-4C-3CR). The product formed provides biologically interesting products in excellent yields in a short reaction time. The structures of the synthesized compounds were elucidated using spectroscopic data and elemental analysis.

The study on molecular structure and microbiological activity of alkali metal 3-hydroxyphenylycetates

NASA Astrophysics Data System (ADS)

Samsonowicz, M.; Regulska, E.; Kowczyk-Sadowy, M.; Butarewicz, A.; Lewandowski, W.

2017-10-01

The biological activity of chemical compounds depends on their molecular structure. In this paper molecular structure of 3-hydroxyphenylacetates in comparison to 3-hydroxyphenylacetic acid was studied. FT-IR, FT-Raman and NMR spectroscopy and density functional theory (DFT) calculations was used. The B3LYP/6-311++G(d,p) hybrid functional method was used to calculate optimized geometrical structures of studied compounds. The Mulliken, APT, MK, ChelpG and NBO atomic charges as well as dipole moment and energy values were calculated. Theoretical chemical shifts in NMR spectra and the wavenumbers and intensities of the bands in vibrational spectra were analyzed. Calculated parameters were compared to experimental characteristic of studied compounds. Microbiological analysis of studied compounds was performed relative to: Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli and Klebsiella oxytoca. The relationship between spectroscopic and structure parameters of studied compounds in regard to their activity was analyzed.

SYNTHESIS AND BIOLOGICAL EVALUATION OF N-(SUBSTITUTED PHENYL)-2-(5H-[1,2,4]TRIAZINO[5,6-b]INDOL-3-YLSULFANYL)ACETAMIDES AS ANTIMICROBIAL, ANTIDEPRESSANT AND ANTICONVULSANT AGENTS.

PubMed

Shruthi, N; Poojary, Boja; Kumar, Vasantha; Prathibha, A; Hussain, Mumtaz Mohammed; Revanasiddappa, B C; Joshi, Himanshu

2015-01-01

A new series of N-Aryl-2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylsulfanyl)acetamides were synthesized by condensation of tricyclic compound 2,5-dihydro-3H-[1,2,4]triazino[5,6-b]indole-3-thione with chloro N-phenylacetamides. The tricyclic compound was obtained by condensation of Isatin with thiosemicarbazide. Chloro N-phenylacetamides were obtained from different substituted anilines. Their structures were characterized by IR, 1H NMR, LC-MS and elemental analyses. Newly synthesized compounds were screened for antimicrobial, antidepressant and anticonvulsant activities. Preliminary results indicated that most of the compounds showed lesser MIC value than the standard drug used when tested for antimicrobial activity. Some of the compounds were endowed with very good antidepressant and anticonvulsant activity.

In vitro plant tissue culture: means for production of biological active compounds.

PubMed

Espinosa-Leal, Claudia A; Puente-Garza, César A; García-Lara, Silverio

2018-05-07

Plant tissue culture as an important tool for the continuous production of active compounds including secondary metabolites and engineered molecules. Novel methods (gene editing, abiotic stress) can improve the technique. Humans have a long history of reliance on plants for a supply of food, shelter and, most importantly, medicine. Current-day pharmaceuticals are typically based on plant-derived metabolites, with new products being discovered constantly. Nevertheless, the consistent and uniform supply of plant pharmaceuticals has often been compromised. One alternative for the production of important plant active compounds is in vitro plant tissue culture, as it assures independence from geographical conditions by eliminating the need to rely on wild plants. Plant transformation also allows the further use of plants for the production of engineered compounds, such as vaccines and multiple pharmaceuticals. This review summarizes the important bioactive compounds currently produced by plant tissue culture and the fundamental methods and plants employed for their production.

Compounds from the Fruits of the Popular European Medicinal Plant Vitex agnus-castus in Chemoprevention via NADP(H):Quinone Oxidoreductase Type 1 Induction.

PubMed

Li, Shenghong; Qiu, Shengxiang; Yao, Ping; Sun, Handong; Fong, Harry H S; Zhang, Hongjie

2013-01-01

As part of our continuing efforts in the search for potential biologically active compounds from medicinal plants, we have isolated 18 compounds including two novel nitrogen containing diterpenes from extracts of the fruits of Vitex agnus-castus. These isolates, along with our previously obtained novel compound vitexlactam A (1), were evaluated for potential biological effects, including cancer chemoprevention. Chemically, the nitrogenous isolates were found to be two labdane diterpene alkaloids, each containing an α , β -unsaturated γ -lactam moiety. Structurally, they were elucidated to be 9 α -hydroxy-13(14)-labden-16,15-amide (2) and 6 β -acetoxy-9 α -hydroxy-13(14)-labden-15,16-amide (3), which were named vitexlactams B and C, respectively. The 15 known isolates were identified as vitexilactone (4), rotundifuran (5), 8-epi-manoyl oxide (6), vitetrifolin D (7), spathulenol (8), cis-dihydro-dehydro-diconiferylalcohol-9-O- β -D-glucoside (9), luteolin-7-O-glucoside (10), 5-hydroxy-3,6,7,4'-tetramethoxyflavone (11), casticin (12), artemetin (13), aucubin (14), agnuside (15), β -sitosterol (16), p-hydroxybenzoic acid (17), and p-hydroxybenzoic acid glucose ester (18). All compound structures were determined/identified on the basis of 1D and/or 2D NMR and mass spectrometry techniques. Compounds 6, 8, 9, and 18 were reported from a Vitex spieces for the first time. The cancer chemopreventive potentials of these isolates were evaluated for NADP(H):quinone oxidoreductase type 1 (QR1) induction activity. Compound 7 demonstrated promising QR1 induction effect, while the new compound vitexlactam (3) was only slightly active.

Compounds from the Fruits of the Popular European Medicinal Plant Vitex agnus-castus in Chemoprevention via NADP(H):Quinone Oxidoreductase Type 1 Induction

PubMed Central

Li, Shenghong; Qiu, Shengxiang; Yao, Ping; Sun, Handong; Fong, Harry H. S.; Zhang, Hongjie

2013-01-01

As part of our continuing efforts in the search for potential biologically active compounds from medicinal plants, we have isolated 18 compounds including two novel nitrogen containing diterpenes from extracts of the fruits of Vitex agnus-castus. These isolates, along with our previously obtained novel compound vitexlactam A (1), were evaluated for potential biological effects, including cancer chemoprevention. Chemically, the nitrogenous isolates were found to be two labdane diterpene alkaloids, each containing an α, β-unsaturated γ-lactam moiety. Structurally, they were elucidated to be 9α-hydroxy-13(14)-labden-16,15-amide (2) and 6β-acetoxy-9α-hydroxy-13(14)-labden-15,16-amide (3), which were named vitexlactams B and C, respectively. The 15 known isolates were identified as vitexilactone (4), rotundifuran (5), 8-epi-manoyl oxide (6), vitetrifolin D (7), spathulenol (8), cis-dihydro-dehydro-diconiferylalcohol-9-O-β-D-glucoside (9), luteolin-7-O-glucoside (10), 5-hydroxy-3,6,7,4′-tetramethoxyflavone (11), casticin (12), artemetin (13), aucubin (14), agnuside (15), β-sitosterol (16), p-hydroxybenzoic acid (17), and p-hydroxybenzoic acid glucose ester (18). All compound structures were determined/identified on the basis of 1D and/or 2D NMR and mass spectrometry techniques. Compounds 6, 8, 9, and 18 were reported from a Vitex spieces for the first time. The cancer chemopreventive potentials of these isolates were evaluated for NADP(H):quinone oxidoreductase type 1 (QR1) induction activity. Compound 7 demonstrated promising QR1 induction effect, while the new compound vitexlactam (3) was only slightly active. PMID:23662135

Synthesis, Biological Evaluation and Molecular Docking Study of Hydrazone-Containing Pyridinium Salts as Cholinesterase Inhibitors.

PubMed

Parlar, Sulunay; Bayraktar, Gulsah; Tarikogullari, Ayse Hande; Alptüzün, Vildan; Erciyas, Ercin

2016-01-01

A series of pyridinium salts bearing alkylphenyl groups at 1 position and hydrazone structure at 4 position of the pyridinium ring were synthesized and evaluated for the inhibition of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. The cholinesterase (ChE) inhibitory activity studies were carried out by using the Ellman's colorimetric method. All compounds displayed considerable AChE and BuChE inhibitory activity and some of the compounds manifested remarkable anti-AChE activity compared to the reference compound, galantamine. Among the title compounds, the series including benzofuran aromatic ring exhibited the best inhibitory activity both on AChE and BuChE enzymes. Compound 3b, 4-[2-(1-(benzofuran-2-yl)ethylidene)hydrazinyl]-1-(3-phenylpropyl)pyridinium bromide, was the most active compound with IC50 value of 0.23 (0.24) µM against enantiomeric excess (ee)AChE (human (h)AChE) while compound 3a, 4-[2-(1-(benzofuran-2-yl)ethylidene)hydrazinyl]-1-phenethylpyridinium bromide, was the most active compound with IC50 value of 0.95 µM against BuChE. Moreover, 3a and b exhibited higher activity than the reference compound galantamine (eeAChE (hAChE) IC50 0.43 (0.52) µM; BuChE IC50 14.92 µM). Molecular docking studies were carried out on 3b having highest inhibitory activity against AChE.

Biological Evaluation of Azomethine-dihydroquinazolinone Conjugates as Cancer and Cholinesterase Inhibitors.

PubMed

Iqbal, Jamshed; Saeed, Aamer; Shah, Syed J A; al-Rashida, Mariya; Shams-ul Mahmood

2016-01-01

In an attempt to discover novel anti-cancer agents and potent cholinesterase inhibitors, 11 azomethine-dihydroquinazolinone conjugates were evaluated against lung carcinoma cells and cholinesterases. Most of the compounds exhibited significant cytotoxicity at low micromolar concentrations and were less toxic to normal cells. After 24 h incubation period, 2i showed maximum cytotoxicity. The 4-bromine substituted compounds showed higher acetylcholinesterase (AChE) inhibitory activity than other screened compounds. The most active compound 2c, among the series, had an IC50 value 209.8 µM against AChE. The tested compounds showed less inhibition against butyrylcholinesterase. Molecular docking studies were performed in order to investigate the plausible binding modes of synthesized compounds. The compounds can be further optimized to treat cancer and Alzheimer's disease. These derivatives may open new pathways for introducing new therapies for curing cancer and senile dementia.

Antifungal activity of 1'-homo-N-1,2,3-triazol-bicyclic carbonucleosides: A novel type of compound afforded by azide-enolate (3+2) cycloaddition.

PubMed

González-Calderón, Davir; Mejía-Dionicio, María G; Morales-Reza, Marco A; Aguirre-de Paz, José G; Ramírez-Villalva, Alejandra; Morales-Rodríguez, Macario; Fuentes-Benítes, Aydeé; González-Romero, Carlos

2016-12-01

The first report of 1'-homo-N-1,2,3-triazol-bicyclic carbonucleosides (7a and 7b) is described herein. Azide-enolate (3+2) cycloaddition afforded the synthesis of this novel type of compound. Antifungal activity was evaluated in vitro against four filamentous fungi (Aspergillus fumigatus, Trichosporon cutaneum, Rhizopus oryzae and Mucor hiemalis) as well as nine species of Candida spp. as yeast specimens. These pre-clinical studies suggest that compounds 7a and 7b are promising candidates for complementary biological studies due to their good activity against Candida spp. Copyright © 2016 Elsevier Inc. All rights reserved.

USSR Report, Life Sciences Biomedical and Behavioral Sciences.

DTIC Science & Technology

1987-05-13

Activities of Selected Organoboron Compounds (A.N. Lukashik, A.A. Malama, et al.; MIKOLOGIYA I FTTOPATOLOGIYA, No 5, Sep-Oct 86) .35 - e - Mycotic Flora... Compounds (G.B. Pliss, N.N. Antashkova, et al.; VOPROSY ONKOLOGII, No 7, Jul 86). • • 94 Review of Book on Protection of Machinery From Biodegradation...Jul 85) pp 746-751 [Article by K.Ye. Dorokhov and G.L. Grigoryan, Scientific Research Institute for Biological Testing of Chemical Compounds

Cell-Specific Production and Antimicrobial Activity of Naphthoquinones in Roots of Lithospermum erythrorhizon1

PubMed Central

Brigham, Lindy A.; Michaels, Paula J.; Flores, Hector E.

1999-01-01

Pigmented naphthoquinone derivatives of shikonin are produced at specific times and in specific cells of Lithospermum erythrorhizon roots. Normal pigment development is limited to root hairs and root border cells in hairy roots grown on “noninducing” medium, whereas induction of additional pigment production by abiotic (CuSO4) or biotic (fungal elicitor) factors increases the amount of total pigment, changes the ratios of derivatives produced, and initiates production of pigment de novo in epidermal cells. When the biological activity of these compounds was tested against soil-borne bacteria and fungi, a wide range of sensitivity was recorded. Acetyl-shikonin and β-hydroxyisovaleryl-shikonin, the two most abundant derivatives in both Agrobacterium rhizogenes-transformed “hairy-root” cultures and greenhouse-grown plant roots, were the most biologically active of the seven compounds tested. Hyphae of the pathogenic fungi Rhizoctonia solani, Pythium aphanidermatum, and Nectria hematococca induced localized pigment production upon contact with the roots. Challenge by R. solani crude elicitor increased shikonin derivative production 30-fold. We have studied the regulation of this suite of related, differentially produced, differentially active compounds to understand their role(s) in plant defense at the cellular level in the rhizosphere. PMID:9952436

A Genomics-Based Approach Identifies a Thioviridamide-Like Compound with Selective Anticancer Activity.

PubMed

Frattaruolo, Luca; Lacret, Rodney; Cappello, Anna Rita; Truman, Andrew W

2017-11-17

Thioviridamide is a structurally novel ribosomally synthesized and post-translational modified peptide (RiPP) produced by Streptomyces olivoviridis NA005001. It is characterized by a structure that features a series of thioamide groups and possesses potent antiproliferative activity in cancer cell lines. Its unusual structure allied to its promise as an anticancer compound led us to investigate the diversity of thioviridamide-like pathways across sequenced bacterial genomes. We have isolated and characterized three diverse members of this family of natural products. This characterization is supported by transformation-associated recombination cloning and heterologous expression of one of these compounds, thiostreptamide S4. Our work provides an insight into the diversity of this rare class of compound and indicates that the unusual N-terminus of thioviridamide is not introduced biosynthetically but is instead introduced during acetone extraction. A detailed analysis of the biological activity of one of the newly discovered compounds, thioalbamide, indicates that it is highly cytotoxic to cancer cells, while exhibiting significantly less activity toward a noncancerous epithelial cell line.

Screening for fractions of Oxytropis falcata Bunge with antibacterial activity.

PubMed

Jiang, H; Hu, J R; Zhan, W Q; Liu, X

2009-01-01

Preliminary studies with the four extracts of Oxytropis falcate Bunge exhibited that the chloroform and ethyl acetate extracts showed stronger antibacterial activities against the nine tested Gram-positive and Gram-negative bacteria. The HPLC-scanned and bioassay-guided fractionation led to the isolation and identification of the main flavonoid compounds, i.e. rhamnocitrin, kaempferol, rhamnetin, 2',4'-dihydroxychalcone and 2',4',beta-trihydroxy-dihydrochalcon. Except 2',4',beta-trihydroxy-dihydrochalcon, four other compounds had good antibacterial activities. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of the four compounds ranged between 125 and 515 microg mL(-1). Staphylococcus aureus was the most susceptible to these compounds, with MIC and MBC values from 125 to 130 microg mL(-1). This is the first report of antibacterial activity in O. falcate Bunge. In this study, evidence to evaluate the biological functions of O. falcate Bunge is provided, which promote the rational use of this herb.

Synthesis, evaluation and modeling of some triazolothienopyrimidinones as anti-inflammatory and antimicrobial agents.

PubMed

Bekhit, Adnan A; Farghaly, Ahmed M; Shafik, Ragab M; Elsemary, Mona Ma; El-Shoukrofy, Mai S; Bekhit, Alaa El-Din A; Ibrahim, Tamer M

2017-06-01

New triazolotetrahydrobenzothienopyrimidinone derivatives were synthesized. Their structures were confirmed, and their anti-inflammatory, antimicrobial activities and ulcerogenic potentials were evaluated. Compounds 7a, 10a and 11a showed minimal ulcerogenic effect and high selectivity toward human recombinant COX-2 over COX-1 enzyme with IC 50 values of 1.39, 1.22 and 0.56 μM, respectively. Their docking outcome correlated with their biological activity and confirmed the high selectivity binding toward COX-2. Compound 12b displayed antimicrobial activity comparable to that of ampicillin against Escherichia coli while compounds 6 and 11c were similar to ampicillin against Staphylococcus aureus. In addition, compounds 7a, 9a, 10b and 11c showed dual anti-inflammatory/antimicrobial activities. This work represents a promising matrix for developing new potential anti-inflammatory, antimicrobial and dual antimicrobial/anti-inflammatory candidates. [Formula: see text].

Metallic elements in fossil fuel combustion products: amounts and form of emissions and evaluation of carcinogenicity and mutagenicity.

PubMed

Vouk, V B; Piver, W T

1983-01-01

Metallic elements contained in coal, oil and gasoline are mobilized by combustion processes and may be emitted into the atmosphere, mainly as components of submicron particles. The information about the amounts, composition and form of metal compounds is reviewed for some fuels and combustion processes. Since metal compounds are always contained in urban air pollutants, they have to be considered whenever an evaluation of biological impact of air pollutants is made. The value of currently used bioassays for the evaluation of the role of trace metal compounds, either as major biologically active components or as modifiers of biological effects of organic compounds is assessed. The whole animal bioassays for carcinogenicity do not seem to be an appropriate approach. They are costly, time-consuming and not easily amenable to the testing of complex mixtures. Some problems related to the application and interpretation of short-term bioassays are considered, and the usefulness of such bioassays for the evaluation of trace metal components contained in complex air pollution mixtures is examined.

Enhanced degradation of phenolic compounds in coal gasification wastewater by a novel integration of micro-electrolysis with biological reactor (MEBR) under the micro-oxygen condition.

PubMed

Ma, Weiwei; Han, Yuxing; Xu, Chunyan; Han, Hongjun; Ma, Wencheng; Zhu, Hao; Li, Kun; Wang, Dexin

2018-03-01

The aim of this work was to study an integration of micro-electrolysis with biological reactor (MEBR) for strengthening removal of phenolic compounds in coal gasification wastewater (CGW). The results indicated MEBR achieved high efficiencies in removal of COD and phenolic compounds as well as improvement of biodegradability of CGW under the micro-oxygen condition. The integrated MEBR process was more favorable to improvement of the structural stability of activated sludge and biodiversity of specific functional microbial communities. Especially, Shewanella and Pseudomonas were enriched to accelerate the extracellular electron transfer, finally facilitating the degradation of phenolic compounds. Moreover, MEBR process effectively relieved passivation of Fe-C filler surface and prolonged lifespan of Fe-C filler. Accordingly, the synergetic effect between iron-carbon micro-electrolysis (ICME) and biological action played a significant role in performance of the integrated process. Therefore, the integrated MEBR was a promising practical process for enhancing CGW treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metallic elements in fossil fuel combustion products: amounts and form of emissions and evaluation of carcinogenicity and mutagenicity.

PubMed Central

Vouk, V B; Piver, W T

1983-01-01

Metallic elements contained in coal, oil and gasoline are mobilized by combustion processes and may be emitted into the atmosphere, mainly as components of submicron particles. The information about the amounts, composition and form of metal compounds is reviewed for some fuels and combustion processes. Since metal compounds are always contained in urban air pollutants, they have to be considered whenever an evaluation of biological impact of air pollutants is made. The value of currently used bioassays for the evaluation of the role of trace metal compounds, either as major biologically active components or as modifiers of biological effects of organic compounds is assessed. The whole animal bioassays for carcinogenicity do not seem to be an appropriate approach. They are costly, time-consuming and not easily amenable to the testing of complex mixtures. Some problems related to the application and interpretation of short-term bioassays are considered, and the usefulness of such bioassays for the evaluation of trace metal components contained in complex air pollution mixtures is examined. PMID:6337825

A Systematic Screen of FDA-Approved Drugs for Inhibitors of Biological Threat Agents

PubMed Central

Madrid, Peter B.; Chopra, Sidharth; Manger, Ian D.; Gilfillan, Lynne; Keepers, Tiffany R.; Shurtleff, Amy C.; Green, Carol E.; Iyer, Lalitha V.; Dilks, Holli Hutcheson; Davey, Robert A.; Kolokoltsov, Andrey A.; Carrion, Ricardo; Patterson, Jean L.; Bavari, Sina; Panchal, Rekha G.; Warren, Travis K.; Wells, Jay B.; Moos, Walter H.; Burke, RaeLyn L.; Tanga, Mary J.

2013-01-01

Background The rapid development of effective medical countermeasures against potential biological threat agents is vital. Repurposing existing drugs that may have unanticipated activities as potential countermeasures is one way to meet this important goal, since currently approved drugs already have well-established safety and pharmacokinetic profiles in patients, as well as manufacturing and distribution networks. Therefore, approved drugs could rapidly be made available for a new indication in an emergency. Methodology/Principal Findings A large systematic effort to determine whether existing drugs can be used against high containment bacterial and viral pathogens is described. We assembled and screened 1012 FDA-approved drugs for off-label broad-spectrum efficacy against Bacillus anthracis; Francisella tularensis; Coxiella burnetii; and Ebola, Marburg, and Lassa fever viruses using in vitro cell culture assays. We found a variety of hits against two or more of these biological threat pathogens, which were validated in secondary assays. As expected, antibiotic compounds were highly active against bacterial agents, but we did not identify any non-antibiotic compounds with broad-spectrum antibacterial activity. Lomefloxacin and erythromycin were found to be the most potent compounds in vivo protecting mice against Bacillus anthracis challenge. While multiple virus-specific inhibitors were identified, the most noteworthy antiviral compound identified was chloroquine, which disrupted entry and replication of two or more viruses in vitro and protected mice against Ebola virus challenge in vivo. Conclusions/Significance The feasibility of repurposing existing drugs to face novel threats is demonstrated and this represents the first effort to apply this approach to high containment bacteria and viruses. PMID:23577127

Synthesis, molecular properties, toxicity and biological evaluation of some new substituted imidazolidine derivatives in search of potent anti-inflammatory agents

PubMed Central

Husain, Asif; Ahmad, Aftab; Khan, Shah Alam; Asif, Mohd; Bhutani, Rubina; Al-Abbasi, Fahad A.

2015-01-01

The aim of this study was to design and synthesize pharmaceutical agents containing imidazolidine heterocyclic ring in the hope of developing potent, safe and orally active anti-inflammatory agents. A number of substituted-imidazolidine derivatives (3a–k) were synthesized starting from ethylene diamine and aromatic aldehydes. The imidazolidine derivatives (3a–k) were investigated for their anticipated anti-inflammatory, and analgesic activity in Wistar albino rats and Swiss albino mice, respectively. Bioactivity score, molecular and pharmacokinetic properties of the imidazolidine derivatives were calculated by online computer software programs viz. Molinspiration and Osiris property explorer. The results of biological testing indicated that among the synthesized compounds only three imidazolidine derivatives namely 4-[1,3-Bis(2,6-dichlorobenzyl)-2-imidazolidinyl]phenyl-diethylamine (3g), 4-[1,3-Bis(3-hydroxy-4-methoxybenzyl)-2-imidazolidinyl]phenyl-diethylamine (3i) and 4-(1,3-Bis(4-methoxybenzyl)-4-methylimidazolidin-2-yl)-phenyl-diethylamine (3j) possess promising anti-inflammatory and analgesic actions. Additionally these derivatives displayed superior GI safety profile (low severity index) with respect to the positive control, Indomethacin. All synthesized compounds showed promising bioactivity score for drug targets by Molinspiration software. Almost all the compounds were predicted to have very low toxicity risk by Osiris online software. Compound number (3i) emerged as a potential candidate for further research as it obeyed Lipinski’s rule of five for drug likeness, exhibited promising biological activity in-vivo and showed no risk of toxicity in computer aided screening. PMID:26903774

Compounds Released from Biomass Deconstruction: Understanding Their Effect on Cellulose Enzyme Hydrolysis and Their Biological Activity

NASA Astrophysics Data System (ADS)

Djioleu, Angele Mezindjou

The effect of compounds produced during biomass pretreatment on cellulolytic enzyme was investigated. Liquid prehydrolyzates were prepared by pretreating switchgrass using 24 combinations of temperature, time, and sulfuric acid concentration based on a full factorial design. Temperature was varied from 140°C to 180°C; time ranged from 10 to 40 min; and the sulfuric acid concentrations were 0.5% or 1% (v/v). Identified products in the prehydrolyzates included xylose, glucose, hydroxymethylfurfural (HMF), furfural, acetic acid, formic acid, and phenolic compounds at concentration ranging from 0 to 21.4 g/L. Pretreatment conditions significantly affected the concentrations of compounds detected in prehydrolyzates. When assayed in the presence of switchgrass prehydrolyzates against model substrates, activities of cellulase, betaglucosidase, and exoglucanase, were significantly reduced by at least 16%, 31.8%, and 57.8%, respectively, as compared to the control. A strong positive correlation between inhibition of betaglucosidase and concentration of glucose, acetic acid, and furans in prehydrolyzate was established. Exoglucanase inhibition correlated with the presence of phenolic compounds and acetic acid. The prehydrolyzate, prepared at 160°C, 30 min, and 1% acid, was fractionated by centrifugal partition chromatography (CPC) into six fractions; the inhibition effect of these fractions on betaglucosidase and exoglucanase was determined. The initial hydrolysis rate of cellobiose by betaglucosidase was significantly reduced by the CPC sugar-rich fraction; however, exoglucanase was deactivated by the CPC phenolic-rich fraction. Finally, biological activities of water-extracted compounds from sweetgum bark and their effect on cellulase was investigated. It was determined that 12% of solid content of the bark extract could be accounted by phenolic compounds with gallic acid identified as the most concentrated phytochemical. Sweetgum bark extract inhibited Staphylococcus aureus growth and copper-induced peroxidation of human low-density lipoprotein, confirming antimicrobial and antioxidant activities of the extract. On the other hand, bark extract inhibited cellulase cocktail activity by reducing cellulose hydrolysis by 82.32% after 48 h of incubation. Overall, phenolic compounds generated from biomass fractionation are important players in cellulolytic enzyme inhibition; removal of biomass extractives prior to pretreatment could reduce inhibitory compounds in prehydrolyzate while generating phytochemicals with societal benefits.

Physicochemical characterization of silver nanoparticles synthesize using Aloe Vera (Aloe barbadensis)

NASA Astrophysics Data System (ADS)

Kuponiyi, Abiola; Kassama, Lamin; Kukhtareva, Tatiana

2014-08-01

Production of silver nanoparticles (AgNPs) using different biological methods is gaining recognition due to their multiple applications. Although, several physical and chemical methods have been used for the synthesis and stabilizing of AgNPs, yet, a green chemistry method is preferable because it is cost effective and environmentally friendly. The synthesis was done using Aloe Vera (AV) extract because it has chemical compounds such as "Antrokinon" that are known for its antibacterial, antivirus and anticancer properties. We hypothesize that AV extract can produce a stable nanoparticles within the 100 nm range and be biologically active. The biological compounds were extracted from AV skin with water and ethanol which was used as the reduction agent for the synthesis of nanoparticles. The biological extract and AgNO3 were blended and heated to synthesize AgNPs. The reaction process was monitored using UV-Visible spectroscopy. Fourier Transfer Infrared spectroscopy (FTIR) was used for the characterization of biological compounds and their substituent groups before and after the reaction process. Dynamic Light scattering (DLS) method was used to characterize particle size of AgNPs and their biomolecular stability. Results showed that biological compounds such as aliphatic amines, alkenes (=C-H), alkanes (C-H), alcohol (O-H) and unsaturated esters(C-O), which has an average particle size of 109 and 215.8 nm and polydispersity index of 0.451 and 0.375 for ethanol and water extract, respectively. According to TEM measurements the size of AgNPs are in the range 5-20 nm The results suggested that ethanol derived AgNPs contained higher yield of organic compounds, thus has better solubility power than water. Ag NPs can be used to control salmonella in poultry industry.

Synthesis, spectroscopic characterization, DFT optimization and biological activities of Schiff bases and their metal (II) complexes

NASA Astrophysics Data System (ADS)

Rauf, Abdur; Shah, Afzal; Munawar, Khurram Shahzad; Khan, Abdul Aziz; Abbasi, Rashda; Yameen, Muhammad Arfat; Khan, Asad Muhammad; Khan, Abdur Rahman; Qureshi, Irfan Zia; Kraatz, Heinz-Bernhard; Zia-ur-Rehman

2017-10-01

A Novel Schiff base, 3-(((4-chlorophenyl)imino)methyl)benzene-1,2-diol (HL1) was successfully synthesized along with a structurally similar Schiff base 3-(((4-bromophenyl)imino)methyl)benzene-1,2-diol (HL2). Both the Schiff bases were used to synthesize their zinc (II) and cobalt (II) complexes. These compounds were characterized by FTIR, 1H NMR, 13C NMR and elemental analysis. Metal complexes were confirmed by TGA. Crystals of Schiff bases were also characterized by X-ray analysis and experimental parameters were found in line with the theoretical parameters. Quantum mechanical approach was also used to fine useful structural parameters and to ensure the geometry of metal complexes. The photometric behaviors of all the synthesized compounds were investigated in a wide pH range using BR buffers. The appearance of isosbestic points indicated the existence of Schiff bases in more than one isomeric form. Moreover, these compounds were screened for enzyme inhibition; antibacterial, cytotoxic and in vivo antidiabetic activities and compounds were found active against one or other activity. Results indicate that ZnL22 is a good inhibitor of alkaline phosphatase enzyme and possess highest potential against diabetes, blood cholesterol level and cancer cells. This effort just provides preliminary data for some biological properties. Further investigations are required to precisely determine mechanistic pathways of their use towards drug development.

Marine Indole Alkaloids

PubMed Central

Netz, Natalie; Opatz, Till

2015-01-01

Marine indole alkaloids comprise a large and steadily growing group of secondary metabolites. Their diverse biological activities make many compounds of this class attractive starting points for pharmaceutical development. Several marine-derived indoles were found to possess cytotoxic, antineoplastic, antibacterial and antimicrobial activities, in addition to the action on human enzymes and receptors. The newly isolated indole alkaloids of marine origin since the last comprehensive review in 2003 are reported, and biological aspects will be discussed. PMID:26287214

Photoelectron spectra and biological activity of cinnamic acid derivatives revisited.

PubMed

Novak, Igor; Klasinc, Leo; McGlynn, Sean P

2018-01-15

The electronic structures of several derivatives of cinnamic acid have been studied by UV photoelectron spectroscopy (UPS) and Green's function quantum chemical calculations. The spectra reveal the presence of dimers in the gas phase for p-coumaric and ferulic acids. The electronic structure analysis has been related to the biological properties of these compounds through the analysis of some structure-activity relationships (SAR). Copyright © 2017 Elsevier B.V. All rights reserved.

Structure-Based Design, Synthesis, Biological Evaluation, and Molecular Docking of Novel PDE10 Inhibitors with Antioxidant Activities

NASA Astrophysics Data System (ADS)

Li, Jinxuan; Chen, Jing-Yi; Deng, Ya-Lin; Zhou, Qian; Wu, Yinuo; Wu, Deyan; Luo, Hai-Bin

2018-05-01

Phosphodiesterase 10 is a promising target for the treatment of a series of central nervous system (CNS) diseases. Imbalance between oxidative stress and antioxidant defense systems as a universal condition in neurodegenerative disorders is widely studied as a potential therapy for CNS diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). To discover multifunctional pharmaceuticals as a treatment for neurodegenerative diseases, a series of quinazoline-based derivatives with PDE10 inhibitory activities and antioxidant activities were designed and synthesized. Nine out of thirteen designed compounds showed good PDE10 inhibition at the concentration of 1.0 μM. Among these compounds, eight exhibited moderate to excellent antioxidant activity with ORAC (oxygen radical absorbance capacity) value above 1.0. Molecular docking was performed for better understanding of the binding patterns of these compounds with PDE10. Compound 11e, which showed remarkable inhibitory activity against PDE10 and antioxidant activity may serve as a lead for the further modification.

Dapson in heterocyclic chemistry, part V: synthesis, molecular docking and anticancer activity of some novel sulfonylbiscompounds carrying biologically active dihydropyridine, dihydroisoquinoline, 1,3-dithiolan, 1,3-dithian, acrylamide, pyrazole, pyrazolopyrimidine and benzochromenemoieties.

PubMed

Ghorab, Mostafa Mohammed; Al-Said, Mansour Sulaiman; Nissan, Yassin Mohammed

2012-01-01

N,N'-(4,4'-Sulfonylbis(4,1-phenylene))bis(2-cyanoacetamid) 2 was utilized as a key intermediate for the synthesis of novel dihydropyridines 3, 4, 8, dihydroisoquinolines 5-7, dithiolan 10, dithian 11, acrylamide 12, benzochromenes 17 and 18 and chromenopyridones 19 and 20. Compound 2 was the starting material in the synthesis of the acrylamide derivative 14, the pyrazole derivative 15 and the pyrazolopyrimidine derivative 16. All the synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Compound 19 showed the best cytotoxic activity with IC(50) value 19.36 µM. In addition, molecular docking study of the synthesized compounds on the active sites of farnesyltransferase and arginine methyltransferase was performed in order to give a suggestion about the mechanism of action of their cytotoxic activity.

Phenolic content and antioxidant and antimutagenic activities in tomato peel, seeds, and byproducts.

PubMed

Valdez-Morales, Maribel; Espinosa-Alonso, Laura Gabriela; Espinoza-Torres, Libia Citlali; Delgado-Vargas, Francisco; Medina-Godoy, Sergio

2014-06-11

The phenolic content and antioxidant and antimutagenic activities from the peel and seeds of different tomato types (grape, cherry, bola and saladette type), and simulated tomato industrial byproducts, were studied. Methanolic extracts were used to quantify total phenolic content, groups of phenolic compounds, antioxidant activities, and the profile of phenolic compounds (by HPLC-DAD). Antimutagenic activity was determined by Salmonella typhimurium assay. The total phenolic content and antioxidant activity of tomato and tomato byproducts were comparable or superior to those previously reported for whole fruit and tomato pomace. Phenolic compounds with important biological activities, such as caffeic acid, ferulic acid, chlorogenic acids, quercetin-3-β-O-glycoside, and quercetin, were quantified. Differences in all phenolic determinations due to tomato type and part of the fruit analyzed were observed, peel from grape type showing the best results. Positive antimutagenic results were observed in all samples. All evaluated materials could be used as a source of potential nutraceutical compounds.

Synthesis, characterization and molecular docking studies of substituted 4-coumarinylpyrano[2,3-c]pyrazole derivatives as potent antibacterial and anti-inflammatory agents.

PubMed

Chougala, Bahubali M; Samundeeswari, S; Holiyachi, Megharaja; Shastri, Lokesh A; Dodamani, Suneel; Jalalpure, Sunil; Dixit, Sheshagiri R; Joshi, Shrinivas D; Sunagar, Vinay A

2017-01-05

A green, eco-friendly and efficient protocol has been developed and synthesized a series of coumarin based pyrano[2,3-c]pyrazole derivatives (3) by multi-component reaction (MCR). Unexpected 3-coumarinyl-3-pyrazolylpropanoic acids (4) have been isolated by the reaction of compound (3) in acidic conditions. Further, intramolecular cyclization of compounds (4) leads to C 4 C 4 chromons (9) and these compounds were screened for their biological activities using array of techniques. Most of the compounds exhibited promising antibacterial activity, in particular Gram-positive bacteria. The anti-inflammatory assay was evaluated against protein denaturation as well as HRBC membrane stabilization methods and compounds exhibit excellent anti-inflammatory activity in both methods. Molecular docking study has been performed for all the synthesized compounds with S. aureus dihydropteroate synthetase (DHPS) and results obtained are quite promising. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Three-component, one-pot synthesis of anthranilamide Schiff bases bearing 4-aminoquinoline moiety as Mycobacterium tuberculosis gyrase inhibitors.

PubMed

Salve, Preeti S; Alegaon, Shankar G; Sriram, Dharmarajan

2017-04-15

An efficient three-component, one-pot protocol is described for the synthesis of biologically interesting 2-(benzylideneamino)-N-(7-chloroquinolin-4-yl)benzohydrazide derivatives from isatoic anhydride, 7-chloro-4-hydrazinylquinoline and aromatic and/or hetero aromatic aldehydes under catalyst free condensation by using water as reaction media. All synthesized compounds were evaluated for their antimycobacterial activity against Mycobacterium tuberculosis (MTB) and cytotoxicity activity against normal VERO cell lines. The synthesized compounds exhibited minimum inhibitory concentration (MIC) ranging from 0.78 to 25μM. Among the tested compounds 4c, 4o, 4r, and 4u exhibited promising inhibitory activity (MIC=3.12μM). Compounds 4h and 4i stand out, showing MIC values of 0.78 and 1.56μM respectively. Both compounds were further screened for their Mycobacterium tuberculosis DNA gyrase inhibitory assay which suggested that these compounds have a great potential for further optimization and development as antitubercular agents. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis and biological evaluation of febrifugine analogues.

PubMed

Mai, Huong Doan Thi; Thanh, Giang Vo; Tran, Van Hieu; Vu, Van Nam; Vu, Van Loi; Le, Cong Vinh; Nguyen, Thuy Linh; Phi, Thi Dao; Truong, Bich Ngan; Chau, Van Minh; Pham, Van Cuong

2014-12-01

A series of febrifugine analogues were designed and synthesized. Antimalarial activity evaluation of the synthetic compounds indicated that these derivatives had a strong inhibition against both chloroquine-sensitive and -resistant Plasmodium falciparum parasites. Many of them were found to be more active than febrifugine hydrochloride. The tested analogues had also a significant cytotoxicity against four cancer cell lines (KB, MCF7, LU1 and HepG2). Among the synthetic analogues, two compounds 17b and 17h displayed a moderate cytotoxicity while they exhibited a remarkable antimalarial activity.

David and Goliath: chemical perturbation of eukaryotes by bacteria.

PubMed

Ho, Louis K; Nodwell, Justin R

2016-03-01

Environmental microbes produce biologically active small molecules that have been mined extensively as antibiotics and a smaller number of drugs that act on eukaryotic cells. It is known that there are additional bioactives to be discovered from this source. While the discovery of new antibiotics is challenged by the frequent discovery of known compounds, we contend that the eukaryote-active compounds may be less saturated. Indeed, despite there being far fewer eukaryotic-active natural products these molecules interact with a far richer diversity of molecular and cellular targets.

Discovery of aliphatic-chain hydroxamates containing indole derivatives with potent class I histone deacetylase inhibitory activities.

PubMed

Chao, Shi-Wei; Chen, Liang-Chieh; Yu, Chia-Chun; Liu, Chang-Yi; Lin, Tony Eight; Guh, Jih-Hwa; Wang, Chen-Yu; Chen, Chun-Yung; Hsu, Kai-Cheng; Huang, Wei-Jan

2018-01-01

Histone deacetylase (HDAC) is a validated drug target for various diseases. This study combined indole recognition cap with SAHA, an FDA-approved HDAC inhibitor used to treat cutaneous T-cell lymphoma (CTCL). The structure activity relationship of the resulting compounds that inhibited HDAC was disclosed as well. Some compounds exhibited much stronger inhibitory activities than SAHA. We identified two meta-series compounds 6j and 6k with a two-carbon linker had IC 50 values of 3.9 and 4.5 nM for HDAC1, respectively. In contrast, the same oriented compounds with longer carbon chain linkers showed weaker inhibition. The result suggests that the linker chain length greatly contributed to enzyme inhibitory potency. In addition, comparison of enzyme-inhibiting activity between the compounds and SAHA showed that compounds 6j and 6k displayed higher inhibiting activity for class I (HDAC1, -2, -3 and -8). The molecular docking and structure analysis revealed structural differences with the inhibitor cap and metal-binding regions between the HDAC isozymes that affect interactions with the inhibitors and play a key role for selectivity. Further biological evaluation showed multiple cellular effects associated with compounds 6j- and 6k-induced HDAC inhibitory activity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Schiff bases in medicinal chemistry: a patent review (2010-2015).

PubMed

Hameed, Abdul; Al-Rashida, Mariya; Uroos, Maliha; Abid Ali, Syed; Khan, Khalid Mohammed

2017-01-01

Schiff bases are synthetically accessible and structurally diverse compounds, typically obtained by facile condensation between an aldehyde, or a ketone with primary amines. Schiff bases contain an azomethine (-C = N-) linkage that stitches together two or more biologically active aromatic/heterocyclic scaffolds to form various molecular hybrids with interesting biological properties. Schiff bases are versatile metal complexing agents and have been known to coordinate all metals to form stable metal complexes with vast therapeutic applications. Areas covered: This review aims to provide a comprehensive overview of the various patented therapeutic applications of Schiff bases and their metal complexes from 2010 to 2015. Expert opinion: Schiff bases are a popular class of compounds with interesting biological properties. Schiff bases are also versatile metal complexing ligands and have been used to coordinate almost all d-block metals as well as lanthanides. Therapeutically, Schiff bases and their metal complexes have been reported to exhibit a wide range of biological activities such as antibacterial including antimycobacterial, antifungal, antiviral, antimalarial, antiinflammatory, antioxidant, pesticidal, cytotoxic, enzyme inhibitory, and anticancer including DNA damage.

Lipids and Fatty Acids of Nudibranch Mollusks: Potential Sources of Bioactive Compounds

PubMed Central

Zhukova, Natalia V.

2014-01-01

The molecular diversity of chemical compounds found in marine animals offers a good chance for the discovery of novel bioactive compounds of unique structures and diverse biological activities. Nudibranch mollusks, which are not protected by a shell and produce chemicals for various ecological uses, including defense against predators, have attracted great interest for their lipid composition. Lipid analysis of eight nudibranch species revealed dominant phospholipids, sterols and monoalkyldiacylglycerols. Among polar lipids, 1-alkenyl-2-acyl glycerophospholipids (plasmalogens) and ceramide-aminoethyl phosphonates were found in the mollusks. The fatty acid compositions of the nudibranchs differed greatly from those of other marine gastropods and exhibited a wide diversity: very long chain fatty acids known as demospongic acids, a series of non-methylene-interrupted fatty acids, including unusual 21:2∆7,13, and an abundance of various odd and branched fatty acids typical of bacteria. Symbiotic bacteria revealed in some species of nudibranchs participate presumably in the production of some compounds serving as a chemical defense for the mollusks. The unique fatty acid composition of the nudibranchs is determined by food supply, inherent biosynthetic activities and intracellular symbiotic microorganisms. The potential of nudibranchs as a source of biologically active lipids and fatty acids is also discussed. PMID:25196731

A glimpse on biological activities of tellurium compounds.

PubMed

Cunha, Rodrigo L O R; Gouvea, Iuri E; Juliano, Luiz

2009-09-01

Tellurium is a rare element which has been regarded as a toxic, non-essential trace element and its biological role is not clearly established to date. Besides of that, the biological effects of elemental tellurium and some of its inorganic and organic derivatives have been studied, leading to a set of interesting and promising applications. As an example, it can be highlighted the uses of alkali-metal tellurites and tellurates in microbiology, the antioxidant effects of organotellurides and diorganoditellurides and the immunomodulatory effects of the non-toxic inorganic tellurane, named AS-101, and the plethora of its uses. Inasmuch, the nascent applications of organic telluranes (organotelluranes) as protease inhibitors and its applications in disease models are the most recent contribution to the scenario of the biological effects and applications of tellurium and its compounds discussed in this manuscript.

Selectivity on-target of bromodomain chemical probes by structure-guided medicinal chemistry and chemical biology

PubMed Central

Galdeano, Carles; Ciulli, Alessio

2017-01-01

Targeting epigenetic proteins is a rapidly growing area for medicinal chemistry and drug discovery. Recent years have seen an explosion of interest in developing small molecules binding to bromodomains, the readers of acetyl-lysine modifications. A plethora of co-crystal structures has motivated focused fragment-based design and optimization programs within both industry and academia. These efforts have yielded several compounds entering the clinic, and many more are increasingly being used as chemical probes to interrogate bromodomain biology. High selectivity of chemical probes is necessary to ensure biological activity is due to an on-target effect. Here, we review the state-of-the-art of bromodomain-targeting compounds, focusing on the structural basis for their on-target selectivity or lack thereof. We also highlight chemical biology approaches to enhance on-target selectivity. PMID:27193077

Synthesis, structure characterization, in vitro and in silico biological evaluation of a new series of thiazole nucleus integrated with pyrazoline scaffolds

NASA Astrophysics Data System (ADS)

Sadashiva, Rajitha; Naral, Damodara; Kudva, Jyothi; Madan Kumar, S.; Byrappa, K.; Mohammed Shafeeulla, R.; Kumsi, Manjunatha

2017-10-01

In the current study, a series of 2,4-disubstituted-1,3-thiazoles linked with pyrazoline scaffolds 3a-o were rationally designed and synthesized. The structures of the title compounds were elucidated by spectroscopic data (UV-Vis, IR, NMR and Mass spectra) and elemental analysis. Single crystal X-Ray diffraction studies revealed that, the compounds 3i and 3k crystallized in monoclinic crystal system with P21/n space group and Z = 4. The molecules 3i and 3k were connected with intermolecular hydrogen bonds N2-H2 … O1, N3sbnd H3 … Cl1 and short contacts (Csbnd H … π and Csbnd Cl … π). Intramolecular hydrogen bonds, N3sbnd H3 … N5 and C5sbnd H5 ….N1 were also existed. The compounds were evaluated for their anticancer activity against A549 and MCF-7 human cancer cell lines and in vitro antimicrobial activity against pathogenic microbial strains. The compounds bearing chloro atom at the para position of phenyl ring A like 3f, 3j and 3k with the IC50: 7.5, 5.0 and 5.0 μM respectively, exhibited better activity than standard drug Cisplatin (IC50: 10.0 μM). In addition, the compounds 3a, 3f, 3j and 3l have exhibited the similar antimicrobial activity as that of standard drug Ciprofloxacin and Fluconazole. Furthermore, to support the biological potency of the compounds, in silico molecular docking studies were carried out against the E. coli MurB (PDB code: pdb:2MBR)

Effects of biologically-active chemical mixtures on fish in a wastewater-impacted urban stream

USGS Publications Warehouse

Barber, L.B.; Brown, G.K.; Nettesheim, T.G.; Murphy, E.W.; Bartell, S.E.; Schoenfuss, H.L.

2011-01-01

Stream flow in urban aquatic ecosystems often is maintained by water-reclamation plant (WRP) effluents that contain mixtures of natural and anthropogenic chemicals that persist through the treatment processes. In effluent-impacted streams, aquatic organisms such as fish are continuously exposed to biologically-active chemicals throughout their life cycles. The North Shore Channel of the Chicago River (Chicago, Illinois) is part of an urban ecosystem in which > 80% of the annual flow consists of effluent from the North Side WRP. In this study, multiple samplings of the effluent and stream water were conducted and fish (largemouth bass and carp) were collected on 2 occasions from the North Shore Channel. Fish also were collected once from the Outer Chicago Harbor in Lake Michigan, a reference site not impacted by WRP discharges. Over 100 organic chemicals with differing behaviors and biological effects were measured, and 23 compounds were detected in all of the water samples analyzed. The most frequently detected and highest concentration (> 100 ??g/L) compounds were ethylenediaminetetraacetic acid and 4-nonylphenolmono-to-tetraethoxycarboxylic acids. Other biologically-active chemicals including bisphenol A, 4-nonylphenol, 4-nonylphenolmono-to-tetraethoxylates, 4- tert-octylphenol, and 4- tert-octylphenolmono-to-tetraethoxylates were detected at lower concentrations (< 5 ??g/L). The biogenic steroidal hormones 17??-estradiol, estrone, testosterone, 4-androstene-3,17-dione, and cis-androsterone were detected at even lower concentrations (< 0.005 ??g/L). There were slight differences in concentrations between the North Side WRP effluent and the North Shore Channel, indicating minimal in-stream attenuation. Fish populations are continuously exposed to mixtures of biologically-active chemicals because of the relative persistency of the chemicals with respect to stream hydraulic residence time, and the lack of a fresh water source for dilution. The majority of male fish exhibited vitellogenin induction, a physiological response consistent with exposure to estrogenic compounds. Tissue-level signs of reproductive disruption, such as ovatestis, were not observed. ?? 2011.

Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs

PubMed Central

Padhye, Subhash; Ahmad, Aamir; Oswal, Nikhil; Sarkar, Fazlul H

2009-01-01

Garcinol, harvested from Garcinia indica, has traditionally been used in tropical regions and appreciated for centuries; however its biological properties are only beginning to be elucidated. There is ample data to suggest potent antioxidant properties of this compound which have been used to explain most of its observed biological activities. However, emerging evidence suggests that garcinol could be useful as an anti-cancer agent, and it is increasingly being realized that garcinol is a pleiotropic agent capable of modulating key regulatory cell signaling pathways. Here we have summarized the progress of our current research knowledge on garcinol and its observed biological activities. We have also provided an explanation of observed properties based on its chemical structure and provided an insight into the structure and properties of chalcones, the precursors of garcinol. The available data is promising but more detailed investigations into the various properties of this compound, particularly its anti-cancer activity are urgently needed, and it is our hope that this review will stimulate further research for elucidating and appreciating the value of this nature's wonder agent. PMID:19725977

Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs.

PubMed

Padhye, Subhash; Ahmad, Aamir; Oswal, Nikhil; Sarkar, Fazlul H

2009-09-02

Garcinol, harvested from Garcinia indica, has traditionally been used in tropical regions and appreciated for centuries; however its biological properties are only beginning to be elucidated. There is ample data to suggest potent antioxidant properties of this compound which have been used to explain most of its observed biological activities. However, emerging evidence suggests that garcinol could be useful as an anti-cancer agent, and it is increasingly being realized that garcinol is a pleiotropic agent capable of modulating key regulatory cell signaling pathways. Here we have summarized the progress of our current research knowledge on garcinol and its observed biological activities. We have also provided an explanation of observed properties based on its chemical structure and provided an insight into the structure and properties of chalcones, the precursors of garcinol. The available data is promising but more detailed investigations into the various properties of this compound, particularly its anti-cancer activity are urgently needed, and it is our hope that this review will stimulate further research for elucidating and appreciating the value of this nature's wonder agent.

Web server to identify similarity of amino acid motifs to compounds (SAAMCO).

PubMed

Casey, Fergal P; Davey, Norman E; Baran, Ivan; Varekova, Radka Svobodova; Shields, Denis C

2008-07-01

Protein-protein interactions are fundamental in mediating biological processes including metabolism, cell growth, and signaling. To be able to selectively inhibit or induce protein activity or complex formation is a key feature in controlling disease. For those situations in which protein-protein interactions derive substantial affinity from short linear peptide sequences, or motifs, we can develop search algorithms for peptidomimetic compounds that resemble the short peptide's structure but are not compromised by poor pharmacological properties. SAAMCO is a Web service ( http://bioware.ucd.ie/ approximately saamco) that facilitates the screening of motifs with known structures against bioactive compound databases. It is built on an algorithm that defines compound similarity based on the presence of appropriate amino acid side chain fragments and a favorable Root Mean Squared Deviation (RMSD) between compound and motif structure. The methodology is efficient as the available compound databases are preprocessed and fast regular expression searches filter potential matches before time-intensive 3D superposition is performed. The required input information is minimal, and the compound databases have been selected to maximize the availability of information on biological activity. "Hits" are accompanied with a visualization window and links to source database entries. Motif matching can be defined on partial or full similarity which will increase or reduce respectively the number of potential mimetic compounds. The Web server provides the functionality for rapid screening of known or putative interaction motifs against prepared compound libraries using a novel search algorithm. The tabulated results can be analyzed by linking to appropriate databases and by visualization.

The Genus Spilanthes Ethnopharmacology, Phytochemistry, and Pharmacological Properties: A Review

PubMed Central

Paulraj, Jayaraj; Govindarajan, Raghavan; Palpu, Pushpangadan

2013-01-01

Spilanthes spp. are popular, over-the-counter remedies; they are sold over the internet under various names and are widely used in traditional medicine in various cultures. This review will summarize the important reports on the ethnopharmacology, botany, phytochemistry, and pharmacological properties as described in the literature from recent years (1920 to 2013). Spilanthes spp. are used for more than 60 types of disorders. They are reported to contain a number of biologically active phytochemicals, although a large number of ethnopharmacological uses have been documented; only a few of these species have been investigated for their chemical and biological activities. The studies are carried out mainly on Spilanthes extracts and a few metabolites substantiate the uses of these plants in traditional medicine. Well-conducted pharmacological studies are still needed for several traditional indications, and the mechanisms of action by which the plant extracts and the active compounds exert their pharmacological effects remain to be studied. They are predominantly used as extracts in personal care products, traditional medicines, and the pharmaceutical and culinary areas. Suggestions are made regarding some of the possible mechanisms of action as to how the known compounds may exert their biological activity. PMID:24454346

Synthesis of Some New Tetrahydropyrimidine Derivatives as Possible Antibacterial Agents.

PubMed

Foroughifar, Naser; Karimi Beromi, Somayeh; Pasdar, Hoda; Shahi, Masoumeh

2017-01-01

Heterocyclic compounds containing a pyrimidine nucleus are of special interests thanks to their applications in medicinal chemistry as they are the basic skeleton of several bioactive compounds such as antifungal, antibacterial, antitumor and antitubercular. As a part of our research in the synthesis of pyrimidine derivatives containing biological activities, some new tetrahydropyrimidine derivatives (1-10) were synthesized via Biginelli reaction using HCl or DABCO as a catalyst with good yields. All structures of products were confirmed by IR, 1 H NMR and 13 C NMR spectroscopy. The antibacterial activity of some synthesized compounds was investigated against Staphylococcus aureus (ATCC 6538), Staphylococcus epidermidis (ATCC 12228) , Bacillus cereus (ATCC14579) , Esherichia coli (ATCC 25922), Klebsiella pneumonia (ATCC 13883) and Pseudomonas aeruginosa (PAO1) bacteria. Some of these compounds such as 8 and 10 exhibited a good to significant antibacterial activity.

Synthesis of Some New Tetrahydropyrimidine Derivatives as Possible Antibacterial Agents

PubMed Central

Foroughifar, Naser; Karimi Beromi, Somayeh; Pasdar, Hoda; Shahi, Masoumeh

2017-01-01

Heterocyclic compounds containing a pyrimidine nucleus are of special interests thanks to their applications in medicinal chemistry as they are the basic skeleton of several bioactive compounds such as antifungal, antibacterial, antitumor and antitubercular. As a part of our research in the synthesis of pyrimidine derivatives containing biological activities, some new tetrahydropyrimidine derivatives (1-10) were synthesized via Biginelli reaction using HCl or DABCO as a catalyst with good yields. All structures of products were confirmed by IR, 1H NMR and 13C NMR spectroscopy. The antibacterial activity of some synthesized compounds was investigated against Staphylococcus aureus (ATCC 6538), Staphylococcus epidermidis (ATCC 12228), Bacillus cereus (ATCC14579), Esherichia coli (ATCC 25922), Klebsiella pneumonia (ATCC 13883) and Pseudomonas aeruginosa (PAO1) bacteria. Some of these compounds such as 8 and 10 exhibited a good to significant antibacterial activity. PMID:28979312

Synthesis, crystal structure and antimicrobial potential of some fluorinated chalcone-1,2,3-triazole conjugates.

PubMed

Yadav, Pinki; Lal, Kashmiri; Kumar, Lokesh; Kumar, Ashwani; Kumar, Anil; Paul, Avijit K; Kumar, Rajnish

2018-06-02

A simple and green synthesis of some fluorinated chalcone-triazole hybrids from propargylated chalcones and organic azides catalyzed by cellulose supported copper nanoparticles click reaction is reported. All the synthesized compounds were well characterized by various analytical and spectroscopic methods. The X-rays crystallographic study of compounds 6k revealed the self assembling properties. The antimicrobial screening results of all the synthesized compounds revealed that most of the triazole hybrids exhibited significant efficacy against tested bacterial and fungal strains. The activity results showed the synergistic effect of biological activity when two pharmacophoric units, i.e. chalcone and 1,2,3-triazole are conjugated. Further, docking simulation of the most active compounds 6p into Escherichia coli topoisomerase II DNA Gyrase B was also carried out. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Isolation, structures, and structure - cytotoxic activity relationships of withanolides and physalins from Physalis angulata.

PubMed

Damu, Amooru G; Kuo, Ping-Chung; Su, Chung-Ren; Kuo, Tsung-Hsiao; Chen, Tzu-Hsuan; Bastow, Kenneth F; Lee, Kuo-Hsiung; Wu, Tian-Shung

2007-07-01

Phytochemical investigation of Physalis angulata was initiated following primary biological screening. Fractionation of CHCl3 and n-BuOH solubles of the MeOH extract from the whole plant was guided by in vitro cytotoxic activity assay using cultured HONE-1 and NUGC cells and led to the isolation of seven new withanolides, withangulatins B-H (1-7), and a new minor physalin, physalin W (8), along with 14 known compounds, including physaprun A, withaphysanolide, dihydrowithanolide E, physanolide A, withaphysalin A, and physalins B, D, F, G, I, J, T, U, and V. New compounds (1-8) were fully characterized by a combination of spectroscopic methods (1D and 2D NMR and MS) and the relative stereochemical assignments based on NOESY correlations and analysis of coupling constants. Biological evaluation of these compounds against a panel of human cancer cell lines showed broad cytotoxic activity. Withangulatin B (1) and physalins D (10) and F (11) displayed potent cytotoxic activity against a panel of human cancer cell lines with EC50 values ranging from 0.2 to 1.6 microg/mL. Structure-activity relationship analysis indicated that withanolides and physalins with 4beta-hydroxy-2-en-1-one and 5beta,6beta-epoxy moieties are potential cytotoxic agents.

Combining activated carbon adsorption with heterogeneous photocatalytic oxidation: Lack of synergy for biologically treated greywater and tetraethylene glycol dimethyl ether

PubMed Central

Gulyas, Holger; Argáez, Ángel Santiago Oria; Kong, Fanzhuo; Jorge, Carlos Liriano; Eggers, Susanne; Otterpohl, Ralf

2013-01-01

The aim of the study was to evaluate whether the addition of activated carbon in the photocatalytic oxidation of biologically pretreated greywater and of a polar aliphatic compound gives synergy, as previously demonstrated with phenol. Photocatalytic oxidation kinetics were recorded with fivefold concentrated biologically pretreated greywater and with aqueous tetraethylene glycol dimethyl ether solutions using a UV lamp and the photocatalyst TiO2 P25 in the presence and the absence of powdered activated carbon. The synergy factor, SF, was quantified as the ratio of photocatalytic oxidation rate constant in the presence of powdered activated carbon to the rate constant without activated carbon. No synergy was observed for the greywater concentrate (SF ≈ 1). For the aliphatic compound, tetraethylene glycol dimethyl ether, addition of activated carbon actually had an inhibiting effect on photocatalysis (SF < 1), while synergy was confirmed in reference experiments using aqueous phenol solutions. The absence of synergy for the greywater concentrate can be explained by low adsorbability of its organic constituents by activated carbon. Inhibition of the photocatalytic oxidation of tetraethylene glycol dimethyl ether by addition of powdered activated carbon was attributed to shading of the photocatalyst by the activated carbon particles. It was assumed that synergy in the hybrid process was limited to aromatic organics. Regardless of the lack of synergy in the case of biologically pretreated greywater, the addition of powdered activated carbon is advantageous since, due to additional adsorptive removal of organics, photocatalytic oxidation resulted in a 60% lower organic concentration when activated carbon was present after the same UV irradiation time. PMID:24191472

OliveNet™: a comprehensive library of compounds from Olea europaea

PubMed Central

Bonvino, Natalie P; Liang, Julia; McCord, Elizabeth D; Zafiris, Elena; Benetti, Natalia; Ray, Nancy B; Hung, Andrew; Boskou, Dimitrios

2018-01-01

Abstract Accumulated epidemiological, clinical and experimental evidence has indicated the beneficial health effects of the Mediterranean diet, which is typified by the consumption of virgin olive oil (VOO) as a main source of dietary fat. At the cellular level, compounds derived from various olive (Olea europaea), matrices, have demonstrated potent antioxidant and anti-inflammatory effects, which are thought to account, at least in part, for their biological effects. Research efforts are expanding into the characterization of compounds derived from Olea europaea, however, the considerable diversity and complexity of the vast array of chemical compounds have made their precise identification and quantification challenging. As such, only a relatively small subset of olive-derived compounds has been explored for their biological activity and potential health effects to date. Although there is adequate information describing the identification or isolation of olive-derived compounds, these are not easily searchable, especially when attempting to acquire chemical or biological properties. Therefore, we have created the OliveNet™ database containing a comprehensive catalogue of compounds identified from matrices of the olive, including the fruit, leaf and VOO, as well as in the wastewater and pomace accrued during oil production. From a total of 752 compounds, chemical analysis was sufficient for 676 individual compounds, which have been included in the database. The database is curated and comprehensively referenced containing information for the 676 compounds, which are divided into 13 main classes and 47 subclasses. Importantly, with respect to current research trends, the database includes 222 olive phenolics, which are divided into 13 subclasses. To our knowledge, OliveNet™ is currently the only curated open access database with a comprehensive collection of compounds associated with Olea europaea. Database URL: https://www.mccordresearch.com.au PMID:29688352

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

Synthesis and screening of one-bead-one-compound cyclic peptide libraries.

PubMed

Qian, Ziqing; Upadhyaya, Punit; Pei, Dehua

2015-01-01

Cyclic peptides have been a rich source of biologically active molecules. Herein we present a method for the combinatorial synthesis and screening of large one-bead-one-compound (OBOC) libraries of cyclic peptides against biological targets such as proteins. Up to ten million different cyclic peptides are rapidly synthesized on TentaGel microbeads by the split-and-pool synthesis method and subjected to a multistage screening protocol which includes magnetic sorting, on-bead enzyme-linked and fluorescence-based assays, and in-solution binding analysis of cyclic peptides selectively released from single beads by fluorescence anisotropy. Finally, the most active hit(s) is identified by the partial Edman degradation-mass spectrometry (PED-MS) method. This method allows a single researcher to synthesize and screen up to ten million cyclic peptides and identify the most active ligand(s) in ~1 month, without the time-consuming and expensive hit resynthesis or the use of any special equipment.

Active machine learning-driven experimentation to determine compound effects on protein patterns.

PubMed

Naik, Armaghan W; Kangas, Joshua D; Sullivan, Devin P; Murphy, Robert F

2016-02-03

High throughput screening determines the effects of many conditions on a given biological target. Currently, to estimate the effects of those conditions on other targets requires either strong modeling assumptions (e.g. similarities among targets) or separate screens. Ideally, data-driven experimentation could be used to learn accurate models for many conditions and targets without doing all possible experiments. We have previously described an active machine learning algorithm that can iteratively choose small sets of experiments to learn models of multiple effects. We now show that, with no prior knowledge and with liquid handling robotics and automated microscopy under its control, this learner accurately learned the effects of 48 chemical compounds on the subcellular localization of 48 proteins while performing only 29% of all possible experiments. The results represent the first practical demonstration of the utility of active learning-driven biological experimentation in which the set of possible phenotypes is unknown in advance.

Plant oligosaccharides - outsiders among elicitors?

PubMed

Larskaya, I A; Gorshkova, T A

2015-07-01

This review substantiates the need to study the plant oligoglycome. The available information on oligosaccharins - physiologically active fragments of plant cell wall polysaccharides - is summarized. The diversity of such compounds in chemical composition, origin, and proved biological activity is highlighted. At the same time, plant oligosaccharides can be considered as outsiders among elicitors of various natures in research intensity of recent decades. This review discusses the reasons for such attitude towards these regulators, which are largely connected with difficulties in isolation and identification. Together with that, approaches are suggested whose potentials can be used to study oligosaccharins. The topics of oligosaccharide metabolism in plants, including the ways of formation, transport, and inactivation are presented, together with data on biological activity and interaction with plant hormones. The current viewpoints on the mode of oligosaccharin action - perception, signal transduction, and possible "targets" - are considered. The potential uses of such compounds in medicine, food industry, agriculture, and biotechnology are discussed.

Structural characterization of tetranortriterpenes from Pseudrocedrela kotschyi and Trichilia emetica and study of their activity towards the chaperone Hsp90.

PubMed

Piaz, Fabrizio Dal; Malafronte, Nicola; Romano, Adriana; Gallotta, Dario; Belisario, Maria Antonietta; Bifulco, Giuseppe; Gualtieri, Maria Josefine; Sanogo, Rokia; Tommasi, Nunziatina De; Pisano, Claudio

2012-03-01

Investigation of roots extracts Pseudrocedrela kotschyi and Trichilia emetica led to identification of 5 limonoid derivatives, Kotschyins D-H, and 11 known compounds. Their structures were elucidated by extensive 1D and 2D NMR experiments in conjunction with mass spectrometry. A surface plasmon resonance (SPR) approach was adopted to screen their Hsp90 binding capability and kotschyin D showed a significant affinity for the chaperone. Therefore, the characterization of the biological activity of kotschyin D by means of a panel of chemical and biological approaches, including limited proteolysis, molecular docking and biochemical and cellular assays, was performed. Our result indicated this compound as a type of client selective Hsp90 inhibitor, directly binding to the middle domain of the protein and possibly preventing its interaction with the activator of Hsp90 ATPase 1 (Aha1). Copyright © 2011 Elsevier Ltd. All rights reserved.

Synthesis, biological evaluation, and structure-activity relationship of clonazepam, meclonazepam, and 1,4-benzodiazepine compounds with schistosomicidal activity.

PubMed

Menezes, Carla M S; Rivera, Gildardo; Alves, Marina A; do Amaral, Daniel N; Thibaut, Jean Pierre B; Noël, François; Barreiro, Eliezer J; Lima, Lídia M

2012-06-01

The inherent morbidity and mortality caused by schistosomiasis is a serious public health problem in developing countries. Praziquantel is the only drug in therapeutic use, leading to a permanent risk of parasite resistance. In search for new schistosomicidal drugs, meclonazepam, the 3-methyl-derivative of clonazepam, is still considered an interesting lead-candidate because it has a proven schistosomicidal effect in humans but adverse effects on the central nervous system did not allow its clinical use. Herein, the synthesis, in vitro biological evaluation, and molecular modeling of clonazepam, meclonazepam, and analogues are reported to establish the first structure-activity relationship for schistosomicidal benzodiazepines. Our findings indicate that the amide moiety [N(1) H-C(2) (=O)] is the principal pharmacophoric unit of 1,4-benzodiazepine schistosomicidal compounds and that substitution on the amide nitrogen atom (N(1) position) is not tolerated. © 2012 John Wiley & Sons A/S.

Jasmonic and salicylic acids enhanced phytochemical production and biological activities in cell suspension cultures of spine gourd (Momordica dioica Roxb).

PubMed

Chung, Ill-Min; Rekha, Kaliyaperumal; Rajakumar, Govindasamy; Thiruvengadam, Muthu

2017-03-01

In vitro cell suspension culture was established for the production of commercially valuable phytochemicals in Momordica dioica. The influence of elicitors in jasmonic acid (JA) and salicylic acid (SA) increased their effect on phytochemical production and biomass accumulation in M. dioica. The results indicate that compared with non-elicited cultures, JA- and SA-elicited cell suspension cultures had significantly enhanced phenolic, flavonoid, and carotenoid production, as well as antioxidant, antimicrobial, and antiproliferative activities. Furthermore, elicited cultures produced 22 phenolic compounds, such as flavonols, hydroxycinnamic acids, and hydroxybenzoic acids. Greater biomass production, phytochemical accumulation, and biological activity occurred in JA- than in SA-elicited cell cultures. This study is the first to successfully establish M. dioica cell suspension cultures for the production of phenolic compounds and carotenoids, as well as for biomass accumulation.

Toxicity and metabolism of nitroalkanes and substituted nitroalkanes

USDA-ARS?s Scientific Manuscript database

A series of low molecular weight nitro- containing compounds has recently been discovered to have a variety of biological activities including the reduction of anaerobic methane production in ruminant animals and activity against economically important human pathogens, including Salmonella sp. and s...

Design, synthesis, and biological characterization of metabolically stable selective androgen receptor modulators.

PubMed

Marhefka, Craig A; Gao, Wenqing; Chung, Kiwon; Kim, Juhyun; He, Yali; Yin, Donghua; Bohl, Casey; Dalton, James T; Miller, Duane D

2004-02-12

A series of nonsteroidal ligands were synthesized as second-generation agonists for the androgen receptor (AR). These ligands were designed to eliminate metabolic sites identified in one of our first-generation AR agonists, which was inactive in vivo due to its rapid metabolism to inactive constituents. The binding affinity of these compounds was evaluated using AR isolated from rat ventral prostate. These second-generation compounds bound the AR in a high affinity and stereoselective manner, with K(i) values ranging from about 4 to 130 nM. The ability of these ligands to stimulate AR-mediated transcriptional activation was examined in cells transfected with the human AR and a hormone-dependent luciferase reporter gene. Although some compounds were unable to stimulate AR-mediated transcription, several demonstrated activity similar to that of dihydrotestosterone (DHT, an endogenous steroidal ligand for the AR). We also evaluated the in vivo pharmacologic activity of selected compounds in castrated male rats. Three compounds were identified as selective androgen receptor modulators (SARMs), exhibiting significant anabolic activity while having only moderate to minimal androgenic activity in vivo.

Design, Synthesis, and Biological Characterization of Metabolically Stable Selective Androgen Receptor Modulators

PubMed Central

Marhefka, Craig A.; Gao, Wenqing; Chung, Kiwon; Kim, Juhyun; He, Yali; Yin, Donghua; Bohl, Casey; Dalton, James T.; Miller, Duane D.

2007-01-01

A series of nonsteroidal ligands were synthesized as second-generation agonists for the androgen receptor (AR). These ligands were designed to eliminate metabolic sites identified in one of our first-generation AR agonists, which was inactive in vivo due to its rapid metabolism to inactive constituents. The binding affinity of these compounds was evaluated using AR isolated from rat ventral prostate. These second-generation compounds bound the AR in a high affinity and stereoselective manner, with Ki values ranging from about 4 to 130 nM. The ability of these ligands to stimulate AR-mediated transcriptional activation was examined in cells transfected with the human AR and a hormone-dependent luciferase reporter gene. Although some compounds were unable to stimulate AR-mediated transcription, several demonstrated activity similar to that of dihydrotestosterone (DHT, an endogenous steroidal ligand for the AR). We also evaluated the in vivo pharmacologic activity of selected compounds in castrated male rats. Three compounds were identified as selective androgen receptor modulators (SARMs), exhibiting significant anabolic activity while having only moderate to minimal androgenic activity in vivo. PMID:14761201

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.

Design and preliminary structure-activity relationship of redox-silent semisynthetic tocotrienol analogues as inhibitors for breast cancer proliferation and invasion.

PubMed

Elnagar, Ahmed Y; Wali, Vikram B; Sylvester, Paul W; El Sayed, Khalid A

2010-01-15

Vitamin E (VE) is a generic term that represents a family of compounds composed of various tocopherol and tocotrienol isoforms. Tocotrienols display potent anti-angiogenic and antiproliferative activities. Redox-silent tocotrienol analogues also display potent anticancer activity. The ultimate objective of this study was to develop semisynthetically C-6-modified redox-silent tocotrienol analogues with enhanced antiproliferative and anti-invasive activities as compared to their parent compound. Examples of these are carbamate and ether analogues of alpha-, gamma-, and delta-tocotrienols (1-3). Various aliphatic, olefinic, and aromatic substituents were used. Steric limitation, electrostatic, hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) properties were varied at this position and the biological activities of these derivatives were tested. Three-dimensional quantitative structure-activity relationship (3D QSAR) studies were performed using Comparative Molecular Field (CoMFA) and Comparative Molecular Similarity Indices Analyses (CoMSIA) to better understand the structural basis for biological activity and guide the future design of more potent VE analogues. Copyright 2009 Elsevier Ltd. All rights reserved.

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.

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

Molecular Docking, Synthesis And Biological Evaluation Of Sulphonylureas/Guanidine Derivatives As Promising Antidiabetics Agent.

PubMed

Panchal, Ishan; Sen, Dhrubo Jyoti; Patel, Ashish D; Shah, Umang; Patel, Mehul; Navle, Archana; Bhavsar, Vashisth

2017-10-02

A series of novel sulphonylureas/guanidine derivatives were designed, synthesized, and evaluated for the treatment of diabetes mellitus. In this study, the designed compounds were docked with AKR1C1 complexes by using glide docking program and docking calculations were performed to predict the binding affinity of the designed compounds with the binding pocket of protein 4YVP and QikProp program was used to predict the ADME/T properties of the analogues. All the targeted derivatives were synthesized and purified by recrystallization. Synthesize compounds were characterized by various physicochemical and various spectroscopic techniques like melting point, thin layer chromatography, infrared spectroscopy (KBr pellets), mass spectroscopy(m/z), 1H NMR (DMSO-d6), and 13C NMR. The synthesized compounds were further studied for biological evolution by alloxan (150 mg/dl, intraperitonial) induced diabetic rat model for in-vivo studies. Among all the synthesized derivatives, 5c and 5d were most potent as per binding energy. Compound 5i have shown a better plasma glucose reduction compared to glibenclamide. Hence, it will further use as a lead compound to develop a more such kind of agent. The docking study revealed that in all designed sulphonylureas/guanidine series of compounds 5c and 5d were found to be most potent compounds as per the binding energy compared to glibenclamide. With the help of details study of in vivo biological activity we observed that compound 5i gives better result compared to glibenclamide as standard. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

Facile synthesis and biological evaluation of novel symmetrical biphenyls as antitumor agents.

PubMed

Zhang, Jie; Zhang, Yanmin; Pan, Xiaoyan; Wang, Chen; Hu, Zhigang; Wang, Sicen; He, Langchong

2012-03-01

As a continuation to our previous work in developing anticancer agents, eighteen symmetrical biphenyl derivatives structurally related to taspine were synthesized and evaluated in vitro and in vivo. All the compounds were prepared with varied substitutions in the phenyl ring of aniline moiety. The cytotoxicity and anticancer activity of biphenyls was evaluated against various human tumor and normal cell line. Antiproliferative assays indicated that some of them exhibited potent anticancer activity. The potent antiproliferative activity of these compounds against ECV304 suggested that these biphenyls could be served as antiangiogenic agents. The highly active compound (2) also exhibited potent growth inhibition against cancer cell lines in vivo. Our findings demonstrated that these symmetrical biphenyl derivatives would be a promising candidate as novel anticancer agents.

Synthesis and biological evaluation of some novel substituted 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxamides

NASA Astrophysics Data System (ADS)

Jaismy Jacob, P.; Thomas, Anoop; Venkataraman, S.; Hareeshbabu, E.; Manju, S. L.

2017-11-01

A novel class of substituted 4-aryl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxamide has been synthesized by simple, modified Hantzsch condensation reaction using N-arylacetoacetamides, aryl aldehydes and ammonia. Characterisation of the newly synthesized compounds was carried out by spectral analysis (IR, 1H NMR and Mass Spectroscopy). Antimicrobial activity against Staphylococcus aureus, Escherichia coli and Candida albicans and antiulcer activity by aspirin induced and pyloric ligation ulcer model was studied. Results revealed that most of the compounds exhibit significant antimicrobial activity along with antiulcer activity. The compound 6i 4-dimethylamino phenyl group at 4th position of 1,4-dihydropyridine had shown 65% ulcer protection at 10 mg/kg administration in male albino rats.

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.

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 and Biological Evaluation of Thiosemicarbazide Derivatives Endowed with High Activity toward Mycobacterium Bovis.

PubMed

Sardari, Soroush; Feizi, Samaneh; Rezayan, Ali Hossein; Azerang, Parisa; Shahcheragh, Seyyed Mohammad; Ghavami, Ghazaleh; Habibi, Azizollah

2017-01-01

Thiosemicarbazides are potent intermediates for the synthesis of pharmaceutical and bioactive materials and thus, they are used extensively in the field of medicinal chemistry. The imine bond (-N=CH-) in this compounds are useful in organic synthesis, in particular for the preparation of heterocycles and non-natural β-aminoacids. In this paper the synthesis of some new thiosemicarbazide derivatives by condensation reaction of various aldehydes or ketones with 4-phenylthiosemicarbazide or thiosemicarbazide is reported. This synthesis method has the advantages of high yields and good bioactivity. The structures of these compounds were confirmed by IR, mass, 1 H NMR, 13 C NMR, and single-crystal X-ray diffraction studies. All of these compounds were tested for their in-vitro anti-mycobacterial activity. The influence of the functional group and position of substituent on anti-bacterial activity of compounds is investigated too. The preliminary results indicated that all of the tested compounds showed good activity against the test organism. The compounds 11 and 30 showed the highest anti-tubercular activity (0.39 μg/mL). This synthesis method has the advantages of high yields and good bioactivity.

Synthesis, Characterization and Biological Activities of Creatinine Amides and Creatinine Schiff Bases.

PubMed

Mumtaz, Amara; Zahoor, Fareeha; Zaib, Sumera; Nawaz, Muhammad Azhar H; Saeed, Aamer; Waseem, Amir; Khan, Afsar; Hussain, Izhar; Iqbal, Jamshed

2017-01-30

In spite of substantial progress in scientific cognizance and medical technology, still infectious diseases are among the leading cause of morbidity and mortality. Creatinine and Schiff bases are well known for their diverse range of biological activities and thought to be emerging and useful therapeutic target for the treatment of several diseases. The present work was aimed to illustrate the influence of substitution of amides and Schiff bases on creatinine and their antimicrobial, antioxidant and anti-urease effectiveness was determined. Creatinine substituted amides (1-2) and creatinine Schiff bases (3-7) were synthesized and characterized by NMR and IR spectral data in combination with elemental analysis. All the compounds (1-7) were investigated on Jack bean urease for their urease inhibitory potential. Investigation of antimicrobial activity of the compounds was made by the agar dilution method. Moreover, 1,1-diphenyl-2- picrylhydrazyl (DPPH) method was used to determine their antioxidant potential. Molecular docking studies were also carried out to elucidate their relationship with the binding pockets of the enzyme. The compounds were found to be potent inhibitors of urease. The synthesized derivatives exhibited significant inhibition against Gram-positive and Gram-negative bacterial strains, as compared to standard, ciprofloxacin. Creatinine based derivatives exhibited potential antifungal activity when tested on infectious and pathogenic fungal strains. Similarly, most of the compounds exhibited good antioxidant activity. These derivatives may serve as a source of potential antioxidants and also help to retard microbial growth in food industry. Similarly, the studies provide a basis for further research to develop more potent urease inhibitory compounds of medicinal /agricultural interest. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Design, synthesis and biological evaluation of multifunctional tacrine-curcumin hybrids as new cholinesterase inhibitors with metal ions-chelating and neuroprotective property.

PubMed

Liu, Zhikun; Fang, Lei; Zhang, Huan; Gou, Shaohua; Chen, Li

2017-04-15

Total sixteen tacrine-curcumin hybrid compounds were designed and synthesized for the purpose of searching for multifunctional anti-Alzheimer agents. In vitro studies showed that these hybrid compounds showed good cholinesterase inhibitory activity. Particularly, the potency of K 3-2 is even beyond tacrine. Some of the compounds exhibited different selectivity on acetylcholinesterase or butyrylcholinesterase due to the structural difference. Thus, the structure and activity relationship is summarized and further discussed based on molecular modeling studies. The ORAC and MTT assays indicated that the hybrid compounds possessed pronounced antioxidant activity and could effectively protect PC12 cells from the H 2 O 2 /Aβ42-induced toxicity. Moreover, the hybrid compounds also showed positive metal ions-chelating ability in vitro, suggesting a potential to halt ion-induced Aβ aggregation. All the obtained results demonstrated that the tacrine-curcumin hybrid compounds, in particular compound K 3-2 , can be considered as potential therapeutic agents for Alzheimer's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

The antioxidant effect of derivatives pyroglutamic lactam

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

Rohadi, Atisya; Lazim, Azwani Mat; Hasbullah, Siti Aishah

Diphenylpicrylhydrazyl (DPPH) is widely used for quickly accessing the ability of polyphenols to transfer labile H atoms to radicals. The antioxidant activity of all the synthesized compounds was screened by DPPH method. Compound (4) showed 54% antioxidant potential while all other compounds were found to have moderate to have moderate to mild antioxidant activity ranging from 47–52%. Pyroglutamic lactams have been synthesized stereoselectively in racemic form from levulinic acid as bifunctional adduct using convertible isocyanide in one-pot Ugi 4-center-3-component condensation reaction (U-4C-3CR). The product formed provides biologically interesting products in excellent yields in a short reaction time. The structures ofmore » the synthesized compounds were elucidated using spectroscopic data and elemental analysis.« less

Influence of the π-coordinated arene on the anticancer activity of ruthenium(II) carbohydrate organometallic complexes

NASA Astrophysics Data System (ADS)

Hanif, Muhammad; Meier, Samuel; Nazarov, Alexey; Risse, Julie; Legin, Anton; Casini, Angela; Jakupec, Michael; Keppler, Bernhard; Hartinger, Christian

2013-10-01

The synthesis and in vitro cytotoxicity of a series of RuII(arene) complexes with carbohydrate-derived phosphite ligands and various arene co-ligands is described. The arene ligand has a strong influence on the in vitro anticancer activity of this series of compounds, which correlates fairly well with cellular accumulation. The most lipophilic compound bearing a biphenyl moiety and a cyclohexylidene-protected carbohydrate is the most cytotoxic with unprecedented IC50 values for the compound class in three human cancer cell lines. This compound shows reactivity to the DNA model nucleobase 9-ethylguanine, but does not alter the secondary structure of plasmid DNA indicating that other biological targets are responsible for its cytotoxic effect.

Aryloxyalkanoic Acids as Non-Covalent Modifiers of the Allosteric Properties of Hemoglobin

PubMed Central

Omar, Abdelsattar M.; Mahran, Mona A.; Ghatge, Mohini S.; Bamane, Faida H. A.; Ahmed, Mostafa H.; El-Araby, Moustafa E.; Abdulmalik, Osheiza; Safo, Martin K.

2017-01-01

Hemoglobin (Hb) modifiers that stereospecifically inhibit sickle hemoglobin polymer formation and/or allosterically increase Hb affinity for oxygen have been shown to prevent the primary pathophysiology of sickle cell disease (SCD), specifically, Hb polymerization and red blood cell sickling. Several such compounds are currently being clinically studied for the treatment of SCD. Based on the previously reported non-covalent Hb binding characteristics of substituted aryloxyalkanoic acids that exhibited antisickling properties, we designed, synthesized and evaluated 18 new compounds (KAUS II series) for enhanced antisickling activities. Surprisingly, select test compounds showed no antisickling effects or promoted erythrocyte sickling. Additionally, the compounds showed no significant effect on Hb oxygen affinity (or in some cases, even decreased the affinity for oxygen). The X-ray structure of deoxygenated Hb in complex with a prototype compound, KAUS-23, revealed that the effector bound in the central water cavity of the protein, providing atomic level explanations for the observed functional and biological activities. Although the structural modification did not lead to the anticipated biological effects, the findings provide important direction for designing candidate antisickling agents, as well as a framework for novel Hb allosteric effectors that conversely, decrease the protein affinity for oxygen for potential therapeutic use for hypoxic- and/or ischemic-related diseases. PMID:27529207

Biological inactivation of adhering Listeria monocytogenes by listeriaphages and a quaternary ammonium compound.

PubMed Central

Roy, B; Ackermann, H W; Pandian, S; Picard, G; Goulet, J

1993-01-01

The use of listeriaphages as a means of disinfecting contaminated stainless-steel and polypropylene surfaces was investigated. Surfaces artificially contaminated with L. monocytogenes 10401 and 8427 were sanitized with suspensions of listeriaphages (H387, H387-A, and 2671), all belonging to the Siphoviridae family. Phage suspensions at concentrations of up to 3.5 x 10(8) PFU/ml were at least as efficient as a 20 ppm solution of a quaternary ammonium compound (QUATAL) in reducing L. monocytogenes populations. A synergistic activity was observed when two or more phages were used in combination and when phages were suspended in QUATAL. The biological activity of the three phages was not affected by QUATAL concentrations of 50 ppm and a contact time of 4 h. PMID:8215364

[Studies by means of 1H NMR spectroscopy of complex formation of aromatic biologically active compounds with antibiotic topotecan].

PubMed

Mosunov, A A; Kostiukov, V V; Evstigneev, M P

2012-01-01

The analysis of heteroassociation of antibiotic topotecan (TPT) with aromatic biologically active compounds (BAC): caffeine, mutagens ethidium bromide and proflavine, antibiotic daunomycin, vitamins flavin-mononucleotide and nicotinamide, has been carried out in the work using 1H NMR spectroscopy data. The equilibrium constants of heteroassociation and induced chemical shifts of the protons have been obtained in the complexes with BAC. It is found that the complex formation TPT-BAC has the nature of stacking of the chromophores, additionally stabilized in the case of proflavine by intermolecular hydrogen bond. Calculation of the basic components of the Gibbs free energy of the complexation reactions is carried out, and the factors which stabilize and destabilize the heterocomplexes of molecules are revealed.

Defensive strategies in Geranium sylvaticum, Part 2: Roles of water-soluble tannins, flavonoids and phenolic acids against natural enemies.

PubMed

Tuominen, Anu

2013-11-01

Geranium sylvaticum is a common herbaceous plant in Fennoscandia, which has a unique phenolic composition. Ellagitannins, proanthocyanidins, galloylglucoses, gallotannins, galloyl quinic acids and flavonoids possess variable distribution in its different organs. These phenolic compounds are thought to have an important role in plant-herbivore interactions. The aim of this study was to quantify these different water-soluble phenolic compounds and measure the biological activity of the eight organs of G. sylvaticum. Compounds were characterized and quantified using HPLC-DAD/MS, in addition, total proanthocyanidins were determined by BuOH-HCl assay and total phenolics by the Folin-Ciocalteau method. Two in vitro biological activity measurements were used: the prooxidant activity was measured by the browning assay and antioxidant activity by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Organ extracts were fractionated using column chromatography on Sephadex LH-20 and the activities of fractions was similarly measured to evaluate which polyphenol groups contributed the most to the biological activity of each organ. The data on the activity of fractions were examined by multivariate data analysis. The water-soluble extracts of leaves and pistils, which contained over 30% of the dry weight as ellagitannins, showed the highest pro-oxidant activity among the organ extracts. Fraction analysis revealed that flavonoids and galloyl quinic acids also exhibited high pro-oxidant activity. In contrast, the most antioxidant active organ extracts were those of the main roots and hairy roots that contained high amounts of proanthocyanidins in addition to ellagitannins. Analysis of the fractions showed that especially ellagitannins and galloyl quinic acids have high antioxidant activity. We conclude that G. sylvaticum allocates a significant amount of tannins in those plant parts that are important to the fitness of the plant and susceptible to natural enemies, i.e. pistil and leaf tannins protect against insect herbivores and root tannins against soil pathogens. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mexican Arnica (Heterotheca inuloides Cass. Asteraceae: Astereae): Ethnomedical uses, chemical constituents and biological properties.

PubMed

Rodríguez-Chávez, José Luis; Egas, Verónica; Linares, Edelmira; Bye, Robert; Hernández, Tzasna; Espinosa-García, Francisco J; Delgado, Guillermo

2017-01-04

Heterotheca inuloides Cass. (Asteraceae) has been traditionally used to treat a wide range of diseases in Mexico in the treatment of rheumatism, topical skin inflammation, muscular pain colic, and other painful conditions associated with inflammatory processes, additionally has been used to treat dental diseases, and gastrointestinal disorders. This species has also been used for the treatment of cancer and diabetes. This review provides up-to-date information on the botanical characterization, traditional uses, chemical constituents, as well as the biolological activities of H. inuloides. A literature search was conducted by analyzing the published scientific material. Information related to H. inuloides was collected from various primary information sources, including books, published articles in peer-reviewed journals, monographs, theses and government survey reports. The electronic search of bibliographic information was gathered from accepted scientific databases such as Scienfinder, ISI Web of Science, Scielo, LILACS, Redalyc, Pubmed, SCOPUS and Google Scholar. To date, more than 140 compounds have been identified from H. inuloides, including cadinane sesquiterpenes, flavonoids, phytosterols, triterpenes, benzoic acid derivatives, and other types of compounds. Many biological properties associated with H. inuloides. Many studies have shown that the extracts and some compounds isolated from this plant exhibit a broad spectrum of biological activities such as antioxidant, antitumor, anti-inflammatory, cytotoxic, and chelating activities, as well as insecticidal and phytotoxic activity. To date, reports on the toxicity of H. inuloides are limited. A comprehensive analysis of the literature obtained through the above-mentioned sources confirmed that ethnomedical uses of H. inuloides have been recorded in Mexico to treat rheumatism, pain, and conditions associated with inflammatory processes. Pharmacological studies have demonstrated the activity of certain compounds associated with the traditional use of the plant such as the anti-inflammatory and cytotoxic activities of the species. The available literature showed that cadinene sesquiterpenes are the major bioactive components of H. inuloides with potential pharmacological activities. Further investigations are needed to fully understand the mode of action of the major active constituents. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

Synthesis and biological evaluation of N-acylhydrazones as inhibitors of MurC and MurD ligases.

PubMed

Sink, Roman; Kovac, Andreja; Tomasić, Tihomir; Rupnik, Veronika; Boniface, Audrey; Bostock, Julieanne; Chopra, Ian; Blanot, Didier; Masic, Lucija Peterlin; Gobec, Stanislav; Zega, Anamarija

2008-09-01

The Mur ligases have an essential role in the intracellular biosynthesis of bacterial peptidoglycan, and they represent attractive targets for the design of novel antibacterials. A series of compounds with an N-acylhydrazone scaffold were synthesized and screened for inhibition of the MurC and MurD enzymes from Escherichia coli. Compounds with micromolar inhibitory activities against both MurC and MurD were identified, and some of them also showed antibacterial activity.

Polyphenols, their metabolites and derivatives as drug leads.

PubMed

Almeida, Filipa A; Dos Santos, Cláudia Nunes; Ventura, Maria Rita

2018-05-15

In this non-comprehensive review, the potential of natural polyphenols as lead compounds for the design and synthesis of new molecules with potential application in several diseases was highlighted. Organic synthesis has been essential for the development of new analogues of naturally found polyphenols, providing a wide range of structural modifications for structure-activity relationship studies and improving or modulating the biological activity of the promising compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Contraceptive agents from cycloaddition reactions of diarylcyclopropenones and diarylthiirene 1, 1-dioxides.

PubMed

Rosen, M H; Fengler, I; Bonet, G; Steinetz, B G; Giannina, T; Dopick, F R; Butler, M C

1976-03-01

The potential for compounds with antifertility activity from the reactions of diphenylcyclopropernone (1) and 2, 3-diphenylthiirene 1, 1-dioxide (2) with enamines is described. In certain instances, a marked dissociation of antifertility from estrogenic activity was possible. Two series were studied extensively, one was stilbene amides (7) and the other stilbene amino ketones (8). The latter series (8) afforded several materials from which, on further biological work-up, was singled out compound 21 as a potent antifertility agent in rats and hamsters.

Prediction of new bioactive molecules using a Bayesian belief network.

PubMed

Abdo, Ammar; Leclère, Valérie; Jacques, Philippe; Salim, Naomie; Pupin, Maude

2014-01-27

Natural products and synthetic compounds are a valuable source of new small molecules leading to novel drugs to cure diseases. However identifying new biologically active small molecules is still a challenge. In this paper, we introduce a new activity prediction approach using Bayesian belief network for classification (BBNC). The roots of the network are the fragments composing a compound. The leaves are, on one side, the activities to predict and, on another side, the unknown compound. The activities are represented by sets of known compounds, and sets of inactive compounds are also used. We calculated a similarity between an unknown compound and each activity class. The more similar activity is assigned to the unknown compound. We applied this new approach on eight well-known data sets extracted from the literature and compared its performance to three classical machine learning algorithms. Experiments showed that BBNC provides interesting prediction rates (from 79% accuracy for high diverse data sets to 99% for low diverse ones) with a short time calculation. Experiments also showed that BBNC is particularly effective for homogeneous data sets but has been found to perform less well with structurally heterogeneous sets. However, it is important to stress that we believe that using several approaches whenever possible for activity prediction can often give a broader understanding of the data than using only one approach alone. Thus, BBNC is a useful addition to the computational chemist's toolbox.

Identification of novel saponins from edible seeds of Japanese horse chestnut (Aesculus turbinata Blume) after treatment with wooden ashes and their nutraceutical activity.

PubMed

Kimura, Hideto; Ogawa, Satoshi; Jisaka, Mitsuo; Kimura, Yasuo; Katsube, Takuya; Yokota, Kazushige

2006-08-28

Natural seeds of Japanese horse chestnut (Aesculus turbinata Blume) contain large amounts of mixed triterpenoidal saponins called escins. Recent studies have shown that escins have several biological activities including anti-inflammatory action and inhibitory effects on the absorption of ethanol and glucose. For the edible utilization of the seeds, natural seeds are usually treated with wooden ashes to remove harshness. Here, we found the novel compounds derived from escins in the edible seeds after the food processing with wooden ashes. The instrumental analyses revealed the chemical structures of escins and the derivatives. These compounds are identified as four types of deacetylescins Ia, IIa, Ib, and IIb as well as two types of desacylescins I and II. To determine their biological activity, the purified compounds were tested for their potential nutraceutical activity. The oral glucose tolerance test in mice revealed that a single oral administration of the isolated components of deacetylescins at a dose of 100 mg/kg was clearly effective in attenuating the elevation of blood glucose levels. The inhibitory effects of escins and their derivatives were in the order of escins>deacetylescins>desacylescins. Moreover, we found the inhibitory activity of those compounds on pancreatic lipase. Escins were the most potent in inhibiting the enzyme activity, and followed by desacylescins and then deacetylescins. Taken together, our results suggest the potential usefulness of novel saponins including deacetylescins and desacylescins from edible seeds as novel sources for nutraceutical foods with anti-obese effects.

2-Amino-1,3,4-thiadiazole as a potential scaffold for promising antimicrobial agents.

PubMed

Serban, Georgeta; Stanasel, Oana; Serban, Eugenia; Bota, Sanda

2018-01-01

Pathogenic microorganisms are causative agents for different types of serious and even lethal infectious diseases. Despite advancements in medication, bacterial and fungal infections continue to be a growing problem in health care. As more and more bacteria become resistant to antibiotics used in therapy and an increasing number of invasive fungal species become resistant to current antifungal medications, there is considerable interest in the development of new compounds with antimicrobial activity. The compounds containing a heterocyclic ring play an important role among organic compounds with biological activity used as drugs in human and veterinary medicine or as insecticides and pesticides in agriculture. Thiadiazoles belong to the classes of nitrogen-sulfur heterocycles with extensive application as structural units of biologically active molecules and as useful intermediates in medicinal chemistry. The potency of the thiadiazole nucleus is demonstrated by the drugs currently used. 1,3,4-Thiadiazoles and some of their derivatives are extensively studied because of their broad spectrum of pharmacological activities. The aim of this review was to highlight the main antimicrobial properties exhibited by derivatives possessing 2-amino-1,3,4-thiadiazole moiety. Many of the reported 2-amino-1,3,4-thiadiazole derivatives can be considered as lead compounds for drug synthesis, and several of them have demonstrated higher antimicrobial activity in comparison to standard drugs. Furthermore, taking into account the reactivity of the amine group in the derivatization process, 2-amino-1,3,4-thiadiazole moiety may be a good scaffold for future pharmacologically active 1,3,4-thiadiazole derivatives.

Synthesis and in vitro evaluation of new derivatives of 2-substituted-6-fluorobenzo[d]thiazoles as cholinesterase inhibitors.

PubMed

Imramovský, Aleš; Pejchal, Vladimír; Štěpánková, Šárka; Vorčáková, Katarína; Jampílek, Josef; Vančo, Ján; Šimůnek, Petr; Královec, Karel; Brůčková, Lenka; Mandíková, Jana; Trejtnar, František

2013-04-01

A series of novel cholinesterase inhibitors based on 2-substituted 6-fluorobenzo[d]thiazole were synthesised and characterised by IR, (1)H, (13)C and (19)F NMR spectroscopy and HRMS. Purity was checked by elemental analyses. The novel carbamates were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The toxicity of the most active compounds was investigated using a standard in vitro test with HepG2 cells, and the ratio between biological activity and toxicity was determined. In addition, the toxicity of the most active compounds was evaluated against MCF7 cells using the xCELLigence system. Structure-activity relationships reflecting the dependence of cholinesterase inhibitors on the lipophilicity of the compounds as well as on the Taft polar and steric substituent constants are discussed. The specific orientation of the inhibitors in the binding site of acetylcholinesterase was determined using molecular docking of the most active compound. Copyright © 2013 Elsevier Ltd. All rights reserved.

Synthesis, characterization, antibacterial activities and carbonic anhydrase enzyme inhibitor effects of new arylsulfonylhydrazone and their Ni(II), Co(II) complexes

NASA Astrophysics Data System (ADS)

Özdemir, Ümmühan Özmen; Arslan, Fatma; Hamurcu, Fatma

2010-01-01

Ethane sulfonic acide hydrazide ( esh: CH 3CH 2SO 2NHNH 2) derivatives as 5-methylsalicyl-aldehydeethanesulfonylhydrazone ( 5msalesh), 5-methyl-2-hydroxyacetophenoneethane sulfonylhydrazone ( 5mafesh) and their Ni(II), Co(II) complexes have been synthesized for the first time. The structure of these compounds has been investigated by elemental analysis, FT-IR, 1H NMR, 13C NMR, LC/MS, UV-vis spectrophotometric method, magnetic susceptibility, thermal studies and conductivity measurements. The antibacterial activities of synthesized compounds were studied against Gram positive bacteria; Staphylococcus aureus, Bacillus subtilis, Bacillus magaterium and Gram negative bacteria; Salmonella enteritidis, Escherichia coli by using the microdilution broth method. The biological activity screening showed that ligands have more activity than complexes against the tested bacteria. The inhibition activities of these compounds on carbonic anhydrase II (CA II) have been investigated by comparing IC 50 and Ki values and it has been found that 5msalesh and its complexes have more enzyme inhibition efficiency than other compounds.

Jasmonate signaling in plant stress responses and development - active and inactive compounds.

PubMed

Wasternack, Claus; Strnad, Miroslav

2016-09-25

Jasmonates (JAs) are lipid-derived signals mediating plant responses to biotic and abiotic stresses and in plant development. Following the elucidation of each step in their biosynthesis and the important components of perception and signaling, several activators, repressors and co-repressors have been identified which contribute to fine-tuning the regulation of JA-induced gene expression. Many of the metabolic reactions in which JA participates, such as conjugation with amino acids, glucosylation, hydroxylation, carboxylation, sulfation and methylation, lead to numerous compounds with different biological activities. These metabolites may be highly active, partially active in specific processes or inactive. Hydroxylation, carboxylation and sulfation inactivate JA signaling. The precursor of JA biosynthesis, 12-oxo-phytodienoic acid (OPDA), has been identified as a JA-independent signaling compound. An increasing number of OPDA-specific processes is being identified. To conclude, the numerous JA compounds and their different modes of action allow plants to respond specifically and flexibly to alterations in the environment. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthesis and preliminary biological evaluation of potent and selective 2-(3-alkoxy-1-azetidinyl) quinolines as novel PDE10A inhibitors with improved solubility.

PubMed

Rzasa, Robert M; Frohn, Michael J; Andrews, Kristin L; Chmait, Samer; Chen, Ning; Clarine, Jeffrey G; Davis, Carl; Eastwood, Heather A; Horne, Daniel B; Hu, Essa; Jones, Adrie D; Kaller, Matthew R; Kunz, Roxanne K; Miller, Silke; Monenschein, Holger; Nguyen, Thomas; Pickrell, Alexander J; Porter, Amy; Reichelt, Andreas; Zhao, Xiaoning; Treanor, James J S; Allen, Jennifer R

2014-12-01

We report the discovery of a novel series of 2-(3-alkoxy-1-azetidinyl) quinolines as potent and selective PDE10A inhibitors. Structure-activity studies improved the solubility (pH 7.4) and maintained high PDE10A activity compared to initial lead compound 3, with select compounds demonstrating good oral bioavailability. X-ray crystallographic studies revealed two distinct binding modes to the catalytic site of the PDE10A enzyme. An ex vivo receptor occupancy assay in rats demonstrated that this series of compounds covered the target within the striatum.

Lipo-chitin oligosaccharides, plant symbiosis signalling molecules that modulate mammalian angiogenesis in vitro.

PubMed

Djordjevic, Michael A; Bezos, Anna; Susanti; Marmuse, Laurence; Driguez, Hugues; Samain, Eric; Vauzeilles, Boris; Beau, Jean-Marie; Kordbacheh, Farzaneh; Rolfe, Barry G; Schwörer, Ralf; Daines, Alison M; Gresshoff, Peter M; Parish, Christopher R

2014-01-01

Lipochitin oligosaccharides (LCOs) are signaling molecules required by ecologically and agronomically important bacteria and fungi to establish symbioses with diverse land plants. In plants, oligo-chitins and LCOs can differentially interact with different lysin motif (LysM) receptors and affect innate immunity responses or symbiosis-related pathways. In animals, oligo-chitins also induce innate immunity and other physiological responses but LCO recognition has not been demonstrated. Here LCO and LCO-like compounds are shown to be biologically active in mammals in a structure dependent way through the modulation of angiogenesis, a tightly-regulated process involving the induction and growth of new blood vessels from existing vessels. The testing of 24 LCO, LCO-like or oligo-chitin compounds resulted in structure-dependent effects on angiogenesis in vitro leading to promotion, or inhibition or nil effects. Like plants, the mammalian LCO biological activity depended upon the presence and type of terminal substitutions. Un-substituted oligo-chitins of similar chain lengths were unable to modulate angiogenesis indicating that mammalian cells, like plant cells, can distinguish between LCOs and un-substituted oligo-chitins. The cellular mode-of-action of the biologically active LCOs in mammals was determined. The stimulation or inhibition of endothelial cell adhesion to vitronectin or fibronectin correlated with their pro- or anti-angiogenic activity. Importantly, novel and more easily synthesised LCO-like disaccharide molecules were also biologically active and de-acetylated chitobiose was shown to be the primary structural basis of recognition. Given this, simpler chitin disaccharides derivatives based on the structure of biologically active LCOs were synthesised and purified and these showed biological activity in mammalian cells. Since important chronic disease states are linked to either insufficient or excessive angiogenesis, LCO and LCO-like molecules may have the potential to be a new, carbohydrate-based class of therapeutics for modulating angiogenesis.

Biological Activities of Stilbenoids.

PubMed

Akinwumi, Bolanle C; Bordun, Kimberly-Ann M; Anderson, Hope D

2018-03-09

Stilbenoids are a group of naturally occurring phenolic compounds found in various plant species. They share a common backbone structure known as stilbene, but differ in the nature and position of substituents. Stilbenoids are classified as phytoalexins, which are antimicrobial compounds produced de novo in plants to protect against fungal infection and toxins. In this review, the biological effects of stilbenoids such as resveratrol, pterostilbene, gnetol and piceatannol are discussed. Stilbenoids exert various biological activities ranging from cardioprotection, neuroprotection, anti-diabetic properties, depigmentation, anti-inflammation, cancer prevention and treatment. The results presented cover a myriad of models, from cell culture to animal studies as well as clinical human trials. Although positive results were obtained in most cell culture and animal studies, further human studies are needed to substantiate beneficial effects of stilbenoids. Resveratrol remains the most widely studied stilbenoid. However, there is limited information regarding the potential of less common stilbenoids. Therefore, further research is warranted to evaluate the salutary effects of various stilbenoids.

Biological Activities of Stilbenoids

PubMed Central

Bordun, Kimberly-Ann M.

2018-01-01

Stilbenoids are a group of naturally occurring phenolic compounds found in various plant species. They share a common backbone structure known as stilbene, but differ in the nature and position of substituents. Stilbenoids are classified as phytoalexins, which are antimicrobial compounds produced de novo in plants to protect against fungal infection and toxins. In this review, the biological effects of stilbenoids such as resveratrol, pterostilbene, gnetol and piceatannol are discussed. Stilbenoids exert various biological activities ranging from cardioprotection, neuroprotection, anti-diabetic properties, depigmentation, anti-inflammation, cancer prevention and treatment. The results presented cover a myriad of models, from cell culture to animal studies as well as clinical human trials. Although positive results were obtained in most cell culture and animal studies, further human studies are needed to substantiate beneficial effects of stilbenoids. Resveratrol remains the most widely studied stilbenoid. However, there is limited information regarding the potential of less common stilbenoids. Therefore, further research is warranted to evaluate the salutary effects of various stilbenoids. PMID:29522491

Antifungal agents. 10. New derivatives of 1-[(aryl)[4-aryl-1H-pyrrol-3-yl]methyl]-1H-imidazole, synthesis, anti-candida activity, and quantitative structure-analysis relationship studies.

PubMed

Tafi, Andrea; Costi, Roberta; Botta, Maurizio; Di Santo, Roberto; Corelli, Federico; Massa, Silvio; Ciacci, Andrea; Manetti, Fabrizio; Artico, Marino

2002-06-20

The synthesis, anti-Candida activity, and quantitative structure-activity relationship (QSAR) studies of a series of 2,4-dichlorobenzylimidazole derivatives having a phenylpyrrole moiety (related to the antibiotic pyrrolnitrin) in the alpha-position are reported. A number of substituents on the phenyl ring, ranging from hydrophobic (tert-butyl, phenyl, or 1-pyrrolyl moiety) to basic (NH(2)), polar (CF(3), CN, SCH(3), NO(2)), or hydrogen bond donors and acceptor (OH) groups, were chosen to better understand the interaction of these compounds with cytochrome P450 14-alpha-lanosterol demethylase (P450(14DM)). Finally, the triazole counterpart of one of the imidazole compounds was synthesized and tested to investigate influence of the heterocyclic ring on biological activity. The in vitro antifungal activities of the newly synthesized azoles 10p-v,x-c' were tested against Candida albicans and Candida spp. at pH 7.2 and pH 5.6. A CoMFA model, previously derived for a series of antifungal agents belonging to chemically diverse families related to bifonazole, was applied to the new products. Because the results produced by this approach were not encouraging, Catalyst software was chosen to perform a new 3D-QSAR study. Catalyst was preferred this time because of the possibility of considering each compound as a collection of energetically reasonable conformations and of considering alternative stereoisomers. The pharmacophore model developed by Catalyst, named HYPO1, showed good performances in predicting the biological activity data, although it did not exhibit an unequivocal preference for one enantiomeric series of inhibitors relative to the other. One aromatic nitrogen with a lone pair in the ring plane (mapped by all of the considered compounds) and three aromatic ring features were recognized to have pharmacophoric relevance, whereas neither hydrogen bond acceptor nor hydrophobic features were found. These findings confirmed that the key interaction of azole antifungals with the demethylase enzyme is the coordination bond to the iron ion of the porphyrin system, while interactions with amino acids localized in proximity of heme could modulate the biological activity of diverse antifungal agents. In conclusion, HYPO1 conveys important information in an intuitive manner and can provide predictive capability for evaluating new compounds.

NPCARE: database of natural products and fractional extracts for cancer regulation.

PubMed

Choi, Hwanho; Cho, Sun Young; Pak, Ho Jeong; Kim, Youngsoo; Choi, Jung-Yun; Lee, Yoon Jae; Gong, Byung Hee; Kang, Yeon Seok; Han, Taehoon; Choi, Geunbae; Cho, Yeeun; Lee, Soomin; Ryoo, Dekwoo; Park, Hwangseo

2017-01-01

Natural products have increasingly attracted much attention as a valuable resource for the development of anticancer medicines due to the structural novelty and good bioavailability. This necessitates a comprehensive database for the natural products and the fractional extracts whose anticancer activities have been verified. NPCARE (http://silver.sejong.ac.kr/npcare) is a publicly accessible online database of natural products and fractional extracts for cancer regulation. At NPCARE, one can explore 6578 natural compounds and 2566 fractional extracts isolated from 1952 distinct biological species including plants, marine organisms, fungi, and bacteria whose anticancer activities were validated with 1107 cell lines for 34 cancer types. Each entry in NPCARE is annotated with the cancer type, genus and species names of the biological resource, the cell line used for demonstrating the anticancer activity, PubChem ID, and a wealth of information about the target gene or protein. Besides the augmentation of plant entries up to 743 genus and 197 families, NPCARE is further enriched with the natural products and the fractional extracts of diverse non-traditional biological resources. NPCARE is anticipated to serve as a dominant gateway for the discovery of new anticancer medicines due to the inclusion of a large number of the fractional extracts as well as the natural compounds isolated from a variety of biological resources.

Spectroscopic, molecular docking and structural activity studies of (E)-N‧-(substituted benzylidene/methylene) isonicotinohydrazide derivatives for DNA binding and their biological screening

NASA Astrophysics Data System (ADS)

Arshad, Nasima; Perveen, Fouzia; Saeed, Aamer; Channar, Pervaiz Ali; Farooqi, Shahid Iqbal; Larik, Fayaz Ali; Ismail, Hammad; Mirza, Bushra

2017-07-01

Acid catalyzed condensation of isoniazid with a number of suitably substituted aromatic and heterocyclic aldehydes was carried out in dry ethanol to afford the title (E)-N‧-(substituted benzylidene/methylene) isonicotinohydrazides (SF 1 - SF 4) in good yields. These compounds were characterized and further investigated for their binding with ds.DNA using UV- spectroscopy and molecular docking and for antitumor and antimicrobial potentials. A good correlation was found among spectroscopic, theoretical and biological results. UV- spectra in the presence of DNA concentrations and their data interpretation in terms binding constant "Kb" and free energy change (ΔG) provided evidences for the significant and spontaneous binding of the compounds with DNA. Molecular docking studies and structural analysis further supported the UV-findings and indicated that the modes of interactions between bromo- (SF 1) and flouro- (SF 4) substituted isonicotinohydrazides is intercalation while methoxy- (SF 2) and hydroxy- (SF 3) substituted isonicotinohydrazides interact with DNA helix via groove binding. SF 1 exhibited comparatively higher Kb value (UV-; 8.07 × 103 M-1, docking; 8.11 × 103 M-1) which inferred that the respective compound muddles to DNA most powerfully. SF 1 has shown the lowest IC50 (345.3 μg/mL) value among all the compounds indicating its comparatively highest activity towards tumor inhibition. None of the compound has shown perceptible antibacterial and antifungal activities.

Biological activities and medicinal properties of Cajanus cajan (L) Millsp.

PubMed Central

Pal, Dilipkumar; Mishra, Pragya; Sachan, Neetu; Ghosh, Ashoke K.

2011-01-01

Cajanus cajan (L) Millsp. (Sanskrit: Adhaki, Hindi: Arhar, English: Pigeon pea, Bengali: Tur) (family: Fabaceae) is the most important grain legume crop of rain-fed agriculture in semi-arid tropics. It is both a food crop and a cover/forage crop with high levels of proteins and important amino acids like methionine, lysine and tryptophan. During the last few decades extensive studies have been carried out regarding the chemistry of C. cajan and considerable progress has been achieved regarding its biological activities and medicinal applications. This review article gives an overview on the biological activities of the compounds isolated, pharmacological actions and clinical studies of C. cajan extracts apart from its general details. PMID:22247887

BIOLOGICALLY ACTIVE COMPOUNDS IN SOME FLOWERING PLANTS.

DTIC Science & Technology

and were analyzed chemically for the presence or absence of alkaloids, saponins, tannins , and flavonoids. Twenty-five species of plants, representing...19 families and 25 genera, were used. Pharmacological activity, mostly depressant, was recorded for 10 of the 25 plants. Tannins were present in 22

ALTERED MAMMARY GLAND DEVELOPMENT IN MALE RATS EXPOSED TO GENISTEIN AND METHOXYCHLOR

EPA Science Inventory

Genistein is a prevalent phytoestrogen whose presence in human and animal foods may affect biological actions of synthetic endocrine active compounds. We have previously reported that in utero and lactational exposure to genistein and the endocrine active pesticide methoxychlor c...

[Secondary Metabolites from Marine Microorganisms. I. Secondary Metabolites from Marine Actinomycetes].

PubMed

Orlova, T I; Bulgakova, V G; Polin, A N

2015-01-01

Review represents data on new active metabolites isolated from marine actinomycetes published in 2007 to 2014. Marine actinomycetes are an unlimited source of novel secondary metabolites with various biological activities. Among them there are antibiotics, anticancer compounds, inhibitors of biochemical processes.

Design and synthesis of tetraol derivatives of 1,12-dicarba-closo-dodecaborane as non-secosteroidal vitamin D analogs.

PubMed

Fujii, Shinya; Kano, Atsushi; Masuno, Hiroyuki; Songkram, Chalermkiat; Kawachi, Emiko; Hirano, Tomoya; Tanatani, Aya; Kagechika, Hiroyuki

2014-09-15

Vitamin D receptor (VDR), a nuclear receptor for 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3, 1), is a promising target for multiple clinical applications. We recently developed non-secosteroidal VDR ligands based on a carbon-containing boron cluster, 1,12-dicarba-closo-dodecaborane (p-carborane), and examined the binding of one of them to VDR by means of crystallographic analysis. Here, we utilized that X-ray structure to design novel p-carborane-based tetraol-type vitamin D analogs, and we examined the biological activities of the synthesized compounds. Structure-activity relationship study revealed that introduction of an ω-hydroxyalkoxy functionality enhanced the biological activity, and the configuration of the substituent significantly influenced the potency. Among the synthesized compounds, 4-hydroxybutoxy derivative 9a exhibited the most potent activity, which was equal to that of the secosteroidal vitamin D analog, 19-nor-1α,25-dihydroxyvitamin D3 (2). Copyright © 2014 Elsevier Ltd. All rights reserved.

Preparation and characterization of new biologically active polyurethane foams.

PubMed

Savelyev, Yuri; Veselov, Vitali; Markovskaya, Ludmila; Savelyeva, Olga; Akhranovich, Elena; Galatenko, Natalya; Robota, Ludmila; Travinskaya, Tamara

2014-12-01

Biologically active polyurethane foams are the fast-developed alternative to many applications of biomedical materials. Due to the polyurethane structure features and foam technology it is possible to incorporate into their structure the biologically active compounds of target purpose via structural-chemical modification of macromolecule. A series of new biologically active polyurethane foams (PUFs) was synthesized with polyethers (MM 2500-5000), polyesters MM (500-2200), 2,4(2,6) toluene diisocyanate, water as a foaming agent, catalysts, foam stabilizers and functional compounds. Different functional compounds: 1,4-di-N-oxy-2,3-bis-(oxymethyl)-quinoxaline (DOMQ), partial sodium salt of poly(acrylic acid) and 2,6-dimethyl-N,N-diethyl aminoacetatanilide hydrochloride were incorporated into the polymer structure/composition due to the chemical and/or physical bonding. Structural peculiarities of PUFs were studied by FTIR spectroscopy and X-ray scattering. Self-adhesion properties of PUFs were estimated by measuring of tensile strength at break of adhesive junction. The optical microscopy method was performed for the PUF morphology studies. Toxicological estimation of the PUFs was carried out in vitro and in vivo. The antibacterial action towards the Gram-positive and Gram-negative bacteria (Escherichia coli ATC 25922, E. coli ATC 2150, Klebsiella pneumoniae 6447, Staphylococcus aureus 180, Pseudomonas aeruginosa 8180, Proteus mirabilis F 403, P. mirabilis 6054, and Proteus vulgaris 8718) was studied by the disc method on the solid nutrient. Physic-chemical properties of the PUFs (density, tensile strength and elongation at break, water absorption and vapor permeability) showed that all studied PUFs are within the operational requirements for such materials and represent fine-cellular foams. Spectral studies confirmed the incorporation of DOMQ into the PUF's macrochain. PUFs are characterized by microheterogeneous structure. They are antibacterially active, non-toxic materials with high affinity to the tissue body, self-adhesive properties and local anesthetic effect. Copyright © 2014 Elsevier B.V. All rights reserved.

Bacterial symbionts and natural products.

PubMed

Crawford, Jason M; Clardy, Jon

2011-07-21

The study of bacterial symbionts of eukaryotic hosts has become a powerful discovery engine for chemistry. This highlight looks at four case studies that exemplify the range of chemistry and biology involved in these symbioses: a bacterial symbiont of a fungus and a marine invertebrate that produce compounds with significant anticancer activity, and bacterial symbionts of insects and nematodes that produce compounds that regulate multilateral symbioses.

Anemone medicinal plants: ethnopharmacology, phytochemistry and biology.

PubMed

Hao, Da-Cheng; Gu, Xiaojie; Xiao, Peigen

2017-03-01

The Ranunculaceae genus Anemone (order Ranunculales), comprising more than 150 species, mostly herbs, has long been used in folk medicine and worldwide ethnomedicine. Various medicinal compounds have been found in Anemone plants, especially triterpenoid saponins, some of which have shown anti-cancer activities. Some Anemone compounds and extracts display immunomodulatory, anti-inflammatory, antioxidant, and antimicrobial activities. More than 50 species have ethnopharmacological uses, which provide clues for modern drug discovery. Anemone compounds exert anticancer and other bioactivities via multiple pathways. However, a comprehensive review of the Anemone medicinal resources is lacking. We here summarize the ethnomedical knowledge and recent progress on the chemical and pharmacological diversity of Anemone medicinal plants, as well as the emerging molecular mechanisms and functions of these medicinal compounds. The phylogenetic relationships of Anemone species were reconstructed based on nuclear ITS and chloroplast markers. The molecular phylogeny is largely congruent with the morphology-based classification. Commonly used medicinal herbs are distributed in each subgenus and section, and chemical and biological studies of more unexplored taxa are warranted. Gene expression profiling and relevant "omics" platforms could reveal differential effects of phytometabolites. Genomics, transcriptomics, proteomics, and metabolomics should be highlighted in deciphering novel therapeutic mechanisms and utilities of Anemone phytometabolites.

Effect of solvents extraction on phytochemical components and biological activities of Tunisian date seeds (var. Korkobbi and Arechti).

PubMed

Thouri, Amira; Chahdoura, Hassiba; El Arem, Amira; Omri Hichri, Amel; Ben Hassin, Rihab; Achour, Lotfi

2017-05-04

The interest in natural antioxidants, especially polyphenols, is growing more and more thanks to their positive contribution to human health. Thus, the prevention from the harmful action of oxidative stress which has been involved in many diseases such as cancer, inflammation diabetes, and cardiovascular illness. Recent research proved the bioactive compounds richness of date seeds which could be a good biological matrix of natural antioxidants. Unfortunately, an important quantity of Tunisian dates seed is discarded yearly. In this study, different solvents extraction (water, methanol, absolute acetone and aqueous acetone 80%) were used and the evaluation of its effect on phytochemical level, in vitro antioxidant activities, in vitro hyperglycemia key enzymes inhibition and in vivo anti-inflammatory proprieties were established for Tunisian date seeds. The result revealed that the polar solvent exhibited the highest amount of bioactive compounds. The correlation between polyphenol compounds and the antioxidant potentiality explains the powerful effect of used polar solvents on inflammation, TBARS and hyperglycemia inhibition. Furthermore, it showed its higher capacity to scavenge radicals. Therefore, this big waste of Tunisian seeds could be used as cheap source of natural antioxidant compounds which are considered as a health challenge for the poor countries.

Enantioselective separation of biologically active basic compounds in ultra-performance supercritical fluid chromatography.

PubMed

Geryk, Radim; Kalíková, Květa; Schmid, Martin G; Tesařová, Eva

2016-08-17

The enantioseparation of basic compounds represent a challenging task in modern SFC. Therefore this work is focused on development and optimization of fast SFC methods suitable for enantioseparation of 27 biologically active basic compounds of various structures. The influences of the co-solvent type as well as different mobile phase additives on retention, enantioselectivity and enantioresolution were investigated. Obtained results confirmed that the mobile phase additives, especially bases (or the mixture of base and acid), improve peak shape and enhance enantioresolution. The best results were achieved with isopropylamine or the mixture of isopropylamine and trifluoroacetic acid as additives. In addition, the effect of temperature and back pressure were evaluated to optimize the enantioseparation process. The immobilized amylose-based chiral stationary phase, i.e. tris(3,5-dimethylphenylcarbamate) derivative of amylose proved to be useful tool for the enantioseparation of a broad spectrum of chiral bases. The chromatographic conditions that yielded baseline enantioseparations of all tested compounds were discovered. The presented work can serve as a guide for simplifying the method development for enantioseparation of basic racemates in SFC. Copyright © 2016 Elsevier B.V. All rights reserved.