Isolation and characterization of the compounds responsible for the antimutagenic activity of Combretum microphyllum (Combretaceae) leaf extracts.

PubMed

Makhafola, Tshepiso Jan; Elgorashi, Esameldin Elzein; McGaw, Lyndy Joy; Awouafack, Maurice Ducret; Verschaeve, Luc; Eloff, Jacobus Nicolaas

2017-09-06

Mutations play a major role in the pathogenesis and development of several chronic degenerative diseases including cancer. It follows, therefore that antimutagenic compound may inhibit the pathological process resulting from exposure to mutagens. Investigation of the antimutagenic potential of traditional medicinal plants and compounds isolated from plant extracts provides one of the tools that can be used to identify compounds with potential cancer chemopreventive properties. The aim of this study was to isolate and characterise the compounds responsible for the antimutagenic activity of Combretum microphyllum. The methanol leaf extract of C. microphyllum was evaluated for antimutagenicity in the Ames/microsome assay using Salmonella typhimurium TA98. TA100 and TA102. Solvent-solvent fractionation was used to partition the extracts and by using bioassay-guided fractionation, three compounds were isolated. The antimutagenic activity of the three compounds were determined in the Ames test using Salmonella typhimurium TA98, TA100 and TA102. The antioxidant activity of the three compounds were determined by the quantitative 2,2-diphenyl-1-picrylhydrazyl (DPPH)-free radical scavenging method. The cytotoxicity was determined in the MTT assay using human hepatocytes. A bioassay-guided fractionation of the crude extracts for antimutagenic activity led to the isolation of three compounds; n-tetracosanol, eicosanoic acid and arjunolic acid. Arjunolic acid was the most active in all three tested strains with a antimutagenicity of 42 ± 9.6%, 36 ± 1.5% and 44 ± 0.18% in S. typhimurium TA98, TA100 and TA102 respectively at the highest concentration (500 μg/ml) tested, followed by eicosanoic acid and n-tetracosanol. The antioxidant activity of the compounds were determined using the quantitative 2,2 diphenyl-1-picryhydrazyl (DPPH)-free radical scavenging method. Only arjunolic acid had pronounced antioxidant activity (measured as DPPH-free scavenging activity) with an

Acute oral toxicity test of chemical compounds in silkworms.

PubMed

Usui, Kimihito; Nishida, Satoshi; Sugita, Takuya; Ueki, Takuro; Matsumoto, Yasuhiko; Okumura, Hidenobu; Sekimizu, Kazuhisa

2016-02-01

This study performed an acute oral toxicity test of 59 compounds in silkworms. These compounds are listed in OECD guidelines as standard substances for a cytotoxicity test, and median lethal dose (LD(50)) werecalculated for each compound. Acute oral LD(50) values in mammals are listed in OECD guidelines and acute oral LD(50) values in silkworms were determined in this study. R(2) for the correlation between LD(50) values in mammals and LD(50) values in silkworms was 0.66. In addition, the acute oral toxicity test in silkworms was performed by two different facilities, and test results from the facilities were highly reproducible. These findings suggest that an acute oral toxicity test in silkworms is a useful way to evaluate the toxicity of compounds in mammals.

Herbicidal activity of pure compound isolated from rhizosphere inhabiting Aspergillus flavus.

PubMed

Khattak, Saeed Ullah; Lutfullah, Ghosia; Iqbal, Zafar; Rehman, Irshad Ur; Ahmad, Jamshaid; Khan, Abid Ali

2018-05-01

In the quest for bioactive natural products of fungal origin, Aspergillus flavus was isolated from rhizosphere of Mentha piperita using Potato Dextrose Agar (PDA) and Czapec Yeast Broth (CYB) nutrient media for metabolites production. In total, three different metabolites were purified using HPLC/LCMS and the structures were established using 500 Varian NMR experiments. Further the isolated metabolites in different concentrations (10, 100, 1000 μg/mL) were tested for herbicidal activity using Completely Randomized design (CRD) against the seeds of Silybum marianum and Avena fatua which are major threats to wheat crop in Pakistan. Among the isolated metabolites, one compound was found active against the test weed species whose activity is reported in the present work. The chemical name of the compound is 2-(1, 4-dihydroxybutan-2-yl)-1, 3-dihydroxy-6, 8-dimethoxyanthracene-9, 10(4aH, 9aH)-dione with mass of 388. Results showed that all seeds germinated in control treatment; however, with the metabolite treated, the growth was retarded to different levels in all parts of the weeds. At a dose of 1000 μg/mL of the pure compound, 100% seeds of S. marianum and 60% seeds of A. fatua were inhibited. Interestingly, the pure compound exhibited less inhibition of 10% towards the seeds of common wheat (Triticum aestivum).

The Antimicrobial Activity of Annona emarginata (Schltdl.) H. Rainer and Most Active Isolated Compounds against Clinically Important Bacteria.

PubMed

Dolab, Juan G; Lima, Beatriz; Spaczynska, Ewelina; Kos, Jiri; Cano, Natividad H; Feresin, Gabriela; Tapia, Alejandro; Garibotto, Francisco; Petenatti, Elisa; Olivella, Monica; Musiol, Robert; Jampilek, Josef; Enriz, Ricardo D

2018-05-16

Annona emarginata (Schltdl.) H. Rainer, commonly known as "arachichú", "araticú", "aratigú", and "yerba mora", is a plant that grows in Argentina. Infusions and decoctions are used in folk medicine as a gargle against throat pain and for calming toothache; another way to use the plant for these purposes is chewing its leaves. Extracts from bark, flowers, leaves, and fruits from A. emarginata were subjected to antibacterial assays against a panel of Gram (+) and Gram (-) pathogenic bacteria according to Clinical and Laboratory Standards Institute protocols. Extracts from the stem bark and leaves showed moderate activity against the bacteria tested with values between 250⁻1000 µg/mL. Regarding flower extracts, less polar extracts (hexane, dichloromethane) showed very strong antibacterial activity against methicillin-sensitive Staphylococcus aureus ATCC 25923 and methicillin-resistant S. aureus ATCC 43300 with values between 16⁻125 µg/mL. Additionally, hexane extract showed activity against Klebsiella pneumoniae (MIC = 250 µg/mL). The global methanolic extract of the fruits (MeOHGEF) was also active against the three strains mentioned above, with MICs values 250⁻500 µg/mL. Bioassay-guided fractionation of MeOHGEF led to the isolation of a new main compound-( R )-2-(4-methylcyclohex-3-en-1-yl)propan-2-yl ( E )-3-(4-hydroxyphenyl)acrylate ( 1 ). The structure and relative configurations have been determined by means of 1D and 2D NMR techniques, including COSY, HMQC, HMBC, and NOESY correlations. Compound 1 showed strong antimicrobial activity against all Gram (+) species tested (MICs = 3.12⁻6.25 µg/mL). In addition, the synthesis and antibacterial activity of some compounds structurally related to compound 1 (including four new compounds) are reported. A SAR study for these compounds was performed based on the results obtained by using molecular calculations.

Synthesis of new 1,2,4-triazole compounds containing Schiff and Mannich bases (morpholine) with antioxidant and antimicrobial activities.

PubMed

Ünver, Yasemin; Deniz, Sadik; Çelik, Fatih; Akar, Zeynep; Küçük, Murat; Sancak, Kemal

2016-01-01

Compound 2 was synthesized by reacting CS 2 /KOH with compound 1. The treatment of compound 2 with hydrazine hydrate produced compound 3. Then, compound 3 was converted to Schiff bases (4a-d) by the handling with several aromatic aldehydes. The treatment of triazole compounds 4a-d containing Schiff base with morpholine gave compounds 5a-d. All compounds were tested for their antioxidant and antimicrobial activities. The antioxidant test results of DPPH• radical scavenging and ferric reducing/antioxidant power methods showed good antioxidant activity. The triazole-thiol (3) was the most active, and the effect of the substituent type of the thiophene ring on the activity was same for both Schiff bases (4a-d) and Mannich bases (5a-d). Among the newly synthesized triazole derivatives, the Schiff base 4d and the Mannich base 5d carrying nitro substituent on the thiophene ring showed promising antibacterial and antifungal activity, with lower MIC values than the standard antibacterial ampicillin.

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

PubMed Central

2012-01-01

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

Microbiologic Testing for 503A Sterile-Compounding Pharmacies.

PubMed

Mixon, William; Roth, Abby

2017-01-01

Compounding pharmacists must ensure that the sterile preparations they dispense are free of microbiologic contamination. Working in a cleanroom under controlled conditions (proper differential air pressure, temperature, and humidity; acceptable levels of viable and nonviable airborne particles and surface counts, etc.) and testing the efficacy of cleaning and disinfecting practices via environmental monitoring (viable-air and surface testing, glove-fingertip-thumb testing, etc.) are essential to preparing contamination-free medications. Sterile-compounding pharmacists must understand how to monitor their cleanroom environment and, if they perform testing in house, to interpret the results of simple microbiologic tests (a skill helpful even when tests are outsourced to a contract laboratory). In this article, which pertains to 503A sterile compounding, and is based on the current version of United States Pharmacopeia (USP) Chapter <797>, basic concepts in microbiology and the microbial tests that can be performed and interpreted in house and those that must be outsourced are discussed. Streamlining communication with contract laboratory personnel is reviewed. Requirements for an inhouse microbiology laboratory are presented, and the advantages and disadvantages of inhouse and outsourced testing are examined. A list of suggested reading is provided for easy reference. In a subsequent article, environmental monitoring and analysis will be addressed in detail. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Anticancer activity of botanical compounds in ancient fermented beverages (review).

PubMed

McGovern, P E; Christofidou-Solomidou, M; Wang, W; Dukes, F; Davidson, T; El-Deiry, W S

2010-07-01

Humans around the globe probably discovered natural remedies against disease and cancer by trial and error over the millennia. Biomolecular archaeological analyses of ancient organics, especially plants dissolved or decocted as fermented beverages, have begun to reveal the preliterate histories of traditional pharmacopeias, which often date back thousands of years earlier than ancient textual, ethnohistorical, and ethnological evidence. In this new approach to drug discovery, two case studies from ancient Egypt and China illustrate how ancient medicines can be reconstructed from chemical and archaeological data and their active compounds delimited for testing their anticancer and other medicinal effects. Specifically, isoscopoletin from Artemisia argyi, artemisinin from Artemisia annua, and the latter's more easily assimilated semi-synthetic derivative, artesunate, showed the greatest activity in vitro against lung and colon cancers. In vivo tests of these compounds previously unscreened against lung and pancreatic cancers are planned for the future.

The influence of interactions among phenolic compounds on the antiradical activity of chokeberries (Aronia melanocarpa).

PubMed

Jakobek, Lidija; Seruga, Marijan; Krivak, Petra

2011-06-01

In the present work, interactions between phenolic compounds from chokeberries and their influence on the antiradical activity was studied. Three fractions were isolated from chokeberries containing different classes of phenolic compounds. The first fraction contained a major part of phenolic acids and flavonols, the second anthocyanins, and the third insoluble phenols and proanthocyanidins. The phenolic compound content was determined using high-performance liquid chromatography, and the antiradical activity using the DPPH test. In order to evaluate the effects of interactions between phenolic compounds on the antiradical activity, the antiradical activity of individual phenolic fractions was compared with that obtained by mixing phenolic fractions. Phenolic mixtures showed the decrease in the antiradical activity in comparison with the individual phenolic fractions. These results suggest the existence of complex interactions among phenolic compounds that caused the decrease of the antiradical activity. Interactions among chokeberry phenols promoted a negative synergism.

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

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

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

2005-12-01

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

Fish embryo toxicity test: identification of compounds with weak toxicity and analysis of behavioral effects to improve prediction of acute toxicity for neurotoxic compounds.

PubMed

Klüver, Nils; König, Maria; Ortmann, Julia; Massei, Riccardo; Paschke, Albrecht; Kühne, Ralph; Scholz, Stefan

2015-06-02

The fish embryo toxicity test has been proposed as an alternative for the acute fish toxicity test, but concerns have been raised for its predictivity given that a few compounds have been shown to exhibit a weak acute toxicity in the fish embryo. In order to better define the applicability domain and improve the predictive capacity of the fish embryo test, we performed a systematic analysis of existing fish embryo and acute fish toxicity data. A correlation analysis of a total of 153 compounds identified 28 compounds with a weaker or no toxicity in the fish embryo test. Eleven of these compounds exhibited a neurotoxic mode of action. We selected a subset of eight compounds with weaker or no embryo toxicity (cyanazine, picloram, aldicarb, azinphos-methyl, dieldrin, diquat dibromide, endosulfan, and esfenvalerate) to study toxicokinetics and a neurotoxic mode of action as potential reasons for the deviating fish embryo toxicity. Published fish embryo LC50 values were confirmed by experimental analysis of zebrafish embryo LC50 according to OECD guideline 236. Except for diquat dibromide, internal concentration analysis did not indicate a potential relation of the low sensitivity of fish embryos to a limited uptake of the compounds. Analysis of locomotor activity of diquat dibromide and the neurotoxic compounds in 98 hpf embryos (exposed for 96 h) indicated a specific effect on behavior (embryonic movement) for the neurotoxic compounds. The EC50s of behavior for neurotoxic compounds were close to the acute fish toxicity LC50. Our data provided the first evidence that the applicability domain of the fish embryo test (LC50s determination) may exclude neurotoxic compounds. However, neurotoxic compounds could be identified by changes in embryonic locomotion. Although a quantitative prediction of acute fish toxicity LC50 using behavioral assays in fish embryos may not yet be possible, the identification of neurotoxicity could trigger the conduction of a conventional fish

Molecular modeling and snake venom phospholipase A2 inhibition by phenolic compounds: Structure-activity relationship.

PubMed

Alam, Md Iqbal; Alam, Mohammed A; Alam, Ozair; Nargotra, Amit; Taneja, Subhash Chandra; Koul, Surrinder

2016-05-23

In our earlier study, we have reported that a phenolic compound 2-hydroxy-4-methoxybenzaldehyde from Janakia arayalpatra root extract was active against Viper and Cobra envenomations. Based on the structure of this natural product, libraries of synthetic structurally variant phenolic compounds were studied through molecular docking on the venom protein. To validate the activity of eight selected compounds, we have tested them in in vivo and in vitro models. The compound 21 (2-hydroxy-3-methoxy benzaldehyde), 22 (2-hydroxy-4-methoxybenzaldehyde) and 35 (2-hydroxy-3-methoxybenzylalcohol) were found to be active against venom-induced pathophysiological changes. The compounds 20, 15 and 35 displayed maximum anti-hemorrhagic, anti-lethal and PLA2 inhibitory activity respectively. In terms of SAR, the presence of a formyl group in conjunction with a phenolic group was seen as a significant contributor towards increasing the antivenom activity. The above observations confirmed the anti-venom activity of the phenolic compounds which needs to be further investigated for the development of new anti-snake venom leads. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Synthesis and antioxidant, anti-inflammatory and gastroprotector activities of anethole and related compounds.

PubMed

Freire, Rosemayre S; Morais, Selene M; Catunda-Junior, Francisco Eduardo A; Pinheiro, Diana C S N

2005-07-01

Some derivatives of trans-anethole [1-methoxy-4-(1-propenyl)-benzene] (1) were synthesized, by introducing hydroxyl groups in the double bond of the propenyl moiety. Two types of reactions were performed: (i) oxymercuration/demercuration that formed two products, the mono-hydroxyl derivative, 1-hydroxy-1-(4-methoxyphenyl)-propane (2) and in lesser extent the dihydroxyl derivative, 1,2-dihydroxy-1-(4-methoxyphenyl)-propane (3) and (ii) epoxidation with m-chloroperbenzoic acid that also led to the formation of two products, the dihydroxyl derivative (3) and the correspondent m-chloro-benzoic acid mono-ester, 1-hydroxy-1(4-methoxyphenyl)-2-m-chlorobenzoyl-propane (4). The structures of these compounds were confirmed mainly by mass, IR, 1H and 13C NMR spectral data. The activity of anethole and hydroxylated derivatives was evaluated using antioxidant, anti-inflammatory and gastroprotector tests. Compounds (2) and (3) were more active antioxidant agents than (1) and (4). In the anti-inflammatory assay, anethole showed lower activity than hydroxylated derivatives. Anethole and in lesser extent its derivatives 2 and 4 showed significant gastroprotector activity. All tested compounds do not alter significantly the total number of white blood cells.

The Antimicrobial Activities of Extract and Compounds Isolated from Brillantaisia lamium

PubMed Central

Tamokou, Jean De Dieu; Kuiate, Jules Roger; Tene, Mathieu; Kenla Nwemeguela, Timothée Julbelin; Tane, Pierre

2011-01-01

Background: Brillantaisia lamium is an erect branched herb, which grows to a height of 1.50 m in moist tropical areas, both in full sun and partial shade. In , the aerial part of this plant is used in the treatment of various microbial infections such as skin diseases and infections of urinary tract. The aim of this study was to evaluate the antimicrobial activities of CH2Cl2: MeOH (1:1) extract, fractions and compounds from the aerial part of B. lamium. Methods: The plant was dried and extracted by maceration in CH2Cl2: MeOH (1:1 v/v). Structures of the compounds from the CH2Cl2: MeOH (1:1) soluble fraction were determined by spectroscopic methods and compared with published data. The broth micro dilution method was used to evaluate the antimicrobial activities against bacteria and fungal species. Results: Four known compounds: aurantiamide acetate (1), lupeol (2), lespedin (3), sitosterol 3-O-β-D-glucopyranoside (4) and a mixture of sterols: campesterol (5), stigmasterol (6) and β-sitosterol (7) were isolated from CH2Cl2: MeOH (1:1) extract of B. lamium aerial parts. The crude extract, fractions and isolated compounds exhibited both antibacterial and antifungal activities that varied with microorganism (MIC=6.25 – 1000 µg/ml). Compound 3 was the most active (MIC=6.25 – 100 µg/ml) while Staphylococcus aureus, Enterococcus faecalis, Candida tropicalis and Cryptococcus neoformans were the most sensitive to all the tested compounds. Conclusion: The overall results of this study indicate that the CH2Cl2: MeOH (1:1) extract and some of isolated compounds have interesting antimicrobial properties and can be used for the treatment of fungal and bacterial infections. PMID:23365474

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

PubMed

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

2008-01-01

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

Isolation and Identification of Active Compounds from Papaya Plants and Activities as Antimicrobial

NASA Astrophysics Data System (ADS)

Prasetya, A. T.; Mursiti, S.; Maryan, S.; Jati, N. K.

2018-04-01

Extraction and isolation of papaya seeds and leaves (Carica papaya L) has been performed using n-hexane and ethanol solvents. Further isolation of the extract obtained using ethyl acetate and diethyl ether solvents. The result of the phytochemical test of papaya extract obtained by mixture of an active compound of flavonoids, alkaloids, tannins, steroids, and saponins. Ethyl acetate isolates containing only flavonoids and diethyl ether isolates contain only alkaloids. Extracts and isolates from papaya plants had gram-positive antibacterial activity greater than the gram-negative bacteria, but both did not have antifungal activity. Papaya extracts have greater antibacterial activity than flavonoid isolates and alkaloid isolates. Strong antibacterial inhibitory sequences are extracts of papaya plants, flavonoid isolates, and alkaloid isolates.

Characterization of phenolic compounds and antinociceptive activity of Sempervivum tectorum L. leaf juice.

PubMed

Alberti, Ágnes; Béni, Szabolcs; Lackó, Erzsébet; Riba, Pál; Al-Khrasani, Mahmoud; Kéry, Ágnes

2012-11-01

Sempervivum tectorum L. (houseleek) leaf juice has been known as a traditional herbal remedy. The aim of the present study was the chemical characterization of its phenolic compounds and to develop quantitation methods for its main flavonol glycoside, as well as to evaluate its antinociceptive activity. Lyophilized houseleek leaf juice was studied by HPLC-DAD coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) to identify flavonol glycosides, hydroxy-benzoic and hydroxy-cinnamic acids. Ten flavonol glycosides and sixteen phenolic acid compounds were identified or tentatively characterized. Structure of the main flavonol compound was identified by nuclear magnetic resonance spectroscopy. Three characteristic kaempferol glycosides were isolated and determined by LC-ESI-MS/MS with external calibration method, using the isolated compounds as standard. The main flavonol glycoside was also determined by HPLC-DAD. Validated HPLC-DAD and LC-ESI-MS/MS methods were developed to quantify kaempferol-3-O-rhamnosyl-glucoside-7-O-rhamnoside and two other kaempferol glycosides. Antinociceptive activity of houseleek leaf juice was investigated by writhing test of mice. Sempervivum extract significantly reduced pain in the mouse writhing test. Copyright © 2012 Elsevier B.V. All rights reserved.

HPLC-based activity profiling for antiplasmodial compounds in the traditional Indonesian medicinal plant Carica papaya L.

PubMed

Julianti, Tasqiah; De Mieri, Maria; Zimmermann, Stefanie; Ebrahimi, Samad N; Kaiser, Marcel; Neuburger, Markus; Raith, Melanie; Brun, Reto; Hamburger, Matthias

2014-08-08

Leaf decoctions of Carica papaya have been traditionally used in some parts of Indonesia to treat and prevent malaria. Leaf extracts and fraction have been previously shown to possess antiplasmodial activity in vitro and in vivo. Antiplasmodial activity of extracts was confirmed and the active fractions in the extract were identified by HPLC-based activity profiling, a gradient HPLC fractionation of a single injection of the extract, followed by offline bioassay of the obtained microfractions. For preparative isolation of compounds, an alkaloidal fraction was obtained via adsorption on cationic ion exchange resin. Active compounds were purified by HPLC-MS and MPLC-ELSD. Structures were established by HR-ESI-MS and NMR spectroscopy. For compounds 5 and 7 absolute configuration was confirmed by comparison of experimental and calculated electronic circular dichroism (ECD) spectroscopy data, and by X-ray crystallography. Compounds were tested for bioactivity in vitro against four parasites (Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum), and in the Plasmodium berghei mouse model. Profiling indicated flavonoids and alkaloids in the active time windows. A total of nine compounds were isolated. Four were known flavonols--manghaslin, clitorin, rutin, and nicotiflorin. Five compounds isolated from the alkaloidal fraction were piperidine alkaloids. Compounds 5 and 6 were inactive carpamic acid and methyl carpamate, while three alkaloids 7-9 showed high antiplasmodial activity and low cytotoxicity. When tested in the Plasmodium berghei mouse model, carpaine (7) did not increase the survival time of animals. The antiplasmodial activity of papaya leaves could be linked to alkaloids. Among these, carpaine was highly active and selective in vitro. The high in vitro activity could not be substantiated with the in vivo murine model. Further investigations are needed to clarify the divergence between our negative in vivo results

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.

Design of cinnamaldehyde amino acid Schiff base compounds based on the quantitative structure-activity relationship.

PubMed

Wang, Hui; Jiang, Mingyue; Li, Shujun; Hse, Chung-Yun; Jin, Chunde; Sun, Fangli; Li, Zhuo

2017-09-01

Cinnamaldehyde amino acid Schiff base (CAAS) is a new class of safe, bioactive compounds which could be developed as potential antifungal agents for fungal infections. To design new cinnamaldehyde amino acid Schiff base compounds with high bioactivity, the quantitative structure-activity relationships (QSARs) for CAAS compounds against Aspergillus niger ( A. niger ) and Penicillium citrinum (P. citrinum) were analysed. The QSAR models ( R 2  = 0.9346 for A. niger , R 2  = 0.9590 for P. citrinum, ) were constructed and validated. The models indicated that the molecular polarity and the Max atomic orbital electronic population had a significant effect on antifungal activity. Based on the best QSAR models, two new compounds were designed and synthesized. Antifungal activity tests proved that both of them have great bioactivity against the selected fungi.

Design of cinnamaldehyde amino acid Schiff base compounds based on the quantitative structure–activity relationship

PubMed Central

Wang, Hui; Jiang, Mingyue; Hse, Chung-Yun; Jin, Chunde; Sun, Fangli; Li, Zhuo

2017-01-01

Cinnamaldehyde amino acid Schiff base (CAAS) is a new class of safe, bioactive compounds which could be developed as potential antifungal agents for fungal infections. To design new cinnamaldehyde amino acid Schiff base compounds with high bioactivity, the quantitative structure–activity relationships (QSARs) for CAAS compounds against Aspergillus niger (A. niger) and Penicillium citrinum (P. citrinum) were analysed. The QSAR models (R2 = 0.9346 for A. niger, R2 = 0.9590 for P. citrinum,) were constructed and validated. The models indicated that the molecular polarity and the Max atomic orbital electronic population had a significant effect on antifungal activity. Based on the best QSAR models, two new compounds were designed and synthesized. Antifungal activity tests proved that both of them have great bioactivity against the selected fungi. PMID:28989758

Feasibility of Active Machine Learning for Multiclass Compound Classification.

PubMed

Lang, Tobias; Flachsenberg, Florian; von Luxburg, Ulrike; Rarey, Matthias

2016-01-25

A common task in the hit-to-lead process is classifying sets of compounds into multiple, usually structural classes, which build the groundwork for subsequent SAR studies. Machine learning techniques can be used to automate this process by learning classification models from training compounds of each class. Gathering class information for compounds can be cost-intensive as the required data needs to be provided by human experts or experiments. This paper studies whether active machine learning can be used to reduce the required number of training compounds. Active learning is a machine learning method which processes class label data in an iterative fashion. It has gained much attention in a broad range of application areas. In this paper, an active learning method for multiclass compound classification is proposed. This method selects informative training compounds so as to optimally support the learning progress. The combination with human feedback leads to a semiautomated interactive multiclass classification procedure. This method was investigated empirically on 15 compound classification tasks containing 86-2870 compounds in 3-38 classes. The empirical results show that active learning can solve these classification tasks using 10-80% of the data which would be necessary for standard learning techniques.

Compounds from Sedum caeruleum with antioxidant, anticholinesterase, and antibacterial activities.

PubMed

Bensouici, Chawki; Kabouche, Ahmed; Karioti, Anastasia; Öztürk, Mehmet; Duru, Mehmet Emin; Bilia, Anna Rita; Kabouche, Zahia

2016-01-01

This is the first study on the phytochemistry, antioxidant, anticholinesterase, and antibacterial activities of Sedum caeruleum L. (Crassulaceae). The objective of this study is to isolate the secondary metabolites and determine the antioxidant, anticholinesterase, and antibacterial activities of S. caeruleum. Six compounds (1-6) were isolated from the extracts of S. caeruleum and elucidated using UV, 1D-, 2D-NMR, and MS techniques. Antioxidant activity was investigated using DPPH(•), CUPRAC, and ferrous-ions chelating assays. Anticholinesterase activity was determined against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes using the Ellman method. Antibacterial activity was performed according to disc diffusion and minimum inhibitory concentration (MIC) methods. Isolated compounds were elucidated as ursolic acid (1), daucosterol (2), β-sitosterol-3-O-β-D-galactopyranoside (3), apigenin (4), apigetrin (5), and apiin (6). The butanol extract exhibited highest antioxidant activity in all tests (IC50 value: 28.35 ± 1.22 µg/mL in DPPH assay, IC50 value: 40.83 ± 2.24 µg/L in metal chelating activity, and IC50 value: 23.52 ± 0.44 µg/L in CUPRAC), and the highest BChE inhibitory activity (IC50 value: 36.89 ± 0.15 µg/L). Moreover, the chloroform extract mildly inhibited (MIC value: 80 µg/mL) the growth of all the tested bacterial strains. Ursolic acid (1), daucosterol (2), β-sitosterol-3-O-β-D-galactopyranoside (3), apigenin (4), apigetrin (5), and apiin (6) were isolated from Sedum caeruleum for the first time. In addition, a correlation was observed between antioxidant and anticholinesterase activities of bioactive ingredients of this plant.

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

PubMed

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

2005-01-01

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

Genotoxicity testing of two lead-compounds in somatic cells of Drosophila melanogaster.

PubMed

Carmona, Erico R; Creus, Amadeu; Marcos, Ricard

2011-09-18

The in vivo genotoxic activity of two inorganic lead compounds was studied in Drosophila melanogaster by measurement of two different genetic endpoints. We used the wing-spot test and the comet assay. The comet assay was conducted with larval haemocytes. The results from the wing-spot test showed that neither lead chloride, PbCl(2), nor lead nitrate, Pb(NO(3))(2), were able to induce significant increases in the frequency of mutant spots. In addition, the combined treatments with gamma-radiation and PbCl(2) or Pb(NO(3))(2) did not show significant variations in the frequency of the three categories of mutant spots recorded, compared with the frequency induced by gamma-radiation alone. This seems to indicate that the lead compounds tested do not interact with the repair of the genetic damage induced by ionizing radiation. When the lead compounds were evaluated in the in vivo comet assay with haemocytes, Pb(NO(3))(2) was effective in inducing significant increases of DNA damage with a direct dose-response pattern. These results confirm the usefulness of the comet assay with haemocytes as an in vivo model and support the assumption that there is a genotoxic risk associated with lead exposure. Copyright © 2011 Elsevier B.V. All rights reserved.

Antioxidant activity and phenolic compounds in organic red wine using different winemaking techniques.

PubMed

Mulero, Juana; Zafrilla, Pilar; Cayuela, Jose M; Martínez-Cachá, Adela; Pardo, Francisco

2011-04-01

Wine phenolic composition depends on the grapes used to make wine and on vinification conditions. The occurrence of these biological compounds has stimulated numerous studies focused on understanding the mechanisms that influence their concentrations in wine. This article studied the effect of different vinification techniques on the antioxidant activity and on the phenolic compounds of red wine made from the variety of Monastrell grapes obtained by organic culture. To this purpose, 3 different vinification procedures were carried out: vinification after prolonged maceration, vinification with the addition of enological enzymes, and traditional vinification procedures (used as control).The results showed similar values of antioxidant activity in all 3 types of wine elaborated and found no differences in the concentrations of the different types of phenolic compounds in wine made with the 3 different methods. The evolution of antioxidant activity and phenolic compounds tested in wines during 3 mo of storage showed a similar pattern. Organic wine has acquired an important role in the economic world and its important, working in oenology to research in this field.

Microscale Group Test for Carbonyl Compounds.

ERIC Educational Resources Information Center

Horak, V.; Klein, R. F. X.

1985-01-01

Procedures are provided for a test that (1) demonstrates principles of derivatization with 2,4-dinitrophenylhydrazine; (2) is a thin layer chromatography experiment that visually demonstrates separation of colored compounds of different polarities; and (3) introduces microscale experimentation to students in sophomore organic chemistry…

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

Mesoionic compounds with antifungal activity against Fusarium verticillioides.

PubMed

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

2015-02-04

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

Anti-HIV-1 Integrase Activity and Molecular Docking Study of Compounds from Caesalpinia  sappan L.

PubMed

Tewtrakul, Supinya; Chaniad, Prapaporn; Pianwanit, Somsak; Karalai, Chatchanok; Ponglimanont, Chanita; Yodsaoue, Orapun

2015-05-01

Caesalpinia sappan L. (Caesalpiniaceae) has been traditionally used as blood tonic, expectorant, and astringent by boiling with water. Searching for HIV-1 integrase (IN) inhibitors from this plant is a promising approach. The EtOH extract of C. sappan and its isolated compounds were tested for their anti-HIV-1 IN effect using the multiplate integration assay, and the active compounds were determined for their mechanisms by molecular docking technique. Extraction from the heartwoods and roots of C. sappan led to the isolation of nine compounds. Among the compounds tested, sappanchalcone (2) displayed the strongest effect against HIV-1 IN with an IC50 value of 2.3 μM followed by protosappanin A (9, IC50  = 12.6 μM). Structure-activity relationships of compounds from C. sappan were found, in which the vicinal hydroxyl moiety were essential for anti-HIV-1 IN effect of compounds 2 and 9 by binding with the amino acid residues Gln148 and Thr66 in the core domain of the HIV- 1 IN enzyme, respectively. Copyright © 2015 John Wiley & Sons, Ltd.

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

PubMed

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

1998-11-01

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

6-Methylsulfinylhexyl isothiocyanate and its homologues as food-originated compounds with antibacterial activity against Escherichia coli and Staphylococcus aureus.

PubMed

Ono, H; Tesaki, S; Tanabe, S; Watanabe, M

1998-02-01

Cruciferae plants, banana and coriander each showed antibacterial activity. The highest activity among the food-stuffs tested was found in the stems of wasabi. An ethereal extract from wasabi stems had potent antibacterial activity and we isolated the active compound from the extract. Instrumental analysis identified the compound as 6-methylsulfinylhexyl isothiocyanate. Some homologues of 6-methylsulfinylhexyl isothiocyanate were also active against Escherichia coli and Staphylococcus aureus.

Synthesis of Hydroxide-TiO2 Compounds with Photocatalytic Activity for Degradation of Phenol

NASA Astrophysics Data System (ADS)

Contreras-Ruiz, J. C.; Martínez-Gallegos, S.; Ordoñez, E.; González-Juárez, J. C.; García-Rivas, J. L.

2017-03-01

Photocatalytic degradation of phenol using titanium dioxide (TiO2), either alone or in combination with other materials, has been tested. Mg/Al hydrotalcites prepared by two methods using inorganic (HC) or organic (HS) chemical reagents, along with mixed oxides produced by calcination of these products (HCC and HSC), were mixed with titanium isopropoxide to obtain hydroxide-TiO2 compounds (HCC-TiO2 and HSC-TiO2) and their photocatalytic activity tested in solutions of 10 mg/L phenol at 120 min under illumination at λ UV = 254 nm with power of 4 W or 8 W. The obtained materials were characterized by various techniques, revealing that TiO2 was incorporated into the mixed oxides of the calcined hydrotalcite to form the above-mentioned compounds. The photocatalytic test results indicate that the activity of HCC-TiO2 can be attributed to increased phenol adsorption by hydrotalcite for transfer to the active photocatalytic phase of the impregnated TiO2 particles, while the better results obtained for HSC-TiO2 are due to greater catalyst impregnation on the surface of the calcined hydrotalcite, reducing the screening phenomenon and achieving HSC-TiO2 degradation of up to 21.0% at 8 W. Reuse of both compounds indicated tight combination of HCC or HSC with TiO2, since in four successive separation cycles there was little reduction of activity, being associated primarily with material loss during recovery.

Corrosion Preventive Compounds Lifetime Testing

NASA Technical Reports Server (NTRS)

Hale, Stephanie M.; Kammerer, Catherine C.; Copp, Tracy L.

2007-01-01

Lifetime Testing of Corrosion Preventive Compounds (CPCs) was performed to quantify performance in the various environments to which the Space Shuttle Orbiter is exposed during a flight cycle. Three CPCs are approved for use on the Orbiter: RD Calcium Grease, Dinitrol AV-30, and Braycote 601 EF. These CPCs have been rigorously tested to prove that they mitigate corrosion in typical environments, but little information is available on how they perform in the unique combination of the coastal environment at the launch pad, the vacuum of low-earth orbit, and the extreme heat of reentry. Currently, there is no lifetime or reapplication schedule established for these compounds that is based on this combination of environmental conditions. Aluminum 2024 coupons were coated with the three CPCs and exposed to conditions that simulate the environments to which the Orbiter is exposed. Uncoated Aluminum 2024 coupons were exposed to the environmental conditions as a control. Visual inspection and Electro- Impedance Spectroscopy (EIS) were performed on the samples in order to determine the effectiveness of the CPCs. The samples were processed through five mission life cycles or until the visual inspection revealed the initiation of corrosion and EIS indicated severe degradation of the coating.

Corrosion Preventive Compounds Lifetime Testing

NASA Technical Reports Server (NTRS)

Hale, Stephanie M.; Kammerer, Catherine C.

2007-01-01

Lifetime Testing of Corrosion Preventive Compounds (CPCs) was performed to quantify performance in the various environments to which the Space Shuttle Orbiter is exposed during a flight cycle. Three CPCs are approved for use on the Orbiter: HD Calcium Grease, Dinitrol AV-30, and Braycote 601 EF. These CPCs have been rigorously tested to prove that they mitigate corrosion in typical environments, but little information is available on how they perform in the unique combination of the coastal environment at the launch pad, the vacuum of low-earth orbit, and the extreme heat of reentry. Currently, there is no lifetime or reapplication schedule established for these compounds that is based on this combination of environmental conditions. Aluminum 2024 coupons were coated with the three CPCs and exposed to conditions that simulate the environments to which the Orbiter is exposed. Uncoated Aluminum 2024 coupons were exposed to the environmental conditions as a control. Visual inspection and Electro- Impedance Spectroscopy (EIS) were performed on the samples in order to determine the effectiveness of the CPCs. The samples were processed through five mission life cycles or until the visual inspection revealed the initiation of corrosion and EIS indicated severe degradation of the coating.

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.

Phenolic compounds from the leaf extract of artichoke (Cynara scolymus L.) and their antimicrobial activities.

PubMed

Zhu, Xianfeng; Zhang, Hongxun; Lo, Raymond

2004-12-01

A preliminary antimicrobial disk assay of chloroform, ethyl acetate, and n-butanol extracts of artichoke (Cynara scolymus L.) leaf extracts showed that the n-butanol fraction exhibited the most significant antimicrobial activities against seven bacteria species, four yeasts, and four molds. Eight phenolic compounds were isolated from the n-butanol soluble fraction of artichoke leaf extracts. On the basis of high-performance liquid chromatography/electrospray ionization mass spectrometry, tandem mass spectrometry, and nuclear magnetic resonance techniques, the structures of the isolated compounds were determined as the four caffeoylquinic acid derivatives, chlorogenic acid (1), cynarin (2), 3,5-di-O-caffeoylquinic acid (3), and 4,5-di-O-caffeoylquinic acid (4), and the four flavonoids, luteolin-7-rutinoside (5), cynaroside (6), apigenin-7-rutinoside (7), and apigenin-7-O-beta-D-glucopyranoside (8), respectively. The isolated compounds were examined for their antimicrobial activities on the above microorganisms, indicating that all eight phenolic compounds showed activity against most of the tested organisms. Among them, chlorogenic acid, cynarin, luteolin-7-rutinoside, and cynaroside exhibited a relatively higher activity than other compounds; in addition, they were more effective against fungi than bacteria. The minimum inhibitory concentrations of these compounds were between 50 and 200 microg/mL.

Disruption of ion homeostasis by verrucosin and a related compound.

PubMed

Akiyama, Koichi; Tone, Junichi; Yamauchi, Satoshi; Sugahara, Takuya; Maruyama, Masafumi; Kakinuma, Yoshimi

2011-01-01

We have found that (-)-virgatusin and related compounds have antimicrobial and antifungal activity. To identify further biological activities of these compounds, we tested the activity of acridine orange efflux, which shows ionophore-like disruption of cellular ion homeostasis activity. After testing 31 compounds, we found that verrucosin and a related compound had disruption activity.

Effects of temperature and medium composition on inhibitory activities of gossypol-related compounds against aflatoxigenic fungi.

PubMed

Mellon, J E; Dowd, M K; Beltz, S B

2013-07-01

To investigate the effects of temperature and medium composition on growth/aflatoxin inhibitory activities of terpenoids gossypol, gossypolone and apogossypolone against Aspergillus flavus and A. parasiticus. The compounds were tested at a concentration of 100 μg ml(-1) in a Czapek Dox (Czapek) agar medium at 25, 31 and 37°C. Increased incubation temperature marginally increased growth inhibition caused by these compounds, but reduced the aflatoxin inhibition effected by gossypol. Gossypolone and apogossypolone retained good aflatoxin inhibitory activity against A. flavus and A. parasiticus at higher incubation temperatures. However, increased temperature also significantly reduced aflatoxin production in control cultures. The effects of the terpenoids on fungal growth and aflatoxin production against the same fungi were also determined in Czapek, Czapek with a protein/amino acid addendum and yeast extract sucrose (YES) media. Growth of these fungi in the protein-supplemented Czapek medium or in the YES medium greatly reduced the growth inhibition effects of the terpenoids. Apogossypolone displayed strong anti-aflatoxigenic activity in the Czapek medium, but this activity was significantly reduced in the protein-amended Czapek and YES media. Gossypol, which displayed little to no aflatoxin inhibitory activity in the Czapek medium, did yield significant anti-aflatoxigenic activity in the YES medium. Incubation temperature and media composition are important parameters involved in the regulation of aflatoxin production in A. flavus and A. parasiticus. These parameters also affect the potency of growth and aflatoxin inhibitory activities of these gossypol-related compounds against aflatoxigenic fungi. Studies utilizing gossypol-related compounds as inhibitory agents of biological activities should be interpreted with caution due to compound interaction with multiple components of the test system, especially serum proteins. Published [2013]. This article is a

Prediction of cloud condensation nuclei activity for organic compounds using functional group contribution methods

DOE PAGES

Petters, M. D.; Kreidenweis, S. M.; Ziemann, P. J.

2016-01-19

A wealth of recent laboratory and field experiments demonstrate that organic aerosol composition evolves with time in the atmosphere, leading to changes in the influence of the organic fraction to cloud condensation nuclei (CCN) spectra. There is a need for tools that can realistically represent the evolution of CCN activity to better predict indirect effects of organic aerosol on clouds and climate. This work describes a model to predict the CCN activity of organic compounds from functional group composition. Following previous methods in the literature, we test the ability of semi-empirical group contribution methods in Kohler theory to predict themore » effective hygroscopicity parameter, kappa. However, in our approach we also account for liquid–liquid phase boundaries to simulate phase-limited activation behavior. Model evaluation against a selected database of published laboratory measurements demonstrates that kappa can be predicted within a factor of 2. Simulation of homologous series is used to identify the relative effectiveness of different functional groups in increasing the CCN activity of weakly functionalized organic compounds. Hydroxyl, carboxyl, aldehyde, hydroperoxide, carbonyl, and ether moieties promote CCN activity while methylene and nitrate moieties inhibit CCN activity. Furthermore, the model can be incorporated into scale-bridging test beds such as the Generator of Explicit Chemistry and Kinetics of Organics in the Atmosphere (GECKO-A) to evaluate the evolution of kappa for a complex mix of organic compounds and to develop suitable parameterizations of CCN evolution for larger-scale models.« less

Immunomodulatory potencies of isolated compounds from Crataegus azarolus through their antioxidant activities.

PubMed

Mustapha, Nadia; Mokdad-Bzéouich, Imèn; Sassi, Aicha; Abed, Besma; Ghedira, Kamel; Hennebelle, Thierry; Chekir-Ghedira, Leila

2016-06-01

The search of natural immunomodulatory agents has become an area of great interest in order to reduce damage to the human body. In this study, the immunomodulatory potential of Crataegus azarolus and its isolated hyperoside on mouse lymphocytes and macrophages in vitro was assessed. The effect of C. azarolus natural compounds on splenocytes proliferation, natural killer (NK) and cytotoxic T lymphocytes (CTL) activities, and on macrophage-mediated cytotoxicity were assessed by MTT test. Phagocytic activity and inhibition of nitric oxide (NO) release by macrophages were also evaluated. The antioxidant capacity of these products was evaluated by determining their cellular antioxidant activity (CAA) in splenocytes and macrophages. Depending on the concentrations, both ethyl acetate (EA) extract and hyperoside (Hyp) from C. azarolus affect macrophage functions by modulating their lysosomal enzyme activity and nitric oxide release. Whereas, the above-mentioned products significantly promote LPS and lectin-stimulated splenocyte proliferation, implying a potential activation of lymphocytes B and T enhancing humoral and cellular immune responses. Moreover, EA extract and Hyp could enhance the activity of NK and T lymphocytes cells, as well as the macrophages-mediated cytotoxicity against B16F10 cells. The anti-inflammatory activity was concomitant with the cellular antioxidant effect of the tested compounds against macrophages and splenocytes. Collectively, C. azarolus and its isolated hyperoside exhibited an immunomodulatory effect through their antioxidant activity. These findings suggest that C. azarolus should be explored as a novel potential immunomodulatory agent for the treatment of inflammatory diseases.

Test for Non-Synergistic Interactions in Phytomedicine, Just as You Do for Isolated Compounds

PubMed Central

Patel, Areeba; Mondal, Amit

2018-01-01

Phytomedicine has often been used as “alternative therapy,” which in our opinion is unfortunate as it prevents its main actions being systematically studied, side effects explored, and toxicity tested, like all single-compound-based medicine. Our group is interested in finding which traditional or modern phytomedicines actually work and which are simply “working” through placebo, standardizing phytomedicine preparations, studying their toxicity, and finding active molecules in plants for modification and chemical synthesis as single compounds. Although fluctuation in efficacy due to seasonal and geographical variations in phytomedicine remains a concern, if well regulated, even plant extracts without isolated compounds can serve medicinal needs where single-compound options are currently not great. A potential concern with such phytomedicine is frequent mixing of ingredients in commercial formulations without test of synergism. Our study on the use of 2 traditional plants for Parkinson disease shows a clear lack of synergism, and to study nonsynergism better, we developed a new visualization approach. In this commentary, using our study on Parkinson disease as an example, we make a case for better evaluation of phytomedicines, especially testing for synergistic interactions. We also critique our own exploration of oxidative stress and few behavioral parameters alone to lay grounds for what we and hopefully others can do in future to extract more information from their phytomedicine studies. We hope this commentary acts as a good warning for anyone mixing 2 phytomedicines without testing. PMID:29706766

Test for Non-Synergistic Interactions in Phytomedicine, Just as You Do for Isolated Compounds.

PubMed

Patel, Areeba; Khan, Farooq Ali; Sikdar, Arindam; Mondal, Amit; Shukla, Sunil Dutt; Khurana, Sukant

2018-01-01

Phytomedicine has often been used as "alternative therapy," which in our opinion is unfortunate as it prevents its main actions being systematically studied, side effects explored, and toxicity tested, like all single-compound-based medicine. Our group is interested in finding which traditional or modern phytomedicines actually work and which are simply "working" through placebo, standardizing phytomedicine preparations, studying their toxicity, and finding active molecules in plants for modification and chemical synthesis as single compounds. Although fluctuation in efficacy due to seasonal and geographical variations in phytomedicine remains a concern, if well regulated, even plant extracts without isolated compounds can serve medicinal needs where single-compound options are currently not great. A potential concern with such phytomedicine is frequent mixing of ingredients in commercial formulations without test of synergism. Our study on the use of 2 traditional plants for Parkinson disease shows a clear lack of synergism, and to study nonsynergism better, we developed a new visualization approach. In this commentary, using our study on Parkinson disease as an example, we make a case for better evaluation of phytomedicines, especially testing for synergistic interactions. We also critique our own exploration of oxidative stress and few behavioral parameters alone to lay grounds for what we and hopefully others can do in future to extract more information from their phytomedicine studies. We hope this commentary acts as a good warning for anyone mixing 2 phytomedicines without testing.

Superior bactericidal activity of N-bromine compounds compared to their N-chlorine analogues can be reversed under protein load.

PubMed

Gottardi, W; Klotz, S; Nagl, M

2014-06-01

To investigate and compare the bactericidal activity (BA) of active bromine and chlorine compounds in the absence and presence of protein load. Quantitative killing tests against Escherichia coli and Staphylococcus aureus were performed both in the absence and in the presence of peptone with pairs of isosteric active chlorine and bromine compounds: hypochlorous and hypobromous acid (HOCl and HOBr), dichloro- and dibromoisocyanuric acid, chlorantine and bromantine (1,3-dibromo- and 1,3 dichloro-5,5-dimethylhydantoine), chloramine T and bromamine T (N-chloro- and N-bromo-4-methylbenzenesulphonamide sodium), and N-chloro- and N-bromotaurine sodium. To classify the bactericidal activities on a quantitative basis, an empirical coefficient named specific bactericidal activity (SBA), founded on the parameters of killing curves, was defined: SBA= mean log reductions/(mean exposure times x concentration) [mmol 1(-1) min (-1)]. In the absence of peptone, tests with washed micro-organisms revealed a throughout higher BA of bromine compounds with only slight differences between single substances. This was in contrast to chlorine compounds, whose killing times differed by a factor of more than four decimal powers. As a consequence, also the isosteric pairs showed according differences. In the presence of peptone, however, bromine compounds showed an increased loss of BA, which partly caused a reversal of efficacy within isosteric pairs. In medical practice, weakly oxidizing active chlorine compounds like chloramines have the highest potential as topical anti-infectives in the presence of proteinaceous material (mucous membranes, open wounds). Active bromine compounds, on the other hand, have their chance at insensitive body regions with low organic matter, for example skin surfaces. The expected protein load is one of the most important parameters for selection of a suited active halogen compound. © 2014 The Society for Applied Microbiology.

Antioxidative activities and active compounds of extracts from Catalpa plant leaves.

PubMed

Xu, Hongyu; Hu, Gege; Dong, Juane; Wei, Qin; Shao, Hongbo; Lei, Ming

2014-01-01

In order to screen the Catalpa plant with high antioxidant activity and confirm the corresponding active fractions from Catalpa ovata G. Don, C. fargesii Bur., and C. bungei C. A. Mey., total flavonoid contents and antioxidant activities of the extracts/fractions of Catalpa plant leaves were determined. The determined total flavonoid content and antioxidant activity were used as assessment criteria. Those compounds with antioxidant activity were isolated with silica gel column chromatography and ODS column chromatography. Our results showed that the total flavonoid content in C. bungei C. A. Mey. (30.07 mg/g · DW) was the highest, followed by those in C. fargesii Bur. (25.55 mg/g · DW) and C. ovata G. Don (24.96 mg/g · DW). According to the determination results of total flavonoid content and antioxidant activity in 3 clones of leaves of C. bungei C. A. Mey., the total flavonoid content and antioxidant activity in crude extracts from C. bungei C. A. Mey. 6 (CA6) leaves were the highest. Moreover, the results showed that the total flavonoid content and antioxidant activities of ethyl acetate (EA) fraction in ethanol crude extracts in CA6 leaves were the highest, followed by n-butanol, petroleum ether (PE), and water fractions. Two flavonoid compounds with antioxidant activity were firstly isolated based on EA fraction. The two compounds were luteolin (1) and apigenin (2), respectively.

An in vitro comparative study of the antioxidant activity and SIRT1 modulation of natural compounds.

PubMed

Fusi, Jonathan; Bianchi, Sara; Daniele, Simona; Pellegrini, Silvia; Martini, Claudia; Galetta, Fabio; Giovannini, Luca; Franzoni, Ferdinando

2018-05-01

Oxidative stress arises from an imbalance between the production of free radicals and antioxidant defences. Several studies have suggested that dietary antioxidants (such as polyphenols and berberine) may counteract oxidative stress through the involvement of the Sirtuin 1/Adenosine Monophosphate-Activated Protein Kinase (SIRT1/AMPK) pathway. The aim of this study was to evaluate the direct and specific antioxidant activity of some natural compounds, as well as their ability to modulate the expression of SIRT1 and the activation of AMPK. Quercetin, tyrosol, ferulic acid, catechin, berberine and curcumin were evaluated for their specific and direct antioxidant activity with TOSC assay. Their ability to modulate SIRT1 and AMPK was assessed by immunoblotting assay, while their cytotoxicity by CellTiter-Blue Cell Viability Assay. No statistically significant decrease (p > 0.05) in the number of viable cells was found upon challenging with the natural compounds. Quercetin exhibited the highest antioxidant activity against peroxyl radical and peroxinitrate derivates, while curcumin showed the best anti-hydroxyl activity with respect to the other compounds and, most importantly, respect to the reference antioxidants. Finally, all the tested compounds significantly increased the SIRT1 expression and the activation of AMPK. Our results clearly disclose the specific antioxidant activity of these natural compounds and their ability to increase SIRT1 expression and AMPK activation. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Phytochemical Analysis, Identification and Quantification of Antibacterial Active Compounds in Betel Leaves, Piper betle Methanolic Extract.

PubMed

Syahidah, A; Saad, C R; Hassan, M D; Rukayadi, Y; Norazian, M H; Kamarudin, M S

2017-01-01

The problems of bacterial diseases in aquaculture are primarily controlled by antibiotics. Medicinal plants and herbs which are seemed to be candidates of replacements for conventional antibiotics have therefore gained increasing interest. Current study was performed to investigate the presence of phytochemical constituents, antibacterial activities and composition of antibacterial active compounds in methanolic extract of local herb, Piper betle . Qualitative phytochemical analysis was firstly carried out to determine the possible active compounds in P. betle leaves methanolic extract. The antibacterial activities of major compounds from this extract against nine fish pathogenic bacteria were then assessed using TLC-bioautography agar overlay assay and their quantity were determined simultaneously by HPLC method. The use of methanol has proved to be successful in extracting numerous bioactive compounds including antibacterial compounds. The TLC-bioautography assay revealed the inhibitory action of two compounds which were identified as hydroxychavicol and eugenol. The $-caryophyllene however was totally inactive against all the tested bacterial species. In this study, the concentration of hydroxychavicol in extract was found to be 374.72±2.79 mg g-1, while eugenol was 49.67±0.16 mg g-1. Based on these findings, it could be concluded that hydroxychavicol and eugenol were the responsible compounds for the promising antibacterial activity of P. betle leaves methanolic extract. This inhibitory action has significantly correlated with the amount of the compounds in extract. Due to its potential, the extract of P. betle leaves or it compounds can be alternative source of potent natural antibacterial agents for aquaculture disease management.

Antioxidant Activity of Phenolic Compounds from Fava Bean Sprouts.

PubMed

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

2016-06-01

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

Supercritical fluid extraction and analysis of compounds from Clivia miniata for uterotonic activity.

PubMed

Sewram, V; Raynor, M W; Mulholland, D A; Raidoo, D M

2001-07-01

In this descriptive study, the superciritical fluid extract of the roots of Clivia miniata L. was tested for uterotonic activity using guinea pig uterine smooth muscle in vitro. Extraction was performed with water modified supercritical carbon dioxide at 400 atm and 80 degrees C. The uterine contractions induced by this extract were compared to those induced by the aqueous extract and found to be active at lower doses. The active compounds were isolated and the structures elucidated by spectroscopic and chromatographic techniques. Both linoleic acid and 5-hydroxymethyl-2-furancarboxaldehyde isolated from the extract were found to induce muscle contractions individually. The pharmacological mode of action of 5-hydroxymethyl-2-furancarboxaldehyde was assessed using two receptor agonists and antagonists. This compound was found to mediate its effect through cholinergic receptors.

Antioxidative Activities and Active Compounds of Extracts from Catalpa Plant Leaves

PubMed Central

Xu, Hongyu; Hu, Gege; Dong, Juane; Wei, Qin; Shao, Hongbo; Lei, Ming

2014-01-01

In order to screen the Catalpa plant with high antioxidant activity and confirm the corresponding active fractions from Catalpa ovata G. Don, C. fargesii Bur., and C. bungei C. A. Mey., total flavonoid contents and antioxidant activities of the extracts/fractions of Catalpa plant leaves were determined. The determined total flavonoid content and antioxidant activity were used as assessment criteria. Those compounds with antioxidant activity were isolated with silica gel column chromatography and ODS column chromatography. Our results showed that the total flavonoid content in C. bungei C. A. Mey. (30.07 mg/g·DW) was the highest, followed by those in C. fargesii Bur. (25.55 mg/g·DW) and C. ovata G. Don (24.96 mg/g·DW). According to the determination results of total flavonoid content and antioxidant activity in 3 clones of leaves of C. bungei C. A. Mey., the total flavonoid content and antioxidant activity in crude extracts from C. bungei C. A. Mey. 6 (CA6) leaves were the highest. Moreover, the results showed that the total flavonoid content and antioxidant activities of ethyl acetate (EA) fraction in ethanol crude extracts in CA6 leaves were the highest, followed by n-butanol, petroleum ether (PE), and water fractions. Two flavonoid compounds with antioxidant activity were firstly isolated based on EA fraction. The two compounds were luteolin (1) and apigenin (2), respectively. PMID:25431795

The Mast Cell Degranulator Compound 48/80 Directly Activates Neurons

PubMed Central

Schemann, Michael; Kugler, Eva Maria; Buhner, Sabine; Eastwood, Christopher; Donovan, Jemma; Jiang, Wen; Grundy, David

2012-01-01

Background Compound 48/80 is widely used in animal and tissue models as a “selective” mast cell activator. With this study we demonstrate that compound 48/80 also directly activates enteric neurons and visceral afferents. Methodology/Principal Findings We used in vivo recordings from extrinsic intestinal afferents together with Ca++ imaging from primary cultures of DRG and nodose neurons. Enteric neuronal activation was examined by Ca++ and voltage sensitive dye imaging in isolated gut preparations and primary cultures of enteric neurons. Intraluminal application of compound 48/80 evoked marked afferent firing which desensitized on subsequent administration. In egg albumen-sensitized animals, intraluminal antigen evoked a similar pattern of afferent activation which also desensitized on subsequent exposure to antigen. In cross-desensitization experiments prior administration of compound 48/80 failed to influence the mast cell mediated response. Application of 1 and 10 µg/ml compound 48/80 evoked spike discharge and Ca++ transients in enteric neurons. The same nerve activating effect was observed in primary cultures of DRG and nodose ganglion cells. Enteric neuron cultures were devoid of mast cells confirmed by negative staining for c-kit or toluidine blue. In addition, in cultured enteric neurons the excitatory action of compound 48/80 was preserved in the presence of histamine H1 and H2 antagonists. The mast cell stabilizer cromolyn attenuated compound 48/80 and nicotine evoked Ca++ transients in mast cell-free enteric neuron cultures. Conclusions/Significance The results showed direct excitatory action of compound 48/80 on enteric neurons and visceral afferents. Therefore, functional changes measured in tissue or animal models may involve a mast cell independent effect of compound 48/80 and cromolyn. PMID:23272218

Antialgal compounds with antialgal activity against the common red tide microalgae from a green algae Ulva pertusa.

PubMed

Sun, Ying-Ying; Zhou, Wen-Jing; Wang, Hui; Guo, Gan-Lin; Su, Zhen-Xia; Pu, Yin-Fang

2018-08-15

Nine antialgal active compounds, (i.e. trehalose (1), twenty-two methyl carbonate (2), (-)-dihydromenisdaurilide (3), 3,7,11,15-tetramethyl-2-hexadecen-1-ol (4), isophytol (5), 8-hexadecenol (6), 17-hydroxyheptadecanoic acid (7), trans-asarone (8) and 2-amino-3-mercaptopropanoic acid (9)) were isolated from Ulva pertusa for the first time by sephadex LH-20 column chromatography, silica gel column chromatography and repeated preparative TLC. Except for compound 4, all compounds represented novel isolated molecules from marine macroalgae. Further, antialgal activities of these compounds against Amphidinium carterae, Heterosigma akashiwo, Karenia mikimitoi, Phaeocystis globosa, Prorocentrum donghaiense and Skeletonema costatum were investigated for the first time. Results showed these nine compounds have selectivity antialgal effects on all test red tide microalgae, and antialgal activities against red tide microalgae obviously enhanced with the increase of concentration of antialgal compounds. Based on this, EC 50-96 h values of these nine compounds for six red tide microalgae were obtained for the first time. By analyzing and comparing EC 50-96 h values, it has been determined that seven compounds (1, 3, 4, 6, 7, 8 and 9) showed the superior application potential than potassium dichromate or gossonorol and other six compounds as a characteristic antialgal agent against Heterosigma akashiwo, Karenia mikimitoi and Prorocentrum donghaiense. Overall this study has suggested that green algae Ulva pertusa is a new source of bioactive compounds with antialgal activity. Copyright © 2018. Published by Elsevier Inc.

Targeting the epigenome: Screening bioactive compounds that regulate histone deacetylase activity

PubMed Central

Godoy, Luis D.; Lucas, Julianna E.; Bender, Abigail J.; Romanick, Samantha S.; Ferguson, Bradley S.

2017-01-01

Scope Nutrigenomics is a rapidly expanding field that elucidates the link between diet-genome interactions. Recent evidence demonstrates that regulation of the epigenome, and in particular inhibition of HDACs, impact pathogenetic mechanisms involved in chronic disease. Few studies, to date, have screened libraries of bioactive compounds that act as epigenetic modifiers. This study screened a library of 131 natural compounds to determine bioactive compounds that inhibit Zn-dependent HDAC activity. Methods and results Using class-specific HDAC substrates, we screened 131 natural compounds for HDAC activity in bovine cardiac tissue. From this screen, we identified 18 bioactive compound HDAC inhibitors. Using our class-specific HDAC substrates, we next screened these 18 bioactive compounds against recombinant HDAC proteins. Consistent with inhibition of HDAC activity, these compounds were capable of inhibiting activity of individual HDAC isoforms. Lastly, we report that treatment of H9c2 cardiac myoblasts with bioactive HDAC inhibitors was sufficient to increase lysine acetylation as assessed via immunoblot. Conclusion This study provided the first step in identifying multiple bioactive compound HDAC inhibitors. Taken together, this report sets the stage for future exploration of these bioactive compounds as epigenetic regulators to potentially ameliorate chronic disease. PMID:27981795

Identification and preclinical testing of novel antiepileptic compounds.

PubMed

Meldrum, B S

1997-01-01

Procedures for identifying novel antiepileptic drugs (AEDs) are changing and need to change more. Widespread reliance on two primary screens has led to the identification of novel compounds that resemble either phenytoin (suppressing high-frequency repetitive firing in cultured neurons and prolonging inactivation of voltage-dependent sodium channels identified by the maximal electroshock test) or benzodiazepines (potentiating the inhibitory effect of gamma-aminobutyric acid (GABA), identified by the threshold pentylenetetrazol test). Advances in molecular neurobiology have identified specific molecular targets (subunits of ion channels, neurotransmitter receptors, and transporters) and have made them available in a form permitting high-throughput screening. AEDs can be designed to interact with specific sites on the target molecules. Alternatively, the molecular screens can be used to identify active components in natural products, including folk remedies. Preclinical in vivo screens can be improved by using animals with genetic or acquired epilepsies that have similar modifications in the properties of the target molecules as do human epilepsy syndromes. Future work is likely to define molecular targets for AEDs that will block or reverse chronic epileptogenesis.

Larvicidal and antifeedant activity of some plant-derived compounds to Lymantria dispar L. (Lepidoptera: Limantriidae).

PubMed

Kostić, Miroslav; Popović, Zorica; Brkić, Dejan; Milanović, Slobodan; Sivcev, Ivan; Stanković, Sladjan

2008-11-01

Ethanol solutions of essential oil of Ocimum basilicum and its main component, linalool (both isomer forms), all in three concentrations, as well as botanical standard Bioneem (0.5%), were tested for their toxicity and antifeedant activity against the second instar gypsy moth larvae in the laboratory bioassay. The essential oil of O. basilicum was subjected to gas chromatography analysis, and totally 37 compounds were detected, of which linalool was predominantly present. All tested solutions showed low to moderate larvicidal effect in both residual toxicity test and in chronic larval mortality bioassay. Chronic mortality tests showed that obtained mortality was a consequence of starving rather than ingestion of treated leaves. However, antifeedant index achieved by application of tested solutions in feeding choice assay was remarkable. Foliar application of all tested compounds deterred feeding by L2 in the same percent as Bioneem. Antifeedant index was relatively high at all tested treatments (85-94%); moreover, the larval desensitization to repelling volatiles has not occurred after five days of observation. Low toxic and high antifeedant properties make these plant-derived compounds suitable for incorporation in integrated pest management programs, especially in urban environments.

End-preparation assessments and tests for compounded sterile preparations.

PubMed

McElhiney, Linda F

2013-01-01

Outsourcing has become a necessity to obtain sterile products that are currently on backorder. Because of the expense of outsourcing sterile compounding, pharmacy leadership in health systems are now considering the option of insourcing and batch preparing compounded sterile preparations, which can be a viable option for a health system. It can significantly decrease drug-spending costs, and the pharmacy has a complete record of the compounding process. The key to preparing high-quality, safe, sterile preparations and meeting United States Pharmacopeia standards is end-preparation assessments and tests.

Antiviral Screening of Multiple Compounds against Ebola Virus.

PubMed

Dowall, Stuart D; Bewley, Kevin; Watson, Robert J; Vasan, Seshadri S; Ghosh, Chandradhish; Konai, Mohini M; Gausdal, Gro; Lorens, James B; Long, Jason; Barclay, Wendy; Garcia-Dorival, Isabel; Hiscox, Julian; Bosworth, Andrew; Taylor, Irene; Easterbrook, Linda; Pitman, James; Summers, Sian; Chan-Pensley, Jenny; Funnell, Simon; Vipond, Julia; Charlton, Sue; Haldar, Jayanta; Hewson, Roger; Carroll, Miles W

2016-10-27

In light of the recent outbreak of Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests. Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine). A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna). The three most promising compounds (17-DMAG; BGB324; and NCK-8) were further screened for in vivo activity in the guinea pig model of EBOV disease. Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation. Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease.

Phytochemical screening and in-vitro antioxidant activity isolated bioactive compounds from Tridax procumbens Linn.

PubMed

Saxena, Manjusha; Mir, Abrar Hussain; Sharma, Manik; Malla, Mohd Yousu; Qureshi, Sumeerah; Mir, Mohd Iqbal; Chaturvedi, Yogesh

2013-12-15

Tridax procumbens L., Asteraceae, has been extensively used for various ailments in the Ayurvedic system of medicine. Previous studies have revealed remarkable phytoconstituents from Tridax procumbens L. with significant antioxidant activity. The aim of the present study is to measure the anti-DPPH activity of the purified isolated compounds from n butanol soluble part and ethyl acetate soluble part of successive methanolic extract of Tridax procumbens L. We thus quantified the total phenolic and total flavonoids in different purified isolated compounds, the whole of the tests were evaluated with a sample cone. of 100 microg mL(-1) and were determined spectrophotometrically using Folin-ciocaltue and AlCl3 reagents, respectively. DPPH (1,1-diphenyl, 2-picryl hydrazyl) assay was used to determine the in vitro antioxidant activity of different isolated compounds. Isolated compounds, one from ethyl acetate soluble part (EF-I) and one from n butanol soluble part (BF-II) were reported to possess a significant anti DPPH activity with lowest IC50 values 67.26 and 80.90 microg mL(-1), respectively while comparable to standard ascorbic acid with IC50 value of 59.62 microg mL(-1), due to the high concentration of phenols 146.4 microg mL(-1) from EF-I and 142.2 microg mL(-1) from BF-II and flavonoids 48 and 42.5 microg mL(-1) found in EF-I and BF-II isolated compounds, respectively.

Antifouling Compounds from Marine Macroalgae

PubMed Central

Dahms, Hans Uwe; Dobretsov, Sergey

2017-01-01

Marine macroalgae produce a wide variety of biologically-active metabolites that have been developed into commercial products, such as antibiotics, immunosuppressive, anti-inflammatory, cytotoxic agents, and cosmetic products. Many marine algae remain clean over longer periods of time, suggesting their strong antifouling potential. Isolation of biogenic compounds and the determination of their structure could provide leads for the development of environmentally-friendly antifouling paints. Isolated substances with potent antifouling activity belong to fatty acids, lipopeptides, amides, alkaloids, lactones, steroids, terpenoids, and pyrroles. It is unclear as yet to what extent symbiotic microorganisms are involved in the synthesis of these compounds. Algal secondary metabolites have the potential to be produced commercially using genetic and metabolic engineering techniques. This review provides an overview of publications from 2010 to February 2017 about antifouling activity of green, brown, and red algae. Some researchers were focusing on antifouling compounds of brown macroalgae, while metabolites of green algae received less attention. Several studies tested antifouling activity against bacteria, microalgae and invertebrates, but in only a few studies was the quorum sensing inhibitory activity of marine macroalgae tested. Rarely, antifouling compounds from macroalgae were isolated and tested in an ecologically-relevant way. PMID:28846625

Antifouling Compounds from Marine Macroalgae.

PubMed

Dahms, Hans Uwe; Dobretsov, Sergey

2017-08-28

Marine macroalgae produce a wide variety of biologically-active metabolites that have been developed into commercial products, such as antibiotics, immunosuppressive, anti-inflammatory, cytotoxic agents, and cosmetic products. Many marine algae remain clean over longer periods of time, suggesting their strong antifouling potential. Isolation of biogenic compounds and the determination of their structure could provide leads for the development of environmentally-friendly antifouling paints. Isolated substances with potent antifouling activity belong to fatty acids, lipopeptides, amides, alkaloids, lactones, steroids, terpenoids, and pyrroles. It is unclear as yet to what extent symbiotic microorganisms are involved in the synthesis of these compounds. Algal secondary metabolites have the potential to be produced commercially using genetic and metabolic engineering techniques. This review provides an overview of publications from 2010 to February 2017 about antifouling activity of green, brown, and red algae. Some researchers were focusing on antifouling compounds of brown macroalgae, while metabolites of green algae received less attention. Several studies tested antifouling activity against bacteria, microalgae and invertebrates, but in only a few studies was the quorum sensing inhibitory activity of marine macroalgae tested. Rarely, antifouling compounds from macroalgae were isolated and tested in an ecologically-relevant way.

Targeting the epigenome: Screening bioactive compounds that regulate histone deacetylase activity.

PubMed

Godoy, Luis D; Lucas, Julianna E; Bender, Abigail J; Romanick, Samantha S; Ferguson, Bradley S

2017-04-01

Nutrigenomics is a rapidly expanding field that elucidates the link between diet-genome interactions. Recent evidence demonstrates that regulation of the epigenome, and in particular inhibition of histone deacetylases (HDACs), impact pathogenetic mechanisms involved in chronic disease. Few studies, to date, have screened libraries of bioactive compounds that act as epigenetic modifiers. This study screened a library of 131 natural compounds to determine bioactive compounds that inhibit Zn-dependent HDAC activity. Using class-specific HDAC substrates, we screened 131 natural compounds for HDAC activity in bovine cardiac tissue. From this screen, we identified 18 bioactive compound HDAC inhibitors. Using our class-specific HDAC substrates, we next screened these 18 bioactive compounds against recombinant HDAC proteins. Consistent with inhibition of HDAC activity, these compounds were capable of inhibiting activity of individual HDAC isoforms. Lastly, we report that treatment of H9c2 cardiac myoblasts with bioactive HDAC inhibitors was sufficient to increase lysine acetylation as assessed via immunoblot. This study provided the first step in identifying multiple bioactive compound HDAC inhibitors. Taken together, this report sets the stage for future exploration of these bioactive compounds as epigenetic regulators to potentially ameliorate chronic disease. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antibacterial activities of plant-derived compounds and essential oils toward Cronobacter sakazakii and Cronobacter malonaticus.

PubMed

Fraňková, Adéla; Marounek, Milan; Mozrová, Věra; Weber, Jaroslav; Klouček, Pavel; Lukešová, Daniela

2014-10-01

Cronobacter sakazakii and C. malonaticus are opportunistic pathogens that cause infections in children and immunocompromised adults. In the present study, the antibacterial activity of 19 plant-derived compounds, 5 essential oils, and an extract of propolis were assessed against C. sakazakii and C. malonaticus. The effects of most of these antimicrobials have not been reported previously. Both strains were susceptible to thymol, carvacrol, thymoquinone, p-cymene, linalool, camphor, citral, eugenol, and trans-cinnamaldehyde as well as cinnamon, lemongrass, oregano, clove, and laurel essential oils; their minimum inhibitory concentrations varied between 0.1 and 2.0 mg/mL. As an alternative treatment method, vapors of the volatiles were tested as an indirect treatment. Vapors of trans-cinnamaldehyde, eugenol, oregano, and cinnamon essential oils inhibited both tested strains, while vapors of linalool were only active against C. sakazakii. To our knowledge, this study is the first time that the inhibitory activity of the vapors of these compounds and essential oils has been reported against Cronobacter spp.

21 CFR 862.1185 - Compound S (11-deoxycortisol) test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...-dioxycortisol) test system is a device intended to measure the level of compound S (11-dioxycortisol) in plasma. Compound S is a steroid intermediate in the biosynthesis of the adrenal hormone cortisol. Measurements of...

A Multiplexed Assay That Monitors Effects of Multiple Compound Treatment Times Reveals Candidate Immune-Enhancing Compounds.

PubMed

Zhao, Ziyan; Henowitz, Liza; Zweifach, Adam

2018-05-01

We previously developed a flow cytometry assay that monitored lytic granule exocytosis in cytotoxic T lymphocytes stimulated by contacting beads coated with activating anti-CD3 antibodies. That assay was multiplexed in that responses of cells that did or did not receive the activating stimulus were distinguished via changes in light scatter accompanying binding of cells to beads, allowing us to discriminate compounds that activate responses on their own from compounds that enhance responses in cells that received the activating stimulus, all within a single sample. Here we add a second dimension of multiplexing by developing means to assess in a single sample the effects of treating cells with test compounds for different times. Bar-coding cells before adding them to test wells lets us determine compound treatment time while also monitoring activation status and response amplitude at the point of interrogation. This multiplexed assay is suitable for screening 96-well plates. We used it to screen compounds from the National Cancer Institute, identifying several compounds that enhance anti-LAMP1 responses. Multiple-treatment-time (MTT) screening enabled by bar-coding and read via high-throughput flow cytometry may be a generally useful method for facilitating the discovery of compounds of interest.

Antimicrobial activities of the methanol extract and compounds from Artocarpus communis (Moraceae)

PubMed Central

2011-01-01

Background Artocarpus communis is used traditionally in Cameroon to treat several ailments, including infectious and associated diseases. This work was therefore designed to investigate the antimicrobial activities of the methanol extract (ACB) and compounds isolated from the bark of this plant, namely peruvianursenyl acetate C (1), α-amyrenol or viminalol (2), artonin E (4) and 2-[(3,5-dihydroxy)-(Z)-4-(3-methylbut-1-enyl)phenyl]benzofuran-6-ol (5). Methods The liquid microdilution assay was used in the determination of the minimal inhibitory concentration (MIC) and the minimal microbicidal concentration (MMC), against seven bacterial and one fungal species. Results The MIC results indicated that ACB as well as compounds 4 and 5 were able to prevent the growth of all tested microbial species. All other compounds showed selective activities. The lowest MIC value of 64 μg/ml for the crude extract was recorded on Staphylococcus aureus ATCC 25922 and Escherichia coli ATCC 8739. The corresponding value of 32 μg/ml was recorded with compounds 4 and 5 on Pseudomonas aeruginosa PA01 and compound 5 on E. coli ATCC 8739, their inhibition effect on P. aeruginosa PA01 being more than that of chloramphenicol used as reference antibiotic. Conclusion The overall results of this study provided supportive data for the use of A. communis as well as some of its constituents for the treatment of infections associated with the studied microorganisms. PMID:21612612

Antibacterial activities of the methanol extracts, fractions and compounds from Fagara tessmannii.

PubMed

Tankeo, Simplice B; Damen, Francois; Awouafack, Maurice D; Mpetga, James; Tane, Pierre; Eloff, Jacobus N; Kuete, Victor

2015-07-01

Fagara tessmannii is a shrub of the African rainforests used to treat bacterial infections, cancers, swellings and inflammation. In the present study, the methanol extract from the leaves (FTL), bark (FTB), and roots (FTR) of this plant as well as fractions (FTR1-5) and compounds isolated from FTR namely β-sitosterol-3-O-β-d-glucopyranoside (1), nitidine chloride (2) and buesgenine (3), were tested for their antimicrobial activities against a panel of Gram-negative bacteria including multidrug resistant (MDR) phenotypes. The broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the above samples; Column chromatography was used for the fractionation and purification of the roots extract whilst the chemical structures of compounds were determined using spectroscopic techniques. Results of the MIC determinations indicated that the crude extracts from the roots as well as fraction FTRa4 were active on all the 26 tested bacterial strains. MIC values below 100µg/mL were obtained with roots, leaves and bark extract respectively against 30.8%, 15.4% and 11.5% tested bacteria. The lowest MIC value below of 8µg/mL was obtained with extract from the roots against Escherichia coli MC100 strain. The lowest MIC value of 4µg/mL was also obtained with compound 3 against E. coli AG102 and Klebsiella pneumoniae ATCC11296 CONCLUSIONS: The present study demonstrates that F. tessmannii is a potential source of antimicrobial drugs to fight against MDR bacteria. Benzophenanthrine alkaloids 2 and 3 are the main antibacterial consituents of the roots of the plant. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

MEASUREMENT OF ORGANIC COMPOUND EMISSIONS USING SMALL TEST CHAMBERS

EPA Science Inventory

Organic compounds emitted from a variety of indoor materials have been measured using small (166 L) environmental test chambers. The paper discusses: a) factors to be considered in small chamber testing; b) parameters to be controlled; c) the types of results obtained. The follow...

Screening for Antiviral Activities of Isolated Compounds from Essential Oils

PubMed Central

Astani, Akram; Reichling, Jürgen; Schnitzler, Paul

2011-01-01

Essential oil of star anise as well as phenylpropanoids and sesquiterpenes, for example, trans-anethole, eugenol, β-eudesmol, farnesol, β-caryophyllene and β-caryophyllene oxide, which are present in many essential oils, were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro. Antiviral activity was analyzed by plaque reduction assays and mode of antiviral action was determined by addition of the drugs to uninfected cells, to the virus prior to infection or to herpesvirus-infected cells. Star anise oil reduced viral infectivity by >99%, phenylpropanoids inhibited HSV infectivity by about 60–80% and sesquiterpenes suppressed herpes virus infection by 40–98%. Both, star anise essential oil and all isolated compounds exhibited anti-HSV-1 activity by direct inactivation of free virus particles in viral suspension assays. All tested drugs interacted in a dose-dependent manner with herpesvirus particles, thereby inactivating viral infectivity. Star anise oil, rich in trans-anethole, revealed a high selectivity index of 160 against HSV, whereas among the isolated compounds only β-caryophyllene displayed a high selectivity index of 140. The presence of β-caryophyllene in many essential oils might contribute strongly to their antiviral ability. These results indicate that phenylpropanoids and sesquiterpenes present in essential oils contribute to their antiviral activity against HSV. PMID:20008902

Different phenolic compounds activate distinct human bitter taste receptors.

PubMed

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

2013-02-20

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

Iron-targeting antitumor activity of gallium compounds and novel insights into triapine(®)-metal complexes.

PubMed

Chitambar, Christopher R; Antholine, William E

2013-03-10

Despite advances made in the treatment of cancer, a significant number of patients succumb to this disease every year. Hence, there is a great need to develop new anticancer agents. Emerging data show that malignant cells have a greater requirement for iron than normal cells do and that proteins involved in iron import, export, and storage may be altered in cancer cells. Therefore, strategies to perturb these iron-dependent steps in malignant cells hold promise for the treatment of cancer. Recent studies show that gallium compounds and metal-thiosemicarbazone complexes inhibit tumor cell growth by targeting iron homeostasis, including iron-dependent ribonucleotide reductase. Chemical similarities of gallium(III) with iron(III) enable the former to mimic the latter and interpose itself in critical iron-dependent steps in cellular proliferation. Newer gallium compounds have emerged with additional mechanisms of action. In clinical trials, the first-generation-compound gallium nitrate has exhibited activity against bladder cancer and non-Hodgkin's lymphoma, while the thiosemicarbazone Triapine(®) has demonstrated activity against other tumors. Novel gallium compounds with greater cytotoxicity and a broader spectrum of antineoplastic activity than gallium nitrate should continue to be developed. The antineoplastic activity and toxicity of the existing novel gallium compounds and thiosemicarbazone-metal complexes should be tested in animal tumor models and advanced to Phase I and II clinical trials. Future research should identify biologic markers that predict tumor sensitivity to gallium compounds. This will help direct gallium-based therapy to cancer patients who are most likely to benefit from it.

Antileishmanial activities of dihydrochalcones from piper elongatum and synthetic related compounds. Structural requirements for activity.

PubMed

Hermoso, Alicia; Jiménez, Ignacio A; Mamani, Zulma A; Bazzocchi, Isabel L; Piñero, José E; Ravelo, Angel G; Valladares, Basilio

2003-09-01

Two dihydrochalcones (1 and 2) were isolated from Piper elongatum Vahl by activity-guided fractionation against extracellular promastigotes of Leishmania braziliensis in vitro. Their structures were elucidated by spectral analysis, including homonuclear and heteronuclear correlation NMR experiments. Derivatives 3-7 and 20 synthetic related compounds (8-27) were also assayed to establish the structural requirements for antileishmanial activity. Compounds 1-11 that proved to be more active that ketoconazol, used as positive control, were further assayed against promastigotes of Leishmania tropica and Leishmania infantum. Compounds 7 and 11, with a C(6)-C(3)-C(6) system, proved to be the most promising compounds, with IC(50) values of 2.98 and 3.65 microg/mL, respectively, and exhibited no toxic effect on macrophages (around 90% viability). Correlation between the molecular structures and antileishmanial activity is discussed in detail.

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

PubMed

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

2012-07-01

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

Activities of various compounds against murine and primate polyomaviruses.

PubMed Central

Andrei, G; Snoeck, R; Vandeputte, M; De Clercq, E

1997-01-01

Polyomavirus infections in humans are due to BK virus (BKV) and JC virus (JCV). Diseases associated with human polyomaviruses occur mostly in immunocompromised adults, e.g., progressive multifocal leukoencephalopathy (PML), caused by JCV, in AIDS patients and hemorrhagic cystitis and uretral stenosis, caused by BKV, in transplant recipients. No therapy is available for these diseases, which necessitates the development of chemical entities that are active against polyomaviruses. Several antiviral compounds were evaluated to determine their effects on the in vitro replication of mouse polyomavirus and the primate viruses simian virus 40 (SV40), SV40 PML-1, and SV40 PML-2. The activity of the different compounds was assessed by a cytopathic effect reduction assay and confirmed in a virus yield assay. Cidofovir [HPMPC; (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine] and its cyclic counterpart emerged as the most selective antipolyomavirus agents. The 50% inhibitory concentrations for HPMPC were in the range of 4 to 7 micrograms/ml, and its selectivity index varied from 11 to 20 for mouse polyomavirus and from 23 to 33 for SV40 strains in confluent cell monolayers. Cell cytotoxicity was up to 15-fold greater in growing cells. Other acyclic nucleoside phosphonates (i.e., HPMPA; [(S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine] and PMEG [9-(2-phosphonylmethoxyethyl)-guanine]) also showed some activity but had low selectivity. None of the other drugs tested against these animal viruses (i.e., acyclovir, ganciclovir, brivudine, ribavirin, foscarnet, and cytarabine) showed significant activity. Thus, HPMPC deserves further evaluation as a candidate drug for polyomavirus infections in the immunocompromised host. PMID:9055998

An In Ovo Model for Testing Insulin-mimetic Compounds.

PubMed

Haselgrübler, Renate; Stübl, Flora; Stadlbauer, Verena; Lanzerstorfer, Peter; Weghuber, Julian

2018-04-23

Elevated blood glucose levels in type 2 diabetes mellitus (T2DM), a complex and multifactorial metabolic disease, are caused by insulin resistance and β-cell failure. Various strategies, including the injection of insulin or the usage of insulin-sensitizing drugs, were pursued to treat T2DM or at least reduce the symptoms. In addition, the application of herbal compounds has attracted increasing attention. Thus, it is necessary to find efficient test systems to identify and characterize insulin-mimetic compounds. Here we developed a modified chick embryo model, which enables testing of synthetic compounds and herbal extracts with insulin-mimetic properties. Using a fluorescence microscopy-based primary screen, which quantifies the translocation of Glucose transporter 4 (Glut4) to the plasma membrane, we were able to identify compounds, mainly herbal extracts, which lead to an increase of intracellular glucose concentrations in adipocytes. However, the efficacy of these substances requires further verification in a living organism. Thus, we used an in-ovo approach to identify their blood glucose-reducing properties. The approval by an ethics committee is not needed since the use of chicken embryos during the first two-thirds of embryonic development is not considered an animal experiment. Here, the application of this model is described in detail.

Biodegradation tests of mercaptocarboxylic acids, their esters, related divalent sulfur compounds and mercaptans.

PubMed

Rücker, Christoph; Mahmoud, Waleed M M; Schwartz, Dirk; Kümmerer, Klaus

2018-04-17

Mercaptocarboxylic acids and their esters, a class of difunctional compounds bearing both a mercapto and a carboxylic acid or ester functional group, are industrial chemicals of potential environmental concern. Biodegradation of such compounds was systematically investigated here, both by literature search and by experiments (Closed Bottle Test OECD 301D and Manometric Respirometry Test OECD 301F). These compounds were found either readily biodegradable or at least biodegradable to a significant extent. Some related compounds of divalent sulfur were tested for comparison (mercaptans, sulfides, disulfides). For the two relevant monofunctional compound classes, carboxylic acids/esters and mercaptans, literature data were compiled, and by comparison with structurally similar compounds without these functional groups, the influence of COOH/COOR' and SH groups on biodegradability was evaluated. Thereby, an existing rule of thumb for biodegradation of carboxylic acids/esters was supported by experimental data, and a rule of thumb could be formulated for mercaptans. Concurrent to biodegradation, abiotic processes were observed in the experiments, rapid oxidative formation of disulfides (dimerisation of monomercaptans and cyclisation of dimercaptans) and hydrolysis of esters. Some problems that compromise the reproducibility of biodegradation test results were discussed.

Isolation, identification and antioxidant activity of bound phenolic compounds present in rice bran.

PubMed

Wang, Wei; Guo, Jia; Zhang, Junnan; Peng, Jie; Liu, Tianxing; Xin, Zhihong

2015-03-15

The bound phenolic compounds in rice bran were released and extracted with ethyl acetate based on alkaline digestion. An investigation of the chemical constituents of EtOAc extract has led to the isolation of a new compound, para-hydroxy methyl benzoate glucoside (8), together with nine known compounds, cycloeucalenol cis-ferulate (1), cycloeucalenol trans-ferulate (2), trans-ferulic acid (3), trans-ferulic acid methyl ester (4), cis-ferulic acid (5), cis-ferulic acid methyl ester (6), methyl caffeate (7), vanillic aldehyde (9) and para-hydroxy benzaldehyde (10). The structures of these compounds were determined using a combination of spectroscopic methods and chemical analysis. Among the compounds isolated, compound 3, 5 and 7 exhibited strong DPPH and ABTS(+) radical scavenging activities, followed by compounds 4 and 6. Compound 1 and 2 showed potent DPPH and ABTS(+) radical scavenging activities, compound 8 displayed moderate antioxidant activity against ABTS(+) radical, whereas compound 9 and 10 showed weak antioxidant activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Taste-active compounds in a traditional Italian food: 'lampascioni'.

PubMed

Borgonovo, Gigliola; Caimi, Sara; Morini, Gabriella; Scaglioni, Leonardo; Bassoli, Angela

2008-06-01

Nature is a rich source of taste-active compounds, in particular of plant origin, many of which have unusual tastes. Many of these are found in traditional food, where spontaneous plants are used as ingredients. Some taste-active compounds were identified in the bulbs of Muscari comosum, a spontaneous plant belonging to the family of the Liliaceae, very common in the Mediterranean area, and used in traditional gastronomy (called 'lampascioni' in South Italy). The bulbs were extracted with a series of solvents of different polarity. The different fractions were submitted to a preliminary sensory evaluation, and the most interesting ones, characterized by a strong bitter taste and some chemestetic properties, were submitted to further purification and structural analysis. From the ethereal extract, several 3-benzyl-4-chromanones and one stilbene derivative were isolated. Pure compounds were examined for their taste activity by means of sensory evaluation, and proved to be responsible for the characteristic taste of this food. Some of these compounds have been synthesized de novo to confirm their structure.

Merging the Structural Motifs of Functionalized Amino Acids and α-Aminoamides: Compounds with Significant Anticonvulsant Activities

PubMed Central

Salomé, Christophe; Salomé-Grosjean, Elise; Stables, James P.; Kohn, Harold

2010-01-01

Functional amino acids (FAAs) and α-aminoamides (AAAs) are two classes of antiepileptic drugs (AEDs) that exhibit pronounced anticonvulsant activities. We combined key structural pharmacophores present in FAAs and AAAs to generate a new series of compounds and document that select compounds exhibit activity superior to either the prototypical FAA (lacosamide) or the prototypical AAA (safinamide) in the maximal electroshock (MES) seizure model in rats. A representative compound, (R)-N-4′-((3″-fluoro)benzyloxy)benzyl 2-acetamido-3-methoxypropionamide ((R)-10), was tested in the MES (mice, ip), MES (rat, po), psychomotor 6 Hz (32 mA) (mice, ip), and hippocampal kindled (rat, ip) seizure tests providing excellent protection with ED50 values of 13, 14, ~10 mg/kg, and 12 mg/kg, respectively. In the rat sciatic nerve ligation model (ip), (R)-10 (12 mg/kg) provided an 11.2-fold attenuation of mechanical allodynia. In the mouse biphasic formalin pain model (ip), (R)-10 (15 mg/kg) reduced pain responses in the acute and the chronic inflammatory phases. PMID:20394379

Merging the structural motifs of functionalized amino acids and alpha-aminoamides: compounds with significant anticonvulsant activities.

PubMed

Salomé, Christophe; Salomé-Grosjean, Elise; Stables, James P; Kohn, Harold

2010-05-13

Functional amino acids (FAAs) and alpha-aminoamides (AAAs) are two classes of antiepileptic drugs (AEDs) that exhibit pronounced anticonvulsant activities. We combined key structural pharmacophores present in FAAs and AAAs to generate a new series of compounds and document that select compounds exhibit activity superior to either the prototypical FAA (lacosamide) or the prototypical AAA (safinamide) in the maximal electroshock (MES) seizure model in rats. A representative compound, (R)-N-4'-((3''-fluoro)benzyloxy)benzyl 2-acetamido-3-methoxypropionamide ((R)-10), was tested in the MES (mice, ip), MES (rat, po), psychomotor 6 Hz (32 mA) (mice, ip), and hippocampal kindled (rat, ip) seizure tests providing excellent protection with ED(50) values of 13, 14, approximately 10 mg/kg, and 12 mg/kg, respectively. In the rat sciatic nerve ligation model (ip), (R)-10 (12 mg/kg) provided an 11.2-fold attenuation of mechanical allodynia. In the mouse biphasic formalin pain model (ip), (R)-10 (15 mg/kg) reduced pain responses in the acute and the chronic inflammatory phases.

In vitro and in vivo antiplasmodial activity of three Rwandan medicinal plants and identification of their active compounds.

PubMed

Muganga, Raymond; Angenot, Luc; Tits, Monique; Frédérich, Michel

2014-04-01

In our previous study, we reported the interesting in vitro antiplasmodial activity of some Rwandan plant extracts. This gave rise to the need for these extracts to also be evaluated in vivo and to identify the compounds responsible for their antiplasmodial activity. The aim of our study was, on the one hand, to evaluate the antiplasmodial activity in vivo and the safety of the selected Rwandan medicinal plants used in the treatment of malaria, with the objective of promoting the development of improved traditional medicines and, on the other hand, to identify the active ingredients in the plants. Plant extracts were selected according to their selectivity index. The in vivo antiplasmodial activity of aqueous, methanolic, and dichloromethane extracts was then evaluated using the classical 4-day suppressive test on Plasmodium berghei infected mice. The activity of the plant extracts was estimated by measuring the percentage of parasitemia reduction, and the survival of the experimental animals was recorded. A bioguided fractionation was performed for the most promising plants, in terms of antiplasmodial activity, in order to isolate active compounds identified by means of spectroscopic and spectrometric methods. The highest level of antiplasmodial activity was observed with the methanolic extract of Fuerstia africana (> 70 %) on days 4 and 7 post-treatment after intraperitoneal injection and on day 7 using oral administration. After oral administration, the level of parasitemia reduction observed on day 4 post-infection was 44 % and 37 % with the aqueous extract of Terminalia mollis and Zanthoxylum chalybeum, respectively. However, the Z. chalybeum extract presented a high level of toxicity after intraperitoneal injection, with no animals surviving on day 1 post-treatment. F. africana, on the other hand, was safer with 40 % mouse survival on day 20 post-treatment. Ferruginol is already known as the active ingredient in F. Africana, and ellagic acid (IC50�

Glucosidase inhibitory activity and antioxidant activity of flavonoid compound and triterpenoid compound from Agrimonia Pilosa Ledeb

PubMed Central

2014-01-01

Background In Chinese traditional medicine, Agrimonia pilosa Ledeb (APL) exhibits great effect on treatment of type 2 diabetes mellitus (T2DM), however its mechanism is still unknown. Considering that T2DM are correlated with postprandial hyperglycemia and oxidative stress, we investigated the α-glucosidase inhibitory activity and the antioxidant activity of flavonoid compound (FC) and triterpenoid compound (TC) from APL. Methods Entire plants of APL were extracted using 95% ethanol and 50% ethanol successively. The resulting extracts were partitioned and isolated by applying liquid chromatography using silica gel column and Sephadex LH 20 column to give FC and TC. The content of total flavonoids in FC and the content of total triterpenoids in TC were determined by using UV spectrophotometry. HPLC analysis was used to identify and quantify the monomeric compound in FC and TC. The α-glucosidase inhibitory activities were determined using the chromogenic method with p-nitrophenyl-α-D-glucopyranoside as substrate. Antioxidant activities were assessed through three kinds of radical scavenging assays (DPPH radical, ABTS radical and hydroxyl radical) & β-carotene-linoleic acid assay. Results The results indicate FC is abundant of quercitrin, and hyperoside, and TC is abundant of 1β, 2β, 3β, 19α-tetrahydroxy-12-en-28-oic acid (265.2 mg/g) and corosolic acid (100.9 mg/g). The FC & the TC have strong α-glucosidase inhibitory activities with IC50 of 8.72 μg/mL and 3.67 μg/mL, respectively. We find that FC show competitive inhibition against α-glucosidase, while the TC exhibits noncompetitive inhibition. Furthermore, The FC exhibits significant radical scavenging activity with the EC50 values of 7.73 μg/mL, 3.64 μg/mL and 5.90 μg/mL on DPPH radical, hydroxyl radical and ABTS radical, respectively. The FC also shows moderate anti-lipid peroxidation activity with the IC50 values of 41.77 μg/mL on inhibiting β-carotene bleaching. Conclusion These results

Glucosidase inhibitory activity and antioxidant activity of flavonoid compound and triterpenoid compound from Agrimonia Pilosa Ledeb.

PubMed

Liu, Xi; Zhu, Liancai; Tan, Jun; Zhou, Xuemei; Xiao, Ling; Yang, Xian; Wang, Bochu

2014-01-10

In Chinese traditional medicine, Agrimonia pilosa Ledeb (APL) exhibits great effect on treatment of type 2 diabetes mellitus (T2DM), however its mechanism is still unknown. Considering that T2DM are correlated with postprandial hyperglycemia and oxidative stress, we investigated the α-glucosidase inhibitory activity and the antioxidant activity of flavonoid compound (FC) and triterpenoid compound (TC) from APL. Entire plants of APL were extracted using 95% ethanol and 50% ethanol successively. The resulting extracts were partitioned and isolated by applying liquid chromatography using silica gel column and Sephadex LH 20 column to give FC and TC. The content of total flavonoids in FC and the content of total triterpenoids in TC were determined by using UV spectrophotometry. HPLC analysis was used to identify and quantify the monomeric compound in FC and TC. The α-glucosidase inhibitory activities were determined using the chromogenic method with p-nitrophenyl-α-D-glucopyranoside as substrate. Antioxidant activities were assessed through three kinds of radical scavenging assays (DPPH radical, ABTS radical and hydroxyl radical) & β-carotene-linoleic acid assay. The results indicate FC is abundant of quercitrin, and hyperoside, and TC is abundant of 1β, 2β, 3β, 19α-tetrahydroxy-12-en-28-oic acid (265.2 mg/g) and corosolic acid (100.9 mg/g). The FC & the TC have strong α-glucosidase inhibitory activities with IC50 of 8.72 μg/mL and 3.67 μg/mL, respectively. We find that FC show competitive inhibition against α-glucosidase, while the TC exhibits noncompetitive inhibition. Furthermore, The FC exhibits significant radical scavenging activity with the EC50 values of 7.73 μg/mL, 3.64 μg/mL and 5.90 μg/mL on DPPH radical, hydroxyl radical and ABTS radical, respectively. The FC also shows moderate anti-lipid peroxidation activity with the IC50 values of 41.77 μg/mL on inhibiting β-carotene bleaching. These results imply that the FC and the TC could be

Synthesis, characterization, X-ray crystal structures of heterocyclic Schiff base compounds and in vitro cholinesterase inhibition and anticancer activity

NASA Astrophysics Data System (ADS)

Arafath, Md. Azharul; Adam, Farook; Al-Suede, Fouad Saleih R.; Razali, Mohd R.; Ahamed, Mohamed B. Khadeer; Abdul Majid, Amin Malik Shah; Hassan, Mohd Zaheen; Osman, Hasnah; Abubakar, Saifullah

2017-12-01

Four heterocyclic embedded Schiff base derivatives (1-4) were synthesized and characterized by melting point, elemental analysis, FTIR, 1H, 13C NMR, UV-Visible spectral data. The structures of compounds 1, 2 and 4 were successfully established through single crystal X-ray diffraction analysis. In vitro cholinesterase inhibition assays showed that the cyclized derivative 1 displayed higher BuChE enzyme inhibitory activity with IC50 value of 1.45 ± 0.09 μM. The anti-proliferative efficacies of the compounds were also evaluated using human colorectal HCT 116 and breast MCF-7 adenocarcinoma cell lines. In addition, a human normal endothelial cell line (Ea.hy926) was also tested to assess the safety and selectivity of the compounds towards normal and cancer cells, respectively. Among the compounds tested, compound 2 displayed potent cytotoxic effect (IC50 = 34 μM) against HCT 116 cells with highest selectivity index of 3.1 with respect to the normal endothelial cells. Whereas, compound 4 exhibited significant anti-proliferative effect (IC50 = 21.1 μM) against MCF-7 cells with highest selectivity index of 3.3 with respect to the normal endothelial cells. The docking result of these compounds against hAChE showed potent activities with different binding modes. These compounds could be a promising pharmacological agent to treat cancer and Alzheimer's disease.

Testing of Experimental Compounds for Efficacy Against Leishmania

DTIC Science & Technology

1986-02-01

pentamidine, formycin A, formycin B, amphotericin B, ketaconazole, 6- mercaptopurine riboside, adenosine, nalidixic acid, novobiocin, aphidicolin, 4-mercapto-lH... products of WR06026 as they can be identified and synthesized by officials at WRtAIR. 4. Perform secondary testing of especially promising compounds in

Iron-Targeting Antitumor Activity of Gallium Compounds and Novel Insights Into Triapine®-Metal Complexes

PubMed Central

Antholine, William E.

2013-01-01

Abstract Significance: Despite advances made in the treatment of cancer, a significant number of patients succumb to this disease every year. Hence, there is a great need to develop new anticancer agents. Recent Advances: Emerging data show that malignant cells have a greater requirement for iron than normal cells do and that proteins involved in iron import, export, and storage may be altered in cancer cells. Therefore, strategies to perturb these iron-dependent steps in malignant cells hold promise for the treatment of cancer. Recent studies show that gallium compounds and metal-thiosemicarbazone complexes inhibit tumor cell growth by targeting iron homeostasis, including iron-dependent ribonucleotide reductase. Chemical similarities of gallium(III) with iron(III) enable the former to mimic the latter and interpose itself in critical iron-dependent steps in cellular proliferation. Newer gallium compounds have emerged with additional mechanisms of action. In clinical trials, the first-generation-compound gallium nitrate has exhibited activity against bladder cancer and non-Hodgkin's lymphoma, while the thiosemicarbazone Triapine® has demonstrated activity against other tumors. Critical Issues: Novel gallium compounds with greater cytotoxicity and a broader spectrum of antineoplastic activity than gallium nitrate should continue to be developed. Future Directions: The antineoplastic activity and toxicity of the existing novel gallium compounds and thiosemicarbazone-metal complexes should be tested in animal tumor models and advanced to Phase I and II clinical trials. Future research should identify biologic markers that predict tumor sensitivity to gallium compounds. This will help direct gallium-based therapy to cancer patients who are most likely to benefit from it. Antioxid. Redox Signal. 00, 000–000. PMID:22900955

Gastroprotective effects and antimicrobial activity of Lithraea molleoides and isolated compounds against Helicobacter pylori.

PubMed

Garro, María Filomena; Salinas Ibáñez, Angel Gabriel; Vega, Alba Edith; Arismendi Sosa, Andrea Celeste; Pelzer, Lilian; Saad, José Roberto; Maria, Alejandra Olivia

2015-12-24

Lithraea molleoides (Vell.) Engl. (Anacardiaceae) is a medicinal plant traditionally used in South America to treat various ailments, including diseases of the digestive system. To evaluate the in vivo antiulcer and antimicrobial activities against Helicobacter pylori of L. molleoides and its isolated compounds. Methanolic extract 250 and 500 mg/kg, (LmE 250 and LmE 500, respectively) and infusions, 10 g and 20 g en 100mL (LmI 10 and LmI 20, respectively) of L. molleoides was evaluated for antiulcer activity against 0.6N HCl, 0.2N NaOH, 200mg/kg acetilsalicilic acid and absolute ethanol-induced gastric ulcers in rats. The degree of erosion in the glandular part of the stomach was assessed from a scoring system. Acute toxicity in mice was also evaluated. The antiulcer effect of the isolated compounds (catechol, mannitol, rutin, gallic acid, ferulic acid and caffeic acid, 100mg/kg) was evaluated against absolute ethanol-induced gastric ulcers in rats. The anti-Helicobacter pylori activity of L. molleoides and isolated compounds was performed using broth dilution methods. The LmE 250, LmE 500, LmI 10 and LmI 20 produced significant inhibition on the ulcer index in 0.6N HCl, 0.2N NaOH, 200mg/kg acetilsalicilic acid and absolute ethanol- induced gastric ulcers in rats. The isolated compounds, catechol, mannitol, rutin, ferulic acid and caffeic acid were active in absolute ethanol- induced gastric ulcers in rats. L. molleoides and different compounds showed antimicrobial activity in all strains tested. The lowest MIC value (0. 5 μg/mL) was obtained with catechol in six of eleven strains assayed. No signs of toxicity were observed with doses up to 2g/kg in an acute toxicity assay. These findings indicate that L. molleoides displays potential antiulcerogenic and antimicrobial activities and the identification of active principles could support the use of this plant for the treatment of digestive affections. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Antialgal and antilarval activities of bioactive compounds extracted from the marine dinoflagellate Amphidinium carterae

NASA Astrophysics Data System (ADS)

Kong, Xianyu; Han, Xiurong; Gao, Min; Su, Rongguo; Wang, Ke; Li, Xuzhao; Lu, Wei

2016-12-01

With the global ban on the application of organotin-based marine coatings by the International Maritime Organization, the development of environmentally friendly, low-toxic and nontoxic antifouling compounds for marine industries has become an urgent need. Marine microorganisms have been considered as a potential source of natural antifoulants. In this study, the antifouling potential of marine dinoflagellate Amphidinium carterae, the toxic and red-tide microalgae, was investigated. We performed a series of operations to extract the bioactive substances from Amphidinium carterae and tested their antialgal and antilarval activities. The crude extract of Amphidinium carterae showed significant antialgal activity and the EC50 value against Skeletonema costatum was 55.4 μg mL-1. After purification, the isolated bioactive substances (the organic extract C) exhibited much higher antialgal and antilarval activities with EC50 of 12.9 μg mL-1 against Skeletonema costatum and LC50 of 15.1 μg mL-1 against Amphibalanus amphitrite larvae. Subsequently, IR, Q-TOFMS, and GC-MS were utilized for the structural elucidation of the bioactive compounds, and a series of unsaturated and saturated 16- to 22-carbon fatty acids were detected. The data suggested the bioactive compounds isolated from Amphidinium carterae exhibited a significant inhibiting effect against the diatom Skeletonema costatum and Amphibalanus amphitrite larvae, and could be substitutes for persistent, toxic antifouling compounds.

Chick Heart Invasion Assay for Testing the Invasiveness of Cancer Cells and the Activity of Potentially Anti-invasive Compounds.

PubMed

Bracke, Marc E; Roman, Bart I; Stevens, Christian V; Mus, Liselot M; Parmar, Virinder S; De Wever, Olivier; Mareel, Marc M

2015-06-06

The goal of the chick heart assay is to offer a relevant organ culture method to study tumor invasion in three dimensions. The assay can distinguish between invasive and non-invasive cells, and enables study of the effects of test compounds on tumor invasion. Cancer cells - either as aggregates or single cells - are confronted with fragments of embryonic chick heart. After organ culture in suspension for a few days or weeks the confronting cultures are fixed and embedded in paraffin for histological analysis. The three-dimensional interaction between the cancer cells and the normal tissue is then reconstructed from serial sections stained with hematoxylin-eosin or after immunohistochemical staining for epitopes in the heart tissue or the confronting cancer cells. The assay is consistent with the recent concept that cancer invasion is the result of molecular interactions between the cancer cells and their neighbouring stromal host elements (myofibroblasts, endothelial cells, extracellular matrix components, etc.). Here, this stromal environment is offered to the cancer cells as a living tissue fragment. Supporting aspects to the relevance of the assay are multiple. Invasion in the assay is in accordance with the criteria of cancer invasion: progressive occupation and replacement in time and space of the host tissue, and invasiveness and non-invasiveness in vivo of the confronting cells generally correlates with the outcome of the assay. Furthermore, the invasion pattern of cells in vivo, as defined by pathologists, is reflected in the histological images in the assay. Quantitative structure-activity relation (QSAR) analysis of the results obtained with numerous potentially anti-invasive organic congener compounds allowed the study of structure-activity relations for flavonoids and chalcones, and known anti-metastatic drugs used in the clinic (e.g., microtubule inhibitors) inhibit invasion in the assay as well. However, the assay does not take into account

Alkaline phosphatase activity-guided isolation of active compounds and new dammarane-type triterpenes from Cissus quadrangularis hexane extract.

PubMed

Pathomwichaiwat, Thanika; Ochareon, Pannee; Soonthornchareonnon, Noppamas; Ali, Zulfiqar; Khan, Ikhlas A; Prathanturarug, Sompop

2015-02-03

The stem of Cissus quadrangularis L. (CQ) is used in traditional medicine to treat bone fractures and swelling. Anti-osteoporotic activity of CQ hexane extract has been reported, but the active compounds in this extract remain unknown. Thus, we aimed to identify the active compounds in CQ hexane extract using bioassay-guided isolation. The CQ hexane extract was fractionated sequentially with benzene, dichloromethane, ethyl acetate, and methanol. The examination of CQ extract and its fractions was guided by bioassays for alkaline phosphatase (ALP) activity during the differentiation of MC3T3-E1 osteoblastic cells. The cells were treated with or without the CQ extract and its fractions for a period of time, and then the stimulatory effect of the alkaline phosphatase enzyme, a bone differentiation marker, was investigated. The compounds obtained were structurally elucidated using spectroscopic techniques and re-evaluated for activity during bone differentiation. A total of 29 compounds were isolated, viz., triterpenes, fatty acid methyl esters, glycerolipids, steroids, phytols, and cerebrosides. Four new dammarane-type triterpenes were isolated for the first time from nature, and this report is the first to identify this group of compounds from the Vitaceae family. Seven compounds, viz., glycerolipids and squalene, stimulated ALP activity at a dose of 10μg/mL. Moreover, the synergistic effect of these compounds on bone formation was demonstrated. This report describes, for the first time, the isolation of active compounds from CQ hexane extract; these active compounds will be useful for the quality control of extracts from this plant used to treat osteoporosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Determination of the In Vitro and In Vivo Activity of Compounds Tested Against Punta Toro Virus.

DTIC Science & Technology

1987-12-29

were performed on 295 AVS compounds in LLC-MK2 cells with inhibition of viral cytopathic effect (CPE) as initial endpoint and reduction of virus...ineffective doses of ribavirin were highly active against the infection. 11. Publications and Presentations: One manuscript describing work performed on...USERS unclassifie 22a N4AME QP RESPONSIBE INDIIDUAL 22b. TELEPHONE WInd Area Code) 22. OFFICE SYMBOL WF ir ginia M. Miller- - DD FORM 1473,s4Mat 83

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.

Molding compound trends in a denser packaging world: Qualification tests and reliability concerns

NASA Astrophysics Data System (ADS)

Nguyen, L. T.; Lo, R. H. Y.; Chen, A. S.; Belani, J. G.

1993-12-01

Molding compound development has traditionally been driven by the memory market, then subsequent applications filter down to other IC technologies such as logic, analog, and ASIC. However, this strategy has changed lately with the introduction of thin packages such as PQFP & TSOP. Rather than targeting a compound for a family of IC such as DRAM or SRAM, compound development efforts are now focused at specific classes of packages. The configurations of these thin packages impose new functional requirements that need to be revisited to provide the optimized combination of properties. The evolution of qualification tests mirrors the advances in epoxy and compounding technologies. From the first standard novolac-based epoxies of the 1970s to the latest 3(sup rd)-generation ultra-low stress materials, longer test times at increasingly harsher environments were achieved. This paper benchmarks the current reliability tests used by the electronic industry, examines those tests that affect and are affected by the molding compounds, discusses the relevance of accelerated testing, and addresses the major reliability issues facing current molding compound development efforts. Six compound-related reliability concerns were selected: moldability, package stresses, package cracking, halogen-induced intermetallic growth at bond pads, moisture-induced corrosion, and interfacial delamination. Causes of each failure type are surveyed and remedies are recommended. Accelerated tests are designed to apply to a limited quantity of devices, bias, or environmental conditions larger than usual ratings, to intensify failure mechanisms that would occur under normal operating conditions. The observed behavior is then extrapolated from the lot to the entire population. Emphasis is on compressing the time necessary to obtain reliability data. This approach has two main drawbacks. With increasingly complex devices, even accelerated tests are expensive. And with new technologies, it becomes

Concentration evolution of pharmaceutically active compounds in raw urban and industrial wastewater.

PubMed

Camacho-Muñoz, Dolores; Martín, Julia; Santos, Juan Luis; Aparicio, Irene; Alonso, Esteban

2014-09-01

The distribution of pharmaceutically active compounds in the environment has been reported in several works in which wastewater treatment plants have been identified as the main source of these compounds to the environment. The concentrations of these compounds in influent wastewater can vary widely not only during the day but also along the year, because of the seasonal-consumption patterns of some pharmaceuticals. However, only few studies have attempted to assess the hourly variability of the concentrations of pharmaceutically active compounds in wastewater. In this work, the distribution and seasonal and hourly variability of twenty-one pharmaceuticals, belonging to seven therapeutic groups, have been investigated in urban and industrial wastewater. The highest concentrations of pharmaceutically active compounds, except salicylic acid, were found in urban wastewater, especially in the case of anti-inflammatory drugs and caffeine. The highest concentrations of salicylic acid were measured in industrial wastewater, reaching concentration levels up to 3295μgL(-)(1). The studied pharmaceutically active compounds showed different distribution patterns during winter and summer periods. Temporal variability of pharmaceutically active compounds during a 24-h period showed a distribution in concordance with their consumption and excretion patterns, in the case of urban wastewater, and with the schedule of industrial activities, in the case of industrial wastewater. Copyright © 2014 Elsevier Ltd. All rights reserved.

Phenolic Profiles and Contribution of Individual Compounds to Antioxidant Activity of Apple Powders.

PubMed

Raudone, Lina; Raudonis, Raimondas; Liaudanskas, Mindaugas; Viskelis, Jonas; Pukalskas, Audrius; Janulis, Valdimaras

2016-05-01

Apples (Malus domestica L.) are the most common source of phenolic compounds in northern European diet. Besides pectins, dietary fibers, vitamins, and oligosaccharides they contain phenolic compounds of different classes. Apple powders are convenient functional forms retaining significant amounts of phenolic antioxidants. In this study reducing and radical scavenging profiles of freeze-dried powders of "Aldas,ˮ "Auksis,ˮ "Connel Red,ˮ "Ligol,ˮ "Lodel,ˮ and "Rajkaˮ were determined and phenolic constituents were identified using ultra high-performance liquid chromatography coupled to quadrupole and time-of-flight mass spectrometers. A negative ionization mode was applied and seventeen compounds: phenolic acids (coumaroylquinic, chlorogenic), flavonoids (quercetin derivatives), and procyanidin derivatives (B1, B2, and C1) were identified in all tested apple samples. Total values of Trolox equivalents varied from 7.72 ± 0.32 up to 20.02 ± 0.52 and from 11.10 ± 0.57 up to 21.42 ± 0.75 μmol/g of dry weight of apple powder in FRAP (ferric reducing antioxidant power) and ABTS (2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) postcolumn assays, respectively. The greatest Trolox equivalent values were determined for apples of "Aldasˮ cultivar. Chlorogenic acid and procyanidin C1 were the most significant contributors to total reducing and radical scavenging activity in all apple cultivars tested, therefore they could be considered as markers of antioxidant activity. © 2016 Institute of Food Technologists®

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.

Screening of analgesic activity of Tunisian Urtica dioica and analysis of its major bioactive compounds by GCMS.

PubMed

Dhouibi, Raouia; Moalla, Dorsaf; Ksouda, Kamilia; Ben Salem, Maryem; Hammami, Serria; Sahnoun, Zouheir; Zeghal, Khaled Mounir; Affes, Hanen

2017-11-20

The present study was aimed to evaluate the analgesic properties of Urtica dioica (UD) and to profile phytochemicals by gas chromatography-mass spectrometry (GC-MS). The ethanolic extracts were prepared by maceration method and extraction using rotary evaporator. The analgesic activity was analysed by hot plate method, formalin test, acetic acid-induced writhing test and the tail-flick test with different doses of the ethanolic extract. In all tests, the leaf's ethanolic extract exhibited significant analgesic activity (p < .001) at a dose of 400 mg/kg. Even with a low dose, we noticed an analgesic activity with many tests. The GC-MS analysis of the ethanol extract of leaf revealed many compounds; 2-methyltetradecane dodecane, 2,6,11-trimethyl-; 2,6,11-trimethyldodecane, and trimethylhexane which are pharmaceutically the most important. These findings justify that UD can be a valuable natural analgesic source which seemed to provide potential phototherapeutics against various ailments. The analysis of ethanolic extract of UD by GCMS revealed the presence of several compounds including polyphenols, flavonoids, triterpenes which can explain the analgesic effect of UD and its mechanism of action. Hence, UD could be another therapeutic alternative for relieving pain and for minimising the use of drugs that have long-term secondary effects.

Assessment of Antimicrobial and Antioxidant Activities of Nepeta trachonitica: Analysis of Its Phenolic Compounds Using HPLC-MS/MS

PubMed Central

Köksal, Ekrem; Tohma, Hatice; Kılıç, Ömer; Alan, Yusuf; Aras, Abdülmelik; Gülçin, İlhami; Bursal, Ercan

2017-01-01

Continuing our work on the sources of natural bioactive compounds, we evaluated the antimicrobial and antioxidant activities of Nepeta trachonitica as well as its major phenolic content using the high-performance liquid chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS) technique. For antioxidant activity, ferric reducing antioxidant power (FRAP) and cupric ion reducing antioxidant capacity (CUPRAC) methods were performed to measure the reducing power and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay was employed to evaluate the radical scavenging activity of the sample. For antimicrobial activity, three Gram-positive and four Gram-negative microbial species as well as three fungi species were tested. N. trachonitica appeared to have reasonable antioxidant activity and decent antimicrobial activity as indicated by the inhibition of the organisms’ growth. The most susceptible species were Bacillus subtilis ATCC 6633 and Escherichia coli ATCC 11229 among the organisms tested. Ethanol extract of the plant has the highest effect on Saccharomyces cerevisiae but no effect on Yarrowia lipolytica. The HPLC-MS/MS analysis showed that at least 11 major phenolic compounds of N. trachonitica exist, the major ones being rosmarinic acid, chlorogenic acid and quinic acid. The obtained results suggest that N. trachonitica could be a promising source for food and nutraceutical industries because of its antimicrobial and antioxidant properties and phenolic compounds. PMID:28505129

Phenolic compound concentration and antioxidant activities of edible and medicinal mushrooms from Korea.

PubMed

Kim, Min-Young; Seguin, Philippe; Ahn, Joung-Kuk; Kim, Jong-Jin; Chun, Se-Chul; Kim, Eun-Hye; Seo, Su-Hyun; Kang, Eun-Young; Kim, Sun-Lim; Park, Yool-Jin; Ro, Hee-Myong; Chung, Ill-Min

2008-08-27

A study was conducted to determine the content of phenolic compounds and the antioxidative activity of five edible and five medicinal mushrooms commonly cultivated in Korea. Phenolic compounds were analyzed using high performance liquid chromatography, and antioxidant activity was evaluated by 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and superoxide dismutase activity. A total of 28 phenolic compounds were detected in the mushrooms studied. The average total concentration of phenolic compounds was 326 microg/g, the average being of 174 microg/g in edible mushrooms and 477 microg/g in medicinal mushrooms. The average total flavonoids concentration was 49 microg/g, with averages of 22 and 76 microg/g in edible and medicinal mushrooms, respectively. The DPPH radical scavenging activities ranged between 15 (Pleurotus eryngii) and 70% (Ganoderma lucidum) when reaction time was for 1 min. When reaction time was 30 min, the values ranged between 5 (Pleurotus eryngii) and 78% (Agaricus bisporus). The SOD activity averaged 28% among the 10 mushroom species, averages for edible and medicinal mushrooms being comparable. DPPH activities was significantly correlated (p < 0.01) with total content of phenolic compounds in edible mushrooms, while in medicinal mushrooms there was a significant correlation (p < 0.01) between SOD activity and total concentration of phenolic compounds. Numerous significant positive correlations were observed between phenolic compounds detected and antioxidative potential.

Quantitative structure-activity relationship of the curcumin-related compounds using various regression methods

NASA Astrophysics Data System (ADS)

Khazaei, Ardeshir; Sarmasti, Negin; Seyf, Jaber Yousefi

2016-03-01

Quantitative structure activity relationship were used to study a series of curcumin-related compounds with inhibitory effect on prostate cancer PC-3 cells, pancreas cancer Panc-1 cells, and colon cancer HT-29 cells. Sphere exclusion method was used to split data set in two categories of train and test set. Multiple linear regression, principal component regression and partial least squares were used as the regression methods. In other hand, to investigate the effect of feature selection methods, stepwise, Genetic algorithm, and simulated annealing were used. In two cases (PC-3 cells and Panc-1 cells), the best models were generated by a combination of multiple linear regression and stepwise (PC-3 cells: r2 = 0.86, q2 = 0.82, pred_r2 = 0.93, and r2m (test) = 0.43, Panc-1 cells: r2 = 0.85, q2 = 0.80, pred_r2 = 0.71, and r2m (test) = 0.68). For the HT-29 cells, principal component regression with stepwise (r2 = 0.69, q2 = 0.62, pred_r2 = 0.54, and r2m (test) = 0.41) is the best method. The QSAR study reveals descriptors which have crucial role in the inhibitory property of curcumin-like compounds. 6ChainCount, T_C_C_1, and T_O_O_7 are the most important descriptors that have the greatest effect. With a specific end goal to design and optimization of novel efficient curcumin-related compounds it is useful to introduce heteroatoms such as nitrogen, oxygen, and sulfur atoms in the chemical structure (reduce the contribution of T_C_C_1 descriptor) and increase the contribution of 6ChainCount and T_O_O_7 descriptors. Models can be useful in the better design of some novel curcumin-related compounds that can be used in the treatment of prostate, pancreas, and colon cancers.

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

PubMed

Boulinguiez, B; Le Cloirec, P

2009-01-01

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

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

Heart testing compound

DOEpatents

Knapp, Jr., Furn F.; Goodman, Mark M.

1985-01-01

The compound 15-(p-[.sup.125 I]-iodophenyl)-6-tellurapentadecanoic acid is disclosed as a myocardial imaging agent having rapid and pronounced uptake, prolonged myocardial retention, and low in vivo deiodination.

Heart testing compound

DOEpatents

Knapp, F.F. Jr.; Goodman, M.M.

1983-06-29

The compound 15-(p-(/sup 125/I)-iodophenyl)-6-tellurapentadecanoic acid is disclosed as a myocardial imaging agent having rapid and pronounced uptake, prolonged myocardial retention, and low in vivo deiodination.

Redox-active compounds with a history of human use: antistaphylococcal action and potential for repurposing as topical antibiofilm agents.

PubMed

Ooi, N; Eady, E A; Cove, J H; O'Neill, A J

2015-02-01

To investigate the antistaphylococcal/antibiofilm activity and mode of action (MOA) of a panel of redox-active (RA) compounds with a history of human use and to provide a preliminary preclinical assessment of their potential for topical treatment of staphylococcal infections, including those involving a biofilm component. Antistaphylococcal activity was evaluated by broth microdilution and by time-kill studies with growing and slow- or non-growing cells. The antibiofilm activity of RA compounds, alone and in combination with established antibacterial agents, was assessed using the Calgary Biofilm Device. Established assays were used to examine the membrane-perturbing effects of RA compounds, to measure penetration into biofilms and physical disruption of biofilms and to assess resistance potential. A living skin equivalent model was used to assess the effects of RA compounds on human skin. All 15 RA compounds tested displayed antistaphylococcal activity against planktonic cultures (MIC 0.25-128 mg/L) and 7 eradicated staphylococcal biofilms (minimum biofilm eradication concentration 4-256 mg/L). The MOA of all compounds involved perturbation of the bacterial membrane, whilst selected compounds with antibiofilm activity caused destructuring of the biofilm matrix. The two most promising agents [celastrol and nordihydroguaiaretic acid (NDGA)] in respect of antibacterial potency and selective toxicity against bacterial membranes acted synergistically with gentamicin against biofilms, did not damage artificial skin following topical application and exhibited low resistance potential. In contrast to established antibacterial drugs, some RA compounds are capable of eradicating staphylococcal biofilms. Of these, celastrol and NDGA represent particularly attractive candidates for development as topical antistaphylococcal biofilm treatments. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Compounds from silicones alter enzyme activity in curing barnacle glue and model enzymes.

PubMed

Rittschof, Daniel; Orihuela, Beatriz; Harder, Tilmann; Stafslien, Shane; Chisholm, Bret; Dickinson, Gary H

2011-02-17

Attachment strength of fouling organisms on silicone coatings is low. We hypothesized that low attachment strength on silicones is, in part, due to the interaction of surface available components with natural glues. Components could alter curing of glues through bulk changes or specifically through altered enzyme activity. GC-MS analysis of silicone coatings showed surface-available siloxanes when the coatings were gently rubbed with a cotton swab for 15 seconds or given a 30 second rinse with methanol. Mixtures of compounds were found on 2 commercial and 8 model silicone coatings. The hypothesis that silicone components alter glue curing enzymes was tested with curing barnacle glue and with commercial enzymes. In our model, barnacle glue curing involves trypsin-like serine protease(s), which activate enzymes and structural proteins, and a transglutaminase which cross-links glue proteins. Transglutaminase activity was significantly altered upon exposure of curing glue from individual barnacles to silicone eluates. Activity of purified trypsin and, to a greater extent, transglutaminase was significantly altered by relevant concentrations of silicone polymer constituents. Surface-associated silicone compounds can disrupt glue curing and alter enzyme properties. Altered curing of natural glues has potential in fouling management.

Procaspase-activating compound 1 induces a caspase-3-dependent cell death in cerebellar granule neurons

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

Aziz, Gulzeb; Akselsen, Oyvind W.; Hansen, Trond V.

2010-09-15

Procaspase-activating compound 1, PAC-1, has been introduced as a direct activator of procaspase-3 and has been suggested as a therapeutic agent against cancer. Its activation of procaspase-3 is dependent on the chelation of zinc. We have tested PAC-1 and an analogue of PAC-1 as zinc chelators in vitro as well as their ability to activate caspase-3 and induce cell death in chicken cerebellar granule neuron cultures. These neurons are non-dividing, primary cells with normal caspase-3. The results reported herein show that PAC-1 chelates zinc, activates procaspase-3, and leads to caspase-3-dependent cell death in neurons, as the specific caspase-3-inhibitor Ac-DEVD-cmk inhibitedmore » both the caspase-3 activity and cell death. Thus, chicken cerebellar granule neurons is a suitable model to study mechanisms of interference with apoptosis of PAC-1 and similar compounds. Furthermore, the present study also raises concern about potential neurotoxicity of PAC-1 if used in cancer therapy.« less

Advances in the development of AMPK-activating compounds.

PubMed

Sriwijitkamol, Apiradee; Musi, Nicolas

2008-10-01

AMP-activated protein kinase (AMPK) is an energy sensing enzyme that controls glucose and lipid metabolism. This review summarizes the present data on AMPK as a pharmacologic target for the treatment of metabolic disorders. The mechanisms governing AMPK activity and how this enzyme controls different metabolic pathways are reviewed briefly, and details about the effect that AMPK activators have on glucose metabolism are provided. Evidence obtained using the AMPK-activating compound 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) suggests that AMPK promotes glucose transport into skeletal muscles and that this enzyme inhibits hepatic glucose production. AICAR also induces fatty acid oxidation in muscle and inhibits cholesterol synthesis in the liver. The metabolic effects of AICAR on glucose and lipid metabolism indicate that AMPK may be a good pharmacologic target for the treatment of type 2 diabetes and hypercholesterolemia. Novel AMPK-specific compounds are allowing researchers to examine whether this enzyme is a useful pharmacologic target for the treatment of human disease and whether chronic activation of AMPK will be safe.

Frequency Shift During Mass Properties Testing Using Compound Pendulum Method

NASA Technical Reports Server (NTRS)

Wolfe, David; Regan, Chris

2012-01-01

During mass properties testing on the X-48B Blended Wing Body aircraft (The Boeing Company, Chicago, Illinois) at the National Aeronautics and Space Administration Dryden Flight Research Center, Edwards, California, large inertia measurement errors were observed in results from compound pendulum swings when compared to analytical models. By comparing periods of oscillations as measured from an average over the test period versus the period of each oscillation, it was noticed that the frequency of oscillation was shifting significantly throughout the test. This phenomenon was only noticed during compound pendulum swings, and not during bifilar pendulum swings. The frequency shift was only visible upon extensive data analysis of the frequency for each oscillation, and did not appear in averaged frequency data over the test period. Multiple test articles, test techniques, and hardware setups were used in attempts to eliminate or identify the cause of the frequency shift. Plotting the frequency of oscillation revealed a region of minimal shift that corresponded to a larger amplitude range. This region of minimal shift provided the most accurate results compared to a known test article; however, the amplitudes that produce accurate inertia measurements are amplitudes larger than those generally accepted in mass properties testing. This paper examines two case studies of the frequency shift, using mass properties testing performed on a dummy test article, and on the X-48B Blended Wing Body aircraft.

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

PubMed

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

2016-10-01

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

Fabrication and Testing of High-Speed-Single-Rotor and Compound-Rotor Systems

DTIC Science & Technology

2016-05-04

pitch link loads, hub loads, rotor wakes and performance of high -speed single-rotor and compound-rotor systems to support 1. REPORT DATE (DD-MM-YYYY) 4...Public Release; Distribution Unlimited UU UU UU UU 05-04-2016 14-Jul-2014 13-Jan-2016 Final Report: Fabrication and Testing of High -Speed Single- Rotor and...Final Report: Fabrication and Testing of High -Speed Single-Rotor and Compound-Rotor Systems Report Title The Alfred Gessow Rotorcraft Center has

Fabrication and Testing of High-Speed Single-Rotor and Compound-Rotor Systems

DTIC Science & Technology

2016-04-05

pitch link loads, hub loads, rotor wakes and performance of high -speed single-rotor and compound-rotor systems to support 1. REPORT DATE (DD-MM-YYYY) 4...Public Release; Distribution Unlimited UU UU UU UU 05-04-2016 14-Jul-2014 13-Jan-2016 Final Report: Fabrication and Testing of High -Speed Single- Rotor and...Final Report: Fabrication and Testing of High -Speed Single-Rotor and Compound-Rotor Systems Report Title The Alfred Gessow Rotorcraft Center has

Evaluation of the antinociceptive activities of enaminone compounds on the formalin and hot plate tests in mice

NASA Astrophysics Data System (ADS)

Masocha, Willias; Kombian, Samuel B.; Edafiogho, Ivan O.

2016-02-01

Recently, we found that methyl 4-(4‧-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate (E139), an anticonvulsant enaminone, has antinociceptive activity in the hot plate test. In this study we evaluated the antinociceptive activity of five anilino enaminones E139, ethyl 4-(4‧-chlorophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E121), ethyl 4-(4‧-bromophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E122), methyl 4-(4‧-chlorophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E138) and ethyl 4-(4‧-fluorophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (BRG 19) using the formalin and hot plate tests. E139 has been reported to exert its effects via enhancement of extracellular GABA levels, thus tiagabine, a GABA transporter inhibitor, was evaluated as a control together with indomethacin. Tiagabine had antinociceptive activity in both phase 1 (neurogenic pain) and phase 2 (inflammatory pain) of the formalin test, whereas indomethacin had activity only in phase 2. E139 and E138 had antinociceptive activity in both phases of the formalin test, whereas E121 had activity only in phase 1 and BRG 19 had activity only in phase 2. E122 had no significant activity in either phase. In the hot plate test only E139 had antinociceptive activity. Administration of either bicuculline, a GABAA receptor antagonist, or CGP 35348, a GABAB receptor antagonist, blocked the antinociceptive activity of E139. In conclusion our results indicate that E139 has antinociceptive activity in the formalin and hot plate tests that are dependent on GABA receptors.

Cryptic antifungal compounds active by synergism with polyene antibiotics.

PubMed

Kinoshita, Hiroshi; Yoshioka, Mariko; Ihara, Fumio; Nihira, Takuya

2016-04-01

The majority of antifungal compounds reported so far target the cell wall or cell membrane of fungi, suggesting that other types of antibiotics cannot exert their activity because they cannot penetrate into the cells. Therefore, if the permeability of the cell membrane could be enhanced, many antibiotics might be found to have antifungal activity. We here used the polyene antibiotic nystatin, which binds to ergosterol and forms pores at the cell membrane, to enhance the cellular permeability. In the presence of nystatin, many culture extracts from entomopathogenic fungi displayed antifungal activity. Among all the active extracts, two active components were purified and identified as helvolic acid and terramide A. Because the minimum inhibitory concentration of either compound was reduced four-fold in the presence of nystatin, it can be concluded that this screening method is useful for detecting novel antifungal activity. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Laboratory considerations of United States Pharmacopeia Chapter <71> sterility tests and its application to pharmaceutical compounding.

PubMed

Hyde, Tiffany D

2014-01-01

The purpose of this article is to describe United States Pharmacopeia Chapter <71> Sterility Tests from the perspective of Current Good Manufacturing Practices in order to aid compounding pharmacists in understanding the details and complexities that are required. Compounding pharmacists face a unique challenge in the industry today, with their compounding practice and the U.S. Food and Drug Administration trying to impose Current Good Manufacturing Practices guidelines. Naturally, this becomes a challenge to contract testing laboratories as well, as they are caught between the testing for non-Current Good Manufacturing Practices compounding standards and Current Good Manufacturing Practices manufacturing. It is important that the compounding pharmacist and their partner testing laboratory work closely together to ensure appropriate requirements are being met.

Detailed study of precipitation of a poorly water soluble test compound using methodologies as in activity and solubility screening - mixing and automation effects.

PubMed

Gillespie, Cheska; Kennedy, Alan R; Edwards, Darren; Dowden, Lee; Daublain, Pierre; Halling, Peter

2013-09-01

Storage of pharmaceutical discovery compounds dissolved in dimethylsulfoxide (DMSO) is commonplace within industry. Often, the DMSO stock solution is added to an aqueous system (e.g. in bioassay or kinetic solubility testing)- since most test compounds are hydrophobic, precipitation could occur. Little is known about the factors affecting this precipitation process at the low (µM) concentrations used in screening analyses. Here, a poorly water soluble test compound (tolnaftate) was used to compare manual and automated pipetting, and explore the effect of mixing variables on precipitation. The amount of drug present in the supernatant after precipitation and centrifugation of the samples was quantified. An unusual result was obtained in three different laboratories: results of experiments performed initially were statistically significantly higher than those performed after a few days in the same lab. No significant differences were found between automated and manual pipetting, including in variability. Vortex mixing was found to give significantly lower supernatant amounts compared to milder mixing types. The mixing employed affects the particle growth of the precipitate. These findings are of relevance to discovery stage bioassay and kinetic solubility analyses.

Compounds from Sichuan and Melegueta peppers activate, covalently and non-covalently, TRPA1 and TRPV1 channels

PubMed Central

Riera, CE; Menozzi-Smarrito, C; Affolter, M; Michlig, S; Munari, C; Robert, F; Vogel, H; Simon, SA; le Coutre, J

2009-01-01

Background and purpose: Oily extracts of Sichuan and Melegueta peppers evoke pungent sensations mediated by different alkylamides [mainly hydroxy-α-sanshool (α-SOH)] and hydroxyarylalkanones (6-shogaol and 6-paradol). We assessed how transient receptor potential ankyrin 1 (TRPA1) and TRP vanilloid 1 (TRPV1), two chemosensory ion channels, participate in these pungent sensations. Experimental approach: The structure–activity relationships of these molecules on TRPA1 and TRPV1 was measured by testing natural and synthetic analogues using calcium and voltage imaging on dissociated dorsal root ganglia neurons and human embryonic kidney 293 cells expressing the wild-type channels or specific cysteine mutants using glutathione trapping as a model to probe TRPA1 activation. In addition, using Trpv1 knockout mice, the compounds' aversive responses were measured in a taste brief-access test. Key results: For TRPA1 activation, the cis C6 double bond in the polyenic chain of α-SOH was critical, whereas no structural specificity was required for activation of TRPV1. Both 6-shogaol and 6-paradol were found to activate TRPV1 and TRPA1 channels, whereas linalool, an abundant terpene in Sichuan pepper, activated TRPA1 but not TRPV1 channels. Alkylamides and 6-shogaol act on TRPA1 by covalent bonding whereas none of these compounds activated TRPV1 through such interactions. Finally, TRPV1 mutant mice retained sensitivity to 6-shogaol but were not responsive to α-SOH. Conclusions and implications: The pungent nature of components of Sichuan and Melegueta peppers was mediated via interactions with TRPA1 and TRPV1 channels and may explain the aversive properties of these compounds. PMID:19594761

[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.

Activating AMP-activated protein kinase by an α1 selective activator compound 13 attenuates dexamethasone-induced osteoblast cell death

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

Guo, Shiguang; Mao, Li; Ji, Feng, E-mail: huaiaifengjidr@163.com

Excessive glucocorticoid (GC) usage may lead to non-traumatic femoral head osteonecrosis. Dexamethasone (Dex) exerts cytotoxic effect to cultured osteoblasts. Here, we investigated the potential activity of Compound 13 (C13), a novel α1 selective AMP-activated protein kinase (AMPK) activator, against the process. Our data revealed that C13 pretreatment significantly attenuated Dex-induced apoptosis and necrosis in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. AMPK activation mediated C13′ cytoprotective effect in osteoblasts. The AMPK inhibitor Compound C, shRNA-mediated knockdown of AMPKα1, or dominant negative mutation of AMPKα1 (T172A) almost abolished C13-induced AMPK activation and its pro-survival effect in osteoblasts. On the othermore » hand, forced AMPK activation by adding AMPK activator A-769662 or exogenous expression a constitutively-active (ca) AMPKα1 (T172D) mimicked C13's actions and inhibited Dex-induced osteoblast cell death. Meanwhile, A-769662 or ca-AMPKα1 almost nullified C13's activity in osteoblast. Further studies showed that C13 activated AMPK-dependent nicotinamide adenine dinucleotide phosphate (NADPH) pathway to inhibit Dex-induced reactive oxygen species (ROS) production in MC3T3-E1 cells and primary murine osteoblasts. Such effects by C13 were almost reversed by Compound C or AMPKα1 depletion/mutation. Together, these results suggest that C13 alleviates Dex-induced osteoblast cell death via activating AMPK signaling pathway. - Highlights: • Compound 13 (C13) attenuates dexamethasone (Dex)-induced osteoblast cell death. • C13-induced cytoprotective effect against Dex in osteoblasts requires AMPK activation. • Forced AMPK activation protects osteoblasts from Dex, nullifying C13's activities. • C13 increases NADPH activity and inhibits Dex-induced oxidative stress in osteoblasts.« less

[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.

Abatement of chlorinated compounds in groundwater contaminated by HCH wastes using ISCO with alkali activated persulfate.

PubMed

Santos, A; Fernandez, J; Rodriguez, S; Dominguez, C M; Lominchar, M A; Lorenzo, D; Romero, A

2018-02-15

In this work, in situ chemical oxidation (ISCO) with alkali activated persulfate has been tested for the elimination of HCH isomers and other chlorinated compounds in groundwater from Sabiñanigo (Sardas landfill), which was contaminated by solid and liquid wastes illegally dumped in the area by a company producing lindane. Due to the site lithology and the type of pollutants found in groundwater (HCHs and chlorobenzenes) alkali (NaOH) activated persulfate (PS) was selected as oxidant. The influence of variables such as PS concentration (42-200mM) and NaOH:PS molar ratio (2:1 to 4:1) on chlorinated compound abatement has been studied and a kinetic model to predict the composition of all chlorinated organic compounds (COCs) in the aqueous phase with time was obtained. It was found that a fast initial hydrodechlorination reaction took place in which HCH isomers reacted to trichlorobenzenes (mainly 1,2,4 TCB) at pH≥12. Mono-, di-, tri and tetrachlorobenzenes remaining were oxidized without producing aromatic intermediates. At the condition tested a first order kinetic model for COCs and PS concentration was obtained. Zero order alkali concentration was obtained while pH was being kept at 12 for the whole reaction time. Copyright © 2017 Elsevier B.V. All rights reserved.

Antioxidant properties of ferulic acid and its related compounds.

PubMed

Kikuzaki, Hiroe; Hisamoto, Masashi; Hirose, Kanae; Akiyama, Kayo; Taniguchi, Hisaji

2002-03-27

Antioxidant activity of 24 ferulic acid related compounds together with 6 gallic acid related compounds was evaluated using several different physical systems as well as their radical scavenging activity. The radical scavenging activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) decreased in the order caffeic acid > sinapic acid > ferulic acid > ferulic acid esters > p-coumaric acid. In bulk methyl linoleate, test hydroxycinnamic acids and ferulic acid esters showed antioxidant activity in parallel with their radical scavenging activity. In an ethanol-buffer solution of linoleic acid, the activity of test compounds was not always associated with their radical scavenging activity. Ferulic acid was most effective among the tested phenolic acids. Esterification of ferulic acid resulted in increasing activity. The activity of alkyl ferulates was somewhat influenced by the chain length of alcohol moiety. When the inhibitory effects of alkyl ferulates against oxidation of liposome induced by AAPH were tested, hexyl, octyl, and 2-ethyl-1-hexyl ferulates were more active than the other alkyl ferulates. Furthermore, lauryl gallate is most effective among the tested alkyl gallates. These results indicated that not only the radical scavenging activity of antioxidants, but also their affinity with lipid substrates, might be important factors in their activity.

GC-MS analysis of bio-active compounds in methanolic extract of Lactuca runcinata DC

PubMed Central

Kanthal, Lakshmi Kanta; Dey, Akalanka; Satyavathi, K.; Bhojaraju, P.

2014-01-01

Background: The presence of phytochemical constitutes has been reported from species of the Compositae (Asteraceae). Hitherto no reports exist on the phytochemical components and biological activity of Lactuca runcinata DC. Objective: The present study was designed to determine the bioactive compounds in the whole plant methanol extract of Lactuca runcinata. Materials and Methods: Phytochemical screening of the entire herb of Lactuca runcinata DC revealed the presence of some bio-active components. Gas chromatography-mass spectrometry (GC-MS) analysis of the whole plant methanol extract of Lactuca runcinata was performed on a GC-MS equipment (Thermo Scientific Co.) Thermo GC-TRACE ultra ver.: 5.0, Thermo MS DSQ II. Results: The phytochemical tests showed the presence of alkaloids, cardiac glycosides, flavonoids, phenols, phlobatannin, reducing sugars, saponins, steroids, tannins, terpenoids, volatile oils, carbohydrates, and protein/amino acids in methanolic extract of L. runcinata. The GC-MS analysis has shown the presence of different phytochemical compounds in the methanolic extract of Lactuca runcinata. A total of 21 compounds were identified representing 84.49% of total methanolic extract composition. Conclusion: From the results, it is evident that Lactuca runcinata contains various phytocomponents and is recommended as a plant of phytopharmaceutical importance. PMID:24497744

Removal of pharmaceutically active compounds in nitrifying-denitrifying plants.

PubMed

Suárez, S; Ramil, M; Omil, F; Lema, J M

2005-01-01

The behaviour of nine pharmaceutically active compounds (PhACs) of different diagnostic groups is studied during a nitrifying-denitrifying process in an activated sludge system. The compounds selected cover a wide range of frequently used substances such as anti-epileptics (carbamazepine), tranquillisers (diazepam), anti-depressants (fluoxetine and citalopram), anti-inflammatories (ibuprofen, naproxen and diclofenac) and estrogens (estradiol and ethinylestradiol). The main objective of this research is to investigate the effect of acclimation of biomass on the removal rates of these compounds, either by maintaining a high sludge retention time or at long-term operation. The removal rates achieved for nitrogen and carbon in the experimental unit exceed 90% and were not affected by the addition of PhACs. Carbamazepine, diazepam and diclofenac were only removed to a small extent. On the other hand, higher removal rates have been observed for naproxen and ibuprofen (68% and 82%), respectively.

Caatinga plants: Natural and semi-synthetic compounds potentially active against Trichomonas vaginalis.

PubMed

Vieira, Patrícia de Brum; Silva, Nícolas Luiz Feijó; da Silva, Gloria Narjara Santos; Silva, Denise Brentan; Lopes, Norberto Peporine; Gnoatto, Simone Cristina Baggio; da Silva, Márcia Vanusa; Macedo, Alexandre José; Bastida, Jaume; Tasca, Tiana

2016-05-01

Trichomonas vaginalis causes trichomoniasis; the most common but overlooked non-viral sexually transmitted disease worldwide. The treatment is based at 5'-nitroimidazoles, however, failure are related to resistance of T. vaginalis to chemotherapy. Caatinga is a uniquely Brazilian region representing a biome with type desert vegetation and plants present diverse biological activity, however, with few studies. The aim of this study was to investigate the activity against T. vaginalis of different plants from Caatinga and identify the compounds responsible by the activity. A bioguided fractionation of Manilkara rufula was performed and four major compounds were identified: caproate of α-amyrin (1b), acetate of β-amyrin (2a), caproate of β-amyrin (2b), and acetate of lupeol (3a). In addition, six derivatives of α-amyrin (1), β-amyrin (2) and lupeol (3) were synthesized and tested against the parasite. Ursolic acid (5) reduced about 98% of parasite viability after 2h of incubation and drastic ultrastructural alterations were observed by scanning electron microscopy. Moreover, 5 presented high cytotoxicity to HMVII and HeLa cell line and low cytotoxicity against Vero line at 50 μM (MIC against the parasite). Metronidazole effect against T. vaginalis resistant isolate was improved when in association with 5. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

2018-01-01

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

Compounds from Silicones Alter Enzyme Activity in Curing Barnacle Glue and Model Enzymes

PubMed Central

Rittschof, Daniel; Orihuela, Beatriz; Harder, Tilmann; Stafslien, Shane; Chisholm, Bret; Dickinson, Gary H.

2011-01-01

Background Attachment strength of fouling organisms on silicone coatings is low. We hypothesized that low attachment strength on silicones is, in part, due to the interaction of surface available components with natural glues. Components could alter curing of glues through bulk changes or specifically through altered enzyme activity. Methodology/Principal Findings GC-MS analysis of silicone coatings showed surface-available siloxanes when the coatings were gently rubbed with a cotton swab for 15 seconds or given a 30 second rinse with methanol. Mixtures of compounds were found on 2 commercial and 8 model silicone coatings. The hypothesis that silicone components alter glue curing enzymes was tested with curing barnacle glue and with commercial enzymes. In our model, barnacle glue curing involves trypsin-like serine protease(s), which activate enzymes and structural proteins, and a transglutaminase which cross-links glue proteins. Transglutaminase activity was significantly altered upon exposure of curing glue from individual barnacles to silicone eluates. Activity of purified trypsin and, to a greater extent, transglutaminase was significantly altered by relevant concentrations of silicone polymer constituents. Conclusions/Significance Surface-associated silicone compounds can disrupt glue curing and alter enzyme properties. Altered curing of natural glues has potential in fouling management. PMID:21379573

Extraction, chemical characterization and biological activity determination of broccoli health promoting compounds.

PubMed

Ares, Ana M; Nozal, María J; Bernal, José

2013-10-25

Broccoli (Brassica oleracea L. var. Italica) contains substantial amount of health-promoting compounds such as vitamins, glucosinolates, phenolic compounds, and dietary essential minerals; thus, it benefits health beyond providing just basic nutrition, and consumption of broccoli has been increasing over the years. This review gives an overview on the extraction and separation techniques, as well as the biological activity of some of the above mentioned compounds which have been published in the period January 2008 to January 2013. The work has been distributed according to the different families of health promoting compounds discussing the extraction procedures and the analytical techniques employed for their characterization. Finally, information about the different biological activities of these compounds has been also provided. Copyright © 2013 Elsevier B.V. All rights reserved.

Antibacterial activities of the methanol extract, fractions and compounds from Elaeophorbia drupifera (Thonn.) Stapf. (Euphorbiaceae).

PubMed

Voukeng, Igor K; Nganou, Blaise K; Sandjo, Louis P; Celik, Ilhami; Beng, Veronique P; Tane, Pierre; Kuete, Victor

2017-01-07

Elaeophorbia drupifera (Thonn.) Stapf. (Euphorbiaceae) is used in Cameroonian folk medicine to treat several ailments including bacterial-related diseases such as skin infections. In this study, the methanol extract from the leaves (EDL), fractions (EDLa-d), sub-fractions EDLc1-7 and EDLc31-35 as well as isolated compounds were tested for their antimicrobial activities against a panel of Gram-negative and Gram-positive bacteria including multidrug resistant (MDR) phenotypes. The broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the above samples; column chromatography was used for the fractionation and purification of the leaves extract whilst the chemical structures of compounds were determined using spectroscopic techniques. Phytochemical investigation lead to the isolation of a mixture (1:3) of stigmasterol and β-sitosterol (1 + 2), euphol (3), sitosterol-O-β- D -xylopyranoside (4), 3,3',4'-tri-O-methylellagic acid (5), a mixture (1:1) of afzelin and quercetin-3-O-β- D -xylopyranoside (6 + 7), 3,3',4'-tri-O-methylellagic acid 4-O-β- D -glucopyranoside (8), ellagic acid-4-O-β-xylopyranoside-3,3',4'-trimethyl ether (9) from EDLc. Crude extract and fractions displayed selective activities with MIC values ranged from 32 to 1024 μg/mL for EDL against 84.9% of the 33 tested bacteria, 93.9% for EDLc, 69.7% for EDLb, 33.4% for EDLa and 0.03% for EDLd. MIC values ranged from 16 to 1024 μg/mL were obtained with EDLc3 and EDLc4 on all tested bacteria meanwhile other sub-fractions displayed selective activities. MIC value of 32 μg/mL was obtained with fractions EDLa against Escherichia coli AG100, EDLc against Enterobacer aerogenes ATCC13048 and EA298. For sub-fractions obtained from EDLc, the lowest MIC value of 16 μg/mL was recorded with EDLc3 against Staphylococcus aureus MRSA11. A corresponding value of 8 μg/mL against Providencia stuartii NAE16 was recorded with

Isolation and purification of antialgal compounds from the red alga Gracilaria lemaneiformis for activity against common harmful red tide microalgae.

PubMed

Sun, Ying-Ying; Meng, Kun; Su, Zhen-Xia; Guo, Gan-Lin; Pu, Yin-Fang; Wang, Chang-Hai

2017-02-01

Seven antialgal compounds (1-7) were successfully isolated from the red alga Gracilaria lemaneiformis through a combination of silica gel column chromatography and repeated preparative thin-layer chromatography. On the basis of the spectral data, the compounds were identified as gossonorol (1), 7,10-epoxy-ar-bisabol-11-ol (2), glycerol monopalmitate (3), stigmasterol (4), 15-hydroxymethyl-2, 6, 10, 18, 22, 26, 30-heptamethyl-14-methylene-17-hentriacontene (5), 4-hydroxyphenethyl alcohol (6), and margaric acid (7). These seven compounds were isolated from G. lemaneiformis for the first time, while the compounds 4, 6, and 7 were isolated from marine macroalgae for the first time. Furthermore, a quantitative relationship between the inhibition of algal growth and the concentration of each antialgal compound was determined and important parameters for future practical HAB control, e.g., EC 50-96h , were also obtained. The results indicated that isolated compounds 1-7 possess selective antialgal activity against the growth of several red tide microalgae (including Amphidinium carterae, Heterosigma akashiwo, Karenia mikimitoi, Phaeocystis globsa, Prorocentrum donghaiense, and Skeletonema costatum). Their antialgal activity against test red tide microalgae has not been previously reported. Furthermore, the EC 50-96h of one or more of the compounds towards the tested red microalgae was not only significantly less than 10 μg/mL but also was smaller than that of the characteristic antialgal agent potassium dichromate. The study demonstrates that compounds 1-7 possess significant application potential as antialgal agents against several harmful red tide microalgae.

Chemical composition and antibacterial activity of selected essential oils and some of their main compounds.

PubMed

Wanner, Juergen; Schmidt, Erich; Bail, Stefanie; Jirovetz, Leopold; Buchbauer, Gerhard; Gochev, Velizar; Girova, Tanya; Atanasova, Teodora; Stoyanova, Albena

2010-09-01

The chemical composition of essential oils of cabreuva (Myrocarpus fastigiatus Allemao, Fabaceae) from Brazil, cedarwood (Juniperus ashei, Cupressaceae) from Texas, Juniper berries (Juniperus communis L., Cupressaceae) and myrrh (Commiphora myrrha (Nees) Engl., Burseraceae) were analyzed using GC/FID and GC/MS. The antimicrobial activity of these essential oils and some of their main compounds were tested against eleven different strains of Gram-positive and Gram-negative bacteria by using agar diffusion and agar serial dilution methods. Animal and plant pathogens, food poisoning and spoilage bacteria were selected. The volatile oils exhibited considerable inhibitory effects against all tested organisms, except Pseudomonas, using both test methods. Higher activity was observed against Gram-positive strains in comparison with Gram-negative bacteria. Cabreuva oil from Brazil showed similar results, but in comparison with the other oils tested, only when higher concentrations of oil were used.

Structure-activity relationship and docking studies of thiazolidinedione-type compounds with monoamine oxidase B.

PubMed

Carroll, Richard T; Dluzen, Dean E; Stinnett, Hilary; Awale, Prabha S; Funk, Max O; Geldenhuys, Werner J

2011-08-15

The neuroprotective activity of pioglitazone and rosiglitazone in the MPTP parkinsonian mouse prompted us to evaluate a set of thiazolidinedione (TZD) type compounds for monoamine oxidase A and B inhibition activity. These compounds were able to inhibit MAO-B over several log units of magnitude (82 nM to 600 μM). Initial structure-activity relationship studies identified key areas to modify the aromatic substituted TZD compounds. Primarily, substitutions on the aromatic group and the TZD nitrogen were key areas where activity was enhanced within this group of compounds. Copyright © 2011 Elsevier Ltd. All rights reserved.

Compounds from the aerial parts of Piper bavinum and their anti-cholinesterase activity.

PubMed

Dung, Hoang Viet; Cuong, To Dao; Chinh, Nguyen Minh; Quyen, Do; Kim, Jeong Ah; Byeon, Jeong Su; Woo, Mi Hee; Choi, Jae Sui; Min, Byung Sun

2015-01-01

A new alkenylphenol, bavinol A (1), together with six known compounds (2-7) were isolated from the aerial parts of Piper bavinum (Piperaceae). The chemical structures of these compounds were determined by spectroscopic analyses including 2D NMR spectroscopy. The anti-Alzheimer effects of compounds 1-7 were evaluated from acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity assays. Bavinol A (1), ampelopsin (3), and violanthin (4) exhibited AChE inhibitory activities with IC50 values of 29.80, 59.47 and 79.80 μM. Compound 1 also showed the most potent BChE inhibitory activity with an IC50 value of 19.25 μM.

Alpha-keto acid metabolites of organoselenium compounds inhibit histone deacetylase activity in human colon cancer cells.

PubMed

Nian, Hui; Bisson, William H; Dashwood, Wan-Mohaiza; Pinto, John T; Dashwood, Roderick H

2009-08-01

Methylselenocysteine (MSC) and selenomethionine (SM) are two organoselenium compounds receiving interest for their potential anticancer properties. These compounds can be converted to beta-methylselenopyruvate (MSP) and alpha-keto-gamma-methylselenobutyrate (KMSB), alpha-keto acid metabolites that share structural features with the histone deacetylase (HDAC) inhibitor butyrate. We tested the organoselenium compounds in an in vitro assay with human HDAC1 and HDAC8; whereas SM and MSC had little or no activity up to 2 mM, MSP and KMSB caused dose-dependent inhibition of HDAC activity. Subsequent experiments identified MSP as a competitive inhibitor of HDAC8, and computational modeling supported a mechanism involving reversible interaction with the active site zinc atom. In human colon cancer cells, acetylated histone H3 levels were increased during the period 0.5-48 h after treatment with MSP and KMSB, and there was dose-dependent inhibition of HDAC activity. The proportion of cells occupying G(2)/M of the cell cycle was increased at 10-50 microM MSP and KMSB, and apoptosis was induced, as evidenced by morphological changes, Annexin V staining and increased cleaved caspase-3, -6, -7, -9 and poly(adenosine diphosphate-ribose)polymerase. P21WAF1, a well-established target gene of clinically used HDAC inhibitors, was increased in MSP- and KMSB-treated colon cancer cells at both the messenger RNA and protein level, and there was enhanced P21WAF1 promoter activity. These studies confirm that in addition to targeting redox-sensitive signaling molecules, alpha-keto acid metabolites of organoselenium compounds alter HDAC activity and histone acetylation status in colon cancer cells, as recently observed in human prostate cancer cells.

Isolation, identification, and antibacterial activity of chemical compounds from ethanolic extract of suji leaf (Pleomele angusifolia NE Brown)

NASA Astrophysics Data System (ADS)

Faridah; Natalia; Lina, Maria; W, Hendig

2014-03-01

Suji (Pleomele angustifolia NE Brown) is one of the medicinal plants of the tribe of Liliaceae, empirically useful to treat coughs and respiratory diseases such as tuberculosis (TB) and pneumonia. In this study, ethanolic extract of suji leaves was tested its activity against bacteria that attacks the respiratory organs, namely Mycobacterium tuberculosis and Streptococcus pneumoniae, using a paper disc diffusion and dilution agar method. These extracts have activity in inhibiting the growth of M. tuberculosis at a concentration of 8 mg and against S. pneumoniae at a concentration of 4 mg. The fractions were tested their antibacterial activity against Streptococcus pneumoniae using paper disc diffusion method. The most active fraction was chosen based on the inhibition diameter. The fractions contained flavonoids, steroids, and essential oils. The precipitate isolated from the extraction process shows needle-shaped, white, cold and tasteless crystals. Moreover, the HPLC analysis of isolate revealed a single peak with a retention time of 7.183 minutes. The exact compounds in the isolate could not be determined but it was known the compounds contained the functional groups of alkene, alkane, C=O, -OH. Test results obtained from UV-Vis spectrophotometer provides maximum absorption at a wavelength of 203.0 nm.

Cytotoxicity and antimicrobial activity of the methanol extract and compounds from Polygonum limbatum.

PubMed

Dzoyem, Jean P; Nkuete, Antoine H L; Kuete, Victor; Tala, Michel F; Wabo, Hippolyte K; Guru, Santosh K; Rajput, Vikrant S; Sharma, Akash; Tane, Pierre; Khan, Inshad A; Saxena, Anil K; Laatsch, Hartmut; Tan, Ning-Hua

2012-05-01

The present study was designed to investigate the antimicrobial activity and the cytotoxicity of the methanol extract (PLA) as well as fractions (PLA1-4) and compounds [cardamomin (1), (±)-polygohomoisoflavanone (2), (S)-(-)-pinostrobin (3), 2',4'-dihydroxy-3',6'-dimethoxychalcone (4), (2S)-(-)-5-hydroxy-6,7-dimethoxyflavanone (5), and (2S)-(-)-5,7-dimethoxyflavanone (6)] obtained from leaves of Polygonum limbatum. The microbroth dilution was used to determine the minimal inhibitory concentration (MIC) of the samples against 11 microbial strains including Candida albicans, C. krusei, C. tropicalis, Aspergillus fumigatus, Pseudomonas aeruginosa, Escherichia coli, vancomycin-resistant Enterococcus faecalis (VRE), Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), S.epidermidis, and Mycobacterium tuberculosis H37Rv. The sulphorhodamine B cell growth inhibition assay was used to assess the cytotoxicity of the above samples on lung A549 adenocarcinoma, breast carcinoma MCF-7, prostate carcinoma PC-3, cervical carcinoma HeLa, and the acute monocytic leukemia cell line THP-1. The results of the MIC determination indicated that, apart from fraction PLA3, all other fractions as well as PLA and compound 3 were selectively active. MIC values were noted on 100 % of the 11 tested microorganisms for fraction PLA3, 72.7 % for PLA, fraction PLA2, and compound 4, 63.6 % for PLA1, and 54.5 % for fraction PLA4. The results of the cytotoxicity assay revealed that, except for A459 cells, more than 50 % inhibition of the proliferation was obtained with each of the tested samples on at least one of the four other cell lines. IC₅₀ values below 4 µg/mL were obtained with 1 and 4 on THP-1 cells. The overall results of the present study provided baseline information for the possible use of Polygonum limbatum as well as some of the isolated compounds for the control of cancer diseases and mostly leukemia. Georg Thieme Verlag KG Stuttgart · New York.

Effect of Freeze-Drying on the Antioxidant Compounds and Antioxidant Activity of Selected Tropical Fruits

PubMed Central

Shofian, Norshahida Mohamad; Hamid, Azizah Abdul; Osman, Azizah; Saari, Nazamid; Anwar, Farooq; Dek, Mohd Sabri Pak; Hairuddin, Muhammad Redzuan

2011-01-01

The effects of freeze-drying on antioxidant compounds and antioxidant activity of five tropical fruits, namely starfruit (Averrhoa carambola L.), mango (Mangifera indica L.), papaya (Carica papaya L.), muskmelon (Cucumis melo L.), and watermelon Citruluss lanatus (Thunb.) were investigated. Significant (p < 0.05) differences, for the amounts of total phenolic compounds (TPC), were found between the fresh and freeze-dried fruit samples, except muskmelon. There was no significant (p > 0.05) change, however, observed in the ascorbic acid content of the fresh and freeze-dried fruits. Similarly, freeze-drying did not exert any considerable effect on β-carotene concentration of fruits, except for mango and watermelon, where significantly (p < 0.05) higher levels were detected in the fresh samples. The results of DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging and reducing power assays revealed that fresh samples of starfruit and mango had relatively higher antioxidant activity. In case of linoleic acid peroxidation inhibition measurement, a significant (p < 0.05) but random variation was recorded between the fresh and freeze-dried fruits. Overall, in comparison to β-carotene and ascorbic acid, a good correlation was established between the result of TPC and antioxidant assays, indicating that phenolics might have been the dominant compounds contributing towards the antioxidant activity of the fruits tested. PMID:21845104

Effect of freeze-drying on the antioxidant compounds and antioxidant activity of selected tropical fruits.

PubMed

Shofian, Norshahida Mohamad; Hamid, Azizah Abdul; Osman, Azizah; Saari, Nazamid; Anwar, Farooq; Dek, Mohd Sabri Pak; Hairuddin, Muhammad Redzuan

2011-01-01

The effects of freeze-drying on antioxidant compounds and antioxidant activity of five tropical fruits, namely starfruit (Averrhoa carambola L.), mango (Mangifera indica L.), papaya (Carica papaya L.), muskmelon (Cucumis melo L.), and watermelon Citruluss lanatus (Thunb.) were investigated. Significant (p < 0.05) differences, for the amounts of total phenolic compounds (TPC), were found between the fresh and freeze-dried fruit samples, except muskmelon. There was no significant (p > 0.05) change, however, observed in the ascorbic acid content of the fresh and freeze-dried fruits. Similarly, freeze-drying did not exert any considerable effect on β-carotene concentration of fruits, except for mango and watermelon, where significantly (p < 0.05) higher levels were detected in the fresh samples. The results of DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging and reducing power assays revealed that fresh samples of starfruit and mango had relatively higher antioxidant activity. In case of linoleic acid peroxidation inhibition measurement, a significant (p < 0.05) but random variation was recorded between the fresh and freeze-dried fruits. Overall, in comparison to β-carotene and ascorbic acid, a good correlation was established between the result of TPC and antioxidant assays, indicating that phenolics might have been the dominant compounds contributing towards the antioxidant activity of the fruits tested.

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.

Spectral characterization and antibacterial activity of an isolated compound from Memecylon edule leaves.

PubMed

Srinivasan, R; Natarajan, D; Shivakumar, M S

2017-03-01

Memecylon edule Roxb. (Melastamataceae family) is a small evergreen tree reported as having ethnobotanical and pharmacological properties. The present study was aimed to investigate the spectral characterization and antibacterial activity of isolated pure compound (3β-hydroxyurs-12-en-28-oic acid (ursolic acid)) from Memecylon edule leaves by performing bioassay guided isolation method. The structure derivation of isolated compound was done by different spectral studies like UV, FT-IR, LC-MS, CHNS analysis, 1D ( 1 H, 13 C and DEPT-135) and 2D-NMR (HSQC and HMBC), respectively. About 99.29% purity of the compound was found in LC analysis. 1 H NMR spectrum results of compound shown 48 protons appear at different shielded region and most of the protons were present in aliphatic region. Whereas, 13 C NMR spectral data resulted seven methyl carbons (CH3), nine methylene carbons (CH2), seven methine carbons (CH) and six non-hydrogenated carbons (C) which are characteristic of pentacyclic triterpene. The isolated pure compound was tested for its antibacterial properties against targeted human pathogens by performing agar well diffusion, MIC and MBC assays and the result exhibits better growth inhibitory effects against S. epidermidis and S. pneumoniae, with the MIC values of 1.56 and 3.15μg/ml. The outcome of this study suggests that the bioactive compound is used for development of plant based drugs in pharmaceutical industry for combating microbial mediated diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of phenylated compounds of methylglyoxal bis(guanylhydrazone) on diamine oxidase activity from rat small intestine.

PubMed

Balaña-Fouce, R; Pulido, T G; Escudero, D O; Sanz-Sanchez, F

1986-01-01

Two phenylated compounds of methylglyoxal bis(guanylhydrazone), potentially inhibitors of diamine oxidase activity, have been synthesized: phenylglyoxal bis(guanylhydrazone) and diphenylglyoxal bis(guanylhydrazone). Their inhibitory capacity was tested: while PGBG was able to reduce the enzyme activity by 50% at 1.3 microM, DPGBG was only able to reduce diamine oxidase activity by less than 2% at a concentration 1000-fold higher. The inhibition of PGBG was non-competitive and the Ki calculated by a Dixon plot was estimated as 1.7 microM.

Role of ozone and granular activated carbon in the removal of mutagenic compounds.

PubMed Central

Bourbigot, M M; Hascoet, M C; Levi, Y; Erb, F; Pommery, N

1986-01-01

The identification of certain organic compounds in drinking water has led water treatment specialists to be increasingly concerned about the eventual risks of such pollutants to the health of consumers. Our experiments focused on the role of ozone and granular activated carbon in removing mutagenic compounds and precursors that become toxic after chlorination. We found that if a sufficient dose of ozone is applied, its use does not lead to the creation of mutagenic compounds in drinking water and can even eliminate the initial mutagenicity of the water. The formation of new mutagenic compounds seems to be induced by ozonation that is too weak, although these mutagens can be removed by GAC filtration. Ozone used with activated carbon can be one of the best means for eliminating the compounds contributing to the mutagenicity of water. A combined treatment of ozone and activated carbon also decreases the chlorine consumption of the treated water and consequently reduces the formation of chlorinated organic compounds. PMID:3816720

TTI-237: a novel microtubule-active compound with in vivo antitumor activity.

PubMed

Beyer, Carl F; Zhang, Nan; Hernandez, Richard; Vitale, Danielle; Lucas, Judy; Nguyen, Thai; Discafani, Carolyn; Ayral-Kaloustian, Semiramis; Gibbons, James J

2008-04-01

5-Chloro-6-[2,6-difluoro-4-[3-(methylamino)propoxy]phenyl]-N-[(1S)-2,2,2-trifluoro-1-methylethyl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine butanedioate (TTI-237) is a microtubule-active compound of novel structure and function. Structurally, it is one of a class of compounds, triazolo[1,5a]pyrimidines, previously not known to bind to tubulin. Functionally, TTI-237 inhibited the binding of [(3)H]vinblastine to tubulin, but it caused a marked increase in turbidity development that more closely resembled the effect observed with docetaxel than that observed with vincristine. The morphologic character of the presumptive polymer is unknown at present. When applied to cultured human tumor cells at concentrations near its IC(50) value for cytotoxicity (34 nmol/L), TTI-237 induced multiple spindle poles and multinuclear cells, as did paclitaxel, but not vincristine or colchicine. Flow cytometry experiments revealed that, at low concentrations (20-40 nmol/L), TTI-237 produced sub-G(1) nuclei and, at concentrations above 50 nmol/L, it caused a strong G(2)-M block. The compound was a weak substrate of multidrug resistance 1 (multidrug resistance transporter or P-glycoprotein). In a cell line expressing a high level of P-glycoprotein, the IC(50) of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold, respectively. TTI-237 was not recognized by the MRP or MXR transporters. TTI-237 was active in vivo in several nude mouse xenograft models of human cancer, including LoVo human colon carcinoma and U87-MG human glioblastoma, when dosed i.v. or p.o. Thus, TTI-237 has a set of properties that distinguish it from other classes of microtubule-active compounds.

Laccase Catalyzed Synthesis of Iodinated Phenolic Compounds with Antifungal Activity

PubMed Central

Ihssen, Julian; Schubert, Mark; Thöny-Meyer, Linda; Richter, Michael

2014-01-01

Iodine is a well known antimicrobial compound. Laccase, an oxidoreductase which couples the one electron oxidation of diverse phenolic and non-phenolic substrates to the reduction of oxygen to water, is capable of oxidizing unreactive iodide to reactive iodine. We have shown previously that laccase-iodide treatment of spruce wood results in a wash-out resistant antimicrobial surface. In this study, we investigated whether phenolic compounds such as vanillin, which resembles sub-structures of softwood lignin, can be directly iodinated by reacting with laccase and iodide, resulting in compounds with antifungal activity. HPLC-MS analysis showed that vanillin was converted to iodovanillin by laccase catalysis at an excess of potassium iodide. No conversion of vanillin occurred in the absence of enzyme. The addition of redox mediators in catalytic concentrations increased the rate of iodide oxidation ten-fold and the yield of iodovanillin by 50%. Iodinated phenolic products were also detected when o-vanillin, ethyl vanillin, acetovanillone and methyl vanillate were incubated with laccase and iodide. At an increased educt concentration of 0.1 M an almost one to one molar ratio of iodide to vanillin could be used without compromising conversion rate, and the insoluble iodovanillin product could be recovered by simple centrifugation. The novel enzymatic synthesis procedure fulfills key criteria of green chemistry. Biocatalytically produced iodovanillin and iodo-ethyl vanillin had significant growth inhibitory effects on several wood degrading fungal species. For Trametes versicolor, a species causing white rot of wood, almost complete growth inhibition and a partial biocidal effect was observed on agar plates. Enzymatic tests indicated that the iodinated compounds acted as enzyme responsive, antimicrobial materials. PMID:24594755

Screening Active Compounds from Garcinia Species Native to China Reveals Novel Compounds Targeting the STAT/JAK Signaling Pathway

PubMed Central

Xu, Linfeng; Lao, Yuanzhi; Zhao, Yanhui; Qin, Jian; Fu, Wenwei; Zhang, Yingjia; Xu, Hongxi

2015-01-01

Natural compounds from medicinal plants are important resources for drug development. In a panel of human tumor cells, we screened a library of the natural products from Garcinia species which have anticancer potential to identify new potential therapeutic leads and discovered that caged xanthones were highly effective at suppressing multiple cancer cell lines. Their anticancer activities mainly depended on apoptosis pathways. For compounds in sensitive cancer line, their mechanisms of mode of action were evaluated. 33-Hydroxyepigambogic acid and 35-hydroxyepigambogic acid exhibited about 1 μM IC50 values against JAK2/JAK3 kinases and less than 1 μM IC50 values against NCI-H1650 cell which autocrined IL-6. Thus these two compounds provided a new antitumor molecular scaffold. Our report describes 33-hydroxyepigambogic acid and 35-hydroxyepigambogic acid that inhibited NCI-H1650 cell growth by suppressing constitutive STAT3 activation via direct inhibition of JAK kinase activity. PMID:26090459

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

PubMed

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

2014-06-23

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

Antibacterial activity of isolated phenolic compounds from cranberry (Vaccinium macrocarpon) against Escherichia coli.

PubMed

Rodríguez-Pérez, Celia; Quirantes-Piné, Rosa; Uberos, José; Jiménez-Sánchez, Cecilia; Peña, Alejandro; Segura-Carretero, Antonio

2016-03-01

Phenolic compounds from a cranberry extract were isolated in order to assess their contribution to the antibacterial activity against uropathogenic strains of Escherichia coli (UPEC). With this purpose, a total of 25 fractions from a cranberry extract were isolated using semipreparative high performance liquid chromatography (HPLC) and characterized based on the results obtained by reversed-phase HPLC coupled to mass spectrometry detection. Then, the effects on UPEC surface hydrophobicity and biofilm formation of the cranberry extract as well as the purest fractions (a total of 13) were tested. As expected, the whole extract presented a powerful antibacterial activity against UPEC while the selected fractions presented a different behavior. Myricetin and quercitrin significantly decreased (p < 0.05) E. coli biofilm formation compared with the control, while dihydroferulic acid glucuronide, procyanidin A dimer, quercetin glucoside, myricetin and prodelphinidin B led to a significant decrease of the surface hydrophobicity compared with the control. The results suggest that apart from proanthocyanidins, other compounds, mainly flavonoids, can act against E. coli biofilm formation and also modify UPEC surface hydrophobicity in vitro, one of the first steps of adhesion.

Design of an activity landscape view taking compound-based feature probabilities into account.

PubMed

Zhang, Bijun; Vogt, Martin; Bajorath, Jürgen

2014-09-01

Activity landscapes (ALs) of compound data sets are rationalized as graphical representations that integrate similarity and potency relationships between active compounds. ALs enable the visualization of structure-activity relationship (SAR) information and are thus computational tools of interest for medicinal chemistry. For AL generation, similarity and potency relationships are typically evaluated in a pairwise manner and major AL features are assessed at the level of compound pairs. In this study, we add a conditional probability formalism to AL design that makes it possible to quantify the probability of individual compounds to contribute to characteristic AL features. Making this information graphically accessible in a molecular network-based AL representation is shown to further increase AL information content and helps to quickly focus on SAR-informative compound subsets. This feature probability-based AL variant extends the current spectrum of AL representations for medicinal chemistry applications.

Identification of B. anthracis N(5)-carboxyaminoimidazole ribonucleotide mutase (PurE) active site binding compounds via fragment library screening.

PubMed

Lei, Hao; Jones, Christopher; Zhu, Tian; Patel, Kavankumar; Wolf, Nina M; Fung, Leslie W-M; Lee, Hyun; Johnson, Michael E

2016-02-15

The de novo purine biosynthesis pathway is an attractive target for antibacterial drug design, and PurE from this pathway has been identified to be crucial for Bacillus anthracis survival in serum. In this study we adopted a fragment-based hit discovery approach, using three screening methods-saturation transfer difference nucleus magnetic resonance (STD-NMR), water-ligand observed via gradient spectroscopy (WaterLOGSY) NMR, and surface plasmon resonance (SPR), against B. anthracis PurE (BaPurE) to identify active site binding fragments by initially testing 352 compounds in a Zenobia fragment library. Competition STD NMR with the BaPurE product effectively eliminated non-active site binding hits from the primary hits, selecting active site binders only. Binding affinities (dissociation constant, KD) of these compounds varied between 234 and 301μM. Based on test results from the Zenobia compounds, we subsequently developed and applied a streamlined fragment screening strategy to screen a much larger library consisting of 3000 computationally pre-selected fragments. Thirteen final fragment hits were confirmed to exhibit binding affinities varying from 14μM to 700μM, which were categorized into five different basic scaffolds. All thirteen fragment hits have ligand efficiencies higher than 0.30. We demonstrated that at least two fragments from two different scaffolds exhibit inhibitory activity against the BaPurE enzyme. Published by Elsevier Ltd.

Effect of cadmium on phenolic compounds, antioxidant enzyme activity and oxidative stress in blueberry (Vaccinium corymbosum L.) plantlets grown in vitro.

PubMed

Manquián-Cerda, K; Escudey, M; Zúñiga, G; Arancibia-Miranda, N; Molina, M; Cruces, E

2016-11-01

Cadmium (Cd(2+)) can affect plant growth due to its mobility and toxicity. We evaluated the effects of Cd(2+) on the production of phenolic compounds and antioxidant response of Vaccinium corymbosum L. Plantlets were exposed to Cd(2+) at 50 and 100µM for 7, 14 and 21 days. Accumulation of malondialdehyde (MDA), hydrogen peroxide (H2O2) and the antioxidant enzyme SOD was determined. The profile of phenolic compounds was evaluated using LC-MS. The antioxidant activity was measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the ferric reducing antioxidant power test (FRAP). Cd(2+) increased the content of MDA, with the highest increase at 14 days. The presence of Cd(2+) resulted in changes in phenolic compounds. The main phenolic compound found in blueberry plantlets was chlorogenic acid, whose abundance increased with the addition of Cd(2+) to the medium. The changes in the composition of phenolic compounds showed a positive correlation with the antioxidant activity measured using FRAP. Our results suggest that blueberry plantlets produced phenolic compounds with reducing capacity as a selective mechanism triggered by the highest activity of Cd(2+). Copyright © 2016 Elsevier Inc. All rights reserved.

Phenolic Compounds and Antioxidant Activity of Different Organs of Potentilla fruticosa L. from Two Main Production Areas of China.

PubMed

Yu, Danmeng; Pu, Wenjun; Li, Dengwu; Wang, Dongmei; Liu, Qiaoxiao; Wang, Yongtao

2016-09-01

This report compared the phenolic compounds and antioxidant activity of the leaves, flowers, and stems of Potentilla fruticosa L. collected from two main production areas of P. R. China (Taibai Mountains and the Qinghai Huzhu Northern Mountains). The results indicated that there were significant differences in the phenol contents and antioxidant activities among the different organs and between the two productions. High-performance liquid-chromatography analysis indicated that hyperoside, (+)-catechin, ellagic acid, and rutin were the primary compounds in leaves and flowers; for stems, the content of six phenolic compounds, from two productions, were the lowest. The 1,1-diphenyl-2-picryl hydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) di-ammonium salt (ABTS), ferric reducing power (FRAP), lipid peroxidation assays, and microbial test system (MTS) were used to evaluate the antioxidant activity. The results demonstrated that the leaves from two productions exhibited powerful antioxidant activity than other organs, which did not significantly differ from that of the positive control (rutin), followed by the flowers and stems. The correlation between the content of phytochemicals and the antioxidant activities of different organs showed that the total phenol, tannin, hyperoside, and (+)-catechin contents may influence the antioxidant activity, and these compounds can be used as markers for the quality control of P. fruticosa. © 2016 Wiley-VHCA AG, Zürich.

Content of redox-active compounds (ie, antioxidants) in foods consumed in the United States.

PubMed

Halvorsen, Bente L; Carlsen, Monica H; Phillips, Katherine M; Bøhn, Siv K; Holte, Kari; Jacobs, David R; Blomhoff, Rune

2006-07-01

Supplements containing ascorbic acid, alpha-tocopherol, or beta-carotene do not protect against oxidative stress-related diseases in most randomized intervention trials. We suggest that other redox-active phytochemicals may be more effective and that a combination of different redox-active compounds (ie, antioxidants or reductants) may be needed for proper protection against oxidative damage. We aimed to generate a ranked food table with values for total content of redox-active compounds to test this alternative antioxidant hypothesis. An assay that measures the total concentration of redox-active compounds above a certain cutoff reduction potential was used to analyze 1113 food samples obtained from the US Department of Agriculture National Food and Nutrient Analysis Program. Large variations in the content of antioxidants were observed in different foods and food categories. The food groups spices and herbs, nuts and seeds, berries, and fruit and vegetables all contained foods with very high antioxidant contents. Most food categories also contained products almost devoid of antioxidants. Of the 50 food products highest in antioxidant concentrations, 13 were spices, 8 were in the fruit and vegetables category, 5 were berries, 5 were chocolate-based, 5 were breakfast cereals, and 4 were nuts or seeds. On the basis of typical serving sizes, blackberries, walnuts, strawberries, artichokes, cranberries, brewed coffee, raspberries, pecans, blueberries, ground cloves, grape juice, and unsweetened baking chocolate were at the top of the ranked list. This ranked antioxidant food table provides a useful tool for investigations into the possible health benefit of dietary antioxidants.

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.

Phenolic compounds, antioxidant activity, antiproliferative activity and bioaccessibility of Sea buckthorn (Hippophaë rhamnoides L.) berries as affected by in vitro digestion.

PubMed

Guo, Ruixue; Chang, Xiaoxiao; Guo, Xinbo; Brennan, Charles Stephen; Li, Tong; Fu, Xiong; Liu, Rui Hai

2017-11-15

Phenolics, antioxidant and antiproliferative properties of Sea buckthorn berries were evaluated using a simulated in vitro digestion and compared with a chemical extraction method. Digested samples were subjected to antiproliferation evaluation against human liver, breast and colon cancer cells. Furthermore, the bioaccessibility of digested berries was evaluated using a Caco-2 cell culture model. Results revealed that after enzymatic digestion the phenolic compounds were quite different from the chemical extracts, more flavonoid aglycones were released, whereas less total phenolics, phenolic acids and flavonoid glycosides were detected. Although the extracellular antioxidant activity of the digesta was lower than that of extracts, the cellular antioxidant activity (CAA) and antiproliferative effects of berries were significantly enhanced by digestion. This was attributed to their higher flavonoid aglycone content and could be verified by testing individual active compounds, suggesting that the cellular uptake of samples might be improved, which was also certified by the Caco-2 cell uptake model. The digested samples showed an almost 5-fold cellular accumulative amount of isorhamnetin than pure isorhamnetin, which was attributed to the significant down regulation of the mRNA expression level of efflux transporters MRP2 and P-gp. This finding indicated that the digestion enhanced the bioaccessibility of bioactive compounds of berries.

Antioxidant and antimicrobial activities of ethyl acetate extract, fractions and compounds from stem bark of Albizia adianthifolia (Mimosoideae).

PubMed

Tamokou, Jean de Dieu; Simo Mpetga, Deke James; Keilah Lunga, Paul; Tene, Mathieu; Tane, Pierre; Kuiate, Jules Roger

2012-07-18

Albizia adianthifolia is used traditionally in Cameroon to treat several ailments, including infectious and associated diseases. This work was therefore designed to investigate the antioxidant and antimicrobial activities of ethyl acetate extract, fractions and compounds isolated from the stem bark of this plant. The plant extract was prepared by maceration in ethyl acetate. Its fractionation was done by column chromatography and the structures of isolated compounds were elucidated using spectroscopic data in conjunction with literature data. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) and trolox equivalent antioxidant capacity (TEAC) assays were used to detect the antioxidant activity. Broth micro-dilution method was used for antimicrobial test. Total phenol content was determined spectrophotometrically in the extracts by using Folin-Ciocalteu method. The fractionation of the extract afforded two known compounds: lupeol (1) and aurantiamide acetate (2) together with two mixtures of fatty acids: oleic acid and n-hexadecanoic acid (B₁); n-hexadecanoic acid, octadecanoic acid and docosanoic acid (B₂). Aurantiamide acetate was the most active compound. The total phenol concentration expressed as gallic acid equivalents (GAE) was found to vary from 1.50 to 13.49 μg/ml in the extracts. The antioxidant activities were well correlated with the total phenol content (R² = 0.946 for the TEAC method and R² = 0.980 for the DPPH free-radical scavenging assay). Our results clearly reveal that the ethyl acetate extract from the stem bark of A. adianthifolia possesses antioxidant and antimicrobial principles. The antioxidant activity of this extract as well as that of compound 2 are being reported herein for the first time. These results provide promising baseline information for the potential use of this plant as well as compound 2 in the treatment of oxidative damage and infections associated with the studied microorganisms.

Characterization of Phenolic Compounds and Antioxidant and Anti-inflammatory Activities from Mamuyo (Styrax ramirezii Greenm.) Fruit.

PubMed

Timmers, Michael A; Guerrero-Medina, Jorge L; Esposito, Debora; Grace, Mary H; Paredes-López, Octavio; García-Saucedo, Pedro A; Lila, Mary Ann

2015-12-09

Extracts of Styrax ramirezii Greenm., a fruit traditionally valued for health and wellness in Mexico, were analyzed phytochemically and evaluated for antioxidant and anti-inflammatory activity. Six norneolignans were identified by HPLC-TOF-MS, and the two major compounds were isolated for further evaluation. The effects of the isolated norneolignans, egonol and homoegonol, on lipopolysaccharide (LPS)-induced nitric oxide (NO) production, reactive oxygen species (ROS) production, and biomarkers of inflammation were evaluated. Of the tested compounds, egonol potently inhibited the production of NO and also significantly reduced the release of ROS. Consistent with these observations, the mRNA expression levels of inducible nitric oxide synthase (iNOS) (0.668 ± 0.108), cyclooxygenase-2 (COX-2) (0.553 ± 0.007), interleukin-1β (IL-1β) (0.093 ± 0.005), and interleukin-6 (IL-6) (0.298 ± 0.076) were reduced by egonol. The activity for both egonol and homoegonol increased in a concentration-dependent manner. These results suggest the potential of S. ramirezii Greenm. fruit to contribute to a healthy diet, rich in antioxidant and anti-inflammatory compounds.

Characterization of aroma-active compounds in raw and cooked pine-mushrooms (Tricholoma matsutake Sing.).

PubMed

Cho, In Hee; Kim, Se Young; Choi, Hyung-Kyoon; Kim, Young-Suk

2006-08-23

The characteristic aroma-active compounds in raw and cooked pine-mushrooms (Tricholoma matsutake Sing.) were investigated by gas chromatography-olfactometry using aroma extract dilution analysis. 1-Octen-3-one (mushroom-like) was the major aroma-active compound in raw pine-mushrooms; this compound had the highest flavor dilution factor, followed by ethyl 2-methylbutyrate (floral and sweet), linalool (citrus-like), methional (boiled potato-like), 3-octanol (mushroom-like and buttery), 1-octen-3-ol (mushroom-like), (E)-2-octen-1-ol (mushroom-like), and 3-octanone (mushroom-like and buttery). By contrast, methional, 2-acetylthiazole (roasted), an unknown compound (chocolate-like), 3-hydroxy-2-butanone (buttery), and phenylacetaldehyde (floral and sweet), which could be formed by diverse thermal reactions during the cooking process, together with C8 compounds, were identified as the major aroma-active compounds in cooked pine-mushrooms.

Antioxidant and Anti-Osteoporotic Activities of Aromatic Compounds and Sterols from Hericium erinaceum.

PubMed

Li, Wei; Lee, Sang Hyun; Jang, Hae Dong; Ma, Jin Yeul; Kim, Young Ho

2017-01-11

Hericium erinaceum , commonly called lion's mane mushroom, is a traditional edible mushroom widely used in culinary applications and herbal medicines in East Asian countries. In this study, a new sterol, cerevisterol 6-cinnamate ( 6 ), was isolated from the fruiting bodies of H. erinaceum together with five aromatic compounds 1 - 5 and five sterols 7 - 11 . The chemical structures of these compounds were elucidated using chemical and physical methods and comparison of HRESIMS, ¹D-NMR (¹H, 13 C, and DEPT) and 2D-NMR (COSY, HMQC, HMBC, and NOESY) spectra with previously reported data. The antioxidant and anti-osteoporotic activities of extracts and the isolated compounds 1 - 11 were investigated. All compounds exhibited peroxyl radical-scavenging capacity but only compounds 1 , 3 , and 4 showed potent reducing capacity. Moreover, compounds 1 , 2 , 4 , and 5 showed moderate effects on cellular antioxidant activity and inhibited the receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastic differentiation. These results suggested that H. erinaceum could be utilized in the development of natural antioxidant and anti-osteoporotic nutraceuticals and functional foods.

Development of a test method for carbonyl compounds from stationary source emissions

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

Zhihua Fan; Peterson, M.R.; Jayanty, R.K.M.

1997-12-31

Carbonyl compounds have received increasing attention because of their important role in ground-level ozone formation. The common method used for the measurement of aldehydes and ketones is 2,4-dinitrophenylhydrazine (DNPH) derivatization followed by high performance liquid chromatography and ultra violet (HPLC-UV) analysis. One of the problems associated with this method is the low recovery for certain compounds such as acrolein. This paper presents a study in the development of a test method for the collection and measurement of carbonyl compounds from stationary source emissions. This method involves collection of carbonyl compounds in impingers, conversion of carbonyl compounds to a stable derivativemore » with O-2,3,4,5,6-pentafluorobenzyl hydroxylamine hydrochloride (PFBHA), and separation and measurement by electron capture gas chromatography (GC-ECD). Eight compounds were selected for the evaluation of this method: formaldehyde, acetaldehyde, acrolein, acetone, butanal, methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK), and hexanal.« less

Gastroprotective activity of the hydroethanolic extract and isolated compounds from the leaves of Solanum cernuum Vell.

PubMed

Abreu Miranda, Mariza; Lemos, Marivane; Alves Cowart, Kamila; Rodenburg, Douglas; D McChesney, James; Radwan, Mohamed M; Furtado, Niege Araçari Jacometti Cardoso; Kenupp Bastos, Jairo

2015-08-22

Solanum cernuum Vell. (Solanaceae) is a Brazilian medicinal plant, traditionally known as "panaceia". Its folk name is probably due to its wide range of applications in traditional medicine including the treatment of ulcers. To evaluate the gastroprotective activities of the hydroethanolic extract (ESC) of S. cernuum and its major isolated compounds using in vivo gastric ulcer models. The ESC extract was obtained by maceration followed by percolation of the dried and powdered leaves of S. cernuum in ethanol:water (7:3). The major compounds in the extract were isolated by applying various preparative chromatographic techniques. The gastroprotective activity was evaluated in mice using different gastric ulcer-induced models. The anti-Helicobacter pylori activity was performed using the agar-well diffusion and broth microdilution methods. The ESC extract showed gastroprotective effects in the assay of acute gastric ulcer-induced by HCl/EtOH, nonsteroidal anti-inflammatory drug, and acetic acid-induced chronic ulcer protocols. The results also demonstrated that the gastroprotection induced by ESC extract is related to the activity of nitric oxide and endogenous sulfhydryls, which are important gastroprotective factors. The ESC extract and the alkaloid cernumidine did not show activity against H. pylori in the concentrations tested. The present study showed that the crude extract of S. cernuum possessed gastroprotective activity which corroborating the traditional use of this plant for the treatment of gastric ulcers. The isolated flavonoids, quercitrin and afzelin as well as the phenylpropanoid, isoferulic acid are suggested to be the compounds responsible for the gastroprotective activity of S. cernuum extract. Copyright © 2015. Published by Elsevier Ireland Ltd.

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

NASA Astrophysics Data System (ADS)

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

2008-03-01

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

Pupicidal and repellent activities of Pogostemon cablin essential oil chemical compounds against medically important human vector mosquitoes

PubMed Central

Gokulakrishnan, J; Kuppusamy, Elumalai; Shanmugam, Dhanasekaran; Appavu, Anandan; Kaliyamoorthi, Krishnappa

2013-01-01

Objective To determine the repellent and pupicidal activities of Pogostemon cablin (P. cablin) chemical compositions were assayed for their toxicity against selected important vector mosquitoes, viz., Aedes aegypti (Ae. aegypti), Anopheles stephensi (An. stephensi) and Culex quinquefasciatus (Cx. quinquefasciatus) (Diptera: Culicidae). Methods The plants dry aerial parts were subjected to hydrodistillation using a modified Clevenger-type apparatus. The composition of the essential oil was analyzed by Gas Chromatography (GC) and GC mass spectrophotometry. Evaluation was carried out in a net cage (45 cm×30 cm×45 cm) containing 100 blood starved female mosquitoes and were assayed in the laboratory condition by using the protocol of WHO 2010. The repellent activity of P. cablin chemical compositions at concentration of 2mg/cm2were applied on skin of fore arm in man and exposed against adult female mosquitoes. The pupicidal activity was determined against selected important vector mosquitoes to concentration of 100 mg/L and mortality of each pupa was recorded after 24 h of exposure to the compounds. Results Chemical constituents of 15 compounds were identified in the oil of P.cablin compounds representing to 98.96%. The major components in essential oil were â-patchoulene, á-guaiene, ã-patchoulene, á-bulnesene and patchouli alcohol. The repellent activity of patchouli alcohol compound was found to be most effective for repellent activity and 2 mg/cm2 concentration provided 100% protection up to 280 min against Ae. aegypti, An. stephensi and Cx. quinquefasciatus, respectively. Similarly, pupae exposed to 100 mg/L concentrations of P. cablin chemical compositions. Among five compounds tested patchouli alcoholwas found to be most effective for pupicidal activity provided 28.44, 26.28 and 25.36 against Ae.aegypti, An.stephensi and Cx. quinquefasciatus, respectively. The percent adult emergence was inversely proportional to the concentration of compounds and directly

In vitro antimicrobial activity of extracts and isolated compound from Dalbergia stipulacea Roxb. leaves

NASA Astrophysics Data System (ADS)

Kumar, Arvind; Bhat, Tahir Ahmad; Singh, Rattan Deep

2017-07-01

The study was designed to examine the in vitro antimicrobial efficacy of extracts and isolated compound of Dalbergia stipulacea. Combined extracts (chloroform and methanol) of plant leaves fractionated with n-butanol loaded with column afforded a flavonoid glycoside compound identified as luteolin 4'-rutinoside. Different extracts and isolated compound exhibited pronounced antibacterial and antifungal varied activities against four bacteria (Clostridium acetobutylinium, Bacillus subtilis, Streptococcus mutans, and Pseudomonas sp.) and one fungus (Candida albicans) susceptibility were determined using disc diffusion method. The minimum inhibitory concentration (MIC) of extracts and isolated compounds was determined by broth dilution method. The maximum activity was shown by chloroform extract against C. albicans with a zone of inhibition of 17 mm and minimum activity was displayed by methanolic extract against Pseudomonas sp. with 5 mm. However, isolated compound has shown maximum activity against Pseudomonas sp. with 15 mm. The MIC values higher in methanol extract against Pseudomonas sp. and isolated compound shows good against Pseudomonas sp. and B. subtilis. Our findings indicate that plant could be used as a good antimicrobial agent in food, pharmaceutical and bio-pesticide industries.

Antibacterial assay-guided isolation of active compounds from Artocarpus heterophyllus heartwoods.

PubMed

Septama, Abdi Wira; Panichayupakaranant, Pharkphoom

2015-01-01

Preparations from Artocarpus heterophyllus Lam. (Moraceae) heartwoods are used in the traditional folk medicine for the treatment of inflammation, malarial fever, and to prevent bacterial and fungal infections. The objective of this study was to isolate pure antibacterial compounds from A. heterophyllus heartwoods. The dried and powdered A. heterophyllus heartwoods were successively extracted with the following solvents: hexane, ethyl acetate, and methanol. Each of the extracts was screened for their antibacterial activities using a disc diffusion method (10 mg/disc). Their minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined using a broth microdilution method. The extract that showed the strongest antibacterial activities was fractionated to isolate the active compounds by an antibacterial assay-guided isolation process. The ethyl acetate extract exhibited the strongest antibacterial activities against Streptococcus mutans, S. pyogenes, and Bacillus subtilis with MIC values of 78, 39, and 9.8 µg/mL, respectively. Based on an antibacterial assay-guided isolation, four antibacterial compounds: cycloartocarpin (1), artocarpin (2), artocarpanone (3), and cyanomaclurin (4) were purified. Among these isolated compounds, artocarpin exhibited the strongest antibacterial activity against Gram-positive bacteria, including S. mutans, S. pyogenes, B. subtilis, Staphylococcus aureus, and S. epidermidis with MICs of 4.4, 4.4, 17.8, 8.9, and 8.9 µM, respectively, and MBCs of 8.9, 8.9, 17.8, 8.9, and 8.9 µM, respectively, while artocarpanone showed the strongest activity against Escherichia coli, a Gram-negative bacteria with MIC and MBC values of 12.9 and 25.8 µM, respectively. Only artocarpin showed inhibitory activity against Pseudomonas aeruginosa with an MIC of 286.4 µM.

Total phenolic compounds, flavonoids, and radical scavenging activity of 21 selected tropical plants.

PubMed

Mustafa, R A; Abdul Hamid, A; Mohamed, S; Bakar, F Abu

2010-01-01

Free radical scavenging activity of 21 tropical plant extracts was evaluated using 1,1-diphenyl-2-picrylhydrazyl assay (DPPH). Total phenolic compounds and flavonoids were determined using Folin-Ciocalteu and HPLC, respectively. Results of the study revealed that all the plants tested exhibited excellent antioxidant activity with IC(50) in the range of 21.3 to 89.6 microg/mL. The most potent activity was demonstrated by Cosmos caudatus (21.3 microg/mL) and Piper betle (23.0 microg/mL) that are not significantly different than that of -tocopherol or BHA. L. inermis extract was found to consist of the highest concentration of phenolics, catechin, epicatechin, and naringenin. High content of quercetin, myricetin, and kaempferol were identified in Vitex negundo, Centella asiatica, and Sesbania grandiflora extracts, respectively. Luteolin and apigenin, on the other hand, were found in Premna cordifolia and Kaempferia galanga extracts. Strong correlation (R = 0.8613) between total phenolic compounds and total flavonoids (R = 0.8430) and that of antioxidant activity of the extracts were observed. The study revealed that phenolic, in particular flavonoids, may be the main contributors to the antioxidant activity exhibited by the plants. Potent antioxidant from natural sources is of great interest to replace the use of synthetic antioxidants. In addition, some of the plants have great potential to be used in the development of functional ingredients/foods that are currently in demand for the health benefits associated with their use.

Porritoxins, metabolites of Alternaria porri, as anti-tumor-promoting active compounds.

PubMed

Horiuchi, Masayuki; Tokuda, Harukuni; Ohnishi, Keiichiro; Yamashita, Masakazu; Nishino, Hoyoku; Maoka, Takashi

2006-02-01

To search for possible cancer chemopreventive agents from natural sources, we performed primary screening of metabolites of Alternaria porri by examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. The ethyl acetate extract of A. porri showed the inhibitory effect on EBV-EA activation. Three porritoxins (1-3) were obtained as inhibitory active compounds for EBV-EA from ethyl acetate extract. 6-(3',3'-Dimethylallyloxy)-4-methoxy-5-methylphthalide (2) showed the strongest activity among them. Inhibitory effect of porritoxin (1) and (2) was superior to that of beta-carotene, a well-known anti-tumor promoter. Furthermore, the structure-activity correlation of porritoxins and their related compounds were discussed.

Compounds Derived from the Bhutanese Daisy, Ajania nubigena, Demonstrate Dual Anthelmintic Activity against Schistosoma mansoni and Trichuris muris.

PubMed

Wangchuk, Phurpa; Pearson, Mark S; Giacomin, Paul R; Becker, Luke; Sotillo, Javier; Pickering, Darren; Smout, Michael J; Loukas, Alex

2016-08-01

Whipworms and blood flukes combined infect almost one billion people in developing countries. Only a handful of anthelmintic drugs are currently available to treat these infections effectively; there is therefore an urgent need for new generations of anthelmintic compounds. Medicinal plants have presented as a viable source of new parasiticides. Ajania nubigena, the Bhutanese daisy, has been used in Bhutanese traditional medicine for treating various diseases and our previous studies revealed that small molecules from this plant have antimalarial properties. Encouraged by these findings, we screened four major compounds isolated from A. nubigena for their anthelmintic properties. Here we studied four major compounds derived from A. nubigena for their anthelmintic properties against the nematode whipworm Trichuris muris and the platyhelminth blood fluke Schistosoma mansoni using the xWORM assay technique. Of four compounds tested, two compounds-luteolin (3) and (3R,6R)-linalool oxide acetate (1)-showed dual anthelmintic activity against S. mansoni (IC50 range = 5.8-36.9 μg/mL) and T. muris (IC50 range = 9.7-20.4 μg/mL). Using scanning electron microscopy, we determined luteolin as the most efficacious compound against both parasites and additionally was found effective against the schistosomula, the infective stage of S. mansoni (IC50 = 13.3 μg/mL). Luteolin induced tegumental damage to S. mansoni and affected the cuticle, bacillary bands and bacillary glands of T. muris. Our in vivo assessment of luteolin (3) against T. muris infection at a single oral dosing of 100 mg/kg, despite being significantly (27.6%) better than the untreated control group, was markedly weaker than mebendazole (93.1%) in reducing the worm burden in mice. Among the four compounds tested, luteolin demonstrated the best broad-spectrum activity against two different helminths-T. muris and S. mansoni-and was effective against juvenile schistosomes, the stage that is refractory to the current

Effect of vanadium compounds on acid phosphatase activity.

PubMed

Vescina, C M; Sálice, V C; Cortizo, A M; Etcheverry, S B

1996-01-01

The direct effect of different vanadium compounds on acid phosphatase (ACP) activity was investigated. Vanadate and vanadyl but not pervanadate inhibited the wheat germ ACP activity. These vanadium derivatives did not alter the fibroblast Swiss 3T3 soluble fraction ACP activity. Using inhibitors of tyrosine phosphatases (PTPases), the wheat germ ACP was partially characterized as a PTPase. This study suggests that the inhibitory ability of different vanadium derivatives to modulate ACP activity seems to depend on the geometry around the vanadium atom more than on the oxidation state. Our results indicate a correlation between the PTPase activity and the sensitivity to vanadate and vanadyl cation.

Antimicrobial active herbal compounds against Acinetobacter baumannii and other pathogens.

PubMed

Tiwari, Vishvanath; Roy, Ranita; Tiwari, Monalisa

2015-01-01

Bacterial pathogens cause a number of lethal diseases. Opportunistic bacterial pathogens grouped into ESKAPE pathogens that are linked to the high degree of morbidity, mortality and increased costs as described by Infectious Disease Society of America. Acinetobacter baumannii is one of the ESKAPE pathogens which cause respiratory infection, pneumonia and urinary tract infections. The prevalence of this pathogen increases gradually in the clinical setup where it can grow on artificial surfaces, utilize ethanol as a carbon source and resists desiccation. Carbapenems, a β-lactam, are the most commonly prescribed drugs against A. baumannii. The high level of acquired and intrinsic carbapenem resistance mechanisms acquired by these bacteria makes their eradication difficult. The pharmaceutical industry has no solution to this problem. Hence, it is an urgent requirement to find a suitable alternative to carbapenem, a commonly prescribed drug for Acinetobacter infection. In order to do this, here we have made an effort to review the active compounds of plants that have potent antibacterial activity against many bacteria including carbapenem resistant strain of A. baumannii. We have also briefly highlighted the separation and identification methods used for these active compounds. This review will help researchers involved in the screening of herbal active compounds that might act as a replacement for carbapenem.

Antifungal activity of synthetic antiseptics and natural compounds against Candida dubliniensis before and after in vitro fluconazole exposure.

PubMed

Reginato, Cássia Franco; Bandeira, Laíssa Arévalo; Zanette, Régis Adriel; Santurio, Janio Morais; Alves, Sydney Hartz; Danesi, Cristiane Cademartori

2017-01-01

This study evaluated the susceptibilities of oral candidiasis-derived Candida albicans, fluconazole-resistant (FR) Candida dubliniensis, and fluconazole-susceptible (FS) C. dubliniensis to synthetic antiseptics [chlorhexidine gluconate (CHX), cetylpyridinium chloride (CPC), and triclosan (TRC)] and natural compounds (carvacrol, eugenol and thymol). Susceptibility tests were performed based on the M27-A3 reference method. The fluconazole-resistant C. dubliniensis strains were obtained after prolonged in vitro exposure to increasing fluconazole concentrations. The geometric mean values for minimum inhibitory concentrations and minimum fungicidal concentrations were compared among the groups. Fluconazole-susceptible C. dubliniensis was more sensitive to CPC and TRC than FR C. dubliniensis and C. albicans were. However, eugenol and thymol were more active against FR C. dubliniensis. The fungicidal activities of CHX and TRC were similar for the three groups, and FR C. dubliniensis and C. albicans had similar sensitivities to CPC. The resistance of C. dubliniensis to fluconazole affects its sensitivity the synthetic antiseptics and natural compounds that were tested.

Compound simulator IR radiation characteristics test and calibration

NASA Astrophysics Data System (ADS)

Li, Yanhong; Zhang, Li; Li, Fan; Tian, Yi; Yang, Yang; Li, Zhuo; Shi, Rui

2015-10-01

The Hardware-in-the-loop simulation can establish the target/interference physical radiation and interception of product flight process in the testing room. In particular, the simulation of environment is more difficult for high radiation energy and complicated interference model. Here the development in IR scene generation produced by a fiber array imaging transducer with circumferential lamp spot sources is introduced. The IR simulation capability includes effective simulation of aircraft signatures and point-source IR countermeasures. Two point-sources as interference can move in two-dimension random directions. For simulation the process of interference release, the radiation and motion characteristic is tested. Through the zero calibration for optical axis of simulator, the radiation can be well projected to the product detector. The test and calibration results show the new type compound simulator can be used in the hardware-in-the-loop simulation trial.

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.

Antimicrobial Activity of Extracts of the Oyster Culinary Medicinal Mushroom Pleurotus ostreatus (Higher Basidiomycetes) and Identification of a New Antimicrobial Compound.

PubMed

Younis, Ahmed M; Wu, Fang-Sheng; El Shikh, Hussien H

2015-01-01

Pleurotus ostreatus is an edible mushroom that also has high medicinal values. In this study, P. ostreatus was tested for its ability to inhibit the growth of fungi and bacteria. The freeze-dried fruiting body, broth from submerged culture, and mycelial biomass of P. ostreatus were extracted using alcohols and water as solvents. The extracts were then tested for their antimicrobial activity against the growth of fungi and bacteria. It was observed that the water extract from fruiting bodies had the strongest effect in inhibiting the growth of most fungi. The most sensitive test microfungi to the inhibition were Candida albicans, Cryptococcus humicola, and Trichosporon cutaneum, and the most sensitive test bacteria were Staphylococcus aureus followed by Escherichia coli. Water extracts from culture broth or mycelial biomass were moderately inhibitive to the growth of fungi and bacteria. The alcohol-based solvents from all samples had much less antimicrobial activity against most test microorganisms. An antimicrobial compound was purified from the water extracts of fruiting bodies with Sephadex G 100 column chromatography and characterized by infrared absorption spectrum (IR), nuclear magnetic resonance (NMR), and mass spectroscopic analysis. We have identified this compound to be 3-(2-aminopheny1thio)-3-hydroxypropanoic acid. This purified compound had a minimum inhibitory concentration of 30 µg/mL and 20 µg/mL against the growth of fungi and bacteria, respectively.

Characterization of Compounds with Tumor-Cell Proliferation Inhibition Activity from Mushroom (Phellinus baumii) Mycelia Produced by Solid-State Fermentation.

PubMed

Zhang, Henan; Shao, Qian; Wang, Wenhan; Zhang, Jingsong; Zhang, Zhong; Liu, Yanfang; Yang, Yan

2017-04-27

The inhibition of tumor-cell proliferationbyan organicsolvent extract from the solid-state fermentation of Phellinus baumii mycelia inoculated in rice medium was investigated in vitro. The active compounds inhibiting tumor-cell proliferation were characterized. Results revealed that all (petroleum ether, chloroform, ethyl acetate, and butanol) fractions inhibited tumor-cell proliferation in a dose-dependent fashion. The ethyl acetate extract had the highest inhibitory effecton tumor-cell proliferation, and the butanol fraction had the lowest. Six compounds were isolated and purified from the ethyl acetate extract of P. baumii mycelia by the tandem application of silica-gel column chromatography (SGCC), high-speed countercurrent chromatography (HSCCC), and preparative HPLC. These compounds were identified by NMR and electrospray ionization-mass spectrometry (ESI-MS) spectroscopic methods as ergosterol (RF1), ergosta-7,22-dien-3β-yl pentadecanoate (RF3), 3,4-dihydroxy benzaldehyde(RF6), inoscavinA (RF7), baicalein(RF10), and 24-ethylcholesta-5,22-dien-3β-ol (RF13). To further clarify the activity of these compounds, the cell-proliferation-inhibition tests of these compounds on various tumor cells were carried out and evaluatedin vitro. Results suggested that compounds RF6, RF7, and RF10 had potent inhibition effects on the proliferation of a series of tumor cell lines, including K562, L1210, SW620, HepG2, LNCaP, and MCF-7cells. These findings indicated that P. baumii mycelia produced by solid-state fermentation in rice canbe used to obtain active compounds with the ability to inhibittumor-cell proliferation.

21 CFR 862.1185 - Compound S (11-deoxycortisol) test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Compound S (11-deoxycortisol) test system. 862.1185 Section 862.1185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

21 CFR 862.1185 - Compound S (11-deoxycortisol) test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Compound S (11-deoxycortisol) test system. 862.1185 Section 862.1185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

21 CFR 862.1185 - Compound S (11-deoxycortisol) test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Compound S (11-deoxycortisol) test system. 862.1185 Section 862.1185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

21 CFR 862.1185 - Compound S (11-deoxycortisol) test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Compound S (11-deoxycortisol) test system. 862.1185 Section 862.1185 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

Antibacterial, anti-inflammatory and anti-oxidatant activities of various isolated compounds from Cratoxylum species.

PubMed

Rodanant, Pirasut; Boonnak, Nawong; Surarit, Rudee; Kuvatanasuchati, Jintakorn; Lertsooksawat, Wannee

2017-05-01

The objective of this study was to investigate the bioactivity of twenty-nine known isolated compounds from Cratoxylum species including three anthraquinones, four triterpenes, and twenty-two xanthones. All isolated compounds were subjected to antibacterial, anti-inflammatory and anti-oxidant activities. Cytotoxicity evaluations were performed by MTT assay. The anti-oxidatant activity was performed using DPPH assay. The anti-inflammatory activity was evaluated from the production of cytokines TNF-α and IL1-β using ELISA assay. Human gingival fibroblasts and monocytes could tolerate both anthraquinones and triterpenes. All isolated anthraquinones showed moderate-to-high antibacterial efficacy while compound A3 also demonstrated moderate anti-inflammatory effect. None of the isolated triterpenes, except for T1, inhibited the expression of TNF-α. A number of isolated xanthones was toxic to HGFs and monocytes. Compound X5, X14 and a 1:1 mixture of X5 and X6 showed comparative anti-inflammatory activity to dexamethasone. Several triterpene and xanthone compounds also expressed antibacterial effect against P. gingivalis. Some isolated xanthones exerted anti-oxidant activity comparable to ascorbic acid. Accordingly, selected pure compounds from plants of Cratoxylum genus might be of benefit in developing medications that are important in treating periodontal diseases.

Anti-trypanosomal activities and structural chemical properties of selected compound classes.

PubMed

Ponte-Sucre, Alicia; Bruhn, Heike; Schirmeister, Tanja; Cecil, Alexander; Albert, Christian R; Buechold, Christian; Tischer, Maximilian; Schlesinger, Susanne; Goebel, Tim; Fuß, Antje; Mathein, Daniela; Merget, Benjamin; Sotriffer, Christoph A; Stich, August; Krohne, Georg; Engstler, Markus; Bringmann, Gerhard; Holzgrabe, Ulrike

2015-02-01

Potent compounds do not necessarily make the best drugs in the market. Consequently, with the aim to describe tools that may be fundamental for refining the screening of candidates for animal and preclinical studies and further development, molecules of different structural classes synthesized within the frame of a broad screening platform were evaluated for their trypanocidal activities, cytotoxicities against murine macrophages J774.1 and selectivity indices, as well as for their ligand efficiencies and structural chemical properties. To advance into their modes of action, we also describe the morphological and ultrastructural changes exerted by selected members of each compound class on the parasite Trypanosoma brucei. Our data suggest that the potential organelles targeted are either the flagellar pocket (compound 77, N-Arylpyridinium salt; 15, amino acid derivative with piperazine moieties), the endoplasmic reticulum membrane systems (37, bisquaternary bisnaphthalimide; 77, N-Arylpyridinium salt; 68, piperidine derivative), or mitochondria and kinetoplasts (88, N-Arylpyridinium salt; 68, piperidine derivative). Amino acid derivatives with fumaric acid and piperazine moieties (4, 15) weakly inhibiting cysteine proteases seem to preferentially target acidic compartments. Our results suggest that ligand efficiency indices may be helpful to learn about the relationship between potency and chemical characteristics of the compounds. Interestingly, the correlations found between the physico-chemical parameters of the selected compounds and those of commercial molecules that target specific organelles indicate that our rationale might be helpful to drive compound design toward high activities and acceptable pharmacokinetic properties for all compound families.

Quinolone Amides as Antitrypanosomal Lead Compounds with In Vivo Activity.

PubMed

Hiltensperger, Georg; Hecht, Nina; Kaiser, Marcel; Rybak, Jens-Christoph; Hoerst, Alexander; Dannenbauer, Nicole; Müller-Buschbaum, Klaus; Bruhn, Heike; Esch, Harald; Lehmann, Leane; Meinel, Lorenz; Holzgrabe, Ulrike

2016-08-01

Human African trypanosomiasis (HAT) is a major tropical disease for which few drugs for treatment are available, driving the need for novel active compounds. Recently, morpholino-substituted benzyl amides of the fluoroquinolone-type antibiotics were identified to be compounds highly active against Trypanosoma brucei brucei Since the lead compound GHQ168 was challenged by poor water solubility in previous trials, the aim of this study was to introduce structural variations to GHQ168 as well as to formulate GHQ168 with the ultimate goal to increase its aqueous solubility while maintaining its in vitro antitrypanosomal activity. The pharmacokinetic parameters of spray-dried GHQ168 and the newly synthesized compounds GHQ242 and GHQ243 in mice were characterized by elimination half-lives ranging from 1.5 to 3.5 h after intraperitoneal administration (4 mice/compound), moderate to strong human serum albumin binding for GHQ168 (80%) and GHQ243 (45%), and very high human serum albumin binding (>99%) for GHQ242. For the lead compound, GHQ168, the apparent clearance was 112 ml/h and the apparent volume of distribution was 14 liters/kg of body weight (BW). Mice infected with T. b. rhodesiense (STIB900) were treated in a stringent study scheme (2 daily applications between days 3 and 6 postinfection). Exposure to spray-dried GHQ168 in contrast to the control treatment resulted in mean survival durations of 17 versus 9 days, respectively, a difference that was statistically significant. Results that were statistically insignificantly different were obtained between the control and the GHQ242 and GHQ243 treatments. Therefore, GHQ168 was further profiled in an early-treatment scheme (2 daily applications at days 1 to 4 postinfection), and the results were compared with those obtained with a control treatment. The result was statistically significant mean survival times exceeding 32 days (end of the observation period) versus 7 days for the GHQ168 and control treatments

Quantitative structure-activity relationship of organosulphur compounds as soybean 15-lipoxygenase inhibitors using CoMFA and CoMSIA.

PubMed

Caballero, Julio; Fernández, Michael; Coll, Deysma

2010-12-01

Three-dimensional quantitative structure-activity relationship studies were carried out on a series of 28 organosulphur compounds as 15-lipoxygenase inhibitors using comparative molecular field analysis and comparative molecular similarity indices analysis. Quantitative information on structure-activity relationships is provided for further rational development and direction of selective synthesis. All models were carried out over a training set including 22 compounds. The best comparative molecular field analysis model only included steric field and had a good Q² = 0.789. Comparative molecular similarity indices analysis overcame the comparative molecular field analysis results: the best comparative molecular similarity indices analysis model also only included steric field and had a Q² = 0.894. In addition, this model predicted adequately the compounds contained in the test set. Furthermore, plots of steric comparative molecular similarity indices analysis field allowed conclusions to be drawn for the choice of suitable inhibitors. In this sense, our model should prove useful in future 15-lipoxygenase inhibitor design studies. © 2010 John Wiley & Sons A/S.

Anti-inflammatory activities of compounds from twigs of Morus alba.

PubMed

Tran, Huynh Nguyen Khanh; Nguyen, Van Thu; Kim, Jeong Ah; Rho, Seong Soo; Woo, Mi Hee; Choi, Jae Sui; Lee, Jeong-Hyung; Min, Byung Sun

2017-07-01

Five new compounds, 10-oxomornigrol F (1), (7″R)-(-)-6-(7″-hydroxy-3″,8″-dimethyl-2″,8″-octadien-1″-yl)apigenin (2), ramumorin A (3), ramumorin B (4), and (4S,7S,8R)-trihydroxyoctadeca-5Z-enoic acid (5), together with 31 known compounds (6-36), were isolated from the twigs of Morus alba (Moraceae). The chemical structures of these compounds were established using spectroscopic analyses, 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), and Mosher's methods. The anti-inflammatory activities of the compounds were evaluated by investigating their ability to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW 264.7 cells. Compounds 1, 2, 13, 17, 19, 25-28, and 32 showed inhibitory effects with IC 50 values ranging from 2.2 to 5.3μg/mL. Compounds 1, 2, 17, 25, and 32 reduced LPS-induced inducible nitric oxide synthase (iNOS) expression in a concentration-dependent manner. In addition, pretreating the cells with compound 1, 17, and 32 significantly suppressed LPS-induced expression of cyclooxygenase-2 (COX-2) protein. Copyright © 2017. Published by Elsevier B.V.

Antioxidative and melanogenesis-inhibitory activities of caffeoylquinic acids and other compounds from moxa.

PubMed

Akihisa, Toshihiro; Kawashima, Kohta; Orido, Masashi; Akazawa, Hiroyuki; Matsumoto, Masahiro; Yamamoto, Ayako; Ogihara, Eri; Fukatsu, Makoto; Tokuda, Harukuni; Fuji, Jizaemon

2013-03-01

The MeOH extract of moxa, the processed leaves of Artemisia princeps PAMP. (Asteraceae), exhibited potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and melanogenesis-inhibitory activity in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16 melanoma cells. Eight caffeoylquinic acids, 1 and 6-12, five flavonoids, 13-17, two benzoic acid derivatives, 18 and 19, three coumarin derivatives, 20-22, four steroids, 23-26, and six triterpenoids, 27-32, were isolated from the MeOH extract. Upon evaluation of compounds 1, 6-23, and four semisynthetic caffeoylquinic acid esters, 2-5, for their DPPH radical-scavenging activity, 15 compounds, 1-13, 17, and 19, showed potent activities (IC(50) 3.1-16.8 μM). The 15 compounds exhibited, moreover, potent inhibitory activities (51.1-92.5% inhibition) against peroxidation of linoleic acid emulsion at 10 μg/ml concentration. In addition, when 27 compounds, 1-8, 10, 12, 13, 15-18, 20-25, and 27-32, were evaluated for their inhibitory activity against melanogenesis in α-MSH-stimulated B16 melanoma cells, five caffeoylquinic acids, i.e., chlorogenic acid (1), ethyl chlorogenate (3), propyl chlorogenate (4), isopropyl chlorogenate (5), and butyl chlorogenate (6), along with homoorientin (17) and vanillic acid (18), exhibited inhibitory activities with 33-62% reduction of melanin content at 100 μM concentration with no or almost no toxicity to the cells (89-114% of cell viability at 100 μM). Western blot analysis showed that compound 6 reduced the protein levels of microphtalmia-associated transcription factor (MITF), tyrosinase, tyrosine-related protein 1 (TRP-1), and TRP-2 mostly in a concentration-dependent manner, suggesting that this compound inhibits melanogenesis on α-MSH-stimulated B16 melanoma cells by, at least in part, inhibiting the expression of MITF, followed by decreasing the expression of tyrosinase, TRP-1, and TRP-2. Furthermore, four compounds, 13, 15, 16, and 30, exhibited

Systematic assessment of scaffold hopping versus activity cliff formation across bioactive compound classes following a molecular hierarchy.

PubMed

Stumpfe, Dagmar; Dimova, Dilyana; Bajorath, Jürgen

2015-07-01

Scaffold hopping and activity cliff formation define opposite ends of the activity landscape feature spectrum. To rationalize these events at the level of scaffolds, active compounds involved in scaffold hopping were required to contain topologically distinct scaffolds but have only limited differences in potency, whereas compounds involved in activity cliffs were required to share the same scaffold but have large differences in potency. A systematic search was carried out for compounds involved in scaffold hopping and/or activity cliff formation. Results obtained for compound data sets covering more than 300 human targets revealed clear trends. If scaffolds represented multiple but fewer than 10 active compounds, nearly 90% of all scaffolds were exclusively involved in hopping events. With increasing compound coverage, the fraction of scaffolds involved in both scaffold hopping and activity cliff formation significantly increased to more than 50%. However, ∼40% of the scaffolds representing large numbers of active compounds continued to be exclusively involved in scaffold hopping. More than 200 scaffolds with broad target coverage were identified that consistently represented potent compounds and yielded an abundance of scaffold hops in the low-nanomolar range. These and other subsets of scaffolds we characterized are of prime interest for structure-activity relationship (SAR) exploration and compound design. Therefore, the complete scaffold classification generated in the course of our analysis is made freely available. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cinnamoyl compounds as simple molecules that inhibit p300 histone acetyltransferase.

PubMed

Costi, Roberta; Di Santo, Roberto; Artico, Marino; Miele, Gaetano; Valentini, Paola; Novellino, Ettore; Cereseto, Anna

2007-04-19

Cinnamoly compounds 1a-c and 2a-d were designed, synthesized, and in vitro tested as p300 inhibitors. At different degrees, all tested compounds were proven to inactivate p300, particularly, derivative 2c was the most active inhibitor, also showing high specificity for p300 as compared to other histone acetyltransferases. Most notably, 2c showed anti-acetylase activity in mammalian cells. These compounds represent a new class of synthetic inhibitors of p300, characterized by simple chemical structures.

Identifying relationships between unrelated pharmaceutical target proteins on the basis of shared active compounds.

PubMed

Miljković, Filip; Kunimoto, Ryo; Bajorath, Jürgen

2017-08-01

Computational exploration of small-molecule-based relationships between target proteins from different families. Target annotations of drugs and other bioactive compounds were systematically analyzed on the basis of high-confidence activity data. A total of 286 novel chemical links were established between distantly related or unrelated target proteins. These relationships involved a total of 1859 bioactive compounds including 147 drugs and 141 targets. Computational analysis of large amounts of compounds and activity data has revealed unexpected relationships between diverse target proteins on the basis of compounds they share. These relationships are relevant for drug discovery efforts. Target pairs that we have identified and associated compound information are made freely available.

An in vitro test system for compounds that modulate human inflammatory macrophage polarization.

PubMed

Shiratori, Hiromi; Feinweber, Carmen; Luckhardt, Sonja; Wallner, Nadja; Geisslinger, Gerd; Weigert, Andreas; Parnham, Michael J

2018-06-16

Macrophages undergo activation by pathophysiological stimuli to pro-inflammatory and bactericidal, or wound-healing and anti-inflammatory phenotypes, termed M1 or M2, respectively. Dysregulation of the M1-M2 balance is often associated with inflammatory diseases. Therefore, mechanisms of macrophage polarization may reveal new drug targets. We profiled six compounds with claimed modulatory effects on macrophage polarization using peripheral blood monocyte-derived macrophages. Based on the distinct mRNA or protein expression in macrophages stimulated either with M1 [lipopolysaccharide (LPS) + interferon-γ, IFNγ] or M2 interleukin-4 (IL-4) stimuli, we selected a combination of M1 (IL1β, tumor necrosis factor-α,TNFα, CC chemokine receptor 7, CCR7 and CD80) and M2 (chemokine (C-C motif) ligand 22, CCL22, CD200R and mannose receptor C type 1, MRC1) markers to monitor drug effects on "M1 polarization" or cells "pre-polarized to M1". Azithromycin (25-50μM), tofacitinib (2.5-5μM), hydroxychloroquine (40µg/ml) and pioglitazone (15-60μM) exhibit an anti-inflammatory profile because they downregulated M1 markers and upregulated some M2 markers when given both before and after M1 polarization. Lovastatin given before M1 polarization downregulated M1 marker genes but enhanced the M1 phenotype in macrophages pre-polarized with LPS and IFNγ. Methotrexate (1.25-5μM) did not modulate macrophage polarization. We have, thus, established a test system suitable to identify novel compounds or repurposed drugs that modulate inflammatory macrophage plasticity. Compounds with potential to reduce expression of molecules involved in inflammatory T cell activation (IL-1β, TNFα, CD80), while enhancing production of a major chemokine involved in recruitment of Tregs (CCL22) may be of interest for treating chronic inflammatory diseases. Copyright © 2018. Published by Elsevier B.V.

Predicting adult fish acute lethality with the zebrafish embryo: relevance of test duration, endpoints, compound properties, and exposure concentration analysis.

PubMed

Knöbel, Melanie; Busser, Frans J M; Rico-Rico, Angeles; Kramer, Nynke I; Hermens, Joop L M; Hafner, Christoph; Tanneberger, Katrin; Schirmer, Kristin; Scholz, Stefan

2012-09-04

The zebrafish embryo toxicity test has been proposed as an alternative for the acute fish toxicity test, which is required by various regulations for environmental risk assessment of chemicals. We investigated the reliability of the embryo test by probing organic industrial chemicals with a wide range of physicochemical properties, toxicities, and modes of toxic action. Moreover, the relevance of using measured versus nominal (intended) exposure concentrations, inclusion of sublethal endpoints, and different exposure durations for the comparability with reported fish acute toxicity was explored. Our results confirm a very strong correlation of zebrafish embryo to fish acute toxicity. When toxicity values were calculated based on measured exposure concentrations, the slope of the type II regression line was 1 and nearly passed through the origin (1 to 1 correlation). Measured concentrations also explained several apparent outliers. Neither prolonged exposure (up to 120 h) nor consideration of sublethal effects led to a reduced number of outliers. Yet, two types of compounds were less lethal to embryos than to adult fish: a neurotoxic compound acting via sodium channels (permethrin) and a compound requiring metabolic activation (allyl alcohol).

Leishmanicidal activity of Nystatin (mycostatin): a potent polyene compound.

PubMed

Ali, S A; Iqbal, J; Nabeel; Khalil, Y; Manzoor, A; Bukhari, I; Ahmad, B; Yasinzai, M M

1997-10-01

The susceptibility of promastigote of Leishmania major to Nystatin in vitro was examined. L. major (MHOM/PK/88/DESTO) promastigote were cultured in medium 199 supplemented with 10% heat inactivated foetal bovine serum and 2% urine. The growth of the promastigote was monitored in the absence and presence of the experimental compound (Nystatin) for upto 5 days post-inoculation. The EC50 value (the concentration of drug necessary to inhibit the growth rate of cells to 50% of the control value) obtained for Nystatin against the promastigote of L. major was less than 9.76 iu ml. Certain polyene compounds like Amphotericin-B and Nystatin (mycostatin) are familiar for their fungicidal activity. Amphotericin-B is used since long as antileishmanial drug as well. Results obtained suggest that Nystatin has a very good anti leishmanial activity in vitro. The mode of action proposed for this drug is same as for Amphotericin-B as both of these polyene compounds interact with the various sterols present on the surface of the parasite, thus unusual gaps and pores are formed on the surface that results in the leakage of the ions. This leakage finally leads to the destruction of the parasite.

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.

Development of LLDPE based active nanocomposite films with nanoclays impregnated with volatile compounds.

PubMed

Tornuk, Fatih; Sagdic, Osman; Hancer, Mehmet; Yetim, Hasan

2018-05-01

In this study, a novel procedure was performed for grafting of nanoclays (montmorillonite (MMT) and halloysite (HNT)) with essential oil constituents (thymol (THY), eugenol (EUG) and carvacrol (CRV)) using Tween 80 as surfactant and then the nanoclay particles were incorporated into LLDPE pellets (5 wt%) to produce active nanocomposite films using a twin screw extruder. The resulting nanocomposite films were analyzed for antimicrobial and antioxidant capacity as well as thickness, mechanical, color, barrier, thermal properties and surface morphology and molecular composition. Release of the active compounds from the films at the refrigerated and room temperature conditions were also tested. The results showed that the films had strong in vitro antibacterial activity against pathogenic bacteria (Salmonella Typhimurium, Escherichia coli O157:H7, Listeria monocytogenes, Staphylococcus aureus and Bacillus cereus) while their effect against lactic acid bacteria (Lactobacillus rhamnosus and Lb. casei) was limited. The lowest and highest DPPH scavenging ability levels were 65.59% and % 87.92, belonged to THY-MMT and EUG-MMT, respectively. Release of active compounds at 24 °C was much more rapid than at 4 °C. CRV-HNT and THY-HNT provided slower release than the other films. SEM results showed that nanoclays were uniformly dispersed in the polymer matrix with exceptional agglomerates. Incorporation of the active nanoclays significantly (P > 0.05) improved tensile strength and elongation of the films. The results confirmed that LLDPE based active nanocomposite films could be successfully produced due to its good interaction with MMT and HNT, activated with THY, EUG and CRV. Copyright © 2018 Elsevier Ltd. All rights reserved.

Compound K Attenuates the Development of Atherosclerosis in ApoE−/− Mice via LXRα Activation

PubMed Central

Zhou, Li; Zheng, Yu; Li, Zhuoying; Bao, Lingxia; Dou, Yin; Tang, Yuan; Zhang, Jianxiang; Zhou, Jianzhi; Liu, Ya; Jia, Yi; Li, Xiaohui

2016-01-01

Background: Atherosclerosis is a fundamental pathological process responded to some serious cardiovascular events. Although the cholesterol-lowering drugs are widely prescribed for atherosclerosis therapy, it is still the leading cause of death in the developed world. Here we measured the effects of compound K in atherosclerosis formation and investigated the probably mechanisms of the anti-antherosclerosis roles of compound K. Methods: We treated the atherosclerotic model animals (apoE−/− mice on western diet) with compound K and measured the size of atherosclerotic lesions, inflammatory cytokine levels and serum lipid profile. Peritoneal macrophages were collected in vitro for the foam cell and inflammasome experiments. Results: Our results show that treatment with compound K dose-dependently attenuates the formation of atherosclerotic plaques by 55% through activation of reverse cholesterol transport pathway, reduction of systemic inflammatory cytokines and inhibition of local inflammasome activity. Compound K increases the cholesterol efflux of macrophage-derived foam cells, and reduces the inflammasome activity in cholesterol crystal stimulated macrophages. The activation of LXRα may contribute to the athero-protective effects of compound K. Conclusion: These observations provide evidence for an athero-protective effect of compound K via LXRα activation, and support its further evaluation as a potential effective modulator for the prevention and treatment of atherosclerosis. PMID:27399689

Identification of three novel natural product compounds that activate PXR and CAR and inhibit inflammation

PubMed Central

Kittayaruksakul, Suticha; Zhao, Wenchen; Xu, Meishu; Ren, Songrong; Lu, Jing; Wang, Ju; Downes, Michael; Evans, Ronald M.; Venkataramanan, Raman; Chatsudthipong, Varanuj; Xie, Wen

2013-01-01

The pregnane X receptor (PXR) and constitutive androstane receptor (CAR) have been known to play a role in xenobiotic metabolism by regulating the expression of drug-metabolizing enzymes and transporters. In addition, PXR agonists were found to exert therapeutic effects through multiple mechanisms, such as detoxification of bile acids and inhibition of inflammation. In this study, we first investigated the effects of three natural product compounds, carapin, santonin and isokobusone, on the activity of PXR and CAR. These compounds activated both PXR and CAR in transient transfection and luciferase reporter gene assays. Mutagenesis studies showed that two amino acid residues, Phe305 of the rodent PXR and Leu308 of the human PXR, are critical for the recognition of these compounds by PXR. Importantly, the activation of PXR and CAR by these compounds induced the expression of drug-metabolizing enzymes in primary human and mouse hepatocytes. Furthermore, activation of PXR by these compounds inhibited the expression of inflammatory mediators in response to lipopolysaccharide (LPS). The effects of these natural compounds on drug metabolism and inflammation were abolished in PXR−/− hepatocytes. These natural compounds can be explored for their potential in the treatment of diseases where the PXR activation has been shown to be beneficial, such as inflammatory bowel disease, cholestasis, and hyperbilirubinemia. PMID:23896737

Insights into structure and activity of natural compound inhibitors of pneumolysin

PubMed Central

Li, Hongen; Zhao, Xiaoran; Deng, Xuming; Wang, Jianfeng; Song, Meng; Niu, Xiaodi; Peng, Liping

2017-01-01

Pneumolysin is the one of the major virulence factor of the bacterium Streptococcus pneumoniae. In previous report, it is shown that β-sitosterol, a natural compound without antimicrobial activity, is a potent antagonist of pneumolysin. Here, two new pneumolysin natural compound inhibitors, with differential activity, were discovered via haemolysis assay. To explore the key factor of the conformation for the inhibition activity, the interactions between five natural compound inhibitors with differential activity and pneumolysin were reported using molecular modelling, the potential of mean force profiles. Interestingly, it is found that incorporation of the single bond (C22-C23-C24-C25) to replace the double bond (hydrocarbon sidechain) improved the anti-haemolytic activity. In view of the molecular modelling, binding of the five inhibitors to the conserved loop region (Val372, Leu460, and Tyr461) of the cholesterol binding sites led to stable complex systems, which was consistent with the result of β-sitosterol. Owing to the single bond (C22-C23-C24-C25), campesterol and brassicasterol could form strong interactions with Val372 and show higher anti-haemolytic activity, which indicated that the single bond (C22-C23-C24-C25) in inhibitors was required for the anti-haemolytic activity. Overall, the current molecular modelling work provides a starting point for the development of rational design and higher activity pneumolysin inhibitors. PMID:28165051

Isolation of the active compound in Mauria heterophylla, a Peruvian plant with antibacterial activity.

PubMed

Mori, Tatsuya; Chang, Cecilia; Maurtua, Dora; Hammond, Gerald B

2006-02-01

A fraction from the ethanol extract of the Peruvian medicinal plant Mauria heterophylla (Anacardiaceae) showed antibacterial activity against Escherichia coli 35992, Staphylococcus aureus 20213 and Pseudomonas aeruginosa 15442. Further fractionation led to the isolation and characterization of ethyl gallate as the antibacterial active compound. Copyright 2006 John Wiley & Sons, Ltd.

Treatment with activated carbon and other adsorbents as an effective method for the removal of volatile compounds in agricultural distillates.

PubMed

Balcerek, Maria; Pielech-Przybylska, Katarzyna; Patelski, Piotr; Dziekońska-Kubczak, Urszula; Jusel, Tomaš

2017-05-01

This study investigates the effect of treatment with activated carbon and other adsorbents on the chemical composition and organoleptics of a barley malt-based agricultural distillate. Contact with activated carbon is one of the methods by which the quality of raw distillates and spirit beverages can be improved. Samples placed in contact with 1 g activated carbon (SpiritFerm) per 100 ml distillate with ethanol content of 50% v/v for 1 h showed the largest reductions in the concentrations of most volatile compounds (aldehydes, alcohols, esters). Increasing the dose of adsorbent to over 1 g 100 ml -1 did not improve the purity of the agricultural distillate significantly. Of the tested compounds, acetaldehyde and methanol showed the lowest adsorption on activated carbon. The lowest concentrations of these congeners (expressed in mg l -1 alcohol 100% v/v) were measured in solutions with ethanol contents of 70-80% v/v, while solutions with an alcoholic strength by volume of 40% did not show statistically significant decreases in these compounds in relation the control sample. The reductions in volatile compounds were compared with those for other adsorbents based on silica or activated carbon and silica. An interesting alternative to activated carbon was found to be an adsorbent prepared from activated carbon and silica (Spiricol). Treatment with this adsorbent produced distillate with the lowest concentrations of acetaldehyde and isovaleraldehyde, and led to the greatest improvement in its organoleptics.

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.

Bioactive compounds, RP-HPLC analysis of phenolics, and antioxidant activity of some Portuguese shrub species extracts.

PubMed

Luís, Angelo; Domingues, Fernanda; Duarte, Ana Paula

2011-12-01

In the ecosystem of Serra Da Estrela, some plant species have the potential to be used as raw material for extraction of bioactive products. The goal of this work was to determine the phenolic, flavonoid, tannin and alkaloid contents of the methanolic extracts of some shrubs (Echinospartum ibericum, Pterospartum tridentatum, Juniperus communis, Ruscus aculeatus, Rubus ulmifolius, Hakea sericea, Cytisus multiflorus, Crataegus monogyna, Erica arborea and Ipomoea acuminata), and then to correlate the phenolic compounds and flavonoids with the antioxidant activity of each extract. The Folin-Ciocalteu's method was used for the determination of total phenols, and tannins were then precipitated with polyvinylpolypyrrolidone (PVPP); a colorimetric method with aluminum chloride was used for the determination of flavonoids, and a Dragendorff's reagent method was used for total alkaloid estimation. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and beta-carotene bleaching tests were used to assess the antioxidant activity of extracts. The identification of phenolic compounds present in extracts was performed using RP-HPLC. A positive linear correlation between antioxidant activity index and total phenolic content of methanolic extracts was observed. The RP-HPLC procedure showed that the most common compounds were ferulic and ellagic acids and quercetin. Most of the studied shrubs have significant antioxidant properties that are probably due to the existence of phenolic compounds in the extracts. It is noteworthy to emphasize that for Echinospartum ibericum, Hakea sericea and Ipomoea acuminata, to the best of our knowledge, no phytochemical studies have been undertaken nor their use in traditional medicine been described.

Selecting a Response in Task Switching: Testing a Model of Compound Cue Retrieval

ERIC Educational Resources Information Center

Schneider, Darryl W.; Logan, Gordon D.

2009-01-01

How can a task-appropriate response be selected for an ambiguous target stimulus in task-switching situations? One answer is to use compound cue retrieval, whereby stimuli serve as joint retrieval cues to select a response from long-term memory. In the present study, the authors tested how well a model of compound cue retrieval could account for a…

New ligand-based approach for the discovery of antitrypanosomal compounds.

PubMed

Vega, María Celeste; Montero-Torres, Alina; Marrero-Ponce, Yovani; Rolón, Miriam; Gómez-Barrio, Alicia; Escario, José Antonio; Arán, Vicente J; Nogal, Juan José; Meneses-Marcel, Alfredo; Torrens, Francisco

2006-04-01

The antitrypanosomal activity of 10 already synthesized compounds was in silico predicted as well as in vitro and in vivo explored against Trypanosoma cruzi. For the computational study, an approach based on non-stochastic linear fingerprints to the identification of potential antichagasic compounds is introduced. Molecular structures of 66 organic compounds, 28 with antitrypanosomal activity and 38 having other clinical uses, were parameterized by means of the TOMOCOMD-CARDD software. A linear classification function was derived allowing the discrimination between active and inactive compounds with a confidence of 95%. As predicted, seven compounds showed antitrypanosomal activity (%AE>70) against epimastigotic forms of T. cruzi at a concentration of 100mug/mL. After an unspecific cytotoxic assay, three compounds were evaluated against amastigote forms of the parasite. An in vivo test was carried out for one of the studied compounds.

Repellency and Larvicidal Activity of Essential oils from Xylopia laevigata, Xylopia frutescens, Lippia pedunculosa, and Their Individual Compounds against Aedes aegypti Linnaeus.

PubMed

Nascimento, A M D; Maia, T D S; Soares, T E S; Menezes, L R A; Scher, R; Costa, E V; Cavalcanti, S C H; La Corte, R

2017-04-01

In order to find new alternatives for vector control and personal protection, we evaluated the larvicidal and repellent activity of essentials oils from plants found in the Northeast of Brazil against Aedes aegypti Linnaeus mosquitoes. The plants tested include Xylopia laevigata, Xylopia frutescens, and Lippia pedunculosa and their major compounds, piperitenone oxide, and (R)-limonene. The essential oil of L. pedunculosa and its major volatile compounds were shown to be toxic for Ae. aegypti larvae with a LC 50 lower than 60 ppm. The essential oil of plants from the Xylopia genus, on the other hand, showed no activity against Ae. aegypti, proving to be toxic to mosquito larvae only when concentrations were higher than 1000 ppm. All plants tested provided some degree of protection against mosquitoes landing, but only the essential oil of L. pedunculosa and the volatile compound piperitenone oxide suppressed 100% of mosquitoes landing on human skin, in concentrations lower than 1%. Among the plants studied, the essential oil of L. pedunculosa and its volatiles compounds have shown the potential for the development of safe alternative for mosquito larvae control and protection against Ae. aegypti mosquito bites.

In vivo wound-healing activity of Euphorbia characias subsp. wulfenii: Isolation and quantification of quercetin glycosides as bioactive compounds.

PubMed

Özbilgin, Serkan; Acıkara, Özlem Bahadır; Akkol, Esra Küpeli; Süntar, Ipek; Keleş, Hikmet; İşcan, Gülçin Saltan

2018-06-16

The latex and the aerial parts of Euphorbia characias L. (Euphorbiaceae) have been used as medicinal plant to treat wounds and warts in traditional medicine. The effect of the plant extract was tested in vivo and in vitro with experimental models to find scientific evidence for traditional use in wound healing. Potentially active wound-healer compounds were isolated from the active fraction using fractionation procedures under the guidance of biological assay and the possible role of the compounds in the wound healing process was also determined. N-hexane, ethyl acetate, and methanol extracts were successively prepared from the aerial parts of E. characias subsp. wulfenii. The extracts were tested with linear incision, circular excision wound models and the hydroxyproline assay method to assess the wound-healing activity. The inhibition of the increase in capillary permeability induced by acetic acid, an acute inflammation model, was used to assay the anti-inflammatory activity. Different chromatographic separation techniques on sephadex and silica gel columns, and bioassay guided assay techniques have been used to isolate the active compounds of the plant. Moreover, hyaluronidase, collagenase and elastase enzymes inhibitory effect of active principle were investigated in vitro to find out the mechanism of action. The methanol (MeOH-ex) extract of the aerial parts of E. characias subsp. wulfenii showed significant wound healing activity (linear incision wound model: 43.04%; circular excision wound model 65.24%) and anti-inflammatory activity (34.74%). The methanol extract was separated into its fractions by column chromatography for isolation of efficient compounds. Biological activity of the fractions were assessed and further isolation and purification processes have been carried out in the active fraction. Isolation studies were carried out from the MeOH-ex fraction to obtain active constituents and their structures were elucidated to be quercetin-3-O

LC-MS analysis of phenolic compounds and antioxidant activity of buckwheat at different stages of malting.

PubMed

Terpinc, Petra; Cigić, Blaž; Polak, Tomaž; Hribar, Janez; Požrl, Tomaž

2016-11-01

The impact of malting on the profile of the phenolic compounds and the antioxidant properties of two buckwheat varieties was investigated. The highest relative increases in phenolic compounds were observed for isoorientin, orientin, and isovitexin, which are consequently major inducible phenolic compounds during malting. Only a minor relative increase was observed for the most abundant phenolic compound, rutin. The radical-scavenging activity of buckwheat seeds was evaluated using ABTS and DPPH assays. A considerable increase in total phenolic compounds and higher antioxidant activity were observed after 64h of germination, whereas kilning resulted in decreased total phenolic compounds and antioxidant activity. Higher antioxidant activities for extracts were found for buffered solvents than for pure methanol and water. Changes in the composition of the phenolic compounds and increased antioxidant content were confirmed by several methods, indicating that buckwheat malt can be used as a food rich in antioxidants. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antifeedant compounds from three species of Apiaceae active against the field slug, Deroceras reticulatum (Muller).

PubMed

Birkett, Michael A; Dodds, Catherine J; Henderson, Ian F; Leake, Lucy D; Pickett, John A; Selby, Martin J; Watson, Peter

2004-03-01

Extracts of volatiles from foliage of three plants in the Apiaceae, Conium maculatum L. (hemlock), Coriandrum sativum L. (coriander), and Petroselinum crispum Mill. (Nym.) (parsley), previously shown to exhibit antifeedant activity in assays with the field slug, Deroceras reticulatum (Muller) (Limacidae: Pulmonata), were studied further to identify the active components. Coupled gas chromatography-mass spectrometry (GC-MS) and neurophysiological assays using tentacle nerve preparations resulted in the identification of 11 active compounds from the three extracts. Wheat flour feeding bioassays were used to determine which of these compounds had the highest antifeedant activity. One of the most active compounds was the alkaloid gamma-coniceine, from C. maculatum. The role of potentially toxic alkaloids as semiochemicals and the potential for using such compounds as crop protection agents to prevent slug feeding damage is discussed.

Compounds Derived from the Bhutanese Daisy, Ajania nubigena, Demonstrate Dual Anthelmintic Activity against Schistosoma mansoni and Trichuris muris

PubMed Central

Pearson, Mark S.; Giacomin, Paul R.; Becker, Luke; Sotillo, Javier; Pickering, Darren

2016-01-01

Background Whipworms and blood flukes combined infect almost one billion people in developing countries. Only a handful of anthelmintic drugs are currently available to treat these infections effectively; there is therefore an urgent need for new generations of anthelmintic compounds. Medicinal plants have presented as a viable source of new parasiticides. Ajania nubigena, the Bhutanese daisy, has been used in Bhutanese traditional medicine for treating various diseases and our previous studies revealed that small molecules from this plant have antimalarial properties. Encouraged by these findings, we screened four major compounds isolated from A. nubigena for their anthelmintic properties. Methodology/Principal Findings Here we studied four major compounds derived from A. nubigena for their anthelmintic properties against the nematode whipworm Trichuris muris and the platyhelminth blood fluke Schistosoma mansoni using the xWORM assay technique. Of four compounds tested, two compounds—luteolin (3) and (3R,6R)-linalool oxide acetate (1)—showed dual anthelmintic activity against S. mansoni (IC50 range = 5.8–36.9 μg/mL) and T. muris (IC50 range = 9.7–20.4 μg/mL). Using scanning electron microscopy, we determined luteolin as the most efficacious compound against both parasites and additionally was found effective against the schistosomula, the infective stage of S. mansoni (IC50 = 13.3 μg/mL). Luteolin induced tegumental damage to S. mansoni and affected the cuticle, bacillary bands and bacillary glands of T. muris. Our in vivo assessment of luteolin (3) against T. muris infection at a single oral dosing of 100 mg/kg, despite being significantly (27.6%) better than the untreated control group, was markedly weaker than mebendazole (93.1%) in reducing the worm burden in mice. Conclusions/Significance Among the four compounds tested, luteolin demonstrated the best broad-spectrum activity against two different helminths—T. muris and S. mansoni—and was

Antifungal activity of synthetic naphthoquinones against dermatophytes and opportunistic fungi: preliminary mechanism-of-action tests.

PubMed

Ferreira, Maria do Perpetuo Socorro Borges Carriço; Cardoso, Mariana Filomena do Carmo; da Silva, Fernando de Carvalho; Ferreira, Vitor Francisco; Lima, Emerson Silva; Souza, João Vicente Braga

2014-07-06

This study evaluated the antifungal activities of synthetic naphthoquinones against opportunistic and dermatophytic fungi and their preliminary mechanisms of action. The minimum inhibitory concentrations (MICs) of four synthetic naphthoquinones for 89 microorganisms, including opportunistic yeast agents, dermatophytes and opportunistic filamentous fungi, were determined. The compound that exhibited the best activity was assessed for its action against the cell wall (sorbitol test), for interference associated with ergosterol interaction, for osmotic balance (K+ efflux) and for membrane leakage of substances that absorb at the wavelength of 260 nm. All tested naphthoquinones exhibited antifungal activity, and compound IVS320 (3a,10b-dihydro-1H-cyclopenta [b] naphtho [2,3-d] furan-5,10-dione)-dione) demonstrated the lowest MICs across the tested species. The MIC of IVS320 was particularly low for dermatophytes (values ranging from 5-28 μg/mL) and Cryptococcus spp. (3-5 μg/mL). In preliminary mechanism-of-action tests, IVS320 did not alter the fungal cell wall but did cause problems in terms of cell membrane permeability (efflux of K+ and leakage of substances that absorb at 260 nm). This last effect was unrelated to ergosterol interactions with the membrane.

The Study of Interactions between Active Compounds of Coffee and Willow (Salix sp.) Bark Water Extract

PubMed Central

Durak, Agata; Gawlik-Dziki, Urszula

2014-01-01

Coffee and willow are known as valuable sources of biologically active phytochemicals such as chlorogenic acid, caffeine, and salicin. The aim of the study was to determine the interactions between the active compounds contained in water extracts from coffee and bark of willow (Salix purpurea and Salix myrsinifolia). Raw materials and their mixtures were characterized by multidirectional antioxidant activities; however, bioactive constituents interacted with each other. Synergism was observed for ability of inhibition of lipid peroxidation and reducing power, whereas compounds able to scavenge ABTS radical cation acted antagonistically. Additionally, phytochemicals from willow bark possessed hydrophilic character and thermostability which justifies their potential use as an ingredient in coffee beverages. Proposed mixtures may be used in the prophylaxis or treatment of some civilization diseases linked with oxidative stress. Most importantly, strong synergism observed for phytochemicals able to prevent lipids against oxidation may suggest protective effect for cell membrane phospholipids. Obtained results indicate that extracts from bark tested Salix genotypes as an ingredient in coffee beverages can provide health promoting benefits to the consumers; however, this issue requires further study. PMID:25013777

Phenolic Compounds from Olea europaea L. Possess Antioxidant Activity and Inhibit Carbohydrate Metabolizing Enzymes In Vitro.

PubMed

Dekdouk, Nadia; Malafronte, Nicola; Russo, Daniela; Faraone, Immacolata; De Tommasi, Nunziatina; Ameddah, Souad; Severino, Lorella; Milella, Luigi

2015-01-01

Phenolic composition and biological activities of fruit extracts from Italian and Algerian Olea europaea L. cultivars were studied. Total phenolic and tannin contents were quantified in the extracts. Moreover 14 different phenolic compounds were identified, and their profiles showed remarkable quantitative differences among analysed extracts. Moreover antioxidant and enzymatic inhibition activities were studied. Three complementary assays were used to measure their antioxidant activities and consequently Relative Antioxidant Capacity Index (RACI) was used to compare and easily describe obtained results. Results showed that Chemlal, between Algerian cultivars, and Coratina, among Italian ones, had the highest RACI values. On the other hand all extracts and the most abundant phenolics were tested for their efficiency to inhibit α-amylase and α-glucosidase enzymes. Leccino, among all analysed cultivars, and luteolin, among identified phenolic compounds, were found to be the best inhibitors of α-amylase and α-glucosidase enzymes. Results demonstrated that Olea europaea fruit extracts can represent an important natural source with high antioxidant potential and significant α-amylase and α-glucosidase inhibitory effects.

Phenolic Compounds from Olea europaea L. Possess Antioxidant Activity and Inhibit Carbohydrate Metabolizing Enzymes In Vitro

PubMed Central

Dekdouk, Nadia; Malafronte, Nicola; Russo, Daniela; Faraone, Immacolata; Ameddah, Souad; Severino, Lorella

2015-01-01

Phenolic composition and biological activities of fruit extracts from Italian and Algerian Olea europaea L. cultivars were studied. Total phenolic and tannin contents were quantified in the extracts. Moreover 14 different phenolic compounds were identified, and their profiles showed remarkable quantitative differences among analysed extracts. Moreover antioxidant and enzymatic inhibition activities were studied. Three complementary assays were used to measure their antioxidant activities and consequently Relative Antioxidant Capacity Index (RACI) was used to compare and easily describe obtained results. Results showed that Chemlal, between Algerian cultivars, and Coratina, among Italian ones, had the highest RACI values. On the other hand all extracts and the most abundant phenolics were tested for their efficiency to inhibit α-amylase and α-glucosidase enzymes. Leccino, among all analysed cultivars, and luteolin, among identified phenolic compounds, were found to be the best inhibitors of α-amylase and α-glucosidase enzymes. Results demonstrated that Olea europaea fruit extracts can represent an important natural source with high antioxidant potential and significant α-amylase and α-glucosidase inhibitory effects. PMID:26557862

Pericocins A-D, New Bioactive Compounds from Periconia sp.

PubMed

Wu, Yue-Hua; Xiao, Gao-Keng; Chen, Guo-Dong; Wang, Chuan-Xi; Hu, Dan; Lian, Yun-Yang; Lin, Feng; Guo, Liang-Dong; Yao, Xin-Sheng; Gao, Hao

2015-12-01

One new dihydroisocoumarin, pericocin A (1), one new chromone, pericocin B (2), and two new α-pyrone derivatives, pericocins C-D (3-4), together with two known compounds, 3-(2-oxo-2H-pyran-6-yl)propanoic acid (5) and (E)-3-(2-oxo-2H-pyran-6-yl)acrylic acid (6), were isolated from the culture of the endolichenic fungus Periconia sp.. Their structures were elucidated by spectroscopic methods. All these compounds are derived from the polyketone biosynthetic pathway. Compound 1 was obtained as a mixture of enantiomers. The antimicrobial activity of compounds 1-5 was tested against Escherichia coli, Staphylococcus aureus, Aspergillus niger, and Candida albicans. Compounds 1-5 showed moderate antimicrobial activity against A. niger and weak activity against C. albicans.

Investigation of innovative synthesis of biologically active compounds on the basis of newly developed reactions.

PubMed

Honda, Toshio

2012-01-01

Synthesis of biologically active compounds, including natural products and pharmaceutical agents, is an important and interesting research area since the large structural diversity and complexity of bioactive compounds make them an important source of leads and scaffolds in drug discovery and development. Many structurally and also biologically interesting compounds, including marine natural products, have been isolated from nature and have also been prepared on the basis of a computational design for the purpose of developing medicinal chemistry. In order to obtain a wide variety of derivatives of biologically active compounds from the viewpoint of medicinal chemistry, it is essential to establish efficient synthetic procedures for desired targets. Newly developed reactions should also be used for efficient synthesis of desired compounds. Thus, recent progress in the synthesis of biologically active compounds by focusing on the development of new reactions is summarized in this review article.

Efficient discovery of responses of proteins to compounds using active learning

PubMed Central

2014-01-01

Background Drug discovery and development has been aided by high throughput screening methods that detect compound effects on a single target. However, when using focused initial screening, undesirable secondary effects are often detected late in the development process after significant investment has been made. An alternative approach would be to screen against undesired effects early in the process, but the number of possible secondary targets makes this prohibitively expensive. Results This paper describes methods for making this global approach practical by constructing predictive models for many target responses to many compounds and using them to guide experimentation. We demonstrate for the first time that by jointly modeling targets and compounds using descriptive features and using active machine learning methods, accurate models can be built by doing only a small fraction of possible experiments. The methods were evaluated by computational experiments using a dataset of 177 assays and 20,000 compounds constructed from the PubChem database. Conclusions An average of nearly 60% of all hits in the dataset were found after exploring only 3% of the experimental space which suggests that active learning can be used to enable more complete characterization of compound effects than otherwise affordable. The methods described are also likely to find widespread application outside drug discovery, such as for characterizing the effects of a large number of compounds or inhibitory RNAs on a large number of cell or tissue phenotypes. PMID:24884564

Biodegradation of coal-related model compounds

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

Campbell, J.A.; Stewart, D.L.; McCulloch, M.

1988-06-01

We have studied the reactions of model compounds having coal-related functionalities (ester linkages, ether linkages, PAH) with the intact organism, cell-free filtrate, and cell-free enzyme of C. versicolor to better understand the process of biosolubilization. Many of the degradation products have been identified by gas chromatography/mass spectroscopy (GC/MS). Results indicate that the two compounds tested with the intact fungal organism were completely degraded. Complete degradation refers to no recovery of model compound. We can probably assume that the other two would also be totally degraded, since we have not yet found a simple compound that will survive long-term exposure tomore » the intact fungus. The ease of degradation with the cell-free filtrate appears to be in the order: phenylbenzoate > benzylbenzoate > benzyl ether > methoxybenzophenone. Esters and ethers that are activated by aromatic rings appear to be susceptible to the fungal extract; however, aromatic ketones are not affected by the extract. From the limited results we have obtained from the isolated enzyme, it appears that the activity may parallel the cell-free filtrate. When the cell-free extract was tested with the model compounds indole, dibenzothiophene, and bibenzyl, no degradation with the enzyme was noted: however, exposure of these compounds to the intact organism resulted in complete degradation. Analysis of the controls indicated no degradation. 8 refs., 1 fig., 1 tab.« less

Novel Platinum (Pt)-Vandetanib Hybrid Compounds: Design, Synthesis and Investigation of Anti-cancer Activity and Mechanism of Action

NASA Astrophysics Data System (ADS)

Fei, Rong

Purpose: Lung cancer is one of the most common cancers and non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancers. 70% of individuals with NSCLC harboring somatic mutations in exons of the epidermal growth factor receptor (EGFR) gene that encode tyrosine kinase domain. EGFR tyrosine kinase inhibitors (TKIs) are promising molecular targeted therapy for NSCLC with sensitizing EGFR mutations. However, secondary mutation of EGFR after treatment of TKIs develops resistance. Vandetanib is introduced to overcome erlotinib resistance as a multi-targeted TKI. However, its anticancer effect is still compromised by EGFR T790M mutation. Therefore, new molecular anticancer strategies are necessarily needed. In this study, vandetanib is incorporated with Pt-based anticancer agents as hybrid compounds, aiming to circumvent TKI resistance. Furthermore, hybrid compounds are investigated in cisplatin resistant problem to expect to overcome resistance by introduction of vandetanib. Methods: Three novel Pt-vandetanib hybrid compounds were synthesized and its physicochemical properties were characterized. Anticancer activity and cytotoxicity were evaluated by sulforhodamine B assay and lactate dehydrogenase release. Docking simulation was performed to investigate the interaction of compounds with EGFR harboring different mutations. Inhibition efficacy of hybrids to kinases was evaluated by kinase inhibition profiling service and cell-free kinase inhibition assay. Mechanistic studies on cytotoxicity activity of the hybrid compounds were carried out. DNA damage response of hybrid compounds was further investigated in KB cells. The cytotoxicity of hybrids was tested in cisplatin resistant KB CP20 cells. Mechanistic of anticancer activity was studied to test inhibition on oncoprotein CIP2Aand DNA damage. Results: Platinum-vandetanib hybrid compounds were synthesized and test to be stable under extracellular condition. Hybrids reacted with 5'-GMP2- and glutathione, and both

Synthesis and anti-lung cancer activity of a novel arsenomolybdate compound

NASA Astrophysics Data System (ADS)

Zhu, Tian-Tian; Wang, Juan; Chen, Song-Hu

2017-12-01

The new compound based on Wells-Dawson-type arsenomolybdate: [{Cu10(pz)11Cl4}{As2IIIAs2VMo6VMo12VIO62}]·H2O (1) has been hydrothermally synthesized and characterized by single-crystal X-ray diffraction analysis, X-ray powder diffraction (XRPD), XPS spectroscopy and thermogravimetric analysis (TG). Compound 1 is consisted of two As caps Wells-dawson-type arsenomolybdate and {Cu10(py)11} complexes by chloride bridge. In addition, the antitumor effects of the title compound 1 were studied on three human lung cancer cells (A549, SK-LU-1 and SW1573). The results showed that compared with the positive reference drug carboplatin, compound 1 displayed efficient antitumor activity.

Synthesis and Biological Evaluation of Ginsenoside Compound K Derivatives as a Novel Class of LXRα Activator.

PubMed

Huang, Yan; Liu, Hongmei; Zhang, Yingxian; Li, Jin; Wang, Chenping; Zhou, Li; Jia, Yi; Li, Xiaohui

2017-07-24

Compound K is one of the active metabolites of Panaxnotoginseng saponins, which could attenuate the formation of atherosclerosis in mice modelsvia activating LXRα. We synthesized and evaluated a series of ginsenoside compound K derivatives modified with short chain fatty acids. All of the structures of this class of ginsenoside compound K derivative exhibited comparable or better biological activity than ginsenoside compound K. Especially structure 1 exhibited the best potency (cholesteryl ester content: 41.51%; expression of ABCA1 mRNA: 319%) and low cytotoxicity.

A novel daucosterol derivative and antibacterial activity of compounds from Arctotis arctotoides.

PubMed

Sultana, Nasim; Afolayan, A J

2007-08-01

Arctotis arctotoides is a perennial herb used medicinally for the treatment of various ailments in the Eastern Cape, South Africa. Different extracts of the plant were investigated for their antimicrobial constituents. This led to the isolation and identification of a new daucosterol derivative 3-O-[beta-D-(6'-nonadeanoate)glucopyranosyl]-beta-sitosterol and seven known compounds namely: serratagenic acid, stigmasterol, daucosterol, zaluzanin D, dehydrocostuslactone, nepetin, and pedalitin. The structures of the compounds were elucidated on the basis of spectral analysis, including homo and hetero nuclear correlation NMR experiments (COSY, NOESY, HMQC, HMBC) and mass spectra as well as by comparison with available data in the literature. The compounds exhibited antibacterial activity except stigmasterol, daucosterol and dehydrocostuslactone. Nepetin was the most active against Bacillus subtilis and Staphylococcus aureus with the minimum inhibitory concentrations of 4 microg mL( - 1) and 31 microg mL( - 1), respectively, while others exhibited moderate activity.

Clinically relevant enhancement of human sperm motility using compounds with reported phosphodiesterase inhibitor activity

PubMed Central

Tardif, Steve; Madamidola, Oladipo A.; Brown, Sean G.; Frame, Lorna; Lefièvre, Linda; Wyatt, Paul G.; Barratt, Christopher L.R.; Martins Da Silva, Sarah J.

2014-01-01

STUDY QUESTION Can we identify compound(s) with reported phosphodiesterase inhibitor (PDEI) activity that could be added to human spermatozoa in vitro to enhance their motility without compromising other sperm functions? SUMMARY ANSWER We have identified several compounds that produce robust and effective stimulation of sperm motility and, importantly, have a positive response on patient samples. WHAT IS KNOWN ALREADY For >20 years, the use of non-selective PDEIs, such as pentoxifylline, has been known to influence the motility of human spermatozoa; however, conflicting results have been obtained. It is now clear that human sperm express several different phosphodiesterases and these are compartmentalized at different regions of the cells. By using type-specific PDEIs, differential modulation of sperm motility may be achieved without adversely affecting other functions such as the acrosome reaction (AR). STUDY DESIGN, SIZE, DURATION This was a basic medical research study examining sperm samples from normozoospermic donors and subfertile patients attending the Assisted Conception Unit (ACU), Ninewells Hospital Dundee for diagnostic semen analysis, IVF and ICSI. Phase 1 screened 43 commercially available compounds with reported PDEI activity to identify lead compounds that stimulate sperm motility. Samples were exposed (20 min) to three concentrations (1, 10 and 100 µM) of compound, and selected candidates (n = 6) progressed to Phase 2, which provided a more comprehensive assessment using a battery of in vitro sperm function tests. PARTICIPANTS/MATERIALS, SETTING, METHODS All healthy donors and subfertile patients were recruited at the Medical Research Institute, University of Dundee and ACU, Ninewells Hospital Dundee (ethical approval 08/S1402/6). In Phase 1, poor motility cells recovered from the 40% interface of the discontinuous density gradient were used as surrogates for patient samples. Pooled samples from three to four different donors were utilized in

[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.

Antimalarial activity of compounds comprising a primary benzene sulfonamide fragment.

PubMed

Andrews, Katherine T; Fisher, Gillian M; Sumanadasa, Subathdrage D M; Skinner-Adams, Tina; Moeker, Janina; Lopez, Marie; Poulsen, Sally-Ann

2013-11-15

Despite the urgent need for effective antimalarial drugs with novel modes of action no new chemical class of antimalarial drug has been approved for use since 1996. To address this, we have used a rational approach to investigate compounds comprising the primary benzene sulfonamide fragment as a potential new antimalarial chemotype. We report the in vitro activity against Plasmodium falciparum drug sensitive (3D7) and resistant (Dd2) parasites for a panel of fourteen primary benzene sulfonamide compounds. Our findings provide a platform to support the further evaluation of primary benzene sulfonamides as a new antimalarial chemotype, including the identification of the target of these compounds in the parasite. Copyright © 2013 Elsevier Ltd. All rights reserved.

QSAR-Driven Design and Discovery of Novel Compounds With Antiplasmodial and Transmission Blocking Activities.

PubMed

Lima, Marilia N N; Melo-Filho, Cleber C; Cassiano, Gustavo C; Neves, Bruno J; Alves, Vinicius M; Braga, Rodolpho C; Cravo, Pedro V L; Muratov, Eugene N; Calit, Juliana; Bargieri, Daniel Y; Costa, Fabio T M; Andrade, Carolina H

2018-01-01

Malaria is a life-threatening infectious disease caused by parasites of the genus Plasmodium , affecting more than 200 million people worldwide every year and leading to about a half million deaths. Malaria parasites of humans have evolved resistance to all current antimalarial drugs, urging for the discovery of new effective compounds. Given that the inhibition of deoxyuridine triphosphatase of Plasmodium falciparum ( Pf dUTPase) induces wrong insertions in plasmodial DNA and consequently leading the parasite to death, this enzyme is considered an attractive antimalarial drug target. Using a combi-QSAR (quantitative structure-activity relationship) approach followed by virtual screening and in vitro experimental evaluation, we report herein the discovery of novel chemical scaffolds with in vitro potency against asexual blood stages of both P. falciparum multidrug-resistant and sensitive strains and against sporogonic development of P. berghei . We developed 2D- and 3D-QSAR models using a series of nucleosides reported in the literature as Pf dUTPase inhibitors. The best models were combined in a consensus approach and used for virtual screening of the ChemBridge database, leading to the identification of five new virtual Pf dUTPase inhibitors. Further in vitro testing on P. falciparum multidrug-resistant (W2) and sensitive (3D7) parasites showed that compounds LabMol-144 and LabMol-146 demonstrated fair activity against both strains and presented good selectivity versus mammalian cells. In addition, LabMol-144 showed good in vitro inhibition of P. berghei ookinete formation, demonstrating that hit-to-lead optimization based on this compound may also lead to new antimalarials with transmission blocking 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.

Identification of compounds inhibiting the C-S lyase activity of a cell extract from a Staphylococcus sp. isolated from human skin.

PubMed

Egert, M; Höhne, H-M; Weber, T; Simmering, R; Banowski, B; Breves, R

2013-12-01

The C-S lyase activity of bacteria in the human armpit releases highly malodorous, volatile sulfur compounds from nonvolatile precursor molecules. Such compounds significantly contribute to human body odour. Hence, C-S lyase represents an attractive target for anti-body-odour cosmetic products. Here, aiming at a final use in an ethanol-based deodorant formulation, 267 compounds and compound mixtures were screened for their ability to inhibit the C-S lyase activity of a Stapyhlococcus sp. crude extract. Staphylococcus sp. Isolate 128, closely related to Staphylococcus hominis, was chosen as the test bacterium, as it showed a reproducibly high specific C-S lyase activity on three different culturing media. Using a photometric assay and benzylcysteine as substrate, six rather complex, plant-derived compound mixtures and five well defined chemical compounds or compound mixtures were identified as inhibitors, leading to an inhibition of ≥70% at concentrations of ≤0·5% in the assay. The inhibition data have demonstrated that compounds with two vicinal hydroxyl groups or one hydroxyl and one keto group bound to an aryl residue are characteristic for the inhibition. The substances identified as C-S lyase inhibitors have the potential to improve the performance of anti-body-odour cosmetic products, for example, ethanol-based deodorants. Bacterial C-S lyase represents one of the key enzymes involved in human body odour formation. The aim of this study was to identify compounds inhibiting the C-S lyase activity of a Staphylococcus sp. isolate from the human skin. The compounds identified as the best inhibitors are characterized by the following features: two vicinal hydroxyl groups or one hydroxyl and one keto group bound to an aryl residue. They might be used to improve the performance of cosmetic products aiming to prevent the formation of microbially caused human body odour, for example, ethanol-based deodorants. © 2013 The Society for Applied Microbiology.

Antifouling potential of Nature-inspired sulfated compounds

NASA Astrophysics Data System (ADS)

Almeida, Joana R.; Correia-da-Silva, Marta; Sousa, Emília; Antunes, Jorge; Pinto, Madalena; Vasconcelos, Vitor; Cunha, Isabel

2017-02-01

Natural products with a sulfated scaffold have emerged as antifouling agents with low or nontoxic effects to the environment. In this study 13 sulfated polyphenols were synthesized and tested for antifouling potential using the anti-settlement activity of mussel (Mytilus galloprovincialis) plantigrade post-larvae and bacterial growth inhibition towards four biofilm-forming bacterial strains. Results show that some of these Nature-inspired compounds were bioactive, particularly rutin persulfate (2), 3,6-bis(β-D-glucopyranosyl) xanthone persulfate (6), and gallic acid persulfate (12) against the settlement of plantigrades. The chemical precursors of sulfated compounds 2 and 12 were also tested for anti-settlement activity and it was possible to conclude that bioactivity is associated with sulfation. While compound 12 showed the most promising anti-settlement activity (EC50 = 8.95 μg.mL-1), compound 2 also caused the higher level of growth inhibition in bacteria Vibrio harveyi (EC20 = 12.5 μg.mL-1). All the three bioactive compounds 2, 6, and 12 were also found to be nontoxic to the non target species Artemia salina (<10% mortality at 250 μM) and Vibrio fischeri (LC50 > 1000 μg.mL-1). This study put forward the relevance of synthesizing non-natural sulfated small molecules to generate new nontoxic antifouling agents.

Antifouling potential of Nature-inspired sulfated compounds

PubMed Central

Almeida, Joana R.; Correia-da-Silva, Marta; Sousa, Emília; Antunes, Jorge; Pinto, Madalena; Vasconcelos, Vitor; Cunha, Isabel

2017-01-01

Natural products with a sulfated scaffold have emerged as antifouling agents with low or nontoxic effects to the environment. In this study 13 sulfated polyphenols were synthesized and tested for antifouling potential using the anti-settlement activity of mussel (Mytilus galloprovincialis) plantigrade post-larvae and bacterial growth inhibition towards four biofilm-forming bacterial strains. Results show that some of these Nature-inspired compounds were bioactive, particularly rutin persulfate (2), 3,6-bis(β-D-glucopyranosyl) xanthone persulfate (6), and gallic acid persulfate (12) against the settlement of plantigrades. The chemical precursors of sulfated compounds 2 and 12 were also tested for anti-settlement activity and it was possible to conclude that bioactivity is associated with sulfation. While compound 12 showed the most promising anti-settlement activity (EC50 = 8.95 μg.mL−1), compound 2 also caused the higher level of growth inhibition in bacteria Vibrio harveyi (EC20 = 12.5 μg.mL−1). All the three bioactive compounds 2, 6, and 12 were also found to be nontoxic to the non target species Artemia salina (<10% mortality at 250 μM) and Vibrio fischeri (LC50 > 1000 μg.mL−1). This study put forward the relevance of synthesizing non-natural sulfated small molecules to generate new nontoxic antifouling agents. PMID:28205590

NPACT: Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database

PubMed Central

Mangal, Manu; Sagar, Parul; Singh, Harinder; Raghava, Gajendra P. S.; Agarwal, Subhash M.

2013-01-01

Plant-derived molecules have been highly valued by biomedical researchers and pharmaceutical companies for developing drugs, as they are thought to be optimized during evolution. Therefore, we have collected and compiled a central resource Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database (NPACT, http://crdd.osdd.net/raghava/npact/) that gathers the information related to experimentally validated plant-derived natural compounds exhibiting anti-cancerous activity (in vitro and in vivo), to complement the other databases. It currently contains 1574 compound entries, and each record provides information on their structure, manually curated published data on in vitro and in vivo experiments along with reference for users referral, inhibitory values (IC50/ED50/EC50/GI50), properties (physical, elemental and topological), cancer types, cell lines, protein targets, commercial suppliers and drug likeness of compounds. NPACT can easily be browsed or queried using various options, and an online similarity tool has also been made available. Further, to facilitate retrieval of existing data, each record is hyperlinked to similar databases like SuperNatural, Herbal Ingredients’ Targets, Comparative Toxicogenomics Database, PubChem and NCI-60 GI50 data. PMID:23203877

Evaluation of a Screening System for Obesogenic Compounds: Screening of Endocrine Disrupting Compounds and Evaluation of the PPAR Dependency of the Effect

PubMed Central

Pereira-Fernandes, Anna; Demaegdt, Heidi; Vandermeiren, Karine; Hectors, Tine L. M.; Jorens, Philippe G.; Blust, Ronny; Vanparys, Caroline

2013-01-01

Recently the environmental obesogen hypothesis has been formulated, proposing a role for endocrine disrupting compounds (EDCs) in the development of obesity. To evaluate this hypothesis, a screening system for obesogenic compounds is urgently needed. In this study, we suggest a standardised protocol for obesogen screening based on the 3T3-L1 cell line, a well-characterised adipogenesis model, and direct fluorescent measurement using Nile red lipid staining technique. In a first phase, we characterised the assay using the acknowledged obesogens rosiglitazone and tributyltin. Based on the obtained dose-response curves for these model compounds, a lipid accumulation threshold value was calculated to ensure the biological relevance and reliability of statistically significant effects. This threshold based method was combined with the well described strictly standardized mean difference (SSMD) method for classification of non-, weak- or strong obesogenic compounds. In the next step, a range of EDCs, used in personal and household care products (parabens, musks, phthalates and alkylphenol compounds), were tested to further evaluate the obesogenicity screening assay for its discriminative power and sensitivity. Additionally, the peroxisome proliferator activated receptor γ (PPARγ) dependency of the positive compounds was evaluated using PPARγ activation and antagonist experiments. Our results showed the adipogenic potential of all tested parabens, several musks and phthalate compounds and bisphenol A (BPA). PPARγ activation was associated with adipogenesis for parabens, phthalates and BPA, however not required for obesogenic effects induced by Tonalide, indicating the role of other obesogenic mechanisms for this compound. PMID:24155963

Anti-Chikungunya Viral Activities of Aplysiatoxin-Related Compounds from the Marine Cyanobacterium Trichodesmium erythraeum

PubMed Central

Gupta, Deepak Kumar; Kaur, Parveen; Leong, See Ting; Tan, Lik Tong; Prinsep, Michèle R.; Chu, Justin Jang Hann

2014-01-01

Tropical filamentous marine cyanobacteria have emerged as a viable source of novel bioactive natural products for drug discovery and development. In the present study, aplysiatoxin (1), debromoaplysiatoxin (2) and anhydrodebromoaplysiatoxin (3), as well as two new analogues, 3-methoxyaplysiatoxin (4) and 3-methoxydebromoaplysiatoxin (5), are reported for the first time from the marine cyanobacterium Trichodesmium erythraeum. The identification of the bloom-forming cyanobacterial strain was confirmed based on phylogenetic analysis of its 16S rRNA sequences. Structural determination of the new analogues was achieved by extensive NMR spectroscopic analysis and comparison with NMR spectral data of known compounds. In addition, the antiviral activities of these marine toxins were assessed using Chikungunya virus (CHIKV)-infected cells. Post-treatment experiments using the debrominated analogues, namely compounds 2, 3 and 5, displayed dose-dependent inhibition of CHIKV when tested at concentrations ranging from 0.1 µM to 10.0 µM. Furthermore, debromoaplysiatoxin (2) and 3-methoxydebromoaplysiatoxin (5) exhibited significant anti-CHIKV activities with EC50 values of 1.3 μM and 2.7 μM, respectively, and selectivity indices of 10.9 and 9.2, respectively. PMID:24394406

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.

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

PubMed

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

2012-01-01

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

Synergistic anti-Campylobacter jejuni activity of fluoroquinolone and macrolide antibiotics with phenolic compounds

PubMed Central

Oh, Euna; Jeon, Byeonghwa

2015-01-01

The increasing resistance of Campylobacter to clinically important antibiotics, such as fluoroquinolones and macrolides, is a serious public health problem. The objective of this study is to investigate synergistic anti-Campylobacter jejuni activity of fluoroquinolones and macrolides in combination with phenolic compounds. Synergistic antimicrobial activity was measured by performing a checkerboard assay with ciprofloxacin and erythromycin in the presence of 21 phenolic compounds. Membrane permeability changes in C. jejuni by phenolic compounds were determined by measuring the level of intracellular uptake of 1-N-phenylnaphthylamine (NPN). Antibiotic accumulation assays were performed to evaluate the level of ciprofloxacin accumulation in C. jejuni. Six phenolic compounds, including p-coumaric acid, sinapic acid, caffeic acid, vanillic acid, gallic acid, and taxifolin, significantly increased the susceptibility to ciprofloxacin and erythromycin in several human and poultry isolates. The synergistic antimicrobial effect was also observed in ciprofloxacin- and erythromycin-resistant C. jejuni strains. The phenolic compounds also substantially increased membrane permeability and antibiotic accumulation in C. jejuni. Interestingly, some phenolic compounds, such as gallic acid and taxifolin, significantly reduced the expression of the CmeABC multidrug efflux pump. Phenolic compounds increased the NPN accumulation in the cmeB mutant, indicating phenolic compounds may affect the membrane permeability. In this study, we successfully demonstrated that combinational treatment of C. jejuni with antibiotics and phenolic compounds synergistically inhibits C. jejuni by impacting both antimicrobial influx and efflux. PMID:26528273

Bioactive compounds and antioxidant activities of some cereal milling by-products.

PubMed

Smuda, Sayed Saad; Mohsen, Sobhy Mohamed; Olsen, Karsten; Aly, Mohamed Hassan

2018-03-01

The present study was performed to evaluate the phytochemicals profiles of some cereal milling by-products such as wheat (bran, germ and shorts), rice (bran, germ and husk) and corn (bran, germ and germ meal) to assess their potentiality as bioactive compounds sources. Distilled water, ethanol, methanol, and acetone separately were used as solvents for the extraction of phytochemicals compounds. The antioxidant activity (AOA), total phenolics content (TPC), and total flavonoids content (TFC) of the extracts were investigated using various in vitro assays. The results showed that tannins content was ranged from 113.4 to 389.5 (mg/100 g sample).The study revealed that TPC and TFC of cereal by-products extracts were significantly different for various solvents. TPC content varied from 366.1 to 1924.9 mg/100 g and TFC content varied from 139.3 to 681.6 mg/100 g. High carotenoids content was observed for corn germ meal and minimum for wheat bran. Distilled water, ethanol and methanol extracts showed significantly different antioxidant activity. Significant variations were observed with regard to AOA of different cereal by-products by using various solvents. The ethanol and methanol were observed to be the best solvents to extract phenolic compounds and antioxidant activity, while acetone extract showed less efficiency. Also, the cereal milling by-products were rich in bioactive compounds and could be used as a value added products.

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

Pulse seed germination improves antioxidative activity of phenolic compounds in stripped soybean oil-in-water emulsions.

PubMed

Xu, Minwei; Jin, Zhao; Peckrul, Allen; Chen, Bingcan

2018-06-01

The purpose of this study was to investigate antioxidative activity of phenolic compounds extracted from germinated pulse seed including chickpeas, lentils and yellow peas. Phenolic compounds were extracted at different germination time and total phenolic content was examined by Folin Ciocalteu's reaction. Antioxidative activity of extracts was characterized by in vitro assay including 2, 2-diphenyl-1-picrylhydrazyl radical scavenging capacity (DPPH), oxygen radical absorbance capacity (ORAC), iron-binding assay, and in stripped soybean oil-in-water emulsions. The results suggested that germination time is critical for phenolic compounds production. The form variation of phenolic compounds influenced the antioxidative activity of phenolic compounds both in vitro assay and in emulsion systems. Soluble bound phenolic compounds showed higher antioxidative ability in emulsion system with the order of chickpea > yellow pea > lentil. On the basis of these results, soluble bound phenolic compounds may be considered as a promising natural antioxidant to prevent lipid oxidation in foods. Copyright © 2018 Elsevier Ltd. All rights reserved.

Methanobactin: a copper binding compound having antibiotic and antioxidant activity isolated from methanotrophic bacteria

DOEpatents

DiSpirito, Alan A [Ames, IA; Zahn, James A [Harbor Beach, MI; Graham, David W [Lawrence, KS; Kim, Hyung J [St. Paul, MN; Alterman, Michail [Lawrence, KS; Larive, Cynthia [Lawrence, KS

2007-04-03

A means and method for treating bacterial infection, providing antioxidant activity, and chelating copper using a copper binding compound produced by methanotrophic bacteria is described. The compound, known as methanobactin, is the first of a new class of antibiotics having gram-positive activity. Methanobactin has been sequenced, and its structural formula determined.

Evaluation of the effect of germination on phenolic compounds and antioxidant activities in sorghum varieties.

PubMed

Dicko, Mamoudou H; Gruppen, Harry; Traore, Alfred S; van Berkel, Willem J H; Voragen, Alphons G J

2005-04-06

The screening of 50 sorghum varieties showed that, on average, germination did not affect the content in total phenolic compounds but decreased the content of proanthocyanidins, 3-deoxyanthocyanidins, and flavan-4-ols. Independent of germination, there are intervarietal differences in antioxidant activities among sorghum varieties. Phenolic compounds and antioxidant activities were more positively correlated in ungerminated varieties than in germinated ones. Sorghum grains with pigmented testa layer, chestnut color glumes, and red plants had higher contents, larger diversity of phenolic compounds, and higher antioxidant activities than other sorghums. Some red sorghum varieties had higher antioxidant activities (30-80 mumol of Trolox equiv/g) than several sources of natural antioxidants from plant foods. Among varieties used for "to", "dolo", couscous, and porridge preparation, the "dolo"(local beer) varieties had the highest average content and diversity in phenolic compounds as well as the highest antioxidant activities. The biochemical markers determined are useful indicators for the selection of sorghum varieties for food and agronomic properties.

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.

Predicting the activity of drugs for a group of imidazopyridine anticoccidial compounds.

PubMed

Si, Hongzong; Lian, Ning; Yuan, Shuping; Fu, Aiping; Duan, Yun-Bo; Zhang, Kejun; Yao, Xiaojun

2009-10-01

Gene expression programming (GEP) is a novel machine learning technique. The GEP is used to build nonlinear quantitative structure-activity relationship model for the prediction of the IC(50) for the imidazopyridine anticoccidial compounds. This model is based on descriptors which are calculated from the molecular structure. Four descriptors are selected from the descriptors' pool by heuristic method (HM) to build multivariable linear model. The GEP method produced a nonlinear quantitative model with a correlation coefficient and a mean error of 0.96 and 0.24 for the training set, 0.91 and 0.52 for the test set, respectively. It is shown that the GEP predicted results are in good agreement with experimental ones.

Bioactive compounds and antioxidant activity in scalded Jalapeño pepper industrial byproduct (Capsicum annuum).

PubMed

Sandoval-Castro, Claudia Jaqueline; Valdez-Morales, Maribel; Oomah, B Dave; Gutiérrez-Dorado, Roberto; Medina-Godoy, Sergio; Espinosa-Alonso, L Gabriela

2017-06-01

Bioactive compounds and antioxidant activity were evaluated from industrial Jalapeño pepper byproducts and simulated non processed byproducts from two Mexican states (Chihuahua and Sinaloa) to determine their value added potential as commercial food ingredients. Aqueous 80% ethanol produced about 13% of dry extract of polar compounds. Total phenolic content increased and capsaicin and dihydrocapsaicin decreased on scalding samples (80 °C, 2 min) without affecting ascorbic acid. The major phenolic compounds, rutin, epicatechin and catechin comprised 90% of the total compounds detected by HPLC of each Jalapeño pepper byproducts. ORAC analysis showed that the origin and scalding process affected the antioxidant activity which correlated strongly with capsaicin content. Although scalding decreased capsaicinoids (up to 42%), phenolic content by (up to 16%), and the antioxidant activity (variable). Jalapeño pepper byproduct is a good source of compounds with antioxidant activity, and still an attractive ingredient to develop useful innovative products with potential food/non-food applications simultaneously reducing food loss and waste.

Texas Native Plants Yield Compounds with Cytotoxic Activities against Prostate Cancer Cells.

PubMed

Shaffer, Corena V; Cai, Shengxin; Peng, Jiangnan; Robles, Andrew J; Hartley, Rachel M; Powell, Douglas R; Du, Lin; Cichewicz, Robert H; Mooberry, Susan L

2016-03-25

There remains a critical need for more effective therapies for the treatment of late-stage and metastatic prostate cancers. Three Texas native plants yielded three new and three known compounds with antiproliferative and cytotoxic activities against prostate cancer cells with IC50 values in the range of 1.7-35.0 μM. A new sesquiterpene named espadalide (1), isolated from Gochnatia hypoleuca, had low micromolar potency and was highly effective in clonogenic assays. Two known bioactive germacranolides (2 and 3) were additionally isolated from G. hypoleuca. Dalea frutescens yielded two new isoprenylated chalcones, named sanjuanolide (4) and sanjoseolide (5), and the known sesquiterpenediol verbesindiol (6) was isolated from Verbesina virginica. Mechanistic studies showed that 1-4 caused G2/M accumulation and the formation of abnormal mitotic spindles. Tubulin polymerization assays revealed that 4 increased the initial rate of tubulin polymerization, but did not change total tubulin polymer levels, and 1-3 had no effects on tubulin polymerization. Despite its cytotoxic activity, compound 6 did not initiate changes in cell cycle distribution and has a mechanism of action different from the other compounds. This study demonstrates that new compounds with significant biological activities germane to unmet oncological needs can be isolated from Texas native plants.

Analysis of Indonesian Spice Essential Oil Compounds That Inhibit Locomotor Activity in Mice

PubMed Central

Muchtaridi; Diantini, Adjeng; Subarnas, Anas

2011-01-01

Some fragrance components of spices used for cooking are known to have an effect on human behavior. The aim of this investigation was to examine the effect of the essential oils of basil (Ocimum formacitratum L.) leaves, lemongrass (Cymbopogon citrates L.) herbs, ki lemo (Litsea cubeba L.) bark, and laja gowah (Alpinia malaccencis Roxb.) rhizomes on locomotor activity in mice and identify the active component(s) that might be responsible for the activity. The effect of the essential oils was studied by a wheel cage method and the active compounds of the essential oils were identified by GC/MS analysis. The essential oils were administered by inhalation at doses of 0.1, 0.3, and 0.5 mL/cage. The results showed that the four essential oils had inhibitory effects on locomotor activity in mice. Inhalation of the essential oils of basil leaves, lemongrass herbs, ki lemo bark, and laja gowah rhizomes showed the highest inhibitory activity at doses of 0.5 (57.64%), 0.1 (55.72%), 0.5 (60.75%), and 0.1 mL/cage (47.09%), respectively. The major volatile compounds 1,8-cineole, α-terpineol, 4-terpineol, citronelol, citronelal, and methyl cinnamate were identified in blood plasma of mice after inhalation of the four oils. These compounds had a significant inhibitory effect on locomotion after inhalation. The volatile compounds of essential oils identified in the blood plasma may correlate with the locomotor-inhibiting properties of the oil when administered by inhalation.

Cytotoxicity, antimicrobial and antioxidant activity of eight compounds isolated from Entada abyssinica (Fabaceae).

PubMed

Dzoyem, Jean P; Melong, Raduis; Tsamo, Armelle T; Tchinda, Alembert T; Kapche, Deccaux G W F; Ngadjui, Bonaventure T; McGaw, Lyndy J; Eloff, Jacobus N

2017-03-06

Entada abyssinica is a plant traditionally used against gastrointestinal bacterial infections. Eight compounds including three flavonoids, three terpenoids, a monoglyceride and a phenolic compound isolated from E. abyssinica were investigated for their cytotoxicity, antibacterial and antioxidant activity. Compounds 7 and 2 had remarkable activity against Salmonella typhimurium with the lowest respective minimum inhibitory concentration (MIC) values of 1.56 and 3.12 µg/mL. The antioxidant assay gave IC 50 values varied from 0.48 to 2.87 μg/mL in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, from 2.53 to 17.04 μg/mL in the 2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) assay and from 1.43 to 103.98 µg/mL in the FRAP assay. Compounds had relatively low cytotoxicity (LC 50 values ranging from 22.42 to 80.55 µg/mL) towards Vero cells. Ursolic acid had the most potent cytotoxicity against THP-1 and RAW 264.7 cells with LC 50 values of 9.62 and 4.56 μg/mL respectively, and selectivity index values of 7.32 and 15.44 respectively. Our findings suggest that among the terpenoid and flavonoid compounds studied, entadanin (compound 7) possess tremendous antibacterial activity against S. typhimurium and could be developed for the treatment of bacterial diseases.

Analysis of Phenolic Compounds and Antioxidant Activity in Wild Blackberry Fruits

PubMed Central

Oszmiański, Jan; Nowicka, Paulina; Teleszko, Mirosława; Wojdyło, Aneta; Cebulak, Tomasz; Oklejewicz, Krzysztof

2015-01-01

Twenty three different wild blackberry fruit samples were assessed regarding their phenolic profiles and contents (by LC/MS quadrupole time-of-flight (QTOF) and antioxidant activity (ferric reducing ability of plasma (FRAP) and 2,2-azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS)) by two different extraction methods. Thirty four phenolic compounds were detected (8 anthocyanins, 15 flavonols, 3 hydroxycinnamic acids, 6 ellagic acid derivatives and 2 flavones). In samples, where pressurized liquid extraction (PLE) was used for extraction, a greater increase in yields of phenolic compounds was observed, especially in ellagic acid derivatives (max. 59%), flavonols (max. 44%) and anthocyanins (max. 29%), than after extraction by the ultrasonic technique extraction (UAE) method. The content of phenolic compounds was significantly correlated with the antioxidant activity of the analyzed samples. Principal component analysis (PCA) revealed that the PLE method was more suitable for the quantitative extraction of flavonols, while the UAE method was for hydroxycinnamic acids. PMID:26132562

Pyrrole and Fused Pyrrole Compounds with Bioactivity against Inflammatory Mediators.

PubMed

Said Fatahala, Samar; Hasabelnaby, Sherifa; Goudah, Ayman; Mahmoud, Ghada I; Helmy Abd-El Hameed, Rania

2017-03-17

A new series of pyrrolopyridines and pyrrolopyridopyrimidines have been synthesized from aminocyanopyrroles. The synthesized compounds have been characterized by FTIR, ¹H-NMR and mass spectroscopy. The final compounds have been screened for in vitro pro-inflammatory cytokine inhibitory and in vivo anti-inflammatory activity. The biological results revealed that among all tested compounds some fused pyrroles, namely the pyrrolopyridines 3i and 3l , show promising activity. A docking study of the active synthesized molecules confirmed the biological results and revealed a new binding pose in the COX-2 binding site.

Herb Medicines against Osteoporosis: Active Compounds & Relevant Biological Mechanisms.

PubMed

Wu, Lei; Ling, Zhuoyan; Feng, Xueqin; Mao, Caiping; Xu, Zhice

2017-01-01

Osteoporosis is one of common bone disorders, affecting millions of people worldwide. Treatments of osteoporosis consist of pharmacotherapy and non-pharmacological interventions, such as mineral supplementation, lifestyle changes, and exercise programs. Due to the minimum side effects and favorable cost-effective therapeutic effects, herbal medicine has been widely applied in clinical practices for more than 2,000 years in China. Of the many traditional formulas reported for treating bone diseases, 4 single herbs namely (1) Herba Epimedii, (2) Rhizoma Drynariae, (3) Fructus Psoraleae, and (4) Cortex Eucommiae, are considered as the featured "Kidney-Yang" tonics, and frequently and effectively applied for preventing and treating osteoporosis. With the accruing development of modern chemistry, hundreds of active compounds have been identified and isolated for their anti-osteoporotic effects. This review would first sketch the phytochemistry of these featured "Kidney- Yang" tonics and present the pharmacological characteristics of the most abundant and bioactive compounds derived from the herb Herba Epimedii and Rhizoma Drynariae, including icariin and naringin. Then, the cellular and molecular underpinnings under anti-osteoporotic effects of icariin and naringin are discussed. The concerned structure-function relationships of the featured active herbal compounds would also be reviewed so as to pave the way for future drug design in treating osteoporosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Four new compounds isolated from Psoralea corylifolia and their diacylglycerol acyltransferase (DGAT) inhibitory activity.

PubMed

Lin, Xin; Li, Ban-Ban; Zhang, Le; Li, Hao-Ze; Meng, Xiao; Jiang, Yi-Yu; Lee, Hyun-Sun; Cui, Long

2018-05-14

A new bakuchiol compound Δ 11 -12-hydroxy-12-dimethyl bakuchiol (1), a new flavanone compound 2(S)-6-methoxy-7- hydroxymethylene-4'-hydroxyl-flavanone (8), and two new isoflavanone compounds 4',7-dihydroxy-3'-(6"β-hydroxy-3″,7″-dimethyl-,2″,7″-dibutenyl)-geranylisoflavone (9) and 4',7-dihydroxy-3'-(7″-hydroxy-7″-methyl-2″,5″-dibutenyl)-geranylisoflavone (10) together with eight known compounds (2-7, 11, 12) were isolated from the P. corylifolia. Their structures were elucidated on the basis of spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against DGAT1/2. Among them, compounds 3, 9 and 10 were found to exhibit selective inhibitory activity on DGAT1 with IC 50 values ranging from 93.7 ± 1.3 to 96.2 ± 1.1 μM. Compound 1 showed inhibition activity on DGAT1 with IC 50 values 73.4 ± 1.3 μM and inhibition of DGAT2 with IC 50 value 121.1 ± 1.3 μM. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of anti-Zika virus activities of broad-spectrum antivirals and NIH clinical collection compounds using a cell-based, high-throughput screen assay.

PubMed

Adcock, Robert S; Chu, Yong-Kyu; Golden, Jennifer E; Chung, Dong-Hoon

2017-02-01

Recent studies have clearly underscored the association between Zika virus (ZIKV) and severe neurological diseases such as microcephaly and Guillain-Barre syndrome. Given the historical complacency surrounding this virus, however, no significant antiviral screenings have been performed to specifically target ZIKV. As a result, there is an urgent need for a validated screening method and strategy that is focused on highlighting potential anti-ZIKV inhibitors that can be further advanced via rigorous validation and optimization. To address this critical gap, we sought to test whether a cell-based assay that measures protection from the ZIKV-induced cytopathic effect could serve as a high-throughput screen assay for discovering novel anti-ZIKV inhibitors. Employing this approach, we tested the anti-ZIKV activity of previously known broad-spectrum antiviral compounds and discovered several compounds (e.g., NITD008, SaliPhe, and CID 91632869) with anti-ZIKV activity. Interestingly, while GTP synthesis inhibitors (e.g., ribavirin or mycophenolic acid) were too toxic or showed no anti-ZIKV activity (EC 50  > 50 μM), ZIKV was highly susceptible to pyrimidine synthesis inhibitors (e.g., brequinar) in the assay. We amended the assay into a high-throughput screen (HTS)-compatible 384-well format and then screened the NIH Clinical Compound Collection library, which includes a total of 727 compounds organized, using an 8-point dose response format with two Zika virus strains (MR766 and PRVABC59, a recent human isolate). The screen discovered 6-azauridine and finasteride as potential anti-ZIKV inhibitors with EC 50 levels of 3.18 and 9.85 μM for MR766, respectively. We further characterized the anti-ZIKV activity of 6-azauridine and several pyrimidine synthesis inhibitors such as brequinar in various secondary assays including an antiviral spectrum test within flaviviruses and alphaviruses, Western blot (protein), real-time PCR (RNA), and plaque reduction assays (progeny

Natural low-molecular mass organic compounds with oxidase activity as organocatalysts.

PubMed

Nishiyama, Tatsuya; Hashimoto, Yoshiteru; Kusakabe, Hitoshi; Kumano, Takuto; Kobayashi, Michihiko

2014-12-02

Organocatalysts, low-molecular mass organic compounds composed of nonmetallic elements, are often used in organic synthesis, but there have been no reports of organocatalysts of biological origin that function in vivo. Here, we report that actinorhodin (ACT), a natural product derived from Streptomyces coelicolor A3(2), acts as a biocatalyst. We purified ACT and assayed its catalytic activity in the oxidation of L-ascorbic acid and L-cysteine as substrates by analytical methods for enzymes. Our findings were as follows: (i) oxidation reactions producing H2O2 proceeded upon addition of ACT to the reaction mixture; (ii) ACT was not consumed during the reactions; and (iii) a small amount (catalytic amount) of ACT consumed an excess amount of the substrates. Even at room temperature, atmospheric pressure, and neutral pH, ACT showed catalytic activity in aqueous solution, and ACT exhibited substrate specificity in the oxidation reactions. These findings reveal ACT to be an organocatalyst. ACT is known to show antibiotic activity, but its mechanism of action remains unknown. On the basis of our results, we propose that ACT kills bacteria by catalyzing the production of toxic levels of H2O2. We also screened various other natural products of bacterial, plant, and animal origins and found that several of the compounds exhibited catalytic activity, suggesting that living organisms produce and use these compounds as biocatalysts in nature.

Development and experimental test of support vector machines virtual screening method for searching Src inhibitors from large compound libraries.

PubMed

Han, Bucong; Ma, Xiaohua; Zhao, Ruiying; Zhang, Jingxian; Wei, Xiaona; Liu, Xianghui; Liu, Xin; Zhang, Cunlong; Tan, Chunyan; Jiang, Yuyang; Chen, Yuzong

2012-11-23

Src plays various roles in tumour progression, invasion, metastasis, angiogenesis and survival. It is one of the multiple targets of multi-target kinase inhibitors in clinical uses and trials for the treatment of leukemia and other cancers. These successes and appearances of drug resistance in some patients have raised significant interest and efforts in discovering new Src inhibitors. Various in-silico methods have been used in some of these efforts. It is desirable to explore additional in-silico methods, particularly those capable of searching large compound libraries at high yields and reduced false-hit rates. We evaluated support vector machines (SVM) as virtual screening tools for searching Src inhibitors from large compound libraries. SVM trained and tested by 1,703 inhibitors and 63,318 putative non-inhibitors correctly identified 93.53%~ 95.01% inhibitors and 99.81%~ 99.90% non-inhibitors in 5-fold cross validation studies. SVM trained by 1,703 inhibitors reported before 2011 and 63,318 putative non-inhibitors correctly identified 70.45% of the 44 inhibitors reported since 2011, and predicted as inhibitors 44,843 (0.33%) of 13.56M PubChem, 1,496 (0.89%) of 168 K MDDR, and 719 (7.73%) of 9,305 MDDR compounds similar to the known inhibitors. SVM showed comparable yield and reduced false hit rates in searching large compound libraries compared to the similarity-based and other machine-learning VS methods developed from the same set of training compounds and molecular descriptors. We tested three virtual hits of the same novel scaffold from in-house chemical libraries not reported as Src inhibitor, one of which showed moderate activity. SVM may be potentially explored for searching Src inhibitors from large compound libraries at low false-hit rates.

Development and experimental test of support vector machines virtual screening method for searching Src inhibitors from large compound libraries

PubMed Central

2012-01-01

Background Src plays various roles in tumour progression, invasion, metastasis, angiogenesis and survival. It is one of the multiple targets of multi-target kinase inhibitors in clinical uses and trials for the treatment of leukemia and other cancers. These successes and appearances of drug resistance in some patients have raised significant interest and efforts in discovering new Src inhibitors. Various in-silico methods have been used in some of these efforts. It is desirable to explore additional in-silico methods, particularly those capable of searching large compound libraries at high yields and reduced false-hit rates. Results We evaluated support vector machines (SVM) as virtual screening tools for searching Src inhibitors from large compound libraries. SVM trained and tested by 1,703 inhibitors and 63,318 putative non-inhibitors correctly identified 93.53%~ 95.01% inhibitors and 99.81%~ 99.90% non-inhibitors in 5-fold cross validation studies. SVM trained by 1,703 inhibitors reported before 2011 and 63,318 putative non-inhibitors correctly identified 70.45% of the 44 inhibitors reported since 2011, and predicted as inhibitors 44,843 (0.33%) of 13.56M PubChem, 1,496 (0.89%) of 168 K MDDR, and 719 (7.73%) of 9,305 MDDR compounds similar to the known inhibitors. Conclusions SVM showed comparable yield and reduced false hit rates in searching large compound libraries compared to the similarity-based and other machine-learning VS methods developed from the same set of training compounds and molecular descriptors. We tested three virtual hits of the same novel scaffold from in-house chemical libraries not reported as Src inhibitor, one of which showed moderate activity. SVM may be potentially explored for searching Src inhibitors from large compound libraries at low false-hit rates. PMID:23173901

Development of a canine model to enable the preclinical assessment of pH-dependent absorption of test compounds.

PubMed

Fancher, R Marcus; Zhang, Hongjian; Sleczka, Bogdan; Derbin, George; Rockar, Richard; Marathe, Punit

2011-07-01

A preclinical canine model capable of predicting a compound's potential for pH-dependent absorption in humans was developed. This involved the surgical insertion of a gastrostomy feeding tube into the stomach of a beagle dog. The tube was sutured in position to allow frequent withdrawal of gastric fluid for pH measurement. Therefore, it was possible to measure pH in the stomach and assess the effect of gastric pH-modifying agents on the absorption of various test compounds. Fasted gastric pH in the dog showed considerable inter- and intra-animal variability. Pretreatment of pentagastrin (6 µg/kg intramuscularly) 20 min prior to test compound administration was determined to be adequate for simulating fasting stomach pH in humans. Pretreatment with famotidine [40 mg orally] 1 h prior to test compound administration was determined to be adequate for simulating human gastric pH when acid-reducing agents are coadministered. Pentagastrin and famotidine pretreatments were used to test two discovery compounds and distinct differences in their potential for pH-dependent absorption were observed. The model described herein can be used preclinically to screen out compounds, differentiate compounds, and support the assessment of various formulation- and prodrug-based strategies to mitigate the pH effect. Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

Establishing a system with Drosophila melanogaster (Diptera: Drosophilidae) to assess the non-target effects of gut-active insecticidal compounds.

PubMed

Haller, Simone; Meissle, Michael; Romeis, Jörg

2016-12-01

Potentially adverse effects on ecosystem functioning by the planting of insect-resistant, genetically engineered plants or by the direct application of insecticidal compounds are carefully evaluated in pre-market risk assessments. To date, few studies have assessed the potential risks of genetically engineered crops or insecticidal compounds on the survival and fitness of dipteran species, despite their important contribution to ecosystem services such as decomposition in agricultural systems. Therefore, we propose that Drosophila melanogaster Meigen (Drosophilidae) be used as a surrogate species for the order Diptera and for the functional guild of soil arthropod decomposers in pre-market risk assessments. We developed two assays to assess the toxicity of gut-active insecticidal compounds to D. melanogaster. One assay uses groups of fly larvae, and the other uses individuals. Cryolite, a mineral pesticide, proved to be an adequate positive control. The effects of cryolite on D. melanogaster larvae were comparable between the two assays. Statistical power analyses were used to define the number of replications required to identify different effect sizes between control and treatment groups. Finally, avidin, E-64, GNA, and SBTI were used as test compounds to validate the individual-based assay; only avidin adversely affected D. melanogaster. These results indicate that both D. melanogaster assays will be useful for early tier risk assessment concerning the effects of orally active compounds on non-target dipterans.

Anti-tumour activity of platinum compounds in advanced prostate cancer-a systematic literature review.

PubMed

Hager, S; Ackermann, C J; Joerger, M; Gillessen, S; Omlin, A

2016-06-01

For men with advanced castration-resistant prostate cancer (CRPC), several treatment options are available, including androgen receptor (AR) pathway inhibitors (abiraterone acetate, enzalutamide), taxanes (docetaxel, cabazitaxel) and the radionuclide (radium-223). However, cross-resistance is a clinically relevant problem. Platinum compounds have been tested in a number of clinical trials in molecularly unselected prostate cancer patients. Advances in CRPC molecular profiling have shown that a significant proportion of patients harbour DNA repair defects, which may serve as predictive markers for sensitivity to platinum agents. To systematically identify and analyse clinical trials that have evaluated platinum agents in advanced prostate cancer patients. PubMed was searched to identify published clinical trials of platinum agents in advanced prostate cancer. The PRIMSA statement was followed for the systematic review process. Identified trials are analysed for study design, statistical plan, assessments of anti-tumour activity and the potential value of predictive biomarkers. A total of 163 references were identified by the literature search and 72 publications that met the selection criteria were included in this review; of these 33 used carboplatin, 27 cisplatin, 6 satraplatin, 4 oxaliplatin and 2 other platinum compounds. Overall, anti-tumour activity varies in the range of 10%-40% for objective response and 20%-70% for PSA decline ≥50%. Response seemed highest for the combinations of carboplatin with taxanes or oxaliplatin with gemcitabine. The interpretation of the clinical data is limited by differences in response criteria used and patient populations studied. Platinum compounds have moderate anti-tumour activity in molecularly unselected patients with advanced prostate cancer. Translational evidence of DNA repair deficiency should be leveraged in future studies to select prostate cancer patients most likely to benefit from platinum-based therapy. © The

Evaluation of Natural Compounds for Antimicrobial Activity in the Introductory Microbiology Laboratory.

ERIC Educational Resources Information Center

Finer, Kim R.

1997-01-01

Presents an experiment that provides students with an opportunity to investigate folk medicine and herbal cures and their accompanying claims. Involves isolating some active compounds from plant materials and demonstrating their antibacterial activity. (JRH)

Adsorption of volatile organic compounds by pecan shell- and almond shell-based granular activated carbons.

PubMed

Bansode, R R; Losso, J N; Marshall, W E; Rao, R M; Portier, R J

2003-11-01

The objective of this research was to determine the effectiveness of using pecan and almond shell-based granular activated carbons (GACs) in the adsorption of volatile organic compounds (VOCs) of health concern and known toxic compounds (such as bromo-dichloromethane, benzene, carbon tetrachloride, 1,1,1-trichloromethane, chloroform, and 1,1-dichloromethane) compared to the adsorption efficiency of commercially used carbons (such as Filtrasorb 200, Calgon GRC-20, and Waterlinks 206C AW) in simulated test medium. The pecan shell-based GACs were activated using steam, carbon dioxide or phosphoric acid. An almond shell-based GAC was activated with phosphoric acid. Our results indicated that steam- or carbon dioxide-activated pecan shell carbons were superior in total VOC adsorption to phosphoric acid-activated pecan shell or almond shell carbons, inferring that the method of activation selected for the preparation of activated carbons affected the adsorption of VOCs and hence are factors to be considered in any adsorption process. The steam-activated, pecan shell carbon adsorbed more total VOCs than the other experimental carbons and had an adsorption profile similar to the two coconut shell-based commercial carbons, but had greater adsorption than the coal-based commercial carbon. All the carbons studied adsorbed benzene more effectively than the other organics. Pecan shell, steam-activated and acid-activated GACs showed higher adsorption of 1,1,1-trichloroethane than the other carbons studied. Multivariate analysis was conducted to group experimental carbons and commercial carbons based on their physical, chemical, and adsorptive properties. The results of the analysis conclude that steam-activated and acid-activated pecan shell carbons clustered together with coal-based and coconut shell-based commercial carbons, thus inferring that these experimental carbons could potentially be used as alternative sources for VOC adsorption in an aqueous environment.

Phenolic Compounds of Pomegranate Byproducts (Outer Skin, Mesocarp, Divider Membrane) and Their Antioxidant Activities.

PubMed

Ambigaipalan, Priyatharini; de Camargo, Adriano Costa; Shahidi, Fereidoon

2016-08-31

Pomegranate peel was separated into outer leathery skin (PS), mesocarp (PM), and divider membrane (PD), and its phenolic compounds were extracted as free (F), esterified (E), and insoluble-bound (B) forms for the first time. The total phenolic content followed the order PD > PM > PS. ABTS(•+), DPPH, and hydroxyl radical scavenging activities and metal chelation were evaluated. In addition, pomegranate peel extracts showed inhibitory effects against α-glucosidase activity, lipase activity, and cupric ion-induced LDL-cholesterol oxidation as well as peroxyl and hydroxyl radical-induced DNA scission. Seventy-nine phenolic compounds were identified using HPLC-DAD-ESI-MS(n) mainly in the form of insoluble-bound. Thirty compounds were identified for the first time. Gallic acid was the major phenolic compound in pomegranate peel, whereas kaempferol 3-O-glucoside was the major flavonoid. Moreover, ellagic acid and monogalloyl-hexoside were the major hydrolyzable tannins, whereas the dominant proanthocyanidin was procyanidin dimers. Proanthocyanidins were detected for the first time.

Acquisition of Compound Words in Chinese-English Bilingual Children: Decomposition and Cross-Language Activation

ERIC Educational Resources Information Center

Cheng, Chenxi; Wang, Min; Perfetti, Charles A.

2011-01-01

This study investigated compound processing and cross-language activation in a group of Chinese-English bilingual children, and they were divided into four groups based on the language proficiency levels in their two languages. A lexical decision task was designed using compound words in both languages. The compound words in one language contained…

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.

In Vitro Evaluation of Antileishmanial Activity of Computationally Screened Compounds against Ascorbate Peroxidase To Combat Amphotericin B Drug Resistance

PubMed Central

Mansuri, Rani; Kumar, Ashish; Rana, Sindhuprava; Panthi, Bhavana; Ansari, M. Yousuf; Das, Sushmita; Dikhit, Manas Ranjan

2017-01-01

ABSTRACT In visceral leishmaniasis (VL), the host macrophages generate oxidative stress to destroy the pathogen, while Leishmania combats the harmful effect of radicals by redox homeostasis through its unique trypanothione cascade. Leishmania donovani ascorbate peroxidase (LdAPx) is a redox enzyme that regulates the trypanothione cascade and detoxifies the effect of H2O2. The absence of an LdAPx homologue in humans makes it an excellent drug target. In this study, the homology model of LdAPx was built, including heme, and diverse compounds were prefiltered (PAINS, ADMET, and Lipinski's rule of five) and thereafter screened against the LdAPx model. Compounds having good affinity in terms of the Glide XP (extra precision) score were clustered to select diverse compounds for experimental validation. A total of 26 cluster representatives were procured and tested on promastigote culture, yielding 12 compounds with good antileishmanial activity. Out of them, six compounds were safer on the BALB/c peritoneal macrophages and were also effective against disease-causing intracellular amastigotes. Three out of six compounds inhibited recombinant LdAPx in a noncompetitive manner and also demonstrated partial reversion of the resistance property in an amphotericin B (AmB)-resistant strain, which may be due to an increased level of reactive oxygen species (ROS) and decrease of glutathione (GSH) content. However, inhibition of LdAPx in resistant parasites enhanced annexin V staining and activation of metacaspase-like protease activity, which may help in DNA fragmentation and apoptosis-like cell death. Thus, the present study will help in the search for specific hits and templates of potential therapeutic interest and therefore may facilitate the development of new drugs for combination therapy against VL. PMID:28461317

Synthesis of natural acylphloroglucinol-based antifungal compounds against Cryptococcus species

USDA-ARS?s Scientific Manuscript database

Thirty-five analogs of naturally occurring acylphloroglucinols were designed and synthesized to identify antifungal compounds against Cryptococcus spp. that causes the life-threatening disseminated cryptococcosis. In vitro antifungal testing showed that 17 compounds were active against C. neoformans...

Establishment of alternative potency test for botulinum toxin type A using compound muscle action potential (CMAP) in rats.

PubMed

Torii, Yasushi; Goto, Yoshitaka; Nakahira, Shinji; Ginnaga, Akihiro

2014-11-01

The biological activity of botulinum toxin type A has been evaluated using the mouse intraperitoneal (ip) LD50 test. This method requires a large number of mice to precisely determine toxin activity, and, as such, poses problems with regard to animal welfare. We previously developed a compound muscle action potential (CMAP) assay using rats as an alternative method to the mouse ip LD50 test. In this study, to evaluate this quantitative method of measuring toxin activity using CMAP, we assessed the parameters necessary for quantitative tests according to ICH Q2 (R1). This assay could be used to evaluate the activity of the toxin, even when inactive toxin was mixed with the sample. To reduce the number of animals needed, this assay was set to measure two samples per animal. Linearity was detected over a range of 0.1-12.8 U/mL, and the measurement range was set at 0.4-6.4 U/mL. The results for accuracy and precision showed low variability. The body weight was selected as a variable factor, but it showed no effect on the CMAP amplitude. In this study, potency tests using the rat CMAP assay of botulinum toxin type A demonstrated that it met the criteria for a quantitative analysis method. Copyright © 2014 Elsevier Ltd. All rights reserved.

Extracts of Phenolic Compounds from Seeds of Three Wild Grapevines—Comparison of Their Antioxidant Activities and the Content of Phenolic Compounds

PubMed Central

Weidner, Stanisław; Powałka, Anna; Karamać, Magdalena; Amarowicz, Ryszard

2012-01-01

Phenolic compounds were extracted from three wild grapevine species: Vitis californica, V. riparia and V. amurensis seeds using 80% methanol or 80% acetone. The total content of phenolic compounds was determined utilizing the Folin-Ciocalteu’s phenol reagent while the content of tannins was assayed with the vanillin and BSA precipitation methods. Additionally, the DPPH free radical scavenging activity and the reduction power of the extracts were measured. The RP-HPLC method was applied to identify the phenolic compounds in the extracts, such as phenolic acids and catechins. The seeds contained large amounts of tannins, catechins and gallic acid and observable quantities of p-coumaric acid. The total content of phenolic compounds and tannins was similar in the extracts from V. californica and V. riparia seeds. However, the total content of total phenolic compounds and tannins in the extracts from V. californica and V. riperia seeds were about two-fold higher than that in the extracts from V. amurensis seeds. Extracts from seeds of the American species (V. californica and V. riparia) contained similarly high concentrations of tannins, whereas extracts from seeds of V. amurensis had approximately half that amount of these compounds. The content of catechin and epicatechin was similar in all extracts. The highest DPPH• anti-radical scavenging activity was observed in the acetonic and methanolic extracts of V. californica and V. riparia seeds— while the acetonic extract from the V. californica seeds was the strongest reducing agent. PMID:22489161

Compound A, a Selective Glucocorticoid Receptor Modulator, Enhances Heat Shock Protein Hsp70 Gene Promoter Activation

PubMed Central

Beck, Ilse M.; Drebert, Zuzanna J.; Hoya-Arias, Ruben; Bahar, Ali A.; Devos, Michael; Clarisse, Dorien; Desmet, Sofie; Bougarne, Nadia; Ruttens, Bart; Gossye, Valerie; Denecker, Geertrui; Lievens, Sam; Bracke, Marc; Tavernier, Jan; Declercq, Wim; Gevaert, Kris; Berghe, Wim Vanden; Haegeman, Guy; De Bosscher, Karolien

2013-01-01

Compound A possesses glucocorticoid receptor (GR)-dependent anti-inflammatory properties. Just like classical GR ligands, Compound A can repress NF-κB-mediated gene expression. However, the monomeric Compound A-activated GR is unable to trigger glucocorticoid response element-regulated gene expression. The heat shock response potently activates heat shock factor 1 (HSF1), upregulates Hsp70, a known GR chaperone, and also modulates various aspects of inflammation. We found that the selective GR modulator Compound A and heat shock trigger similar cellular effects in A549 lung epithelial cells. With regard to their anti-inflammatory mechanism, heat shock and Compound A are both able to reduce TNF-stimulated IκBα degradation and NF-κB p65 nuclear translocation. We established an interaction between Compound A-activated GR and Hsp70, but remarkably, although the presence of the Hsp70 chaperone as such appears pivotal for the Compound A-mediated inflammatory gene repression, subsequent novel Hsp70 protein synthesis is uncoupled from an observed CpdA-induced Hsp70 mRNA upregulation and hence obsolete in mediating CpdA’s anti-inflammatory effect. The lack of a Compound A-induced increase in Hsp70 protein levels in A549 cells is not mediated by a rapid proteasomal degradation of Hsp70 or by a Compound A-induced general block on translation. Similar to heat shock, Compound A can upregulate transcription of Hsp70 genes in various cell lines and BALB/c mice. Interestingly, whereas Compound A-dependent Hsp70 promoter activation is GR-dependent but HSF1-independent, heat shock-induced Hsp70 expression alternatively occurs in a GR-independent and HSF1-dependent manner in A549 lung epithelial cells. PMID:23935933

Characterization and Quantification of Compounds in the Hydroalcoholic Extract of the Leaves from Terminalia catappa Linn. (Combretaceae) and Their Mutagenic Activity

PubMed Central

Mininel, Francisco José; Leonardo Junior, Carlos Sérgio; Espanha, Lívia Greghi; Resende, Flávia Aparecida; Varanda, Eliana Aparecida; Leite, Clarice Queico Fujimura; Vilegas, Wagner; dos Santos, Lourdes Campaner

2014-01-01

Terminalia is a genus of Combretaceous plants widely distributed in tropical and subtropical regions. Thus, the aim of this study was to quantify the majority compounds of the hydroalcoholic extract (7 : 3, v/v) of the leaves from T. catappa by HPLC-PDA, chemically characterize by hyphenated techniques (HPLC-ESI-IT-MSn) and NMR, and evaluate its mutagenic activity by the Salmonella/microsome assay on S. typhimurium strains TA98, TA97a, TA100, and TA102. The quantification of analytes was performed using an external calibration standard. Punicalagin is the most abundant polyphenol found in the leaves. The presence of this compound as a mixture of anomers was confirmed using HPLC-PDA and 1H and 13C NMR. Mutagenic activity was observed in strains TA100 and TA97a. As the extract is a complex mixture of punicalagin, its derivatives, and several other compounds, the observed mutagenicity may be explained in part by possible synergistic interaction between the compounds present in the extract. These studies show that mutagenic activity of T. catappa in the Ames test can only be observed when measured at high concentrations. However, considering the mutagenic effects observed for T. catappa, this plant should be used cautiously for medicinal purposes. PMID:24734110

Identification of Trypanocidal Activity for Known Clinical Compounds Using a New Trypanosoma cruzi Hit-Discovery Screening Cascade.

PubMed

De Rycker, Manu; Thomas, John; Riley, Jennifer; Brough, Stephen J; Miles, Tim J; Gray, David W

2016-04-01

Chagas disease is a significant health problem in Latin America and the available treatments have significant issues in terms of toxicity and efficacy. There is thus an urgent need to develop new treatments either via a repurposing strategy or through the development of new chemical entities. A key first step is the identification of compounds with anti-Trypanosoma cruzi activity from compound libraries. Here we describe a hit discovery screening cascade designed to specifically identify hits that have the appropriate anti-parasitic properties to warrant further development. The cascade consists of a primary imaging-based assay followed by newly developed and appropriately scaled secondary assays to predict the cidality and rate-of-kill of the compounds. Finally, we incorporated a cytochrome P450 CYP51 biochemical assay to remove compounds that owe their phenotypic response to inhibition of this enzyme. We report the use of the cascade in profiling two small libraries containing clinically tested compounds and identify Clemastine, Azelastine, Ifenprodil, Ziprasidone and Clofibrate as molecules having appropriate profiles. Analysis of clinical derived pharmacokinetic and toxicity data indicates that none of these are appropriate for repurposing but they may represent suitable start points for further optimisation for the treatment of Chagas disease.

Gene expression profiling in Ishikawa cells: A fingerprint for estrogen active compounds

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

Boehme, Kathleen; Simon, Stephanie; Mueller, Stefan O.

2009-04-01

Several anthropogenous and naturally occurring substances, referred to as estrogen active compounds (EACs), are able to interfere with hormone and in particular estrogen receptor signaling. EACs can either cause adverse health effects in humans and wildlife populations or have beneficial effects on estrogen-dependent diseases. The aim of this study was to examine global gene expression profiles in estrogen receptor (ER)-proficient Ishikawa plus and ER-deficient Ishikawa minus endometrial cancer cells treated with selected well-known EACs (Diethylstilbestrol, Genistein, Zearalenone, Resveratrol, Bisphenol A and o,p'-DDT). We also investigated the effect of the pure antiestrogen ICI 182,780 (ICI) on the expression patterns caused bymore » these compounds. Transcript levels were quantified 24 h after compound treatment using Illumina BeadChip Arrays. We identified 87 genes with similar expression changes in response to all EAC treatments in Ishikawa plus. ICI lowered the magnitude or reversed the expression of these genes, indicating ER dependent regulation. Apart from estrogenic gene regulation, Bisphenol A, o,p'-DDT, Zearalenone, Genistein and Resveratrol displayed similarities to ICI in their expression patterns, suggesting mixed estrogenic/antiestrogenic properties. In particular, the predominant antiestrogenic expression response of Resveratrol could be clearly distinguished from the other test compounds, indicating a distinct mechanism of action. Divergent gene expression patterns of the phytoestrogens, as well as weaker estrogenic gene expression regulation determined for the anthropogenous chemicals Bisphenol A and o,p'-DDT, warrants a careful assessment of potential detrimental and/or beneficial effects of EACs. The characteristic expression fingerprints and the identified subset of putative marker genes can be used for screening chemicals with an unknown mode of action and for predicting their potential to exert endocrine disrupting effects.« less

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

PubMed Central

Wale, Nikil; Karypis, George

2009-01-01

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

Variation of antioxidant activity and the levels of bioactive compounds in lipophilic and hydrophilic extracts from hot pepper (Capsicum spp.) cultivars.

PubMed

Bae, Haejin; Jayaprakasha, G K; Jifon, John; Patil, Bhimanagouda S

2012-10-15

Peppers (Capsicum spp.) are a rich source of diverse bioactive compounds with potential health-promoting properties. This study investigated the extraction efficiency of five solvents on antioxidant activities from cayenne (CA408 and Mesilla), jalapeño (Ixtapa) and serrano (Tuxtlas) pepper cultivars. Freeze-dried peppers were extracted using a Soxhlet extractor with five solvents: hexane, ethyl acetate, acetone, methanol, and methanol:water (80:20). The levels of specific bioactive compounds (phenolics, capsaicinoids, carotenoids and flavonoids) were determined by HPLC and antioxidant activities were assayed by three methods. For all pepper cultivars tested, hexane extracts had the highest levels of capsaicinoids and carotenoids, but methanol extracts had the maximum levels of flavonoids. Hexane extracts showed higher 2,2-diphenyl-1-pricrylhydrozyl (DPPH) radical-scavenging activity and higher reducing power, and acetone extracts (from Mesilla pepper) had a high reducing power. All pepper extracts, except hexane, were effective in preventing deoxyribose degradation, and the inhibition was increased by high concentrations of extracts. The results of the present study indicated that, among the different measures of antioxidant activity, DPPH radical-scavenging activity was strongly correlated with total bioactive compounds (capsaicinoids, carotenoids, flavonoids and total phenolics) in pepper cultivars. Copyright © 2012 Elsevier Ltd. All rights reserved.

Anti-inflammatory activity of different agave plants and the compound cantalasaponin-1.

PubMed

Monterrosas-Brisson, Nayeli; Ocampo, Martha L Arenas; Jiménez-Ferrer, Enrique; Jiménez-Aparicio, Antonio R; Zamilpa, Alejandro; Gonzalez-Cortazar, Manases; Tortoriello, Jaime; Herrera-Ruiz, Maribel

2013-07-10

Species of the agave genus, such as Agave tequilana, Agave angustifolia and Agave americana are used in Mexican traditional medicine to treat inflammation-associated conditions. These plants' leaves contain saponin compounds which show anti-inflammatory properties in different models. The goal of this investigation was to evaluate the anti-inflammatory capacity of these plants, identify which is the most active, and isolate the active compound by a bio-directed fractionation using the ear edema induced in mice with 12-O-tetradecanoylphorbol-13-acetate (TPA) technique. A dose of 6 mg/ear of acetone extract from the three agave species induced anti-inflammatory effects, however, the one from A. americana proved to be the most active. Different fractions of this species showed biological activity. Finally the F5 fraction at 2.0 mg/ear induced an inhibition of 85.6%. We identified one compound in this fraction as (25R)-5α-spirostan-3β,6α,23α-triol-3,6-di-O-β-D-glucopyranoside (cantalasaponin-1) through 1H- and 13C-NMR spectral analysis and two dimensional experiments like DEPT NMR, COSY, HSQC and HMBC. This steroidal glycoside showed a dose dependent effect of up to 90% of ear edema inhibition at the highest dose of 1.5 mg/ear.

Rapid CE-UV binding tests of environmentally hazardous compounds with polymer-modified magnetic nanoparticles.

PubMed

Iqbal, Zafar; Alsudir, Samar; Miah, Musharraf; Lai, Edward P C

2011-08-01

Hazardous compounds and bacteria in water have an adverse impact on human health and environmental ecology. Polydopamine (or polypyrrole)-coated magnetic nanoparticles and polymethacrylic acid-co-ethylene glycol dimethacrylate submicron particles were investigated for their fast binding kinetics with bisphenol A, proflavine, naphthalene acetic acid, and Escherichia coli. A new method was developed for the rapid determination of % binding by sequential injection of particles first and compounds (or E. coli) next into a fused-silica capillary for overlap binding during electrophoretic migration. Only nanolitre volumes of compounds and particles were sufficient to complete a rapid binding test. After heterogeneous binding, separation of the compounds from the particles was afforded by capillary electrophoresis. % binding was influenced by applied voltage but not current flow. In-capillary coating of particles affected the % binding of compounds. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hybrid energy storage systems utilizing redox active organic compounds

DOEpatents

Wang, Wei; Xu, Wu; Li, Liyu; Yang, Zhenguo

2015-09-08

Redox flow batteries (RFB) have attracted considerable interest due to their ability to store large amounts of power and energy. Non-aqueous energy storage systems that utilize at least some aspects of RFB systems are attractive because they can offer an expansion of the operating potential window, which can improve on the system energy and power densities. One example of such systems has a separator separating first and second electrodes. The first electrode includes a first current collector and volume containing a first active material. The second electrode includes a second current collector and volume containing a second active material. During operation, the first source provides a flow of first active material to the first volume. The first active material includes a redox active organic compound dissolved in a non-aqueous, liquid electrolyte and the second active material includes a redox active metal.

Biochemical Screening of Five Protein Kinases from Plasmodium falciparum against 14,000 Cell-Active Compounds

PubMed Central

Crowther, Gregory J.; Hillesland, Heidi K.; Keyloun, Katelyn R.; Reid, Molly C.; Lafuente-Monasterio, Maria Jose; Ghidelli-Disse, Sonja; Leonard, Stephen E.; He, Panqing; Jones, Jackson C.; Krahn, Mallory M.; Mo, Jack S.; Dasari, Kartheek S.; Fox, Anna M. W.; Boesche, Markus; El Bakkouri, Majida; Rivas, Kasey L.; Leroy, Didier; Hui, Raymond; Drewes, Gerard; Maly, Dustin J.; Van Voorhis, Wesley C.; Ojo, Kayode K.

2016-01-01

In 2010 the identities of thousands of anti-Plasmodium compounds were released publicly to facilitate malaria drug development. Understanding these compounds’ mechanisms of action—i.e., the specific molecular targets by which they kill the parasite—would further facilitate the drug development process. Given that kinases are promising anti-malaria targets, we screened ~14,000 cell-active compounds for activity against five different protein kinases. Collections of cell-active compounds from GlaxoSmithKline (the ~13,000-compound Tres Cantos Antimalarial Set, or TCAMS), St. Jude Children’s Research Hospital (260 compounds), and the Medicines for Malaria Venture (the 400-compound Malaria Box) were screened in biochemical assays of Plasmodium falciparum calcium-dependent protein kinases 1 and 4 (CDPK1 and CDPK4), mitogen-associated protein kinase 2 (MAPK2/MAP2), protein kinase 6 (PK6), and protein kinase 7 (PK7). Novel potent inhibitors (IC50 < 1 μM) were discovered for three of the kinases: CDPK1, CDPK4, and PK6. The PK6 inhibitors are the most potent yet discovered for this enzyme and deserve further scrutiny. Additionally, kinome-wide competition assays revealed a compound that inhibits CDPK4 with few effects on ~150 human kinases, and several related compounds that inhibit CDPK1 and CDPK4 yet have limited cytotoxicity to human (HepG2) cells. Our data suggest that inhibiting multiple Plasmodium kinase targets without harming human cells is challenging but feasible. PMID:26934697

Two new compounds from Xanthium strumarium.

PubMed

Yin, Rong-Hua; Bai, Xue; Feng, Tao; Dong, Ze-Jun; Li, Zheng-Hui; Liu, Ji-Kai

2016-01-01

One new lignan, fructusol A (1), and one new thiazine derivative, 2-hydroxy-xanthiazone (2), along with eight known ones, were isolated from the seeds of Xanthium strumarium. The structures of new compounds were elucidated on the basis of extensive spectroscopic methods. Meanwhile, compounds 1-3 were tested for their antifungal activities against Candida albicans (ATCC 10231) in vitro. No one showed obvious inhibitions (MIC90 > 128 μg/ml).

Aldose Reductase Inhibitory Activity of Compounds from  Zea mays L.

PubMed Central

Kim, Tae Hyeon; Kim, Jin Kyu; Kang, Young-Hee; Lee, Jae-Yong; Kang, Il Jun; Lim, Soon Sung

2013-01-01

Aldose reductase (AR) inhibitors have a considerable therapeutic potential against diabetes complications and do not increase the risk of hypoglycemia. Through bioassay-guided fractionation of an EtOH extract of the kernel from purple corn (Zea mays L.), 7 nonanthocyanin phenolic compounds (compound 1–7) and 5 anthocyanins (compound 8–12) were isolated. These compounds were investigated by rat lens aldose reductase (RLAR) inhibitory assays. Kinetic analyses of recombinant human aldose reductase (rhAR) were performed, and intracellular galactitol levels were measured. Hirsutrin, one of 12 isolated compounds, showed the most potent RLAR inhibitory activity (IC50, 4.78 μM). In the kinetic analyses using Lineweaver-Burk plots of 1/velocity and 1/substrate concentration, hirsutrin showed competitive inhibition against rhAR. Furthermore, hirsutrin inhibited galactitol formation in rat lens and erythrocytes sample incubated with a high concentration of galactose; this finding indicates that hirsutrin may effectively prevent osmotic stress in hyperglycemia. Therefore, hirsutrin derived from Zea mays L. may be a potential therapeutic agent against diabetes complications. PMID:23586057

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

PubMed Central

2013-01-01

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

Mutagenicity testing in the Salmonella typhimurium assay of phenolic compounds and phenolic fractions obtained from smokehouse smoke condensates.

PubMed

Pool, B L; Lin, P Z

1982-08-01

Smokehouse smoke, which is used for flavouring meat products, was investigated for its mutagenic activity in the Salmonella typhimurium assay. We were chiefly concerned with the fractions free of polycyclic aromatic hydrocarbons but containing phenol compounds, which are responsible for the preservative and aromatizing properties of the smoke. The most abundantly occurring phenol compounds (phenol, cresols, 2,4-dimethylphenol, brenzcatechine, syringol, eugenol, vanilline and guaiacol) gave negative results when they were tested for mutagenicity at five concentrations up to 5000 micrograms/plate, with and without S-9 mix, using five strains of S. typhimurium. Even when phenol was further investigated in a variety of test conditions, no induction of his+ revertants was observed. When smokehouse smoke was condensed and fractionated the majority of the various phenolic fractions also gave negative results when tested at five concentrations using five strains of S. typhimurium. However there was a slight increase in the number of revertants in a few cases. The presence in the phenolic fractions of very small amounts of mutagenic impurities, the nature of which needs further investigation, cannot be excluded. These results support the further development of non-hazardous smoke-aroma preparations, based on the phenolic components of smokehouse smoke.

Validation of chemical compound library screening for transcriptional co-activator with PDZ-binding motif inhibitors using GFP-fused transcriptional co-activator with PDZ-binding motif.

PubMed

Nagashima, Shunta; Maruyama, Junichi; Kawano, Shodai; Iwasa, Hiroaki; Nakagawa, Kentaro; Ishigami-Yuasa, Mari; Kagechika, Hiroyuki; Nishina, Hiroshi; Hata, Yutaka

2016-06-01

Transcriptional co-activator with PDZ-binding motif (TAZ) plays versatile roles in cell proliferation and differentiation. It is phosphorylated by large tumor suppressor kinases, the core kinases of the tumor-suppressive Hippo pathway. Phosphorylation induces the cytoplasmic accumulation of TAZ and its degradation. In human cancers, the deregulation of the Hippo pathway and gene amplification enhance TAZ activity. TAZ interacts with TEA domain family members (TEAD), and upregulates genes implicated in epithelial-mesenchymal transition. It also confers stemness to cancer cells. Thus, TAZ activation provides cancer cells with malignant properties and worsens the clinical prognosis. Therefore, TAZ attracts attention as a therapeutic target in cancer therapy. We applied 18 606 small chemical compounds to human osteosarcoma U2OS cells expressing GFP-fused TAZ (GFP-TAZ), monitored the subcellular localization of GFP-TAZ, and selected 33 compounds that shifted GFP-TAZ to the cytoplasm. Unexpectedly, only a limited number of compounds suppressed TAZ-mediated enhancement of TEAD-responsive reporter activity. Moreover, the compounds that weakened TEAD reporter activity did not necessarily decrease the unphosphorylated TAZ. In this study, we focused on three compounds that decreased both TEAD reporter activity and unphosphorylated TAZ, and treated several human cancer cells with these compounds. One compound did not show a remarkable effect, whereas the other two compounds compromised the cell viability in certain cancer cells. In conclusion, the GFP-TAZ-based assay can be used as the first screening for compounds that inhibit TAZ and show anticancer properties. To develop anticancer drugs, we need additional assays to select the compounds. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Human aldo-keto reductases 1B1 and 1B10: a comparative study on their enzyme activity toward electrophilic carbonyl compounds.

PubMed

Shen, Yi; Zhong, Linlin; Johnson, Stephen; Cao, Deliang

2011-05-30

Aldo-keto reductase family 1 member B1 (AKR1B1, 1B1 in brief) and aldo-keto reductase family 1 member B10 (AKR1B10, 1B10 in brief) are two proteins with high similarities in their amino acid sequences, stereo structures, and substrate specificity. However, these two proteins exhibit distinct tissue distributions; 1B10 is primarily expressed in the gastrointestinal tract and adrenal gland, whereas 1B1 is ubiquitously present in all tissues/organs, suggesting their difference in biological functions. This study evaluated in parallel the enzyme activity of 1B1 and 1B10 toward alpha, beta-unsaturated carbonyl compounds with cellular and dietary origins, including acrolein, crotonaldehyde, 4-hydroxynonenal, trans-2-hexenal, and trans-2,4-hexadienal. Our results showed that 1B10 had much better enzyme activity and turnover rates toward these chemicals than 1B1. By detecting the enzymatic products using high-performance liquid chromatography, we measured their activity to carbonyl compounds at low concentrations. Our data showed that 1B10 efficiently reduced the tested carbonyl compounds at physiological levels, but 1B1 was less effective. Ectopically expressed 1B10 in 293T cells effectively eliminated 4-hydroxynonenal at 5 μM by reducing to 1,4-dihydroxynonene, whereas endogenously expressed 1B1 did not. The 1B1 and 1B10 both showed enzyme activity to glutathione-conjugated carbonyl compounds, but 1B1 appeared more active in general. Together our data suggests that 1B10 is more effectual in eliminating free electrophilic carbonyl compounds, but 1B1 seems more important in the further detoxification of glutathione-conjugated carbonyl compounds. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Bioactive Compound Contents and Antioxidant Activity in Aronia (Aronia melanocarpa) Leaves Collected at Different Growth Stages.

PubMed

Thi, Nhuan Do; Hwang, Eun-Sun

2014-09-01

The bioactive compounds and antioxidant activity of aronia leaves at different stages of maturity were identified and evaluated. Young and old leaves were approximately 2 months of age and 4 months of age, respectively. The young leaves contained more polyphenols and flavonoids than the old leaves. Three phenolic compounds (i.e., chlorogenic acid, p-coumaric acid, and rutin) were detected by HPLC. Antioxidant activity was measured using 2,2-di-phenyl-1-picrylhydrazyl (DPPH) radical, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical, and superoxide anion radical scavenging assays. The reducing power of aronia leaf extracts increased in a concentration-dependent manner (0~100 μg/mL). The antioxidant activity of the 80% ethanol extract was greater than that of distilled water extract. The high phenolic compound content indicated that these compounds contribute to antioxidant activity. The overall results indicate that aronia leaves contain bioactive compounds, and that younger aronia leaves may be more favorable for extracting antioxidative ingredients because they contain more polyphenols.

Bioactive Compound Contents and Antioxidant Activity in Aronia (Aronia melanocarpa) Leaves Collected at Different Growth Stages

PubMed Central

Thi, Nhuan Do; Hwang, Eun-Sun

2014-01-01

The bioactive compounds and antioxidant activity of aronia leaves at different stages of maturity were identified and evaluated. Young and old leaves were approximately 2 months of age and 4 months of age, respectively. The young leaves contained more polyphenols and flavonoids than the old leaves. Three phenolic compounds (i.e., chlorogenic acid, p-coumaric acid, and rutin) were detected by HPLC. Antioxidant activity was measured using 2,2-di-phenyl-1-picrylhydrazyl (DPPH) radical, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical, and superoxide anion radical scavenging assays. The reducing power of aronia leaf extracts increased in a concentration-dependent manner (0~100 μg/mL). The antioxidant activity of the 80% ethanol extract was greater than that of distilled water extract. The high phenolic compound content indicated that these compounds contribute to antioxidant activity. The overall results indicate that aronia leaves contain bioactive compounds, and that younger aronia leaves may be more favorable for extracting antioxidative ingredients because they contain more polyphenols. PMID:25320718

Algicidal activity of Bacillus sp. Lzh-5 and its algicidal compounds against Microcystis aeruginosa.

PubMed

Li, Zhenghua; Geng, Mengxin; Yang, Hong

2015-01-01

A freshwater algicidal bacterial strain, Lzh-5, isolated from Lake Taihu, with strong algicidal activity against Microcystis aeruginosa, was identified as Bacillus sp. based on its phenotypic characteristics and 16S ribosomal RNA (rRNA) gene sequence. The algicidal mode of Bacillus sp. Lzh-5 was indirect, attacking M. aeruginosa cells by releasing algicidal compounds. Two algicidal compounds (S-5A and S-5B) produced by Bacillus sp. Lzh-5 were purified with ethyl acetate extraction, column chromatography, and high-performance liquid chromatography and identified as hexahydropyrrolo[1,2-a]pyrazine-1,4-dione and 3-isopropyl-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione based on liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and nuclear magnetic resonance analyses. The active algicidal compounds S-5A (hexahydropyrrolo[1,2-a]pyrazine-1,4-dione) and S-5B (3-isopropyl-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione) displayed high levels of algicidal activity against M. aeruginosa 9110, with LD50 values of 5.7 and 19.4 μg/ml, respectively. This is the first report of 3-isopropyl-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione as an algicidal compound. Compounds S-5A and S-5B also induced obvious morphological changes in M. aeruginosa 9110. In cocultures of M. aeruginosa 9110 and Bacillus sp. Lzh-5, the cell density of Bacillus sp. Lzh-5 and the concentrations of S-5A and S-5B correlated positively with the algicidal activity. Our results indicate that strain Lzh-5 and its two algicidal compounds are potentially useful for controlling cyanobacterial blooms in Lake Taihu.

Effect of drying on the bioactive compounds, antioxidant, antibacterial and antityrosinase activities of pomegranate peel.

PubMed

Mphahlele, Rebogile R; Fawole, Olaniyi A; Makunga, Nokwanda P; Opara, Umezuruike L

2016-05-26

The use of pomegranate peel is highly associated with its rich phenolic concentration. Series of drying methods are recommended since bioactive compounds are highly sensitive to thermal degradation. The study was conducted to evaluate the effects of drying on the bioactive compounds, antioxidant as well as antibacterial and antityrosinase activities of pomegranate peel. Dried pomegranate peels with the initial moisture content of 70.30 % wet basis were prepared by freeze and oven drying at 40, 50 and 60 °C. Difference in CIE-LAB, chroma (C*) and hue angle (h°) were determined using colorimeter. Individual polyphenol retention was determined using LC-MS and LC-MS(E) while total phenolics concentration (TPC), total flavonoid concentration (TFC), total tannins concentration (TTC) and vitamin C concentration were measured using colorimetric methods. The antioxidant activity was measured by radical scavenging activity (RSA) and ferric reducing antioxidant power (FRAP). Furthermore, the antibacterial activity of methanolic peel extracts were tested on Gram negative (Escherichia coli and Klebsiella pneumonia) and Gram positive bacteria (Staphylococcus aureus and Bacillus subtilis) using the in vitro microdilution assays. Tyrosinase enzyme inhibition was investigated against monophenolase (tyrosine) and diphenolase (DOPA), with arbutin as positive controls. Oven drying at 60 °C resulted in high punicalin concentration (888.04 ± 141.03 mg CE/kg dried matter) along with poor red coloration (high hue angle). Freeze dried peel contained higher catechin concentration (674.51 mg/kg drying matter) + catechin and -epicatechin (70.56 mg/kg drying matter) compared to oven dried peel. Furthermore, freeze dried peel had the highest total phenolic, tannin and flavonoid concentrations compared to oven dried peel over the temperature range studied. High concentration of vitamin C (31.19 μg AAE/g dried matter) was observed in the oven dried (40 °C) pomegranate peel

Antioxidant compounds and activities of the stem, flower, and leaf extracts of the anti-smoking Thai medicinal plant: Vernonia cinerea Less.

PubMed

Ketsuwan, Nitinet; Leelarungrayub, Jirakrit; Kothan, Suchart; Singhatong, Supawatchara

2017-01-01

Vernonia cinerea (VC) Less has been proposed as a medicinal plant with interesting activities, such as an aid for smoking cessation worldwide. Despite its previous clinical success in smoking cessation by exhibiting reduced oxidative stress, it has not been approved. The aim of this study was to investigate various antioxidant activity and active compounds that have not been approved, including the protective activity in human red blood cells (RBCs), from the stem, flower, and leaf extracts of VC Less in vitro. These extracts were tested for their antioxidant activity in scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and analyzed by high-performance liquid chromatography (HPLC) for their active compounds: total tannin, five catechin (C) compounds (epicatechin gallate [ECG], C, epicatechin [EC], epigallocatechin gallate [EGCG], and (-)-epigallocatechin [EGC]), flavonoid, nitrite, nitrate, caffeine, and nicotine. Moreover, antioxidant activities of the extracts were evaluated in 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-treated RBCs. The results showed that the flower and leaf of VC Less had higher activity than the stem in scavenging DPPH radicals. The tannin content in the flower and leaf was higher than that in the stem. The leaf had the highest content of the five catechins (C, EC, EGCG, ECG, and EGC), the same as in the flavonoid, when compared to the stem and flower. Furthermore, the leaf extract had higher nitrate and nitrite than the stem. Nicotine content was found to be higher in the leaf when compared to the flower. In addition, the leaf showed protective activity in glutathione (GSH), malondialdehyde (MDA), and protein carbonyl, with a dose response in AAPH-oxidized RBCs, the same as in standard EGCG. Thus, this study concluded that radical scavenging and antioxidant compounds such as catechins, flavonoid, nitrate and nitrite, and nicotine are present in different VC Less parts and are included in the AAPH-oxidized RBC model.

Characterization of ToxCast Phase II compounds disruption of ...

EPA Pesticide Factsheets

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

Hammerhead ribozyme activity and oligonucleotide duplex stability in mixed solutions of water and organic compounds

PubMed Central

Nakano, Shu-ichi; Kitagawa, Yuichi; Miyoshi, Daisuke; Sugimoto, Naoki

2014-01-01

Nucleic acids are useful for biomedical targeting and sensing applications in which the molecular environment is different from that of a dilute aqueous solution. In this study, the influence of various types of mixed solutions of water and water-soluble organic compounds on RNA was investigated by measuring the catalytic activity of the hammerhead ribozyme and the thermodynamic stability of an oligonucleotide duplex. The compounds with a net neutral charge, such as poly(ethylene glycol), small primary alcohols, amide compounds, and aprotic solvent molecules, added at high concentrations changed the ribozyme-catalyzed RNA cleavage rate, with the magnitude of the effect dependent on the NaCl concentration. These compounds also changed the thermodynamic stability of RNA base pairs of an oligonucleotide duplex and its dependence on the NaCl concentration. Specific interactions with RNA molecules and reduced water activity could account for the inhibiting effects on the ribozyme catalysis and destabilizing effects on the duplex stability. The salt concentration dependence data correlated with the dielectric constant, but not with water activity, viscosity, and the size of organic compounds. This observation suggests the significance of the dielectric constant effects on the RNA reactions under molecular crowding conditions created by organic compounds. PMID:25161873

Multivariate analysis of PRISMA optimized TLC image for predicting antioxidant activity and identification of contributing compounds from Pereskia bleo.

PubMed

Sharif, K M; Rahman, M M; Azmir, J; Khatib, A; Sabina, E; Shamsudin, S H; Zaidul, I S M

2015-12-01

Multivariate analysis of thin-layer chromatography (TLC) images was modeled to predict antioxidant activity of Pereskia bleo leaves and to identify the contributing compounds of the activity. TLC was developed in optimized mobile phase using the 'PRISMA' optimization method and the image was then converted to wavelet signals and imported for multivariate analysis. An orthogonal partial least square (OPLS) model was developed consisting of a wavelet-converted TLC image and 2,2-diphynyl-picrylhydrazyl free radical scavenging activity of 24 different preparations of P. bleo as the x- and y-variables, respectively. The quality of the constructed OPLS model (1 + 1 + 0) with one predictive and one orthogonal component was evaluated by internal and external validity tests. The validated model was then used to identify the contributing spot from the TLC plate that was then analyzed by GC-MS after trimethylsilyl derivatization. Glycerol and amine compounds were mainly found to contribute to the antioxidant activity of the sample. An alternative method to predict the antioxidant activity of a new sample of P. bleo leaves has been developed. Copyright © 2015 John Wiley & Sons, Ltd.

Environmental bacteria produce abundant and diverse antibiofilm compounds.

PubMed

Farmer, J T; Shimkevitch, A V; Reilly, P S; Mlynek, K D; Jensen, K S; Callahan, M T; Bushaw-Newton, K L; Kaplan, J B

2014-12-01

The aim of this study was to isolate novel antibiofilm compounds produced by environmental bacteria. Cell-free extracts were prepared from lawns of bacteria cultured on agar. A total of 126 bacteria isolated from soil, cave and river habitats were employed. Extracts were tested for their ability to inhibit Staphylococcus aureus biofilm in a 96-well microtitre plate assay. A total of 55/126 extracts (44%) significantly inhibited Staph. aureus biofilm. Seven extracts were selected for further analysis. The antibiofilm activities in all seven extracts exhibited unique patterns of molecular mass, chemical polarity, heat stability and spectrum of activity against Staph. aureus, Staphylococcus epidermidis and Pseudomonas fluorescens, suggesting that these seven antibiofilm activities were mediated by unique chemical compounds with different mechanisms of action. Environmental bacteria produce abundant and diverse antibiofilm compounds. Screening cell-free extracts is a useful method for identifying secreted compounds that regulate biofilm formation. Such compounds may represent a novel source of antibiofilm agents for technological development. © 2014 The Society for Applied Microbiology.

Enhanced photo-activated luminescence for screening polychlorobiphenyls (PCBs) and other related chlorinated compounds

DOEpatents

Vo-Dinh, Tuan

1994-01-01

The presence of polychlorinated biphenyls and other chlorinated compounds in a sample is determined by treating the sample with a photo-activator and then exposing the treated sample to a UV light source. The UV light produces a photo-product complex, which is subsequently excited with UV light to cause luminescence of the complex. The luminescence is detected and characteristics of the luminescence spectra are used to determine the presence of chlorinated compounds and also the quantity of the chlorine in the compounds

Enhanced photo-activated luminescence for screening polychlorobiphenyls (PCBs) and other related chlorinated compounds

DOEpatents

Vo-Dinh, Tuan

1993-01-01

The presence of polychlorinated biphenyls and other chlorinated compounds in a sample is determined by treating the sample with a photo-activator and then exposing the treated sample to a UV light source. The UV light produces a photo-product complex, which is subsequently excited with UV light to cause luminescence of the complex. The luminescence is detected and characteristics of the luminescence spectra are used to determine the presence of chlorinated compounds and also the quantity of the chlorine in the compounds.

Effective adsorption of phenolic compound from aqueous solutions on activated semi coke

NASA Astrophysics Data System (ADS)

Gao, Xiaoming; Dai, Yuan; Zhang, Yu; Fu, Feng

2017-03-01

Activated Semi coke was prepared by KOH activation and employed as adsorbent to study adsorption function of phenolic compound from aqueous solutions. The adsorption result showed that the adsorption capacity of the activated semi coke for phenolic compound increased with contact time and adsorbent dosage, and slightly affected by temperature. The surface structure property of the activated semi coke was characterized by N2 adsorption, indicating that the activated semi coke was essentially macroporous, and the BET surface area was 347.39 m2 g-1. Scanning electron microscopy indicated that the surface of the activated semi coke had a high developed pore. The adsorption kinetics were investigated according to pseudofirst order, pseudosecond order and intraparticle diffusion, and the kinetics data were fitted by pseudosecond order model, and intraparticle diffusion was not the only rate-controlling step. Adsorption isotherm was studied by Langmuir, Freundlich, Temkin, Redlich-Peterson, Sips and Toth models. The result indicated that adsorption isotherm data could fit well with Langmuir, Redlich-Peterson, Sips and Toth models.

Effect of Environmental Conditions and Toxic Compounds on the Locomotor Activity of Pediculus humanus capitis (Phthiraptera: Pediculidae).

PubMed

Ortega-Insaurralde, I; Toloza, A C; Gonzalez-Audino, P; Mougabure-Cueto, G A; Alvarez-Costa, A; Roca-Acevedo, G; Picollo, M I

2015-09-01

In this work, we evaluated the effect of environmental variables such as temperature, humidity, and light on the locomotor activity of Pediculus humanus capitis. In addition, we used selected conditions of temperature, humidity, and light to study the effects of cypermethrin and N,N-diethyl-3-methylbenzamide (DEET) on the locomotor activity of head lice. Head lice increased their locomotor activity in an arena at 30°C compared with activity at 20°C. When we tested the influence of the humidity level, the locomotor activity of head lice showed no significant differences related to humidity level, both at 30°C and 20°C. Concerning light influence, we observed that the higher the intensity of light, the slower the movement of head lice. We also demonstrated that sublethal doses of toxics may alter locomotor activity in adults of head lice. Sublethal doses of cypermethrin induced hyperactivated responses in adult head lice. Sublethal doses of DEET evocated hypoactivated responses in head lice. The observation of stereotyped behavior in head lice elicited by toxic compounds proved that measuring locomotor activity in an experimental set-up where environmental conditions are controlled would be appropriate to evaluate compounds of biological importance, such as molecules involved in the host-parasite interaction and intraspecific relationships. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

4-phenylselenyl-7-chloroquinoline, a novel multitarget compound with anxiolytic activity: Contribution of the glutamatergic system.

PubMed

Reis, Angélica S; Pinz, Mikaela; Duarte, Luis Fernando B; Roehrs, Juliano A; Alves, Diego; Luchese, Cristiane; Wilhelm, Ethel A

2017-01-01

A growing body of evidence demonstrates that quinoline compounds have attracted much attention in the field of drug development. Accordingly, 4-phenylselenyl-7-chloroquinoline (4-PSQ) is a new quinoline derivative containing selenium, which showed a potential antioxidant, antinociceptive and anti-inflammatory effect. The present study was undertaken to evaluate the anxiolytic-like properties of 4-PSQ. Mice were orally pretreated with 4-PSQ (5-50 mg/kg) or vehicle, 30 min prior to the elevated plus-maze (EPM), light-dark (LDT) or open field (OFT) tests. A time-response curve was carried out by administration of 4-PSQ (50 mg/kg) at different times before the EPM test. The involvement of glutamate uptake/release and Na + , K + -ATPase activity in the anxiolytic-like effect was investigated in cerebral cortices. In addition, the effectiveness of acute treatment with 4-PSQ was evaluated in a model of kainate (KA)-induced anxiety-related behavior. Finally, acute toxicity of this compound was investigated. 4-PSQ produced an anxiolytic-like action, both in EPM and LDT. In OFT, 4-PSQ did not affect locomotor and exploratory activities. 4-PSQ anxiolytic-like effect started at 0.5 h and remained significant up to 72 h after administration. Treatment with 4-PSQ reduced [ 3 H] glutamate uptake, but the [ 3 H] glutamate release and Na + , K + -ATPase activity were not altered. KA-induced anxiety-related behavior was protected by 4-PSQ pretreatment. Additionally, 4-PSQ exposure did not alter urea levels, aspartate (AST) and alanine aminotrasferase (ALT) activities in plasma. Parameters of oxidative stress in brain and liver of mice were not modified by 4-PSQ. Taken together these data demonstrated that the anxiolytic-like effect caused by 4-PSQ seems to be mediated by involvement of the glutamatergic system. Copyright © 2016 Elsevier Ltd. All rights reserved.

Asymmetric bioreduction of activated alkenes to industrially relevant optically active compounds

PubMed Central

Winkler, Christoph K.; Tasnádi, Gábor; Clay, Dorina; Hall, Mélanie; Faber, Kurt

2012-01-01

Ene-reductases from the ‘Old Yellow Enzyme’ family of flavoproteins catalyze the asymmetric reduction of various α,β-unsaturated compounds at the expense of a nicotinamide cofactor. They have been applied to the synthesis of valuable enantiopure products, including chiral building blocks with broad industrial applications, terpenoids, amino acid derivatives and fragrances. The combination of these highly stereoselective biocatalysts with a cofactor recycling system has allowed the development of cost-effective methods for the generation of optically active molecules, which is strengthened by the availability of stereo-complementary enzyme homologues. PMID:22498437

The adsorption of pharmaceutically active compounds from aqueous solutions onto activated carbons.

PubMed

Rakić, Vesna; Rac, Vladislav; Krmar, Marija; Otman, Otman; Auroux, Aline

2015-01-23

In this study, the adsorption of pharmaceutically active compounds - salicylic acid, acetylsalicylic acid, atenolol and diclofenac-Na onto activated carbons has been studied. Three different commercial activated carbons, possessing ∼650, 900 or 1500m(2)g(-1) surface areas were used as solid adsorbents. These materials were fully characterized - their textural, surface features and points of zero charge have been determined. The adsorption was studied from aqueous solutions at 303K using batch adsorption experiments and titration microcalorimetry, which was employed in order to obtain the heats evolved as a result of adsorption. The maximal adsorption capacities of investigated solids for all target pharmaceuticals are in the range of 10(-4)molg(-1). The obtained maximal retention capacities are correlated with the textural properties of applied activated carbon. The roles of acid/base features of activated carbons and of molecular structures of adsorbate molecules have been discussed. The obtained results enabled to estimate the possibility to use the activated carbons in the removal of pharmaceuticals by adsorption. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed

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

2012-01-01

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

Compounds from Cynomorium songaricum with Estrogenic and Androgenic Activities Suppress the Oestrogen/Androgen-Induced BPH Process.

PubMed

Wang, Xueni; Tao, Rui; Yang, Jing; Miao, Lin; Wang, Yu; Munyangaju, Jose Edouard; Wichai, Nuttapong; Wang, Hong; Zhu, Yan; Liu, Erwei; Chang, Yanxu; Gao, Xiumei

2017-01-01

To investigate the phytoestrogenic and phytoandrogenic activities of compounds isolated from CS and uncover the role of CS in prevention of oestrogen/androgen-induced BPH. Cells were treated with CS compounds, and immunofluorescence assay was performed to detect the nuclear translocation of ER α or AR in MCF-7 or LNCaP cells; luciferase reporter assay was performed to detect ERs or AR transcriptional activity in HeLa or AD293 cells; MTT assay was performed to detect the cell proliferation of MCF-7 or LNCaP cells. Oestrogen/androgen-induced BPH model was established in rat and the anti-BPH, anti-estrogenic, and anti-androgenic activities of CS in vivo were further investigated. The nuclear translocation of ER α was stimulated by nine CS compounds, three of which also stimulated AR translocation. The transcriptional activities of ER α and ER β were induced by five compounds, within which only ECG induced AR transcriptional activity as well. Besides, ECG stimulated the proliferation of both MCF-7 cells and LNCaP cells. CS extract suppressed oestrogen/androgen-induced BPH progress in vivo by downregulation of E2 and T level in serum and alteration of the expressions of ER α , ER β , and AR in the prostate. Our data demonstrates that compounds from CS exhibit phytoestrogenic and phytoandrogenic activities, which may contribute to inhibiting the oestrogen/androgen-induced BPH development.

Anti-trypanosomal effects of some compounds isolated from the extracts of Warburgia ugandensis.

PubMed

Kioy, D W; Murilla, G; Kofi-Tsekpo, M W; Mukhongo, M; Okwara, J

1998-02-01

The plant kingdom has been used as a source of compounds employed in the treatment of many disease conditions for many years. Even with the new technology in synthetic chemistry, plants are still being used as a source of lead compounds in drug development. In the treatment of trypanosomiasis, the drugs that are currently in the market were developed between 1950-1960's. These drugs are expensive and associated with a number of toxic effects, therefore there is still need to develop newer drugs in the management of trypanosomiasis. The plant Warburgia ugandansis is a common plant that has been used traditionally to treat many disease conditions. The crude and pure compounds from this plant were tested against trypanosomes: T. congolense, T. evansi and T. bruceL In vitro tests using tissue culture method and in vivo tests using mice were carried out The results of the in vitro method indicated that the pure compound was more active than the crude extract The in vivo method indicated that the total extract was not effective, while one of the pure compounds was too toxic, and the other one showed activity. The two compounds investigated were basically of the same structure type with a slight difference on the functional groups. These preliminary results indicate that there is a possibility of finding active compounds against Trypanosomes in plants.

Active compounds, antioxidant activity and α-glucosidase inhibitory activity of different varieties of Chaenomeles fruits.

PubMed

Miao, Jing; Li, Xia; Zhao, Chengcheng; Gao, Xiaoxiao; Wang, Ying; Gao, Wenyuan

2018-05-15

Chaenomeles is an important source for food industry in China, and its planting area is expanding year by year. This study was conducted to evaluate different varieties of Chaenomeles by comparing the chemical compositions, antioxidant activity and α-glucosidase inhibitory activity of peels and fleshes from twelve varieties of Chaenomeles. In the results, peels of Chaenomeles contain more phenolics, flavonoids and triterpenes, and show better antioxidant activity and α-glucosidase inhibitory activity than their fleshes. All varieties of Chaenomeles perform different depend on cultivar and climatic conditions. Oleanolic acid, ursolic acid, protocatechuic acid, rutin, catechin, caffeic acid, syringic acid, epicatechin, hyperin, quercetin, kaempferol and chlorogenic acid are main active compounds in Chaenomeles. Zheng'an, Liufu, Zimugua1, Qijiang and Changjun get Top five scores. This is the first study on the peels and fleshes of twelve varieties of Chaenomeles, and it gives insights into variety selection in the planting and production of Chaenomeles. Copyright © 2017 Elsevier Ltd. All rights reserved.

Analgesic, Anti- inflammatory, Anti- lipoxygenase Activity and Characterization of Three Bioactive Compounds in the Most Active Fraction of Leptadenia reticulata (Retz.)Wight & Arn. – A Valuable Medicinal Plant

PubMed Central

Mohanty, Sudipta Kumar; Swamy, Mallappa Kumara; Middha, Sushil Kumar; Prakash, Lokesh; Subbanarashiman, Balasubramanya; Maniyam, Anuradha

2015-01-01

Leptadenia reticulata was reported to be used for several medicinal purposes. The present study was undertaken to evaluate anti-inflammatory, analgesic and lipid peroxidation inhibition activities of L. reticulata. The anti-inflammatory assay was performed by λ-carrageenan and formalin induced paw edema test. Pro inflammatory mediators (IL2, IL6, TNF-α) in serum of treated and control organism were analyzed by quantitative ELISA. Lipid peroxidation inhibition was measured by thiobarbituric acid reactive substances (TBARS) assay. Analysis of the most active fraction revealed the presence of one phenolic compound (p-coumaric acid), two flavonoids (rutin and quercetin) which also determined quantitatively. The ethyl acetate fraction at 600 mg/Kg significantly inhibited λ-carrageenan and formalin induced paw edema by 60.59% and 59.24% respectively. Notable reduction in percentage of writhing (76.25%), induced by acetic acid signifies the potent analgesic activity. Lower level of pro-inflammatory cytokines (IL-2, IL-6, TNF-α) in serum at the 4th hour of λ-Carrageenan injection indicated the inhibition of cyclooxigenase-2 (Cox-2), Nitric oxide (NO) and release of prostaglandin to prevent inflammation. The study also demonstrated the decrease in malonaldehyde (MDA) concentration which revealed the lipid peroxidation inhibition potential of the plant. Our finding provides evidence for potent biological activities in tested model which is supported by its characterized bioactive compounds and ethnomedicinal relevance. PMID:26330883

Chiral halogenated Schiff base compounds: green synthesis, anticancer activity and DNA-binding study

NASA Astrophysics Data System (ADS)

Ariyaeifar, Mahnaz; Amiri Rudbari, Hadi; Sahihi, Mehdi; Kazemi, Zahra; Kajani, Abolghasem Abbasi; Zali-Boeini, Hassan; Kordestani, Nazanin; Bruno, Giuseppe; Gharaghani, Sajjad

2018-06-01

Eight enantiomerically pure halogenated Schiff base compounds were synthesized by reaction of halogenated salicylaldehydes with 3-Amino-1,2-propanediol (R or S) in water as green solvent at ambient temperature. All compounds were characterized by elemental analyses, NMR (1H and 13C), circular dichroism (CD) and FT-IR spectroscopy. FS-DNA binding studies of these compounds carried out by fluorescence quenching and UV-vis spectroscopy. The obtained results revealed that the ligands bind to DNA as: (Rsbnd ClBr) > (Rsbnd Cl2) > (Rsbnd Br2) > (Rsbnd I2) and (Ssbnd ClBr) > (Ssbnd Cl2) > (Ssbnd Br2) > (Ssbnd I2), indicating the effect of halogen on binding constant. In addition, DNA-binding constant of the Ssbnd and R-enantiomers are different from each other. The ligands can form halogen bonds with DNA that were confirmed by molecular docking. This method was also measured the bond distances and bond angles. The study of obtained data can have concluded that binding affinity of the ligands to DNA depends on strength of halogen bonds. The potential anticancer activity of ligands were also evaluated on MCF-7 and HeLa cancer cell lines by using MTT assay. The results showed that the anticancer activity and FS-DNA interaction is significantly dependent on the stereoisomers of Schiff base compounds as R-enantiomers displayed significantly higher activity than S-enantiomers. The molecular docking was also used to illustrate the specific DNA-binding of synthesized compounds and groove binding mode of DNA interaction was proposed for them. In addition, molecular docking results indicated that there are three types of bonds (Hsbnd and X-bond and hX-bond) between synthesized compounds and base pairs of DNA.

Antimicrobial azobenzene compounds and their potential use in biomaterials

NASA Astrophysics Data System (ADS)

Sessa, L.; Concilio, S.; Iannelli, P.; De Santis, F.; Porta, A.; Piotto, S.

2016-04-01

We recently synthesized a class of active compounds with azobenzene structure [1] and lowest in silico toxicity values. The antimicrobial activity of these molecules and their thermal stability are very promising and indicate that they may have interesting and therapeutically significant applications. This work aims to develop new materials with antibacterial and antifungal activity inserting different percentages of synthetic antimicrobial azo compounds in commercial polymer matrices. We realized thin films using solvent casting and melt compounding techniques. The obtained materials retained the proprieties of the pure matrices. This means that azo dye dissolved in the matrix does not influence the thermal behavior and the morphology of the material. Tested films exhibited the capability to inhibit biofilms formation of S. aureus and C. albicans. Spectrophotometric investigation of the azo compound released from the polymer matrices confirmed that the realized materials might be interesting for biomedical tools, antibacterial surfaces, and films for active packaging.

High-Throughput Gene Expression Profiles to Define Drug Similarity and Predict Compound Activity.

PubMed

De Wolf, Hans; Cougnaud, Laure; Van Hoorde, Kirsten; De Bondt, An; Wegner, Joerg K; Ceulemans, Hugo; Göhlmann, Hinrich

2018-04-01

By adding biological information, beyond the chemical properties and desired effect of a compound, uncharted compound areas and connections can be explored. In this study, we add transcriptional information for 31K compounds of Janssen's primary screening deck, using the HT L1000 platform and assess (a) the transcriptional connection score for generating compound similarities, (b) machine learning algorithms for generating target activity predictions, and (c) the scaffold hopping potential of the resulting hits. We demonstrate that the transcriptional connection score is best computed from the significant genes only and should be interpreted within its confidence interval for which we provide the stats. These guidelines help to reduce noise, increase reproducibility, and enable the separation of specific and promiscuous compounds. The added value of machine learning is demonstrated for the NR3C1 and HSP90 targets. Support Vector Machine models yielded balanced accuracy values ≥80% when the expression values from DDIT4 & SERPINE1 and TMEM97 & SPR were used to predict the NR3C1 and HSP90 activity, respectively. Combining both models resulted in 22 new and confirmed HSP90-independent NR3C1 inhibitors, providing two scaffolds (i.e., pyrimidine and pyrazolo-pyrimidine), which could potentially be of interest in the treatment of depression (i.e., inhibiting the glucocorticoid receptor (i.e., NR3C1), while leaving its chaperone, HSP90, unaffected). As such, the initial hit rate increased by a factor 300, as less, but more specific chemistry could be screened, based on the upfront computed activity predictions.

Enhanced photo-activated luminescence for screening polychlorobiphenyls (PCBs) and other related chlorinated compounds

DOEpatents

Vo-Dinh, T.

1994-06-07

The presence of polychlorinated biphenyls and other chlorinated compounds in a sample is determined by treating the sample with a photo-activator and then exposing the treated sample to a UV light source. The UV light produces a photo-product complex, which is subsequently excited with UV light to cause luminescence of the complex. The luminescence is detected and characteristics of the luminescence spectra are used to determine the presence of chlorinated compounds and also the quantity of the chlorine in the compounds. 14 figs.

Enhanced photo-activated luminescence for screening polychlorobiphenyls (PCBs) and other related chlorinated compounds

DOEpatents

Tuan Vodinh.

1993-12-21

The presence of polychlorinated biphenyls and other chlorinated compounds in a sample is determined by treating the sample with a photo-activator and then exposing the treated sample to a UV light source. The UV light produces a photo-product complex, which is subsequently excited with UV light to cause luminescence of the complex. The luminescence is detected and characteristics of the luminescence spectra are used to determine the presence of chlorinated compounds and also the quantity of the chlorine in the compounds. 14 figures.

Antimicrobial activity of crude fractions and morel compounds from wild edible mushrooms of North western Himalaya.

PubMed

Shameem, Nowsheen; Kamili, Azra N; Ahmad, Mushtaq; Masoodi, F A; Parray, Javid A

2017-04-01

The antimicrobial properties of morel compounds from wild edible mushrooms (Morchella esculenta and Verpa bohemica) from Kashmir valley was investigated against different clinical pathogens. The butanol crude fraction of most popular or true morel M. esculenta showed highest 19 mm IZD against E.coli while as same fraction of Verpa bohemica exhibited 15 mm IZD against same strain. The ethyl acetate and butanol crude fractions of both morels also exhibited good antifungal activity with highest IZD shown against A. fumigates. The three morel compounds showed quite impressive anti bacterial and fungal activities. The Cpd 3 showed highest inhibitory activity almost equivalent to the synthetic antibiotics used as control. The MIC/MBC values revealed the efficiency of isolated compounds against the pathogenic strains. In the current study significant inhibitory activity of morel compounds have been obtained paying the way for their local use from ancient times. Copyright © 2017. Published by Elsevier Ltd.

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

PubMed

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

2008-11-01

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

Bioactive compounds and antioxidant activity of wolfberry infusion

PubMed Central

Sun, Yujing; Rukeya, Japaer; Tao, Wenyang; Sun, Peilong; Ye, Xingqian

2017-01-01

An infusion of the wolfberry (Lycium barbarum L.) is a traditional Asian herbal tea. This is the most commonly consumed form of dried wolfberry worldwide, yet little scientific information on wolfberry infusions is available. We investigated the effects of making infusions with hot water on the color, the content of bioactive compounds (polysaccharides, polyphenols, flavonoids and carotenoids) and the antioxidant ability of wolfberry infusions. The contents of bioactive compounds and the antioxidant activity of a wolfberry infusion increased with increased infusion temperature and time. Total polysaccharides content (TPOC), total polyphenols (TPC), total flavonoids (TFC) and total carotenoids contents (TCC) were important for determining the antioxidant capacity of wolfberry infusions with the contribution to antioxidant activity in the order TPC > TFC > TCC > TPOC. Hierarchical cluster analysis indicated preparation conditions of 100 °C for 1~3 h, 90 °C for 2~3 h and 80 °C for 2.5~3 h were equivalent as regards the value of TPC, TPOC, TFC, TCC, FRAP, DPPH and ABTS. The results of this study suggest the length of time of making a wolfberry infusion in actual real life practice is too short and different dietary habits associated with the intake of wolfberry infusion might provide the same bioactive nutrients. PMID:28102295

A new class of anticonvulsants possessing 6 Hz psychomotor seizure test activity: 2-(1H-benzotriazol-1-yl)-N'-[substituted] acetohydrazides.

PubMed

Kumar, Praveen; Tripathi, Laxmi

2012-05-01

A series of 2-(1H-Benzotriazol-1-yl)-N'-[substituted]acetohydrazides were designed & synthesized keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant activity and neurotoxicity. The new compounds were characterized using FT-IR, 1H NMR, mass spectral data and elemental analysis. The anticonvulsant activity of the titled compounds was assessed using the 6 Hz psychomotor seizure test. The neurotoxicity was assessed using the rotorod method. The most active compound of the series was N'-[4-(1,3-Benzodioxol-5-yloxy)benzylidene]-2-(1H-benzotriazol-1-yl)acetohydrazide (BTA 9), which showed good activity with 75 % protection (3/4, 0.5 h) at a dose of 100 mg/kg in mice. All the compounds exhibited no neurotoxicity. A computational study was carried out for calculation of pharmacophore pattern and prediction of pharmacokinetic properties. Titled compounds have also exhibited good binding properties with epilepsy molecular targets such as glutamate, GABA (A) delta, GABA (A) alpha-1 receptors and Na/H exchanger, in Lamarckian genetic algorithm based flexible docking studies.

Design of cinnamaldehyde amino acid Schiff base compounds based on the quantitative structure–activity relationship

Treesearch

Hui Wang; Mingyue Jiang; Shujun Li; Chung-Yun Hse; Chunde Jin; Fangli Sun; Zhuo Li

2017-01-01

Cinnamaldehyde amino acid Schiff base (CAAS) is a new class of safe, bioactive compounds which could be developed as potential antifungal agents for fungal infections. To design new cinnamaldehyde amino acid Schiff base compounds with high bioactivity, the quantitative structure–activity relationships (QSARs) for CAAS compounds against Aspergillus niger (A. niger) and...

Chemical composition and antioxidant activity of phenolic compounds from Dioscorea (Yam) leaves.

PubMed

Zhou, Li; Shi, Xinmin; Ren, Xiangmei; Qin, Zhihong

2018-05-01

This study was aimed to assess the potential of Dioscorea (yam) leaves as a source of antioxidants. Microwave-assisted extraction (MAE) process was used to prepare the extracts. The phenolic compounds in Dioscorea leaves extracts were analyzed by HPLC-DAD-ESI-MS/MS method and the contents of major compounds were determined. Results indicated that a total of 17 phenolic compounds were separated identified by means of UV and mass spectra compared with authentic reference substances and/or reported values in the literature. The main phenolic compound was rosmarinic acid and its highest amount was found in Dioscorea glabra Roxb. leaves (22.31±1.33 mg/g DW). Rutin was the dominant flavonoid followed by quercetin which highest amount was found in Dioscorea alata leaves (8.66±0.29 mg/g DW). Antioxidant activity of the extracts was estimated by the use of DPPH and ABTS assays. Both kinds of leaves exhibited satisfied antioxidant capacity which was correlated with phenolic contents. In the cytoprotective effect on HUVECs viability assay, Dioscorea glabra Roxb. leaves extract was found to be more active than that of Dioscorea alata against H 2 O 2 -induced oxidative stress. Our findings support the promising role of Dioscorea leaves that can be used as an interesting source of phenolic antioxidants.

Influence of the active compounds of Perilla frutescens leaves on lipid membranes.

PubMed

Duelund, Lars; Amiot, Arnaud; Fillon, Alexandra; Mouritsen, Ole G

2012-02-24

The leaves of the annual plant Perilla frutescens are used widely as a spice and a preservative in Asian food as well as in traditional medicine. The active compounds in the leaves are the cyclic monoterpene limonene (1) and its bio-oxidation products, perillaldehyde (2), perillyl alcohol (3), and perillic acid (4). These compounds are known to be biologically active and exhibit antimicrobial, anticancer, and anti-inflammatory effects that could all be membrane mediated. In order to assess the possible biophysical effects of these compounds on membranes quantitatively, the influence of limonene and its bio-oxidation products has been investigated on a membrane model composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) using differential scanning calorimetry (DSC), isothermal titration calorimetry (ITC), and electron paramagnetic resonance spectroscopy (EPR). It was found that limonene (1), perillyl alcohol (2), and perillaldehyde (3) partitioned into the DMPC membrane, whereas perillic acid (4) did not. The DSC results demonstrated that all the partitioning compounds strongly perturbed the phase transition of DMPC, whereas no perturbation of the local membrane order was detected by EPR spectroscopy. The results of the study showed that limonene (1) and its bio-oxidation products affect membranes in rather subtle ways.

Interactive effects of aluminum and cadmium on phenolic compounds, antioxidant enzyme activity and oxidative stress in blueberry (Vaccinium corymbosum L.) plantlets cultivated in vitro.

PubMed

Manquián-Cerda, K; Cruces, E; Escudey, M; Zúñiga, G; Calderón, R

2018-04-15

To evaluate the potential role of phenolic compounds in Al and Cd stress tolerance mechanisms, Vaccinium corymbosum cv. Legacy plantlets were exposed to different metal concentrations. The present study used an in vitro plant model to test the effects of the following treatments: 100μM Al; 100μMAl + 50μMCd; and 100μMAl + 100μMCd during periods of 7, 14, 21 and 30 days. The oxidative damage was determined by the accumulation of malondialdehyde (MDA) and hydrogen peroxide (H 2 O 2 ). The antioxidant activity values were determined using 1,1-diphenyl-2-picrylhydrazine (DPPH) and the ferric reducing antioxidant power test (FRAP). Additionally, the phenolic compound concentrations were determined using HPLC-DAD. The exposure to Al and Cd increased the MDA and H 2 O 2 contents differentially, while the antioxidant capacity values showed differences between DPPH and FRAP with the largest changes in FRAP relative to Cd. SOD had the highest activity in the first 7 days, leading to a significant increase in phenolic compounds observed after 14 days, and chlorogenic acid was the major compound identified. Our results revealed that phenolic compounds seem to play an important role in the response to ROS. Therefore, the mechanisms of tolerance to Al and Cd in V. corymbosum will be determined by the type of metal and time of exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

Analysis and occurrence of endocrine-disrupting compounds and estrogenic activity in the surface waters of Central Spain.

PubMed

Esteban, S; Gorga, M; Petrovic, M; González-Alonso, S; Barceló, D; Valcárcel, Y

2014-01-01

Endocrine-disrupting compounds (EDCs) are chemical compounds with the ability to alter the hormonal systems of organisms. Such compounds are used in several industrial and domestic activities and reach the aquatic environment via wastewater discharge. The aim of this study is to assess the occurrence of 30 EDCs and related compounds in the surface waters of central Spain and to determine the overall estrogenic activity of environmental samples. This study analyzed a large number of EDCs and other emergent or suspected compounds with endocrine-disrupting activity. The results have shown the presence of 19 EDCs at concentrations ranging from 2 to 5928 ng L(-1). Organophosphorus-based flame retardants, alkylphenolic compounds and anticorrosives were found at the highest concentrations. Furthermore, although insufficient data are available to calculate an average over time, these preliminary results show the need to monitor the waters in both rivers studied. Alkylphenolic compounds, particularly nonylphenol, were the main contributors to overall estrogenicity. A higher concentration of the compounds studied was detected in the river Jarama, although the estrogenicity expressed as estradiol equivalents (EEQs) was higher in the river Manzanares due to a higher concentration of nonylphenol. However, the total estrogenicity did not exceed 1 ng L(-1) (EEQ), which is the level that may cause estrogenic effects in aquatic organisms, in any of the samples. In conclusion, the potential estrogenic risk in both rivers is low, although organophosphorus-based flame retardants may increase this risk as they were found at high levels in all samples. Unfortunately, these compounds could not be taken into account when calculating the estrogenic activity due to the lack of activity data for them. For future investigations, it will be important to assess the estrogenicity provided by these flame retardants. Due to the significant concentrations of EDCs detected in both rivers, further

Assessment of the potential activity of major dietary compounds as selective estrogen receptor modulators in two distinct cell models for proliferation and differentiation

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

Lecomte, Sylvain; Lelong, Marie; Bourgine, Gaëlle

Estrogen receptors (ERs) α and β are distributed in most tissues of women and men. ERs are bound by estradiol (E2), a natural hormone, and mediate the pleiotropic and tissue-specific effects of E2, such as proliferation of breast epithelial cells or protection and differentiation of neuronal cells. Numerous environmental molecules, called endocrine disrupting compounds, also interact with ERs. Phytoestrogens belong to this large family and are considered potent therapeutic molecules that act through their selective estrogen receptor modulator (SERM) activity. Using breast cancer cell lines as a model of estrogen-dependent proliferation and a stably ER-expressing PC12 cell line as amore » model of neuronal differentiating cells, we studied the SERM activity of major dietary compounds, such as apigenin, liquiritigenin, daidzein, genistein, coumestrol, resveratrol and zearalenone. The ability of these compounds to induce ER-transactivation and breast cancer cell proliferation and enhance Nerve Growth Factor (NGF) -induced neuritogenesis was assessed. Surprisingly, although all compounds were able to activate the ER through an estrogen responsive element reporter gene, they showed differential activity toward proliferation or differentiation. Apigenin and resveratrol showed a partial or no proliferative effect on breast cancer cells but fully contributed to the neuritogenesis effect of NGF. However, daidzein and zearalenone showed full effects on cellular proliferation but did not induce cellular differentiation. In summary, our results suggest that the therapeutic potential of phytoestrogens can diverge depending on the molecule and the phenotype considered. Hence, apigenin and resveratrol might be used in the development of therapeutics for breast cancer and brain diseases. - Highlights: • SERM activity of dietary compounds on proliferation and differentiation is studied. • All the dietary compounds tested transactivate estrogen receptors. • Apigenin and

Activation of nitrite. [Interaction of amino compounds to form carcinogenic N-nitroso compounds in digestive tract of animals

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

Lijinsky, W.

At low doses dietary nitrite has no obvious deleterious effect, even when ingested for long periods, and nitrites have been used for a long time as flavoring and coloring additives to meat and fish and as preservatives in food in which there is a danger of botulism. In recent years there has been increasing concern that one form of activation of nitrite might be related to cancer. That is the property of interaction with amino compounds to form N-nitroso compounds, which are potent chemical carcinogens. Results are reported from studies on the carcinogenic effects of nitrite and amines in rats.more » (CH)« less

Exploring sets of molecules from patents and relationships to other active compounds in chemical space networks

NASA Astrophysics Data System (ADS)

Kunimoto, Ryo; Bajorath, Jürgen

2017-09-01

Patents from medicinal chemistry represent a rich source of novel compounds and activity data that appear only infrequently in the scientific literature. Moreover, patent information provides a primary focal point for drug discovery. Accordingly, text mining and image extraction approaches have become hot topics in patent analysis and repositories of patent data are being established. In this work, we have generated network representations using alternative similarity measures to systematically compare molecules from patents with other bioactive compounds, visualize similarity relationships, explore the chemical neighbourhood of patent molecules, and identify closely related compounds with different activities. The design of network representations that combine patent molecules and other bioactive compounds and view patent information in the context of current bioactive chemical space aids in the analysis of patents and further extends the use of molecular networks to explore structure-activity relationships.

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

PubMed

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

2016-02-01

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

A community computational challenge to predict the activity of pairs of compounds.

PubMed

Bansal, Mukesh; Yang, Jichen; Karan, Charles; Menden, Michael P; Costello, James C; Tang, Hao; Xiao, Guanghua; Li, Yajuan; Allen, Jeffrey; Zhong, Rui; Chen, Beibei; Kim, Minsoo; Wang, Tao; Heiser, Laura M; Realubit, Ronald; Mattioli, Michela; Alvarez, Mariano J; Shen, Yao; Gallahan, Daniel; Singer, Dinah; Saez-Rodriguez, Julio; Xie, Yang; Stolovitzky, Gustavo; Califano, Andrea

2014-12-01

Recent therapeutic successes have renewed interest in drug combinations, but experimental screening approaches are costly and often identify only small numbers of synergistic combinations. The DREAM consortium launched an open challenge to foster the development of in silico methods to computationally rank 91 compound pairs, from the most synergistic to the most antagonistic, based on gene-expression profiles of human B cells treated with individual compounds at multiple time points and concentrations. Using scoring metrics based on experimental dose-response curves, we assessed 32 methods (31 community-generated approaches and SynGen), four of which performed significantly better than random guessing. We highlight similarities between the methods. Although the accuracy of predictions was not optimal, we find that computational prediction of compound-pair activity is possible, and that community challenges can be useful to advance the field of in silico compound-synergy prediction.

Lap Shear and Impact Testing of Ochre and Beeswax in Experimental Middle Stone Age Compound Adhesives.

PubMed

Kozowyk, P R B; Langejans, G H J; Poulis, J A

2016-01-01

The production of compound adhesives using disparate ingredients is seen as some of the best evidence of advanced cognition outside of the use of symbolism. Previous field and laboratory testing of adhesives has shown the complexities involved in creating an effective Middle Stone Age glue using Acacia gum. However, it is currently unclear how efficient different adhesive recipes are, how much specific ingredients influence their performance, and how difficult it may have been for those ingredients to be combined to maximum effect. We conducted a series of laboratory-based lap shear and impact tests, following modern adhesion testing standards, to determine the efficacy of compound adhesives, with particular regard to the ingredient ratios. We tested rosin (colophony) and gum adhesives, containing additives of beeswax and ochre in varying ratios. During both lap shear and impact tests compound rosin adhesives performed better than single component rosin adhesives, and pure acacia gum was the strongest. The large difference in performance between each base adhesive and the significant changes in performance that occur due to relatively small changes in ingredient ratios lend further support to the notion that high levels of skill and knowledge were required to consistently produce the most effective adhesives.

Lap Shear and Impact Testing of Ochre and Beeswax in Experimental Middle Stone Age Compound Adhesives

PubMed Central

2016-01-01

The production of compound adhesives using disparate ingredients is seen as some of the best evidence of advanced cognition outside of the use of symbolism. Previous field and laboratory testing of adhesives has shown the complexities involved in creating an effective Middle Stone Age glue using Acacia gum. However, it is currently unclear how efficient different adhesive recipes are, how much specific ingredients influence their performance, and how difficult it may have been for those ingredients to be combined to maximum effect. We conducted a series of laboratory-based lap shear and impact tests, following modern adhesion testing standards, to determine the efficacy of compound adhesives, with particular regard to the ingredient ratios. We tested rosin (colophony) and gum adhesives, containing additives of beeswax and ochre in varying ratios. During both lap shear and impact tests compound rosin adhesives performed better than single component rosin adhesives, and pure acacia gum was the strongest. The large difference in performance between each base adhesive and the significant changes in performance that occur due to relatively small changes in ingredient ratios lend further support to the notion that high levels of skill and knowledge were required to consistently produce the most effective adhesives. PMID:26983080

Characterization of the Key Aroma Compounds in Chinese Vidal Icewine by Gas Chromatography-Olfactometry, Quantitative Measurements, Aroma Recombination, and Omission Tests.

PubMed

Ma, Yue; Tang, Ke; Xu, Yan; Li, Ji-Ming

2017-01-18

The key aroma compounds of Chinese Vidal icewine were characterized by means of gas chromatography-olfactometry (GC-O) coupled with mass spectrometry (MS) on polar and nonpolar columns, and their flavor dilution (FD) factors were determined by aroma extract dilution analysis (AEDA). A total of 59 odor-active aroma compounds in three ranks of Vidal icewines were identified, and 28 odorants (FD ≥ 9) were further quantitated for aroma reconstitution and omission tests. β-Damascenone showed the highest FD value of 2187 in all icewines. Methional and furaneol were first observed as important odorants in Vidal icewine. Aroma recombination experiments revealed a good similarity containing the 28 important aromas. Omission tests corroborated the significant contribution of β-damascenone and the entire group of esters. Besides, 4-hydroxy-2,5-dimethyl-3(2H)-furanone (furaneol) and 3-(methylthio)-1-propanal (methional) also had significant effects on icewine character, especially on apricot, caramel, and tropical fruit characteristics.

Compounds from African Medicinal Plants with Activities Against Selected Parasitic Diseases: Schistosomiasis, Trypanosomiasis and Leishmaniasis.

PubMed

Simoben, Conrad V; Ntie-Kang, Fidele; Akone, Sergi H; Sippl, Wolfgang

2018-05-09

Parasitic diseases continue to represent a threat on a global scale, particularly among the poorest countries in the world. This is particularly because of the absence of vaccines, and in some cases, resistance against available drugs, currently being used for their treatment. In this review emphasis is laid on natural products and scaffolds from African medicinal plants (AMPs) for lead drug discovery and possible further development of drugs for the treatment of parasitic diseases. In the discussion, emphasis has been laid on alkaloids, terpenoids, quinones, flavonoids and narrower compound classes of compounds with micromolar range activities against Schistosoma, Trypanosoma and Leishmania species. In each subparagraph, emphasis is laid on the compound subclasses with most promising in vitro and/or in vivo activities of plant extracts and isolated compounds. Suggestions for future drug development from African medicinal plants have also been provided. This review covering 167 references, including 82 compounds, provides information published within two decades (1997-2017).

Comparison of biodegradation performance of OECD test guideline 301C with that of other ready biodegradability tests.

PubMed

Kayashima, Takakazu; Taruki, Masanori; Katagiri, Kazuomi; Nabeoka, Ryosuke; Yoshida, Tomohiko; Tsuji, Toshiaki

2014-02-01

The Organisation for Economic Co-operatoin and development (OECD) Guidelines for the Testing of Chemicals list 7 types of tests for determining the ready biodegradability of chemical compounds (301A-F and 310). The present study compares the biodegradation performance of test guideline 301C, which is applied in Japan's Chemical Substances Control Law, with the performance of the other 6 ready biodegradability tests (RBTs) listed in the guidelines. Test guideline 301C specifies use of activated sludge precultured with synthetic sewage containing glucose and peptone (301C sludge) as a test inoculum; in the other RBTs, however, activated sludge from wastewater treatment plants (WWTP sludge) is frequently employed. Analysis based on percentage of biodegradation and pass levels revealed that the biodegradation intensity of test guideline 301C is relatively weak compared with the intensities of RBTs using WWTP sludge, and the following chemical compounds are probably not biodegraded under test guideline 301C conditions: phosphorus compounds; secondary, tertiary, and quaternary amines; and branched quaternary carbon compounds. The relatively weak biodegradation intensity of test guideline 301C may be related to the markedly different activities of the 301C and WWTP sludges. These findings will be valuable for evaluating RBT data in relation to Japan's Chemical Substances Control Law. © 2013 SETAC.

The novel antibacterial compound walrycin A induces human PXR transcriptional activity

PubMed Central

Berthier, Alexandre; Oger, Frédérik; Gheeraert, Céline; Boulahtouf, Abdel; Le Guével, Rémy; Balaguer, Patrick; Staels, Bart; Salbert, Gilles; Lefebvre, Philippe

2012-01-01

The human pregnane X receptor (PXR) is a ligand-regulated transcription factor belonging to the nuclear receptor superfamily. PXR is activated by a large, structurally diverse, set of endogenous and xenobiotic compounds, and coordinates the expression of genes central to metabolism and excretion of potentially harmful chemicals and therapeutic drugs in humans. Walrycin A is a novel antibacterial compound targeting the WalK/WalR two-component signal transduction system of Gram (+) bacteria. Here we report that, in hepatoma cells, walrycin A potently activates a gene set known to be regulated by the xenobiotic sensor PXR. Walrycin A was as efficient as the reference PXR agonist rifampicin to activate PXR in a transactivation assay at non cytoxic concentrations. Using a limited proteolysis assay, we show that walrycin A induces conformational changes at a concentration which correlates with walrycin A ability to enhance the expression of prototypic target genes, suggesting that walrycin A interacts with PXR. The activation of the canonical human PXR target gene CYP3A4 by walrycin A is dose- and PXR-dependent. Finally, in silico docking experiments suggest that the walrycin A oxidation product Russig’s blue is the actual a ligand for PXR. Taken together, these results identify walrycin A as novel human PXR activator. PMID:22314385

Photodegradation of fluorene in aqueous solution: Identification and biological activity testing of degradation products.

PubMed

Kinani, Said; Souissi, Yasmine; Kinani, Aziz; Vujović, Svetlana; Aït-Aïssa, Sélim; Bouchonnet, Stéphane

2016-04-15

Degradation of fluorene under UV-vis irradiation in water was investigated and structural elucidation of the main photoproducts was achieved using gas chromatography coupled with mass spectrometry. Twenty-six photoproducts were structurally identified, mainly on the basis of electron ionization mass spectra interpretation. The main generated transformation products are hydroxy derivatives. Some secondary photoproducts including fluorenone, hydroxy fluorenone, 2-biphenyl carboxylic acid, biphenylene, methanol fluorene congeners and hydroxy fluorene dimers were also observed. A photodegradation pathway was suggested on the basis of the chemical structures of photoproducts. Fluorene as well as its main photoproducts for which chemical standards were commercially available were tested for their ability to elicit cytotoxic, estrogenic and dioxin-like activity by using in vitro cell-based bioassays. None of the tested compounds was cytotoxic at concentrations up to 100 μM. However, 2-hydroxyfluorene and 3-hydroxyfluorene exerted significant estrogenic and dioxin-like activity on a concentration range of 3-30 μM, while fluorene and 9-hydroxyfluorene were weakly or not active, respectively, in our assays. This supports the view that photodegradation processes can generate by-products of higher toxicological concern than the parent compound and strengthens the need to further identify transformation products in the aquatic environment. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2018-04-20

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

A SAR and QSAR study of new artemisinin compounds with antimalarial activity.

PubMed

Santos, Cleydson Breno R; Vieira, Josinete B; Lobato, Cleison C; Hage-Melim, Lorane I S; Souto, Raimundo N P; Lima, Clarissa S; Costa, Elizabeth V M; Brasil, Davi S B; Macêdo, Williams Jorge C; Carvalho, José Carlos T

2013-12-30

The Hartree-Fock method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with antimalarial activity. Maps of molecular electrostatic potential (MEPs) and molecular docking were used to investigate the interaction between ligands and the receptor (heme). Principal component analysis and hierarchical cluster analysis were employed to select the most important descriptors related to activity. The correlation between biological activity and molecular properties was obtained using the partial least squares and principal component regression methods. The regression PLS and PCR models built in this study were also used to predict the antimalarial activity of 30 new artemisinin compounds with unknown activity. The models obtained showed not only statistical significance but also predictive ability. The significant molecular descriptors related to the compounds with antimalarial activity were the hydration energy (HE), the charge on the O11 oxygen atom (QO11), the torsion angle O1-O2-Fe-N2 (D2) and the maximum rate of R/Sanderson Electronegativity (RTe+). These variables led to a physical and structural explanation of the molecular properties that should be selected for when designing new ligands to be used as antimalarial agents.

Rodent repellents: Preparation and properties of thiouronium compounds and cyclic imides

USGS Publications Warehouse

Bellack, E.; DeWitt, J.B.

1954-01-01

Syntheses and bioassays of cyclic imides and thiouronium compounds were carried out as part of a search for materials capable of preventing rodent damage to packaged commodities. Previous studies had shown that repellent activity was associated with functional groups containing nitrogen and sulfur, and was enhanced by the presence of ionic linkages. Twenty-seven thiouronium compounds and 40 imides, including 1 0 compounds not described previously, were prepared for these tests. Ten imides and 26 thiouronium compounds were repellent under the conditions of test. Information obtained in these studies will be utilized in the development and selection of more effective materials for prevention of rodent damage to foods and other commodities.

Antileishmanial activity of the hydroalcoholic extract of Miconia langsdorffii, isolated compounds, and semi-synthetic derivatives.

PubMed

Peixoto, Juliana A; Andrade E Silva, Márcio Luis; Crotti, Antônio E M; Cassio Sola Veneziani, Rodrigo; Gimenez, Valéria M M; Januário, Ana H; Groppo, Milton; Magalhães, Lizandra G; Dos Santos, Fransérgio F; Albuquerque, Sérgio; da Silva Filho, Ademar A; Cunha, Wilson R

2011-02-22

The in vitro activity of the crude hydroalcoholic extract of the aerial parts of Miconia langsdorffii Cogn. was evaluated against the promastigote forms of L. amazonensis, the causative agent of cutaneous leishmaniasis in humans. The bioassay-guided fractionation of this extract led to identification of the triterpenes ursolic acid and oleanolic acid as the major compounds in the fraction that displayed the highest activity. Several ursolic acid semi-synthetic derivatives were prepared, to find out whether more active compounds could be obtained. Among these ursolic acid-derived substances, the C-28 methyl ester derivative exhibited the best antileishmanial activity.

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.

Identification of the functional binding pocket for compounds targeting small-conductance Ca2+-activated potassium channels

PubMed Central

Zhang, Miao; Pascal, John M.; Schumann, Marcel; Armen, Roger S.; Zhang, Ji-fang

2012-01-01

Small- and intermediate-conductance Ca2+-activated potassium channels, activated by Ca2+-bound calmodulin, play an important role in regulating membrane excitability. These channels are also linked to clinical abnormalities. A tremendous amount of effort has been devoted to developing small molecule compounds targeting these channels. However, these compounds often suffer from low potency and lack of selectivity, hindering their potentials for clinical use. A key contributing factor is the lack of knowledge of the binding site(s) for these compounds. Here we demonstrate by X-ray crystallography that the binding pocket for the compounds of the 1-EBIO class is located at the calmodulin-channel interface. We show that, based on structure data and molecular docking, mutations of the channel can effectively change the potency of these compounds. Our results provide insight into the molecular nature of the binding pocket and its contribution to the potency and selectivity of the compounds of the 1-EBIO class. PMID:22929778

Exploration of the anti-enterovirus activity of a series of pleconaril/pirodavir-like compounds.

PubMed

Bernard, Angela; Lacroix, Céline; Cabiddu, Maria G; Neyts, Johan; Leyssen, Pieter; Pompei, Raffaello

2015-04-01

The Enterovirus genus of the Picornaviridae is represented by several viral pathogens that are associated with human disease, namely Poliovirus 1, Enterovirus 71 and Rhinoviruses. Enterovirus 71 has been associated with encephalitis, while Rhinoviruses are a major cause of asthma exacerbations and chronic obstructive pulmonary disease. Based on the structure of both pleconaril and pirodavir, we previously synthesized some original compounds as potential inhibitors of Rhinovirus replication. These compounds were explored for in vitro antiviral potential on other human pathogenic Enteroviruses, namely Enterovirus 71 on rhabdo-myosarcoma cells, Coxsackievirus B3 on Vero cells, Poliovirus 1 and Echovirus 11 on BGM cells. Activity was confirmed for compound against Rhinovirus 14. Furthermore, few compounds showed a cell-protective effect on Enterovirus 71, presented a marked improvement as compared to the reference drug pleconaril for inhibitory activity on both Enterovirus 71 and Poliovirus 1. The most striking observation was the clear cell protective effect for the set of analogues in a virus-cell-based assay for Echovirus 11 with an effective concentration (EC50) as low as 0.3 µM (Selectivity index or SI = 483), and selectivity indexes greater than 857 (EC50 = 0.6 µM) and 1524 (EC50 = 0.33 µM). Some of the evaluated compounds showed potent and selective antiviral activity against several enterovirus species, such as Enterovirus 71 (EV-A), Echovirus 11 (EV-B), and Poliovirus 1 (EV-C). This could be used as a starting point for the development of other pleconaril/pirodavir-like enterovirus inhibitors with broad-spectrum activity and improved effects as compared to the reference drugs. © The Author(s) 2015.

Phenolic compounds and antioxidant activity of kernels and shells of Mexican pecan (Carya illinoinensis).

PubMed

de la Rosa, Laura A; Alvarez-Parrilla, Emilio; Shahidi, Fereidoon

2011-01-12

The phenolic composition and antioxidant activity of pecan kernels and shells cultivated in three regions of the state of Chihuahua, Mexico, were analyzed. High concentrations of total extractable phenolics, flavonoids, and proanthocyanidins were found in kernels, and 5-20-fold higher concentrations were found in shells. Their concentrations were significantly affected by the growing region. Antioxidant activity was evaluated by ORAC, DPPH•, HO•, and ABTS•-- scavenging (TAC) methods. Antioxidant activity was strongly correlated with the concentrations of phenolic compounds. A strong correlation existed among the results obtained using these four methods. Five individual phenolic compounds were positively identified and quantified in kernels: ellagic, gallic, protocatechuic, and p-hydroxybenzoic acids and catechin. Only ellagic and gallic acids could be identified in shells. Seven phenolic compounds were tentatively identified in kernels by means of MS and UV spectral comparison, namely, protocatechuic aldehyde, (epi)gallocatechin, one gallic acid-glucose conjugate, three ellagic acid derivatives, and valoneic acid dilactone.

[The content of phenolic compounds and antioxidant activity ready to eat desserts for infants].

PubMed

Filipiak-Florkiewicz, Agnieszka; Dereń, Katarzyna

2011-01-01

The aim of this study was to determine the content of phenolic compounds and antioxidant activity in ready-to-eat desserts for babies. The experimental material consisted of six kinds of fruit desserts taken from the market in 2008, in which the content of dry matter phenolic compounds and antioxidant activity levels on the basis of free radical quenching ability ABTS were determined. The largest share of dry matter was found in apricot mousse with apples and bananas (16.9%). The largest amounts of phenolic compounds were found in the cream with apple and wild rose (186.3 mg/100 g) and apple with forest fruits (170.7 mg/100 g). The highest antioxidant activity among the desserts was determined in cream with apple and wild rose (14.2 micromol Trolox/g) and apple mousse with peaches (12.8 micromol Trolox/g). The antioxidant capacity of the remaining examined purée was slightly lower and ranged from 11.4-11.7 micromol Trolox/g.

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

PubMed

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

2018-05-31

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

VOLATILE ORGANIC COMPOUNDS AS BREATH BIOMARKERS FOR ACTIVE AND PASSIVE SMOKING

EPA Science Inventory

Real-time breath measurement technology was used to investigate the suitability of some volatile organic compounds (VOCs) to serve as breath biomarkers for active and passive smoking and to measure actual exposures and resulting breath concentrations for persons exposed to toba...

Variability of antioxidant and biological activities of Rhus tripartitum related to phenolic compounds

PubMed Central

Ben Miled, Hanène; Saada, Mariem; Jallali, Ines; Ben Barka, Zaineb; Tlili, Mounira; Alimi, Hichem; Sakly, Mohsen; Ben Rhouma, Khémais; Abderrabba, Manef; Abdelmelek, Hafedh; Tebourbi, Olfa; Ksouri, Riadh

2017-01-01

Rhus species are known in traditional medicine for their therapeutic virtue and their extracts showed numerous important properties including antimalarial, antimicrobial, antiviral, and hypoglycemic and anticonvulsant activities. Rhus tripartitum (Ucria) is a medicinal plant widely used in Tunisia folk medicine against chronic diarrhea and gastric ulcer. This study was designed to examine in vitro and ex vivo antioxidant, anti-inflammatory and anticancer activities of four extracts of Rhus tripartitum root cortex with increasing solvent polarity (hexane, dichloromethane, methanol and water). HPLC was used to identify and quantify phenolic compounds in Rhus extract. Water extract showed the highest antioxidant activity using oxygen radical absorbance capacity (ORAC method) with 8.95 ± 0.47 µmol Trolox/mg and a cell based-assay with 0.28 ± 0.12 µmol Trolox/mg as compared to the other fractions. Moreover, methanol extract displayed the strongest anti-cancer activity against human lung carcinoma (A-549) and colon adenocarcinoma cell lines (DLD-1) with an IC50 value of 60.69 ± 2.58 and 39.83 ± 4.56 µg/ml (resazurin test) and 44.52 ± 5.96 and 55.65 ± 6.00 µg/ml (hoechst test), respectively. Besides, the highest anti-inflammatory activity, inhibiting nitric oxide (NO) release, was exhibited by dichloromethane extract with 31.5 % at 160 µg/ml in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The HPLC analysis showed that catechol and kaempferol were the major phenolics. These data suggest the richness of all fractions of Ucria root on interesting bioactive molecules with different polarity and confirm the known traditional therapeutics virtues of this species for the treatment of dysentery, diarrhea and gastric ulcer. PMID:28694749

Variability of antioxidant and biological activities of Rhus tripartitum related to phenolic compounds.

PubMed

Ben Miled, Hanène; Saada, Mariem; Jallali, Ines; Ben Barka, Zaineb; Tlili, Mounira; Alimi, Hichem; Sakly, Mohsen; Ben Rhouma, Khémais; Abderrabba, Manef; Abdelmelek, Hafedh; Tebourbi, Olfa; Ksouri, Riadh

2017-01-01

Rhus species are known in traditional medicine for their therapeutic virtue and their extracts showed numerous important properties including antimalarial, antimicrobial, antiviral, and hypoglycemic and anticonvulsant activities. Rhus tripartitum (Ucria) is a medicinal plant widely used in Tunisia folk medicine against chronic diarrhea and gastric ulcer. This study was designed to examine in vitro and ex vivo antioxidant, anti-inflammatory and anticancer activities of four extracts of Rhus tripartitum root cortex with increasing solvent polarity (hexane, dichloromethane, methanol and water). HPLC was used to identify and quantify phenolic compounds in Rhus extract. Water extract showed the highest antioxidant activity using oxygen radical absorbance capacity (ORAC method) with 8.95 ± 0.47 µmol Trolox/mg and a cell based-assay with 0.28 ± 0.12 µmol Trolox/mg as compared to the other fractions. Moreover, methanol extract displayed the strongest anti-cancer activity against human lung carcinoma (A-549) and colon adenocarcinoma cell lines (DLD-1) with an IC 50 value of 60.69 ± 2.58 and 39.83 ± 4.56 µg/ml (resazurin test) and 44.52 ± 5.96 and 55.65 ± 6.00 µg/ml (hoechst test), respectively. Besides, the highest anti-inflammatory activity, inhibiting nitric oxide (NO) release, was exhibited by dichloromethane extract with 31.5 % at 160 µg/ml in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The HPLC analysis showed that catechol and kaempferol were the major phenolics. These data suggest the richness of all fractions of Ucria root on interesting bioactive molecules with different polarity and confirm the known traditional therapeutics virtues of this species for the treatment of dysentery, diarrhea and gastric ulcer.

A Pharmacological Screening Approach for Discovery of Neuroprotective Compounds in Ischemic Stroke

PubMed Central

Beraki, Simret; Litrus, Lily; Soriano, Liza; Monbureau, Marie; To, Lillian K.; Braithwaite, Steven P.; Nikolich, Karoly; Urfer, Roman; Oksenberg, Donna; Shamloo, Mehrdad

2013-01-01

With the availability and ease of small molecule production and design continuing to improve, robust, high-throughput methods for screening are increasingly necessary to find pharmacologically relevant compounds amongst the masses of potential candidates. Here, we demonstrate that a primary oxygen glucose deprivation assay in primary cortical neurons followed by secondary assays (i.e. post-treatment protocol in organotypic hippocampal slice cultures and cortical neurons) can be used as a robust screen to identify neuroprotective compounds with potential therapeutic efficacy. In our screen about 50% of the compounds in a library of pharmacologically active compounds displayed some degree of neuroprotective activity if tested in a pre-treatment toxicity assay but just a few of these compounds, including Carbenoxolone, remained active when tested in a post-treatment protocol. When further examined, Carbenoxolone also led to a significant reduction in infarction size and neuronal damage in the ischemic penumbra when administered six hours post middle cerebral artery occlusion in rats. Pharmacological testing of Carbenoxolone-related compounds, acting by inhibition of 11-β-hydroxysteroid dehydrogenase-1 (11β-HSD1), gave rise to similarly potent in vivo neuroprotection. This indicates that the increase of intracellular glucocorticoid levels mediated by 11β-HSD1 may be involved in the mechanism that exacerbates ischemic neuronal cell death, and inhibiting this enzyme could have potential therapeutic value for neuroprotective therapies in ischemic stroke and other neurodegenerative disorders associated with neuronal injury. PMID:23874920

A new phenolic compound with antioxidant activity from the branches and leaves of Pyrus pashia.

PubMed

Li, Zhen-Jie; Zheng, Xi; Wan, Chun-Ping; Cai, Le; Li, Ying; Huang, Lin; Ding, Zhong-Tao

2016-01-01

The branches and leaves of Pyrus pashia are used to cure abdominal pain and diarrhoea in Chinese folk medicine. A new phenilic compound, 4-O-β-d-glucopyranosylbenzyl-benzoate ester (1), along with 21 known ones (2-22) were isolated from the branches and leaves of this plant. Compounds 2 and 3 displayed remarkable antioxidant activities against 1,1-diphenyl-2-picrylhydrazyl radical (IC50 = 13.26 ± 0.04 μM, 13.28 ± 0.11 μM, respectively), which were at the same grade as positive control rutin. The caffeoyl group in compounds 2 and 3 was supposed to play an important role in the antioxidant activities.

Design, Development, and Testing of a Compound Wing V/TOL small UAS

NASA Technical Reports Server (NTRS)

Logan, Michael J.; Vranas, Thomas L.

2015-01-01

This paper discusses the development and testing of an innovative small UAS (Unmanned Aircraft System). The design of the vehicle was driven by the need to both have long endurance yet still have the convenience of V/TOL (Vertical Take-Off and Landing) operation. The paper discusses some of the design considerations and configurations evaluated in searching for a configuration that met the demanding mission requirements. The paper also discusses some aspects of the compound wing and experimental testing conducted to discern the optimum parameters for the wing's design. The paper discusses the results of the preliminary flight testing and outlines further research to be conducted.

A successful virtual screening application: prediction of anticonvulsant activity in MES test of widely used pharmaceutical and food preservatives methylparaben and propylparaben.

PubMed

Talevi, Alan; Bellera, Carolina L; Castro, Eduardo A; Bruno-Blanch, Luis E

2007-09-01

A discriminant function based on topological descriptors was derived from a training set composed by anticonvulsants of clinical use or in clinical phase of development and compounds with other therapeutic uses. This model was internally and externally validated and applied in the virtual screening of chemical compounds from the Merck Index 13th. Methylparaben (Nipagin), a preservative widely used in food, cosmetics and pharmaceutics, was signaled as active by the discriminant function and tested in mice in the Maximal Electroshock (MES) test (i.p. administration), according to the NIH Program for Anticonvulsant Drug Development. Based on the results of Methylparaben, Propylparaben (Nipasol), another preservative usually used in association with the former, was also tested. Both methyl and propylparaben were found active in mice at doses of 30, 100, and 300 mg/kg. The discovery of the anticonvulsant activities in the MES test of methylparaben and propylparaben might be useful for the development of new anticonvulsant medications, specially considering the well-known toxicological profile of these drugs.