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Sample records for active compounds responsible

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

  2. Polarimeter with linear response for measuring optical activity in organic compounds

    NASA Astrophysics Data System (ADS)

    Flores, Jorge L.; Montoya, Marcial; Garcia-Torales, G.; Gonzalez Alvarez, Alejandro

    2005-08-01

    A polarimeter designed for measuring small rotation angles on the polarization plane of light is described. The experimental device employs one fixed polarizer and a rotating analyzer. The system generates a periodical intensity signal, which is then Fourier analyzed. The coefficients of Fourier Transform contain information about rotation angles produced by organic compounds that exhibited optical activity. The experimental device can be used to determine the sugar concentration in agave juice.

  3. Antihelminth compound niclosamide downregulates Wnt signaling and elicits antitumor responses in tumors with activating APC mutations.

    PubMed

    Osada, Takuya; Chen, Minyong; Yang, Xiao Yi; Spasojevic, Ivan; Vandeusen, Jeffrey B; Hsu, David; Clary, Bryan M; Clay, Timothy M; Chen, Wei; Morse, Michael A; Lyerly, H Kim

    2011-06-15

    Wnt/β-catenin pathway activation caused by adenomatous polyposis coli (APC) mutations occurs in approximately 80% of sporadic colorectal cancers (CRC). The antihelminth compound niclosamide downregulates components of the Wnt pathway, specifically Dishevelled-2 (Dvl2) expression, resulting in diminished downstream β-catenin signaling. In this study, we determined whether niclosamide could inhibit the Wnt/β-catenin pathway in human CRCs and whether its inhibition might elicit antitumor effects in the presence of APC mutations. We found that niclosamide inhibited Wnt/β-catenin pathway activation, downregulated Dvl2, decreased downstream β-catenin signaling, and exerted antiproliferative effects in human colon cancer cell lines and CRC cells isolated by surgical resection of metastatic disease, regardless of mutations in APC. In contrast, inhibition of NF-κB or mTOR did not exert similar antiproliferative effects in these CRC model systems. In mice implanted with human CRC xenografts, orally administered niclosamide was well tolerated, achieved plasma and tumor levels associated with biologic activity, and led to tumor control. Our findings support clinical explorations to reposition niclosamide for the treatment of CRC.

  4. Classical Nuclear Hormone Receptor Activity as a Mediator of Complex Concentration Response Relationships for Endocrine Active Compounds

    PubMed Central

    Cookman, Clifford J.; Belcher, Scott M.

    2014-01-01

    Nonmonotonic concentration response relationships are frequently observed for endocrine active ligands that act via nuclear receptors. The curve of best fit for nonmonotonic concentration response relationships are often inverted U-shaped with effects at intermediate concentrations that are different from effects at higher or lower concentrations. Cytotoxicity is a major mode of action responsible for inverted U-shaped concentration response relationships. However, evidence suggests that ligand selectivity, activation of multiple molecular targets, concerted regulation of multiple opposing endpoints, and multiple ligand binding sites within nuclear receptors also contribute to nonmonotonic concentration response relationships of endocrine active ligands. This review reports the current understanding of mechanisms involved in classical nuclear receptor mediated nonmonotonic concentration response relationships with a focus on studies published between 2012 and 2014. PMID:25299165

  5. Transcriptional response of zebrafish embryos exposed to neurotoxic compounds reveals a muscle activity dependent hspb11 expression.

    PubMed

    Klüver, Nils; Yang, Lixin; Busch, Wibke; Scheffler, Katja; Renner, Patrick; Strähle, Uwe; Scholz, Stefan

    2011-01-01

    Acetylcholinesterase (AChE) inhibitors are widely used as pesticides and drugs. Their primary effect is the overstimulation of cholinergic receptors which results in an improper muscular function. During vertebrate embryonic development nerve activity and intracellular downstream events are critical for the regulation of muscle fiber formation. Whether AChE inhibitors and related neurotoxic compounds also provoke specific changes in gene transcription patterns during vertebrate development that allow them to establish a mechanistic link useful for identification of developmental toxicity pathways has, however, yet not been investigated. Therefore we examined the transcriptomic response of a known AChE inhibitor, the organophosphate azinphos-methyl (APM), in zebrafish embryos and compared the response with two non-AChE inhibiting unspecific control compounds, 1,4-dimethoxybenzene (DMB) and 2,4-dinitrophenol (DNP). A highly specific cluster of APM induced gene transcripts was identified and a subset of strongly regulated genes was analyzed in more detail. The small heat shock protein hspb11 was found to be the most sensitive induced gene in response to AChE inhibitors. Comparison of expression in wildtype, ache and sop(fixe) mutant embryos revealed that hspb11 expression was dependent on the nicotinic acetylcholine receptor (nAChR) activity. Furthermore, modulators of intracellular calcium levels within the whole embryo led to a transcriptional up-regulation of hspb11 which suggests that elevated intracellular calcium levels may regulate the expression of this gene. During early zebrafish development, hspb11 was specifically expressed in muscle pioneer cells and Hspb11 morpholino-knockdown resulted in effects on slow muscle myosin organization. Our findings imply that a comparative toxicogenomic approach and functional analysis can lead to the identification of molecular mechanisms and specific marker genes for potential neurotoxic compounds.

  6. TRPV1 activation and induction of nociceptive response by a non-pungent capsaicin-like compound, capsiate.

    PubMed

    Iida, T; Moriyama, T; Kobata, K; Morita, A; Murayama, N; Hashizume, S; Fushiki, T; Yazawa, S; Watanabe, T; Tominaga, M

    2003-06-01

    Capsiate is a capsaicin-like ingredient of a non-pungent cultivar of red pepper, CH-19 sweet. To elucidate the mechanisms underlying the non-pungency of capsiate, we investigated whether capsiate activates the cloned capsaicin receptor, TRPV1 (VR1). In patch-clamp experiments, capsiate was found to activate TRPV1 expressed transiently in HEK293 cells with a similar potency as capsaicin. Capsiate induced nociceptive responses in mice when injected subcutaneously into their hindpaws with a similar dose dependency as capsaicin. These data indicate that the non-pungent capsiate is an agonist for TRPV1 and could excite peripheral nociceptors. In contrast to this, capsiate did not induce any significant responses when applied to the skin surface, eye or oral cavity of mice, suggesting that capsiate requires direct access to nerve endings to exhibit its effects. Capsiate was proved to have high lipophilicity and to be easily broken down in normal aqueous conditions, leading to less accessibility to nociceptors. Another highly lipophilic capsaicin analogue, olvanil, was similar to capsiate in that it did not produce irritant responses when applied to the skin surface, although it could activate TRPV1. Taken together, high lipophilicity and instability might be critical determinants for pungency and so help in understanding the effects of capsaicin-related compounds.

  7. Modulation of PPAR Expression and Activity in Response to Polyphenolic Compounds in High Fat Diets

    PubMed Central

    Domínguez-Avila, J. Abraham; González-Aguilar, Gustavo A.; Alvarez-Parrilla, Emilio; de la Rosa, Laura A.

    2016-01-01

    Peroxisome proliferator-activated receptors (PPAR) are transcription factors that modulate energy metabolism in liver, adipose tissue and muscle. High fat diets (HFD) can negatively impact PPAR expression or activity, favoring obesity, dyslipidemia, insulin resistance and other conditions. However, polyphenols (PP) found in vegetable foodstuffs are capable of positively modulating this pathway. We therefore focused this review on the possible effects that PP can have on PPAR when administered together with HFD. We found that PP from diverse sources, such as coffee, olives, rice, berries and others, are capable of inducing the expression of genes involved in a decrease of adipose mass, liver and serum lipids and lipid biosynthesis in animal and cell models of HFD. Since cells or gut bacteria can transform PP into different metabolites, it is possible that a synergistic or antagonistic effect ultimately occurs. PP molecules from vegetable sources are an interesting option to maintain or return to a state of energy homeostasis, possibly due to an adequate PPAR expression and activity. PMID:27367676

  8. Eukaryotic inhibitors or activators elicit responses to chemosensory compounds by ruminal isotrichid and entodiniomorphid protozoa.

    PubMed

    Diaz, H L; Barr, K N; Godden, K R; Plank, J E; Zapata, I; Schappacher, A N; Wick, M P; Firkins, J L

    2014-01-01

    Our objectives were to evaluate potential signaling pathways regulating rumen protozoal chemotaxis using eukaryotic inhibitors potentially coordinated with phagocytosis as assessed by fluorescent bead uptake kinetics. Wortmannin (inhibitor of phosphoinositide 3-kinase), insulin, genistein (purported inhibitor of a receptor tyrosine kinase), U73122 (inhibitor of phospholipase C), and sodium nitroprusside (Snp, nitric oxide generator, activating protein kinase G) were preincubated with mixed ruminal protozoa for 3h before assessing uptake of fluorescent beads and chemosensory behavior to glucose, peptides, and their combination; peptides were also combined with guanosine triphosphate (GTP; a chemorepellent). Entodiniomorphids were chemoattracted to both glucose and peptides, but chemoattraction to glucose was increased by Snp and wortmannin without effect on chemoattraction to peptides. Rate of fluorescent bead uptake by an Entodinium caudatum culture decreased when beads were added simultaneously with feeding and incubated with wortmannin (statistical interaction). Wortmannin also decreased the proportion of mixed entodiniomorphids consuming beads. Isotrichid protozoa exhibited greater chemotaxis to glucose but, compared with entodiniomorphids, were chemorepelled to peptides. Wortmannin increased chemotaxis by entodiniomorphids but decreased chemotaxis to glucose by isotrichids. Motility assays documented that Snp and wortmannin decreased net swimming speed (distance among 2 points per second) but not total swimming speed (including turns) by entodiniomorphids. Wortmannin decreased both net and total swimming behavior in isotrichids. Results mechanistically explain the isotrichid migratory ecology to rapidly take up newly ingested sugars and subsequent sedimentation back to the ventral reticulorumen. In contrast, entodiniomorphids apparently integrate cellular motility with feeding behavior to consume small particulates and thereby stay associated and pass with the

  9. Do laboratory species protect endangered species? Interspecies variation in responses to 17β-estradiol, a model endocrine active compound.

    PubMed

    Jorgenson, Z G; Buhl, K; Bartell, S E; Schoenfuss, H L

    2015-01-01

    Although the effects of estrogens on model laboratory species are well documented, their utility as surrogates for other species, including those listed as endangered, are less clear. Traditionally, conservation policies are evaluated based on model organism responses but are intended to protect all species in an environment. We tested the hypothesis that the endangered Rio Grande silvery minnow (Hybognathus amarus) is more vulnerable to endocrine disruption-as assessed through its larval predator-escape performance, survival, juvenile sex ratios, and whole-body vitellogenin concentration-than the commonly used toxicological model species fathead minnow (Pimephales promelas) and the bluegill sunfish (Lepomis macrochirus). Fish were exposed concurrently for 21 days to the model endocrine active compound (EAC) 17ß-estradiol (E2) at 10 ng E2/L and 30 ng E2/L in a flow-through system using reconstituted water that simulated the physicochemical conditions of the Middle Rio Grande in New Mexico, USA. No significant differences were observed between the fathead and silvery minnow in larval predator-escape response or juvenile sex ratio. Rio Grande silvery minnow survival decreased significantly at day 14 compared with the other two species; by day 21, both cyprinid species (silvery minnow and fathead minnow) exhibited a significant decrease in survival compared with bluegill sunfish, a member of the family Centrarchidae. Male Rio Grande silvery minnow showed a significant increase in whole-body vitellogenin concentration in the 10 ng/L treatment, whereas fathead minnow and bluegill sunfish showed no significant increases in vitellogenin concentrations across treatments. Our study showed response differences to estrogen exposures between the two cyprinid species and further divergence in responses between the families Cyprinidae and Centrarchidae. These results suggest that commonly used laboratory model organisms may be less sensitive to EACs than the endangered Rio

  10. Do laboratory species protect endangered species? Interspecies variation in responses to 17β-estradiol, a model endocrine active compound

    USGS Publications Warehouse

    Jorgenson, Zachary G.; Buhl, Kevin J.; Bartell, Stephen E.; Schoenfuss, Heiko L.

    2015-01-01

    Although the effects of estrogens on model laboratory species are well documented, their utility as surrogates for other species, including those listed as endangered, are less clear. Traditionally, conservation policies are evaluated based on model organism responses but are intended to protect all species in an environment. We tested the hypothesis that the endangered Rio Grande silvery minnow (Hybognathus amarus) is more vulnerable to endocrine disruption—as assessed through its larval predator-escape performance, survival, juvenile sex ratios, and whole-body vitellogenin concentration—than the commonly used toxicological model species fathead minnow (Pimephales promelas) and the bluegill sunfish (Lepomis macrochirus). Fish were exposed concurrently for 21 days to the model endocrine active compound (EAC) 17ß-estradiol (E2) at 10 ng E2/L and 30 ng E2/L in a flow-through system using reconstituted water that simulated the physicochemical conditions of the Middle Rio Grande in New Mexico, USA. No significant differences were observed between the fathead and silvery minnow in larval predator-escape response or juvenile sex ratio. Rio Grande silvery minnow survival decreased significantly at day 14 compared with the other two species; by day 21, both cyprinid species (silvery minnow and fathead minnow) exhibited a significant decrease in survival compared with bluegill sunfish, a member of the family Centrarchidae. Male Rio Grande silvery minnow showed a significant increase in whole-body vitellogenin concentration in the 10 ng/L treatment, whereas fathead minnow and bluegill sunfish showed no significant increases in vitellogenin concentrations across treatments. Our study showed response differences to estrogen exposures between the two cyprinid species and further divergence in responses between the families Cyprinidae and Centrarchidae. These results suggest that commonly used laboratory model organisms may be less sensitive to EACs than the endangered

  11. Occurrence of Endocrine Active Compounds and Biological Responses in the Mississippi River - Study Design and Data, June through August 2006

    USGS Publications Warehouse

    Lee, Kathy E.; Yaeger, Christine S.; Jahns, Nathan D.; Schoenfuss, Heiko L.

    2008-01-01

    Concern that selected chemicals in the environment may act as endocrine active compounds in aquatic ecosystems is widespread; however, few studies have examined the occurrence of endocrine active compounds and identified biological markers of endocrine disruption such as intersex occurrence in fish longitudinally in a river system. This report presents environmental data collected and analyzed by the U.S. Geological Survey, Minnesota Pollution Control Agency and St. Cloud State University as part of an integrated biological and chemical study of endocrine disruption in fish in the Mississippi River. Data were collected from water, bed sediment, and fish at 43 sites along the river from the headwaters at Lake Itasca to 14 miles downstream from Brownsville, Minnesota during June through August 2006. Twenty-four individual compounds were detected in water samples, with cholesterol, atrazine, N,N-diethyl-meta-toluamide, metolachlor, and hexahydrohexamethylcyclopentabenzopyran detected most frequently (in at least 10 percent of the samples). The number of compounds detected in water per site ranged from 0 to 8. Forty individual compounds were detected in bed-sediment samples. The most commonly detected compounds (in at least 50 percent of the samples) were indole, beta-sitosterol, cholesterol, beta-stigmastanol, 3-methyl-1H-indole, p-cresol, pyrene, phenol, fluoranthene, 3-beta coprostanol, benzo[a]pyrene, acetophenone, and 2,6-dimethylnaphthalene. The total number of detections in bed sediment (at a site) ranged from 3 to 31. The compounds NP1EO, NP2EO, and 4-nonylphenol were detected in greater than 10 percent of the samples. Most (80 percent) female fish collected had measurable concentrations of vitellogenin. Vitellogenin also was detected in 62, 63, and 33 percent of male carp, smallmouth bass, and redhorse, respectively. The one male walleye sample plasma sample analyzed had a vitellogenin detection. Vitellogenin concentrations were lower in male fish (not

  12. Optimization of Ultrasonic Extraction of Phenolic Compounds from Epimedium brevicornum Maxim Using Response Surface Methodology and Evaluation of Its Antioxidant Activities In Vitro

    PubMed Central

    Zhao, Yan; Hou, Yingying; Tang, Guosheng; Cai, Enbo; Liu, Shuangli; Yang, He; Zhang, Lianxue; Wang, Shijie

    2014-01-01

    The ultrasound-assisted extraction of phenolic compounds from Epimedium brevicornu Maxim was modeled using response surface methodology. A Central Composite Design (CCD) was employed to optimize three extraction variables, including ethanol concentration (X1), extraction time (X2), and ratio of aqueous ethanol to raw material (X3), for the achievement of high extraction yield of the phenolic compounds. The optimized conditions are X1 of 50% (v/v), X2 of 27.5 min, and X3 of 250 mL/g. Under these conditions, the experimental yield is 4.29 ± 0.033% (n = 3). The antioxidant activity was evaluated using the DPPH assay and ferric-reducing antioxidant power (FRAP). And it indicates that the phenolic compounds from Epimedium brevicornu Maxim possess significant antioxidant activity. HPLC analysis reveals that the main phenolic compound in the extract product was identified as gallic acid, catechin (Cianidanol), p-hydroxybenzoic acid, vanillic acid, caffeic acid, ferulaic acid, rutin, benzoic acid, and quercetin. PMID:25478287

  13. Bioactivity-guided Separation of the Active Compounds in Acacia pennata Responsible for the Prevention of Alzheimer's Disease.

    PubMed

    Lomarat, Pattamapan; Chancharunee, Sirirat; Anantachoke, Natthinee; Kitphati, Worawan; Sripha, Kittisak; Bunyapraphatsara, Nuntavan

    2015-08-01

    The objective of this study was to evaluate the health benefits of plants used in Thai food, specifically Acacia pennata Willd., in Alzheimer's prevention. A. pennata twigs strongly inhibited β-amyloid aggregation. Bioactivity-guided separation of the active fractions yielded six known compounds, tetracosane (1), 1-(heptyloxy)-octadecane (2), methyl tridecanoate (3), arborinone (4), confertamide A (5) and 4-hydroxy-1-methyl-pyrrolidin-2-carboxylic acid (6). The structures were determined by spectroscopic analysis. Biological testing revealed that tetracosane (1) was the most potent inhibitor of β-amyloid aggregation, followed by 1-(heptyloxy)-octadecane (2) with IC50 values of 0.4 and 12.3 μM. Methyl tridecanoate (3), arborinone (4) and 4-hydroxy-1-methyl-pyrrolidin-2-carboxylic acid (6) moderately inhibited β-amyloid aggregation. In addition, tetracosane (1) and methyl tridecanoate (3) weakly inhibited acetylcholinesterase (AChE). These results suggested that the effect of A. pennata on Alzheimer's disease was likely due to the inhibition of β-amyloid aggregation. Thus A. pennata may be beneficial for Alzheimer's prevention.

  14. A Hypothesis: Supplementation with Mushroom-Derived Active Compound Modulates Immunity and Increases Survival in Response to Influenza Virus (H1N1) Infection

    PubMed Central

    Chunchao, Han; Guo, Jian-you

    2011-01-01

    We hypothesize that the mushroom-derived active compound may be a potential strategy for increasing survival in response to influenza virus (H1N1) infection through the stimulation of host innate immune response. The validity of the hypothesis can be tested by immune response to influenza infection as seen through survival percentage, virus clearance, weight loss, natural killer cell cytotoxicity, Tumor Necrosis Factor-α (TNF-α) and Interferon-gamma (IFN-γ) levels, lytic efficiency in the spleens of mice and inducible nitric oxide synthase mRNA expressions in RAW 264.7 murine macrophage cells. The hypothesis may improve people's quality of life, reduce the medical cost of our healthcare system and eliminate people's fears of influenza outbreak. PMID:21660092

  15. Dual neuroprotective pathways of a pro-electrophilic compound via HSF-1-activated heat-shock proteins and Nrf2-activated phase 2 antioxidant response enzymes.

    PubMed

    Satoh, Takumi; Rezaie, Tayebeh; Seki, Masaaki; Sunico, Carmen R; Tabuchi, Takahito; Kitagawa, Tomomi; Yanagitai, Mika; Senzaki, Mutsumi; Kosegawa, Chihiro; Taira, Hideharu; McKercher, Scott R; Hoffman, Jennifer K; Roth, Gregory P; Lipton, Stuart A

    2011-11-01

    Activation of the Keap1/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and consequent induction of phase 2 antioxidant enzymes is known to afford neuroprotection. Here, we present a series of novel electrophilic compounds that protect neurons via this pathway. Natural products, such as carnosic acid (CA), are present in high amounts in the herbs rosemary and sage as ortho-dihydroquinones, and have attracted particular attention because they are converted by oxidative stress to their active form (ortho-quinone species) that stimulate the Keap1/Nrf2 transcriptional pathway. Once activated, this pathway leads to the production of a series of antioxidant phase 2 enzymes. Thus, such dihydroquinones function as redox-activated 'pro-electrophiles'. Here, we explored the concept that related para-dihydroquinones represent even more effective bioactive pro-electrophiles for the induction of phase 2 enzymes without producing toxic side effects. We synthesized several novel para-hydroquinone-type pro-electrophilic compounds (designated D1 and D2) to analyze their protective mechanism. DNA microarray, PCR, and western blot analyses showed that compound D1 induced expression of heat-shock proteins (HSPs), including HSP70, HSP27, and DnaJ, in addition to phase 2 enzymes such as hemeoxygenase-1 (HO-1), NADP(H) quinine-oxidoreductase1, and the Na(+)-independent cystine/glutamate exchanger (xCT). Treatment with D1 resulted in activation of Nrf2 and heat-shock transcription factor-1 (HSF-1) transcriptional elements, thus inducing phase 2 enzymes and HSPs, respectively. In this manner, D1 protected neuronal cells from both oxidative and endoplasmic reticulum (ER)-related stress. Additionally, D1 suppressed induction of 78 kDa glucose-regulated protein (GRP78), an ER chaperone protein, and inhibited hyperoxidation of peroxiredoxin 2 (PRX2), a molecule that is in its reduced state can protect from oxidative stress. These results suggest that D1 is a novel pro

  16. Ginsenoside Metabolite Compound K Promotes Recovery of Dextran Sulfate Sodium-Induced Colitis and Inhibits Inflammatory Responses by Suppressing NF-κB Activation

    PubMed Central

    Li, Juan; Zhong, Wei; Wang, Weiwei; Hu, Shaoping; Yuan, Jiahui; Zhang, Bing; Hu, Tianhui; Song, Gang

    2014-01-01

    Phytogenic compounds with anti-oxidant and anti-inflammatory properties, such as ginsenoside metabolite compound K (CK) or berberine (BBR), are currently discussed as promising complementary agents in the prevention and treatment of cancer and inflammation. The latest study showed that ginsenoside Rb1 and its metabolites could inhibit TNBS-induced colitis injury. However, the functional mechanisms of anti-inflammation effects of ginsenoside, particularly its metabolite CK are still not clear. Here, using dextran sulfate sodium (DSS)-induced colitis in mice, clinical parameters, intestinal integrity, pro-inflammatory cytokines production, and signaling pathways in colonic tissues were determined. In mild and sever colitis mice, CK and BBR (as a positive agent) alleviated colitis histopathology injury, ameliorated myeloperoxidase (MPO) activity, reduced pro-inflammatory cytokines production, such as, IL-6, IL-1β, TNF-α, and increased anti-inflammatory cytokine IL-10 production in both mice colon tissues and blood. Nevertheless, the results revealed that CK and BBR inhibited NF-κB p65 nuclear translocation, downregulated p-IκBα and upregulated IκBα, indicating that CK, as well as BBR, suppressed the activation of the NF-κB pathway in the progression of colitis with immunofluorescence, immunohistochemical and western blotting analysis. Furthermore, CK inhibited pro-inflammatory cytokines production in LPS-activated macrophages via down-regulation of NF-κB signaling pathway. Taken together, our results not only reveal that CK promotes the recovery of the progression of colitis and inhibits the inflammatory responses by suppressing NF-κB activation, but also suggest that CK downregulates intestinal inflammation through regulating the activation of macrophages and pro-inflammatory cytokines production. PMID:24504372

  17. Moracin C, A Phenolic Compound Isolated from Artocarpus heterophyllus, Suppresses Lipopolysaccharide-Activated Inflammatory Responses in Murine Raw264.7 Macrophages.

    PubMed

    Yao, Xue; Wu, Dang; Dong, Ningning; Ouyang, Ping; Pu, Jiaqian; Hu, Qian; Wang, Jingyuan; Lu, Weiqiang; Huang, Jin

    2016-07-25

    Artocarpus heterophyllus, a popular tropical fruit commonly known as the jackfruit tree, is normally planted in subtropical or tropical areas. Since a variety of phytochemicals isolated from A. heterophyllus have been found to possess potently anti-inflammatory, antiviral and antimalarial activities, researchers have devoted much interest to its potential pharmaceutical value. However, the exact mechanism underlying its anti-inflammatory activity is not well characterized. In this study, seven natural products isolated from A. heterophyllus, including 25-Hydroxycycloart-23-en-3-one (HY), Artocarpin (AR), Dadahol A (DA), Morachalcone A (MA), Artoheterophyllin B (AB), Cycloheterophyllin (CY) and Moracin C (MC) were collected. Lipopolysaccharide (LPS)-stimulated inflammatory response in RAW264.7 macrophages were used in this study. Among these compounds, MC significantly inhibited LPS-activated reactive oxygen species (ROS) and nitric oxide (NO) release without marked cytotoxicity. Furthermore, MC effectively reduced LPS stimulated up-regulation of mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and serval pro-inflammatory cytokines (interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α)). Mechanistic studies revealed that the anti-inflammatory effect of MC was associated with the activation of the mitogen activated protein kinases (MAPKs) (including p38, ERK and JNK) and nuclear factor-κB (NF-κB) pathways, especially reducing the nuclear translocation of NF-κB p65 subunit as revealed by nuclear separation experiment and confocal microscopy.

  18. Suppression of NF-κB signaling and NLRP3 inflammasome activation in macrophages is responsible for the amelioration of experimental murine colitis by the natural compound fraxinellone

    SciTech Connect

    Wu, Xue-Feng; Ouyang, Zi-Jun; Feng, Li-Li; Chen, Gong; Guo, Wen-Jie; Shen, Yan; Wu, Xu-Dong; Sun, Yang Xu, Qiang

    2014-11-15

    Inflammatory bowel disease (IBD) affects millions of people worldwide. Although the etiology of this disease is uncertain, accumulating evidence indicates a key role for the activated mucosal immune system. In the present study, we examined the effects of the natural compound fraxinellone on dextran sulfate sodium (DSS)-induced colitis in mice, an animal model that mimics IBD. Treatment with fraxinellone significantly reduced weight loss and diarrhea in mice and alleviated the macroscopic and microscopic signs of the disease. In addition, the activities of myeloperoxidase and alkaline phosphatase were markedly suppressed, while the levels of glutathione were increased in colitis tissues following fraxinellone treatment. This compound also decreased the colonic levels of interleukin (IL)-1β, IL-6, IL-18 and tumor necrosis factor (TNF)-α in a concentration-dependent manner. These effects of fraxinellone in mice with experimental colitis were attributed to its inhibition of CD11b{sup +} macrophage infiltration. The mRNA levels of macrophage-related molecules in the colon, including intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2), were also markedly inhibited following fraxinellone treatment. The results from in vitro assays showed that fraxinellone significantly reduced lipopolysaccharide (LPS)-induced production of nitric oxide (NO), IL-1β and IL-18 as well as the activity of iNOS in both THP-1 cells and mouse primary peritoneal macrophages. The mechanisms responsible for these effects were attributed to the inhibitory role of fraxinellone in NF-κB signaling and NLRP3 inflammasome activation. Overall, our results support fraxinellone as a novel drug candidate in the treatment of colonic inflammation. - Highlights: • Fraxinellone, a lactone compound, alleviated DSS induced colitis. • The effects of fraxinellone were attributed to its inhibition on

  19. Moracin C, A Phenolic Compound Isolated from Artocarpus heterophyllus, Suppresses Lipopolysaccharide-Activated Inflammatory Responses in Murine Raw264.7 Macrophages

    PubMed Central

    Yao, Xue; Wu, Dang; Dong, Ningning; Ouyang, Ping; Pu, Jiaqian; Hu, Qian; Wang, Jingyuan; Lu, Weiqiang; Huang, Jin

    2016-01-01

    Artocarpus heterophyllus, a popular tropical fruit commonly known as the jackfruit tree, is normally planted in subtropical or tropical areas. Since a variety of phytochemicals isolated from A. heterophyllus have been found to possess potently anti-inflammatory, antiviral and antimalarial activities, researchers have devoted much interest to its potential pharmaceutical value. However, the exact mechanism underlying its anti-inflammatory activity is not well characterized. In this study, seven natural products isolated from A. heterophyllus, including 25-Hydroxycycloart-23-en-3-one (HY), Artocarpin (AR), Dadahol A (DA), Morachalcone A (MA), Artoheterophyllin B (AB), Cycloheterophyllin (CY) and Moracin C (MC) were collected. Lipopolysaccharide (LPS)-stimulated inflammatory response in RAW264.7 macrophages were used in this study. Among these compounds, MC significantly inhibited LPS-activated reactive oxygen species (ROS) and nitric oxide (NO) release without marked cytotoxicity. Furthermore, MC effectively reduced LPS stimulated up-regulation of mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and serval pro-inflammatory cytokines (interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α)). Mechanistic studies revealed that the anti-inflammatory effect of MC was associated with the activation of the mitogen activated protein kinases (MAPKs) (including p38, ERK and JNK) and nuclear factor-κB (NF-κB) pathways, especially reducing the nuclear translocation of NF-κB p65 subunit as revealed by nuclear separation experiment and confocal microscopy. PMID:27463712

  20. Study of Compounds for Activity against Leishmania

    DTIC Science & Technology

    1994-03-27

    Comparative Antileishmanial Activity of Selected Compounds Against Leishmania Leishmania donovani and Leishmania Viannia braziliensis 7 IV. Zn vitro...Studies of Oligonucleotides Against Leishmania Leishmania donovani ............................................................ 9 Discussion...for several years in studies to identify new compounds for antileishmanial activity against both visceral (Lelshmania Leishmania donovani ) and

  1. [Organisms producing hypolipidemic compounds with antioxidant activity].

    PubMed

    Puzhevskaia, T O; Grammatikova, N E; Bibikova, M V; Katlinskiĭ, A V

    2009-01-01

    Complex compounds produced by fungal cultures of Lecanicilium and Beauveria with both high hypolipidemic and antioxydant activities were screened. Two fractions of the hypolipipidemic compounds with antioxidant activity of 95 and 75% in a dose of 25 mcg/ml were isolated.

  2. Anomalous Stress Response of Ultrahard WBn Compounds

    NASA Astrophysics Data System (ADS)

    Li, Quan; Zhou, Dan; Zheng, Weitao; Ma, Yanming; Chen, Changfeng

    2015-10-01

    Boron-rich tungsten borides are premier prototypes of a new class of ultrahard compounds. Here, we show by first-principles calculations that their stress-strain relations display surprisingly diverse and anomalous behavior under a variety of loading conditions. Most remarkable is the dramatically changing bonding configurations and deformation modes with rising boron concentration in WBn (n =2 , 3, 4), resulting in significantly different stress responses and unexpected indentation strength variations. This novel phenomenon stems from the peculiar structural arrangements in tungsten borides driven by boron's ability to form unusually versatile bonding states. Our results elucidate the intriguing deformation mechanisms that define a distinct type of ultrahard material. These new insights underscore the need to explore unconventional structure-property relations in a broad range of transition-metal light-element compounds.

  3. Anomalous stress response of ultrahard WBn compounds

    DOE PAGES

    Li, Quan; Zhou, Dan; Zheng, Weitao; ...

    2015-10-29

    Boron-rich tungsten borides are premier prototypes of a new class of ultrahard compounds. Here, we show by first-principles calculations that their stress-strain relations display surprisingly diverse and anomalous behavior under a variety of loading conditions. Most remarkable is the dramatically changing bonding configurations and deformation modes with rising boron concentration in WBn (n=2, 3, 4), resulting in significantly different stress responses and unexpected indentation strength variations. This novel phenomenon stems from the peculiar structural arrangements in tungsten borides driven by boron’s ability to form unusually versatile bonding states. Our results elucidate the intriguing deformation mechanisms that define a distinct typemore » of ultrahard material. Here, these new insights underscore the need to explore unconventional structure-property relations in a broad range of transition-metal light-element compounds.« less

  4. Study of Compounds for Activity against Leishmania

    DTIC Science & Technology

    1992-10-27

    Mrs. Barbara Harris, Miss Laura A. Lamb, and Miss Shannon Waits. tORZWORD Opinions, interpretations, conclusions and recommendations are those of the...antileishmanial activity against both visceral (Leishmania donovani) and cutaneous (Lebs-Qnia, braziliensis panamensis) leishmaniasis . Among the most promising...active compounds found against visceral leishmaniasis durinq these studies is the 8-aminoquinoline, WR06026. This compound is now undergoing clinical

  5. Response of Bioluminescent Bacteria to Alkyltin Compounds.

    DTIC Science & Technology

    1987-12-01

    found in the butyltiri series of compounds; tributyltin was (’Stimes more toxic than dibutyltin and (- 50 times more toxic than (mono)butyltin. When...correlations between compounds, tributyltin was -35 tine more Kicrotxit and fish bLoessays for pure toxic than dibutyltin end -750 times More compounds and...alkyltin " trihalides. Figure 4. Mo values for butyltin tri- D~kyflS chloride, dibutyltin dichloride tributyl- tin chloride and tatrabutyltin. Figures 5, 6

  6. Leptin Suppresses Mouse Taste Cell Responses to Sweet Compounds.

    PubMed

    Yoshida, Ryusuke; Noguchi, Kenshi; Shigemura, Noriatsu; Jyotaki, Masafumi; Takahashi, Ichiro; Margolskee, Robert F; Ninomiya, Yuzo

    2015-11-01

    Leptin is known to selectively suppress neural and behavioral responses to sweet-tasting compounds. However, the molecular basis for the effect of leptin on sweet taste is not known. Here, we report that leptin suppresses sweet taste via leptin receptors (Ob-Rb) and KATP channels expressed selectively in sweet-sensitive taste cells. Ob-Rb was more often expressed in taste cells that expressed T1R3 (a sweet receptor component) than in those that expressed glutamate-aspartate transporter (a marker for Type I taste cells) or GAD67 (a marker for Type III taste cells). Systemically administered leptin suppressed taste cell responses to sweet but not to bitter or sour compounds. This effect was blocked by a leptin antagonist and was absent in leptin receptor-deficient db/db mice and mice with diet-induced obesity. Blocking the KATP channel subunit sulfonylurea receptor 1, which was frequently coexpressed with Ob-Rb in T1R3-expressing taste cells, eliminated the effect of leptin on sweet taste. In contrast, activating the KATP channel with diazoxide mimicked the sweet-suppressing effect of leptin. These results indicate that leptin acts via Ob-Rb and KATP channels that are present in T1R3-expressing taste cells to selectively suppress their responses to sweet compounds.

  7. Leptin Suppresses Mouse Taste Cell Responses to Sweet Compounds

    PubMed Central

    Noguchi, Kenshi; Shigemura, Noriatsu; Jyotaki, Masafumi; Takahashi, Ichiro; Margolskee, Robert F.

    2015-01-01

    Leptin is known to selectively suppress neural and behavioral responses to sweet-tasting compounds. However, the molecular basis for the effect of leptin on sweet taste is not known. Here, we report that leptin suppresses sweet taste via leptin receptors (Ob-Rb) and KATP channels expressed selectively in sweet-sensitive taste cells. Ob-Rb was more often expressed in taste cells that expressed T1R3 (a sweet receptor component) than in those that expressed glutamate-aspartate transporter (a marker for Type I taste cells) or GAD67 (a marker for Type III taste cells). Systemically administered leptin suppressed taste cell responses to sweet but not to bitter or sour compounds. This effect was blocked by a leptin antagonist and was absent in leptin receptor–deficient db/db mice and mice with diet-induced obesity. Blocking the KATP channel subunit sulfonylurea receptor 1, which was frequently coexpressed with Ob-Rb in T1R3-expressing taste cells, eliminated the effect of leptin on sweet taste. In contrast, activating the KATP channel with diazoxide mimicked the sweet-suppressing effect of leptin. These results indicate that leptin acts via Ob-Rb and KATP channels that are present in T1R3-expressing taste cells to selectively suppress their responses to sweet compounds. PMID:26116698

  8. 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

  9. 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.

  10. Natural compounds with anti-ageing activity.

    PubMed

    Argyropoulou, Aikaterini; Aligiannis, Nektarios; Trougakos, Ioannis P; Skaltsounis, Alexios-Leandros

    2013-10-11

    Ageing is a complex molecular process driven by diverse molecular pathways and biochemical events that are promoted by both environmental and genetic factors. Specifically, ageing is defined as a time-dependent decline of functional capacity and stress resistance, associated with increased chance of morbidity and mortality. These effects relate to age-related gradual accumulation of stressors that result in increasingly damaged biomolecules which eventually compromise cellular homeostasis. Nevertheless, the findings that genetic or diet interventions can increase lifespan in evolutionarily diverse organisms indicate that mortality can be postponed. Natural compounds represent an extraordinary inventory of high diversity structural scaffolds that can offer promising candidate chemical entities in the major healthcare challenge of increasing health span and/or delaying ageing. Herein, those natural compounds (either pure forms or extracts) that have been found to delay cellular senescence or in vivo ageing will be critically reviewed and summarized according to affected cellular signalling pathways. Moreover, the chemical structures of the identified natural compounds along with the profile of extracts related to their bioactive components will be presented and discussed. Finally, novel potential molecular targets for screening natural compounds for anti-ageing activity, as well as the idea that anti-ageing interventions represent a systemic approach that is also effective against age-related diseases will be discussed.

  11. Beaver (Castor canadensis) responses to major phenolic and neutral compounds in castoreum.

    PubMed

    Schulte, B A; Müller-Schwarze, D; Tang, R; Webster, F X

    1994-12-01

    North American beaver (Castor canadensis) mark their territories with castoreum, a chemically complex secretion from their castor sacs. The phenolic and neutral fractions of castoreum have been shown to elicit specific behavioral responses from beavers in a field setting. Our objective was to identify compounds/mixtures that evoked responses similar to those stimulated by castoreum. We assayed recently identified phenolic compounds, some phenolics that had been determined to be biologically active in previous studies, the neutral compound borneol, and combinations of phenolic compounds, neutral compounds, and the two combined. Biological activity was measured by the elicitation and extent of specific responses and their strength (duration, frequency, and proportion of beavers responding). Generally, single compounds stimulated fewer responses than mixtures. A 26-compound mixture of phenolic and neutral compounds elicited responses in a similar proportion of trials as castoreum. However, responses to castoreum were stronger than to any synthetic sample. Further investigation of different measures of response, namely, elicitation, completeness, and strength, are deemed necessary to fully decipher the design of social odors.

  12. Biological activity of acetylated phenolic compounds.

    PubMed

    Fragopoulou, Elizabeth; Nomikos, Tzortzis; Karantonis, Haralabos C; Apostolakis, Constantinos; Pliakis, Emmanuel; Samiotaki, Martina; Panayotou, George; Antonopoulou, Smaragdi

    2007-01-10

    In recent years an effort has been made to isolate and identify biologically active compounds that are included in the Mediterranean diet. The existence of naturally occurring acetylated phenolics, as well as studies with synthetic ones, provide evidence that acetyl groups could be correlated with their biological activity. Platelet activating factor (PAF) is implicated in atherosclerosis, whereas its inhibitors seem to play a protective role against cardiovascular disease. The aim of this study was to examine the biological activity of resveratrol and tyrosol and their acetylated derivatives as inhibitors of PAF-induced washed rabbit platelet aggregation. Acetylation of resveratrol and tyrosol was performed, and separation was achieved by HPLC. Acetylated derivatives were identified by negative mass spectrometry. The data showed that tyrosol and its monoacetylated derivatives act as PAF inhibitors, whereas diacetylated derivatives induce platelet aggregation. Resveratrol and its mono- and triacetylated derivatives exert similar inhibitory activity, whereas the diacetylated ones are more potent inhibitors. In conclusion, acetylated phenolics exert the same or even higher antithrombotic activity compared to the biological activity of the initial one.

  13. Antibacterial activity of phenolic compounds against the phytopathogen Xylella fastidiosa.

    PubMed

    Maddox, Christina E; Laur, Lisa M; Tian, Li

    2010-01-01

    Xylella fastidiosa is a pathogenic bacterium that causes diseases in many crop species, which leads to considerable economic loss. Phenolic compounds (a group of secondary metabolites) are widely distributed in plants and have shown to possess antimicrobial properties. The anti-Xylella activity of 12 phenolic compounds, representing phenolic acid, coumarin, stilbene and flavonoid, was evaluated using an in vitro agar dilution assay. Overall, these phenolic compounds were effective in inhibiting X. fastidiosa growth, as indicated by low minimum inhibitory concentrations (MICs). In addition, phenolic compounds with different structural features exhibited different anti-Xylella capacities. Particularly, catechol, caffeic acid and resveratrol showed strong anti-Xylella activities. Differential response to phenolic compounds was observed among X. fastidiosa strains isolated from grape and almond. Elucidation of secondary metabolite-based host resistance to X. fastidiosa will have broad implication in combating X. fastidiosa-caused plant diseases. It will facilitate future production of plants with improved disease resistance properties through genetic engineering or traditional breeding approaches and will significantly improve crop yield.

  14. Factors affecting antibacterial activity of hop compounds and their derivatives.

    PubMed

    Simpson, W J; Smith, A R

    1992-04-01

    The antibacterial effect of weak acids derived from the hop plant (Humulus lupulus L.) increased with decreasing pH. Analysis of the minimum inhibitory concentration of such compounds against Lactobacillus brevis IFO 3960 over pH 4-7 suggests that undissociated molecules were mainly responsible for inhibition of bacterial growth. The antibacterial activity of trans-isohumulone was ca 20 times greater than that of humulone, 11 times greater than that of colupulone and nine times greater than that of trans-humulinic acid when the degree of ionization was taken into account. Monovalent cations (K+, Na+, NH4+, Rb+, Li+) stimulated antibacterial activity of trans-isohumulone but the effect was smaller than that observed with H+. The response to divalent cations varied: Ca2+ had little effect on antibacterial activity, whereas Mg2+ reduced activity. Lipid materials and beta-cyclodextrin also antagonized the antibacterial action of trans-isohumulone.

  15. Engineers and Active Responsibility.

    PubMed

    Pesch, Udo

    2015-08-01

    Knowing that technologies are inherently value-laden and systemically interwoven with society, the question is how individual engineers can take up the challenge of accepting the responsibility for their work? This paper will argue that engineers have no institutional structure at the level of society that allows them to recognize, reflect upon, and actively integrate the value-laden character of their designs. Instead, engineers have to tap on the different institutional realms of market, science, and state, making their work a 'hybrid' activity combining elements from the different institutional realms. To deal with this institutional hybridity, engineers develop routines and heuristics in their professional network, which do not allow societal values to be expressed in a satisfactory manner. To allow forms of 'active' responsibility, there have to be so-called 'accountability forums' that guide moral reflections of individual actors. The paper will subsequently look at the methodologies of value-sensitive design (VSD) and constructive technology assessment (CTA) and explore whether and how these methodologies allow engineers to integrate societal values into the design technological artifacts and systems. As VSD and CTA are methodologies that look at the process of technological design, whereas the focus of this paper is on the designer, they can only be used indirectly, namely as frameworks which help to identify the contours of a framework for active responsibility of engineers.

  16. An indoxyl compound 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, suppresses activation of Fyn kinase in mast cells and IgE-mediated allergic responses in mice.

    PubMed

    Lee, Jun Ho; Kim, Tae Hyung; Kim, Hyuk Soon; Kim, A-Ram; Kim, Do-Kyun; Nam, Seung Taek; Kim, Hyun Woo; Park, Young Hwan; Her, Erk; Park, Yeong Min; Kim, Hyung Sik; Kim, Young Mi; Choi, Wahn Soo

    2015-06-15

    Mast cells, constituents of virtually all organs and tissues, are critical cells in IgE-mediated allergic responses. The aim of this study was to investigate the effect and mechanism of an indoxyl chromogenic compound, 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, on IgE-mediated mast cell activation and allergic responses in mice. CAC-0982 reversibly suppressed antigen-stimulated degranulation in murine mast cells (IC50, ~3.8μM) and human mast cells (IC50, ~3.0μM). CAC-0982 also inhibited the expression and secretion of IL-4 and TNF-α in mast cells. Furthermore, CAC-0982 suppressed the mast cell-mediated allergic responses in mice in a dose-dependent manner (ED50 27.9mg/kg). As for the mechanism, CAC-0982 largely suppressed the phosphorylation of Syk and its downstream signaling molecules, including LAT, Akt, Erk1/2, p38, and JNK. Notably, the tyrosine kinase assay of antigen-stimulated mast cells showed that CAC-0982 inhibited Fyn kinase, one of the upstream tyrosine kinases for Syk activation in mast cells. Taken together, these results suggest that CAC-0982 may be used as a new treatment for regulating IgE-mediated allergic diseases through the inhibition of the Fyn/Syk pathway in mast cells.

  17. An indoxyl compound 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, suppresses activation of Fyn kinase in mast cells and IgE-mediated allergic responses in mice

    SciTech Connect

    Lee, Jun Ho; Kim, Tae Hyung; Kim, Hyuk Soon; Kim, A-Ram; Kim, Do-Kyun; Nam, Seung Taek; Kim, Hyun Woo; Park, Young Hwan; Her, Erk; Park, Yeong Min; Kim, Hyung Sik; Kim, Young Mi; Choi, Wahn Soo

    2015-06-15

    Mast cells, constituents of virtually all organs and tissues, are critical cells in IgE-mediated allergic responses. The aim of this study was to investigate the effect and mechanism of an indoxyl chromogenic compound, 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, on IgE-mediated mast cell activation and allergic responses in mice. CAC-0982 reversibly suppressed antigen-stimulated degranulation in murine mast cells (IC{sub 50}, ~ 3.8 μM) and human mast cells (IC{sub 50}, ~ 3.0 μM). CAC-0982 also inhibited the expression and secretion of IL-4 and TNF-α in mast cells. Furthermore, CAC-0982 suppressed the mast cell-mediated allergic responses in mice in a dose-dependent manner (ED{sub 50} 27.9 mg/kg). As for the mechanism, CAC-0982 largely suppressed the phosphorylation of Syk and its downstream signaling molecules, including LAT, Akt, Erk1/2, p38, and JNK. Notably, the tyrosine kinase assay of antigen-stimulated mast cells showed that CAC-0982 inhibited Fyn kinase, one of the upstream tyrosine kinases for Syk activation in mast cells. Taken together, these results suggest that CAC-0982 may be used as a new treatment for regulating IgE-mediated allergic diseases through the inhibition of the Fyn/Syk pathway in mast cells. - Highlights: • The anti-allergic effect of 5-bromo-4-chloro-3-indolyl 1,3-diacetate, CAC-0982, was measured. • CAC-0982 reversibly suppressed the activation of mast cells by IgE and antigen. • CAC-0982 inhibited passive cutaneous anaphylaxis in mice. • CAC-0982 suppresses mast cells through inhibition of Fyn activation in mast cells.

  18. Vascular responses to compound 48/80 in rat mesenteric vascular beds.

    PubMed

    Jin, Honghua; Li, Zhen; Takatori, Shingo; Koyama, Toshihiro; Jin, Xin; Zamami, Yoshito; Kawasaki, Hiromu; Sun, Pengyuan

    2016-06-01

    A further investigation was performed on the vascular effect of endogenous histamine using the histamine releaser, compound 48/80, in rat mesenteric vascular beds with active tone. In preparations with intact endothelium, low concentrations of compound 48/80 (1.53 × 10(-5) - 3 × 1.53 × 10(-5) mg/mL) perfusion for 1 min only induced a small vasodilation. High concentrations of compound 48/80 (1.53 × 10(-4) - 3 × 1.53 × 10(-2) mg/mL) induced a biphasic vascular responses, an initial vasoconstriction followed a subsequent long-lasting vasodilation. The vasodilation induced by low concentrations of compound 48/80 and the vasoconstriction induced by high concentration of compound 48/80 was inhibited by olopatadine. However, cimetidine did not affect the responses induced by compound 48/80. Endothelium removal enlarged the compound 48/80-induced phase-2 vasoconstriction, while it attenuated the phase-3 vasodilation. Additionally, indomethacin and seratrodast significantly inhibited vasoconstriction but it did not affect the long-lasting vasodilation induced by high concentrations of compound 48/80. Ruthenium red inhibited the vasodilation induced by low concentrations and high concentrations of compound 48/80. These results suggest that the vasoconstriction induce by high concentrations of compound 48/80 is mediated by endogenous histamine released from mast cells. It is also suggested that thromboxane A2 released from mast cells is related to the vasoconstriction.

  19. Ionic surface active compounds in atmospheric aerosols.

    PubMed

    Sukhapan, Jariya; Brimblecombe, Peter

    2002-04-27

    Surfactants in the atmosphere have several potential roles in atmospheric chemistry. They can form films on aqueous surfaces, which lowers the surface tension and possibly delays water evaporation and gaseous transportation across the aqueous interface. They can also increase the solubility of organic compounds in the aqueous phase. Recently, the decrease of surface tension in cloud growing droplets has been suggested as relevant to increases in the number of droplets of smaller size, potentially enhancing cloud albedo. Natural surfactants in the lung aid gas transfer and influence the dissolution rate of aerosol particles, so surfactants in atmospheric aerosols, once inhaled, may interact with pulmonary surfactants. Ambient aerosols were collected from the edge of Norwich, a small city in a largely agricultural region of England, and analysed for surfactants. Methylene blue, a conventional dye for detecting anionic surfactants, has been used as a colorimetric agent. The concentration of surfactants expressed as methylene blue active substances (MBAS) is in the range of 6-170 pmol m(-3)(air). A negative correlation with chloride aerosol indicates that these surfactants are probably not the well-known surfactants derived from marine spray. A more positive correlation with aerosol nitrate and gaseous NOx supports an association with more polluted inland air masses. The surfactants found in aerosols seem to be relatively strong acids, compared with weaker acids such as the long-chain carboxylic acids previously proposed as atmospheric surfactants. Surfactants from the oxidation of organic materials (perhaps vegetation- or soil-derived) seem a likely source of these substances in the atmosphere.

  20. Response of Bacillus Spores to Combinations of Germinative Compounds

    PubMed Central

    Foerster, Harold F.; Foster, J. W.

    1966-01-01

    Foerster, Harold F. (University of Texas, Austin), and J. W. Foster. Response of Bacillus spores to combinations of germinative compounds. J. Bacteriol. 91:1168–1177. 1966.—Spores of 21 strains of Bacillus megaterium and 25 other strains representing 13 species of Bacillus were produced under standardized conditions. The germination of a washed spore suspension of each strain was measured as a response to various combinations of 30 different germinative compounds. The strains were first typed with respect to their response to “primary” germination compounds, i.e., glucose, l-alanine, inosine, and l-alanine-inosine mixture, and also Na+ and K+. The second stage was the determination of the response to various organic and inorganic anions and cations, each strain being supplied with the “primary” compounds best for it. Marked differences in germination patterns were observed among species and strains of the same species. No relation to established taxonomic lines was evident. A nonspecific requirement for ions was found for all strains, but not all ions were effective. A striking degree of interchangeability of germinative chemicals was found. “Fractional germination” was very common. A mixture of l-alanine and inosine and various ions was the best germinative solution for most strains. Some anomalous germination patterns were encountered. Those studied included a strain whose cells lysed spontaneously upon germination and other strains for which l-leucine had striking germinative powers. PMID:4956331

  1. Identification of Important Compounds Isolated from Natural Sources that Have Activity Against Multidrug-resistant Cancer Cell Lines: Effects on Proliferation, Apoptotic Mechanism and the Efflux Pump Responsible for Multi-resistance Phenotype.

    PubMed

    Amaral, Leonard; Spengler, Gabriella; Molnar, Joseph

    2016-11-01

    The focus of this mini-review is to identify non-toxic compounds isolated from natural sources (plants) that exhibit specific activity against efflux pumps of specific multidrug-resistant (MDR) cancer cell lines, inhibit proliferation of the MDR cancer cell lines and inhibit the activity of overexpressed efflux pumps of the MDR cancer cell line.

  2. AMPK-dependent and independent effects of AICAR and compound C on T-cell responses.

    PubMed

    Rao, Enyu; Zhang, Yuwen; Li, Qiang; Hao, Jiaqing; Egilmez, Nejat K; Suttles, Jill; Li, Bing

    2016-06-07

    As a master metabolic sensor, AMP-activated protein kinase (AMPK) is involved in different fundamental cellular processes. Regulation of AMPK activity either by agonists (e.g., AICAR) or by antagonists (e.g., Compound C) has been widely employed to study the physiological functions of AMPK. However, mounting evidence indicates AMPK-independent effects for these chemicals and how they regulate immune cell functions remains largely unknown. Herein, using T cells from AMPK conditional knockout mice and their wild type littermates, we demonstrate that AICAR and Compound C can, indeed, activate or inhibit AMPK activity in T cells, respectively. Specifically, AICAR inhibits, but Compound C promotes, Ca2+-induced T cell death in an AMPK-dependent manner. In contrast, our data also demonstrate that AICAR and Compound C inhibit T cell activation and cytokine production in an AMPK-independent manner. Moreover, we find that the AMPK-independent activity of AICAR and Compound Cis mediated via the mTOR signaling pathway in activated T cells. Our results not only reveal the critical role of AMPK in regulating T cell survival and function, but also demonstrate AMPK-dependent and independent rolesof AICAR/Compound C in regulating T cell responses, thus suggesting a context-dependent effect of these "AMPK regulators".

  3. [Coordination compounds of Pd(II) with potential antitumor activity].

    PubMed

    González Vílchez, F; García Basallote, M; Benítez Ordóñez, J; Vilaplana Serrano, R

    1982-01-01

    The first results about the anti-neoplastic activity of Pd(II) ion coordinative compounds with complexones of the ethylenediamine-tetraacetic acid type are described. The assays employing Ehrlich ascites cancer of the mouse show that the presence of substitutes in the ethylenediamine skeleton originates important changes of the activity of such compounds.

  4. 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

  5. Chemical transformations that yield compounds with distinct activity profiles.

    PubMed

    Hu, Ye; Bajorath, Jürgen

    2011-07-14

    We have systematically searched for chemical changes that generate compounds with distinct biological activity profiles. For this purpose, activity profiles were generated for ∼42000 compounds active against human targets. Unique activity profiles involving multiple target proteins were determined, and all possible matched molecular pairs (MMPs) were identified for compounds representing these profiles. An MMP is defined as a pair of compounds that are distinguished from each other only at a single site such as an R group or ring system. For example, in an MMP, a hydroxyl group might be replaced by a halogen atom or a benzene ring by an amide group. From ∼37500 MMPs, more than 300 nonredundant chemical transformations were isolated that yielded compounds with distinct activity profiles. None of these transformations was found in pairs of compounds with overlapping activity profiles. These transformations were ranked according to the number of MMPs, the number of activity profiles, and the total number of targets that they covered. In many instances, prioritized transformations involved ring systems of varying complexity. All transformations that were found to switch activity profiles are provided to enable further analysis and aid in compound design efforts.

  6. Phenolic compounds with IL-6 inhibitory activity from Aster yomena.

    PubMed

    Kim, A Ryun; Jin, Qinglong; Jin, Hong-Guang; Ko, Hae Ju; Woo, Eun-Rhan

    2014-07-01

    A new biflavonoid, named asteryomenin (1), as well as six known phenolic compounds, esculetin (2), 4-O-β-D-glucopyranoside-3-hydroxy methyl benzoate (3), caffeic acid (4), isoquercitrin (5), isorhamnetin-3-O-glucoside (6), and apigenin (7) were isolated from the aerial parts of Aster yomena. The structures of compounds (1-7) were identified based on 1D and 2D NMR, including (1)H-(1)H COSY, HSQC, HMBC and NOESY spectroscopic analyses. Compounds 2-7 were isolated from this plant for the first time. For these isolates, the inhibitory activity of IL-6 production in the TNF-α stimulated MG-63 cell was examined. Among these isolates, compounds 4 and 7 appeared to have potent inhibitory activity of IL-6 production in the TNF-α stimulated MG-63 cell, while compounds 1-3 and 5-6 showed moderate activity.

  7. Anti-tumoral activity of native compound morelloflavone in glioma

    PubMed Central

    Li, Xianfeng; Ai, Hongyan; Sun, Deke; Wu, Tao; He, Jian; Xu, Zhai; Ding, Li; Wang, Ling

    2016-01-01

    The aim of the study was to investigate the anti-tumoral activity of morelloflavone substances with different structures. We also studied the possible link between morelloflavone structure and its function. Various types of chromatographic techniques were used to isolate and screen morelloflavone substances from the extracts of gambogic tree trunk and the morelloflavone structures were identified by analytical techniques such as high resolution mass spectrometry and nuclear magnetism. Anti-tumoral activities of different compounds were investigated and the link between the antitumor activity and the structure of compound was exaimed. Our results showed that the isolated morelloflavone substances demonstrated a certain level of antitumor activity. The compound no. 1 had the strongest effect to inhibit glioma U87 and C6 cells followed by compound no. 2 while compound no. 5 was the weakest among them. We conducted a preliminary analysis on the structure-function relationship through the structure comparison and we concluded that the antitumor effects of morelloflavone substances with different structures were significantly different from each other. Thus, the glucose chain in C4 position of biflavone structure can enhance the antitumor activity of the compound in glioma cells. Additionally, the formation of intramolecular hydrogen bonds in biflavone compounds may also play a role in enhancing the antitumor activity and inhibition rate. PMID:27900007

  8. 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.

  9. Reconfigurable and responsive droplet-based compound micro-lenses

    NASA Astrophysics Data System (ADS)

    Nagelberg, Sara; Zarzar, Lauren D.; Nicolas, Natalie; Subramanian, Kaushikaram; Kalow, Julia A.; Sresht, Vishnu; Blankschtein, Daniel; Barbastathis, George; Kreysing, Moritz; Swager, Timothy M.; Kolle, Mathias

    2017-03-01

    Micro-scale optical components play a crucial role in imaging and display technology, biosensing, beam shaping, optical switching, wavefront-analysis, and device miniaturization. Herein, we demonstrate liquid compound micro-lenses with dynamically tunable focal lengths. We employ bi-phase emulsion droplets fabricated from immiscible hydrocarbon and fluorocarbon liquids to form responsive micro-lenses that can be reconfigured to focus or scatter light, form real or virtual images, and display variable focal lengths. Experimental demonstrations of dynamic refractive control are complemented by theoretical analysis and wave-optical modelling. Additionally, we provide evidence of the micro-lenses' functionality for two potential applications--integral micro-scale imaging devices and light field display technology--thereby demonstrating both the fundamental characteristics and the promising opportunities for fluid-based dynamic refractive micro-scale compound lenses.

  10. Reconfigurable and responsive droplet-based compound micro-lenses

    PubMed Central

    Nagelberg, Sara; Zarzar, Lauren D.; Nicolas, Natalie; Subramanian, Kaushikaram; Kalow, Julia A.; Sresht, Vishnu; Blankschtein, Daniel; Barbastathis, George; Kreysing, Moritz; Swager, Timothy M.; Kolle, Mathias

    2017-01-01

    Micro-scale optical components play a crucial role in imaging and display technology, biosensing, beam shaping, optical switching, wavefront-analysis, and device miniaturization. Herein, we demonstrate liquid compound micro-lenses with dynamically tunable focal lengths. We employ bi-phase emulsion droplets fabricated from immiscible hydrocarbon and fluorocarbon liquids to form responsive micro-lenses that can be reconfigured to focus or scatter light, form real or virtual images, and display variable focal lengths. Experimental demonstrations of dynamic refractive control are complemented by theoretical analysis and wave-optical modelling. Additionally, we provide evidence of the micro-lenses' functionality for two potential applications—integral micro-scale imaging devices and light field display technology—thereby demonstrating both the fundamental characteristics and the promising opportunities for fluid-based dynamic refractive micro-scale compound lenses. PMID:28266505

  11. Biological activities of lignin hydrolysate-related compounds.

    PubMed

    Lee, Siseon; Monnappa, Ajay Kalanjana; Mitchell, Robert J

    2012-05-01

    Lignin hydrolysates contain many different chemical species, including ferulic acid, coumaric acid, vanillic acid, vanillin, syringaldehyde and furfural. From the perspective of biofuels, these compounds are problematic and can cause downstream loss of product if not removed prior to beginning the fermentative process. In contrast, a search for these compounds within the literature turns up many papers where the same compounds have beneficial properties pertaining to human health, including as antioxidants and in cancer prevention, or are involved in bacterial cell-to-cell signaling. Consequently, this article reviews the dual nature of these and other compounds found in lignin hydrolysates, highlighting both their detrimental and beneficial activities.

  12. [Antibacterial activity of natural compounds - essential oils].

    PubMed

    Hassan, Sherif T S; Majerová, Michaela; Šudomová, Miroslava; Berchová, Kateřina

    2015-12-01

    Since the problem of bacterial resistance has become a serious problem worldwide, it was necessary to search for new active substances that can overcome the problem and enhance the treatment efficacy of bacterial infections. Numerous plant-derived essential oils exhibited significant antibacterial activities. This review aimed to summarize the most promising essential oils that exhibited remarkable antibacterial activities against various bacterial infections, including staphylococcal infections, Helicobacter pylori infections, skin infections, tuberculosis infection and dental bacterial infection. The synergy effect of essential oils in combination with antibiotics, as well as their role in the treatment of bacterial infections have been discussed. Essential oils can be used as models for further studies in vivo and clinical trials.

  13. Bioactive Compounds and Antioxidant Activity in Different Types of Berries

    PubMed Central

    Skrovankova, Sona; Sumczynski, Daniela; Mlcek, Jiri; Jurikova, Tunde; Sochor, Jiri

    2015-01-01

    Berries, especially members of several families, such as Rosaceae (strawberry, raspberry, blackberry), and Ericaceae (blueberry, cranberry), belong to the best dietary sources of bioactive compounds (BAC). They have delicious taste and flavor, have economic importance, and because of the antioxidant properties of BAC, they are of great interest also for nutritionists and food technologists due to the opportunity to use BAC as functional foods ingredients. The bioactive compounds in berries contain mainly phenolic compounds (phenolic acids, flavonoids, such as anthocyanins and flavonols, and tannins) and ascorbic acid. These compounds, either individually or combined, are responsible for various health benefits of berries, such as prevention of inflammation disorders, cardiovascular diseases, or protective effects to lower the risk of various cancers. In this review bioactive compounds of commonly consumed berries are described, as well as the factors influencing their antioxidant capacity and their health benefits. PMID:26501271

  14. Bioactive Compounds and Antioxidant Activity in Different Types of Berries.

    PubMed

    Skrovankova, Sona; Sumczynski, Daniela; Mlcek, Jiri; Jurikova, Tunde; Sochor, Jiri

    2015-10-16

    Berries, especially members of several families, such as Rosaceae (strawberry, raspberry, blackberry), and Ericaceae (blueberry, cranberry), belong to the best dietary sources of bioactive compounds (BAC). They have delicious taste and flavor, have economic importance, and because of the antioxidant properties of BAC, they are of great interest also for nutritionists and food technologists due to the opportunity to use BAC as functional foods ingredients. The bioactive compounds in berries contain mainly phenolic compounds (phenolic acids, flavonoids, such as anthocyanins and flavonols, and tannins) and ascorbic acid. These compounds, either individually or combined, are responsible for various health benefits of berries, such as prevention of inflammation disorders, cardiovascular diseases, or protective effects to lower the risk of various cancers. In this review bioactive compounds of commonly consumed berries are described, as well as the factors influencing their antioxidant capacity and their health benefits.

  15. Hemagglutinating activity in phytopathogenic bacteria surface compounds.

    PubMed

    Serra, M T; Castresana, M C; Tejerina, G

    1987-01-01

    Extracellular components of plant pathogenic bacteria were obtained from their culture medium as well as from the whole cells by using NaCl 1 M, pH 6.0; 20% sucrose dissolved in 0.03 M Tris buffer, pH 8.0; or 0.05 M Na2EDTA. All the extracts from Erwinia carotovora subsp. carotovora, Xanthomonas campestris pv. campestris, Pseudomonas syringae pv. phaseolicola, Xanthomonas campestris pv. phaseoli, Pseudomonas solanacearum, and Erwinia carotovora subsp. atroseptica, were assayed for hemagglutinating activity on sheep, rabbit and chicken red blood cells (RBCs). The only active extracts were those obtained by NaCl treatment. They agglutinated sheep and rabbit erythrocytes. Extracts from E. carotovora subsp. atroseptica gave rise to the high agglutination titer on rabbit RBCs. These extracts had the lowest polysaccharide/protein ratio. E. carotovora subsp. carotovora extracts showed only a low titer (18.5 units). The agglutinating activity present in NaCl extracts of the bacteria tested was inhibited by different carbohydrates to various extent. Extracts from E. carotovora subsp. atroseptica appeared to be the most sensitive ones while those of E. carotovora subsp. carotovora least sensitive to the presence of sugar. It is suggested that hemagglutinins observed in plant pathogenic bacteria and those in plant host are similar and that both may, in some way, be involved in the plant-parasite relationship.

  16. Biomonitoring of estrogenic exposure and identification of responsible compounds in bream from Dutch surface waters.

    PubMed

    Houtman, Corine J; Booij, Petra; van der Valk, Karin M; van Bodegom, Peter M; van den Ende, Frank; Gerritsen, Anton A M; Lamoree, Marja H; Legler, Juliette; Brouwer, Abraham

    2007-05-01

    The exposure to and effects of estrogenic compounds in male breams from Dutch freshwater locations were investigated. Ovotestis was observed infrequently (maximum frequency 16%). However, plasma vitellogenin (VTG) concentration was elevated highly at some locations. Estrogenic activities in male bream plasma, liver, and in gastrointestinal content were measured in the estrogen-responsive chemical-activated luciferase gene expression (ER-CALUX) assay. Plasma concentrations of vitellogenin correlated very well with the estrogenic activities in gastrointestinal content. The ER-CALUX activity in gastrointestinal content thus could provide a biomarker for recent exposure to estrogenic compounds, and the gastrointestinal content was chosen as investigative matrix for the toxicity identification and evaluation ([TIE]; bioassay-directed fractionation) of estrogenic compounds in bream. The approach consisted of a reversed-phase high-performance liquid chromatography fractionation of gastrointestinal content extract, directed by ER-CALUX and followed by gas chromatography analysis. The estrogenic hormones 17beta-estradiol and its metabolite estrone were identified as major contributors to the activity at all locations (except the reference location), independent of the presence or absence of a known source of estrogenic activity, such as a sewage treatment plant. Chemical screening showed the presence of other pollutants, such as a lower chlorinated dioxin and the disinfectants clorophene and triclosan. However, these compounds did not have high estrogenic potencies and their concentrations were not high enough to contribute significantly to the observed estrogenic activity.

  17. Antioxidant Activity of Marine Algal Polyphenolic Compounds: A Mechanistic Approach.

    PubMed

    Fernando, I P Shanura; Kim, Misook; Son, Kwang-Tae; Jeong, Yoonhwa; Jeon, You-Jin

    2016-07-01

    Polyphenolic compounds isolated from marine algae exhibit a broad spectrum of beneficial biological properties, including antioxidant, anticancer, antimicrobial, anti-inflammatory, and antidiabetic activities, along with several other bioactivities centered on their antioxidant properties. Consequently, polyphenolic compounds are increasingly being investigated for their potential use in food, cosmetic, and pharmaceutical applications. The antioxidant activities of these compounds have been explored widely through experimental studies. Nonetheless, a theoretical understanding of the structural and electronic properties could broaden research perspectives, leading to the identification and synthesis of efficient structural analogs with prophylactic uses. This review briefly summarizes the current state of knowledge regarding antioxidant polyphenolic compounds in marine algae with an attempt to describe the structure-activity relationship.

  18. [Antioxidant and antibacterial activities of dimeric phenol compounds].

    PubMed

    Ogata, Masahiro

    2008-08-01

    We studied the antioxidant and antibacterial activities of monomeric and dimeric phenol compounds. Dimeric compounds had higher antioxidant activities than monomeric compounds. Electron spin resonance spin-trapping experiments showed that phenol compounds with an allyl substituent on their aromatic rings directly scavenged superoxide, and that only eugenol trapped hydroxyl radicals. We developed a generation system of the hydroxyl radical without using any metals by adding L-DOPA and DMPO to PBS or MiliQ water in vitro. We found that eugenol trapped hydroxyl radicals directly and is metabolized to a dimer. On the other hand, dipropofol, a dimer of propofol, has strong antibacterial activity against Gram-positive bacteria. However, it lacks solubility in water and this property is assumed to limit its efficacy. We tried to improve the solubility and found a new solubilization method of dipropofol in water with the addition of a monosaccharide or ascorbic acid.

  19. Biologic activities of molecular chaperones and pharmacologic chaperone imidazole-containing dipeptide-based compounds: natural skin care help and the ultimate challenge: implication for adaptive responses in the skin.

    PubMed

    Babizhayev, Mark A; Nikolayev, Gennady M; Nikolayeva, Juliana G; Yegorov, Yegor E

    2012-03-01

    Accumulation of molecular damage and increased molecular heterogeneity are hallmarks of photoaged skin and pathogenesis of human cutaneous disease. Growing evidence demonstrates the ability of molecular chaperone proteins and of pharmacologic chaperones to decrease the environmental stress and ameliorate the oxidation stress-related and glycation disease phenotypes, suggesting that the field of chaperone therapy might hold novel treatments for skin diseases and aging. In this review, we examine the evidence suggesting a role for molecular chaperone proteins in the skin and their inducer and protecting agents: pharmacologic chaperone imidazole dipeptide-based agents (carcinine and related compounds) in cosmetics and dermatology. Furthermore, we discuss the use of chaperone therapy for the treatment of skin photoaging diseases and other skin pathologies that have a component of increased glycation and/or free radical-induced oxidation in their genesis. We examine biologic activities of molecular and pharmacologic chaperones, including strategies for identifying potential chaperone compounds and for experimentally demonstrating chaperone activity in in vitro and in vivo models of human skin disease. This allows the protein to function and traffic to the appropriate location in the skin, thereby increasing protein activity and cellular function and reducing stress on skin cells. The benefits of imidazole dipeptide antioxidants with transglycating activity (such as carcinine) in skin care are that they help protect and repair cell membrane damage and help retain youthful, younger-looking skin. All skin types will benefit from daily, topical application of pharmacologic chaperone antioxidants, anti-irritants, in combination with water-binding protein agents that work to mimic the structure and function of healthy skin. General strategies are presented addressing ground techniques to improve absorption of usually active chaperone proteins and dipeptide compounds, include

  20. Synthesis and Assay of SIRT1-Activating Compounds.

    PubMed

    Dai, H; Ellis, J L; Sinclair, D A; Hubbard, B P

    2016-01-01

    The NAD(+)-dependent deacetylase SIRT1 plays key roles in numerous cellular processes including DNA repair, gene transcription, cell differentiation, and metabolism. Overexpression of SIRT1 protects against a number of age-related diseases including diabetes, cancer, and Alzheimer's disease. Moreover, overexpression of SIRT1 in the murine brain extends lifespan. A number of small-molecule sirtuin-activating compounds (STACs) that increase SIRT1 activity in vitro and in cells have been developed. While the mechanism for how these compounds act on SIRT1 was once controversial, it is becoming increasingly clear that they directly interact with SIRT1 and enhance its activity through an allosteric mechanism. Here, we present detailed chemical syntheses for four STACs, each from a distinct structural class. Also, we provide a general protocol for purifying active SIRT1 enzyme and outline two complementary enzymatic assays for characterizing the effects of STACs and similar compounds on SIRT1 activity.

  1. Synthesis and Assay of SIRT1-Activating Compounds

    PubMed Central

    Dai, H.; Ellis, J.L.; Sinclair, D.A.; Hubbard, B.P.

    2016-01-01

    The NAD+-dependent deacetylase SIRT1 plays key roles in numerous cellular processes including DNA repair, gene transcription, cell differentiation, and metabolism. Over-expression of SIRT1 protects against a number of age-related diseases including diabetes, cancer, and Alzheimer's disease. Moreover, overexpression of SIRT1 in the murine brain extends lifespan. A number of small-molecule sirtuin-activating compounds (STACs) that increase SIRT1 activity in vitro and in cells have been developed. While the mechanism for how these compounds act on SIRT1 was once controversial, it is becoming increasingly clear that they directly interact with SIRT1 and enhance its activity through an allosteric mechanism. Here, we present detailed chemical syntheses for four STACs, each from a distinct structural class. Also, we provide a general protocol for purifying active SIRT1 enzyme and outline two complementary enzymatic assays for characterizing the effects of STACs and similar compounds on SIRT1 activity. PMID:27423864

  2. Characterization of volatile compounds responsible for the aroma in naturally fermented sausages by gas chromatography-olfactometry.

    PubMed

    Olivares, Alicia; Navarro, José Luis; Flores, Mónica

    2015-03-01

    The objective of this study was to characterize naturally fermented dry sausages produced without the use of microbial starters and to determine which odour-active compounds are responsible for their aroma. The traditional manufacture was responsible for different chemical characteristics and consumer's acceptance. The volatile compounds detected in the headspace comprised a complex mixture of volatile compounds derived from bacterial metabolism (mainly esterase activity of Staphyloccoci), spices and lipid auto-oxidation. The odour-active volatile compounds were identified using gas chromatography coupled to olfactometry (GC-O) using the detection frequency method. The aroma profile was characterized by the presence of several compounds such as acetic acid, ethyl butanoate, hexanal, methional, 1-octen-3-ol, benzeneacetaldehyde and 4-methyl-phenol. However, naturally fermented sausages were also characterized by numerous esters, both ethyl and methyl esters, which impart a wide variety of fruity notes.

  3. Antiprotozoal and Antimycobacterial Activities of Pure Compounds from Aristolochia elegans Rhizomes

    PubMed Central

    Jiménez-Arellanes, Adelina; León-Díaz, Rosalba; Meckes, Mariana; Tapia, Amparo; Molina-Salinas, Gloria María; Luna-Herrera, Julieta; Yépez-Mulia, Lilián

    2012-01-01

    We analyzed the antimycobacterial activity of the hexane extract of rhizomes from Aristolochia elegans. Some compounds of this extract were purified and tested against a group of drug-resistant Mycobacterium tuberculosis strains. We also evaluated their antiprotozoal activities. The hexane extract was active against M. tuberculosis H37Rv at a MIC = 100 μg mL−1; the pure compounds eupomatenoid-1, fargesin, and (8R,8′R,9R)-cubebin were active against M. tuberculosis H37Rv (MIC = 50 μg mL−1), while fargesin presented activity against three monoresistant strains of M. tuberculosis H37Rv and a MDR clinical isolate of M. tuberculosis (MIC < 50 μg mL−1). Both the extract and eupomatenoid-1 were very active against E. histolytica and G. lamblia (IC50 < 0.624 μg mL−1); in contrast, fargesin and (8R,8′R,9R)-cubebin were moderately active (IC50 < 275 μg mL−1). In this context, two compounds responsible for the antimycobacterial presented by A. elegans are fargesin and cubebin, although others may exert this activity also. In addition to the antimycobacterial activity, the hexane extract has important activity against E. histolytica and G. lamblia, and eupomatenoid-1 is one of the compounds responsible for the antiparasite activity. PMID:22454670

  4. Isolation and anticomplement activity of compounds from Dendropanax morbifera.

    PubMed

    Park, Bo-Young; Min, Byung-Sun; Oh, Sei-Ryang; Kim, Jung-Hee; Kim, Tae-Jin; Kim, Dong-Hee; Bae, Ki-Hwan; Lee, Hyeong-Kyu

    2004-02-01

    Dendropanax morbifera Leveille (Araliaceae) is used in Korea for a variety of disease, such as migraine headache and dysmenorrhea. A new polyacetylene (1) and six known compounds (2-7) were isolated from the leaves of this plant by conventional chromatographic techniques. The structure of the new polyacetylene (1) was determined as (9Z,16S)-16-hydroxy-9,17-octadecadiene-12,14-diynoic acid by spectroscopic means including 2D NMR, which comprised the determination of a chiral by modified Mosher's ester method. Compounds 1-7 were investigated in vitro for their anticomplement activity against the classical pathway of the complement system. Of these, compound 1 showed significant anticomplement activity with 50% inhibitory concentration (IC50) value of 56.98 microM, whereas compounds 2-7 were inactive.

  5. Endophytic fungi with antitumor activities: Their occurrence and anticancer compounds.

    PubMed

    Chen, Ling; Zhang, Qiao-Yan; Jia, Min; Ming, Qian-Liang; Yue, Wei; Rahman, Khalid; Qin, Lu-Ping; Han, Ting

    2016-05-01

    Plant endophytic fungi have been recognized as an important and novel resource of natural bioactive products, especially in anticancer application. This review mainly deals with the research progress on the production of anticancer compounds by endophytic fungi between 1990 and 2013. Anticancer activity is generally associated with the cytotoxicity of the compounds present in the endophytic fungi. All strains of endophytes producing antitumor chemicals were classified taxonomically and the genera of Pestalotiopsis and Aspergillus as well as the taxol producing endophytes were focused on. Classification of endophytic fungi producing antitumor compounds has received more attention from mycologists, and it can also lead to the discovery of novel compounds with antitumor activity due to phylogenetic relationships. In this review, the structures of the anticancer compounds isolated from the newly reported endophytes between 2010 and 2013 are discussed including strategies for the efficient production of the desired compounds. The purpose of this review is to provide new directions in endophytic fungi research including integrated information relating to its anticancer compounds.

  6. Chemiluminescence response induced by mesenteric ischaemia/reperfusion: effect of antioxidative compounds ex vivo

    PubMed Central

    Nosál'ová, Viera; Sotníková, Ružena; Drábiková, Katarína; Fialová, Silvia; Košťálová, Daniela; Banášová, Silvia; Navarová, Jana

    2010-01-01

    Ischaemia and reperfusion (I/R) play an important role in human pathophysiology as they occur in many clinical conditions and are associated with high morbidity and mortality. Interruption of blood supply rapidly damages metabolically active tissues. Restoration of blood flow after a period of ischaemia may further worsen cell injury due to an increased formation of free radicals. The aim of our work was to assess macroscopically the extent of intestinal pathological changes caused by mesenteric I/R, and to study free radical production by luminol enhanced chemiluminescence (CL) of ileal samples. In further experiments, the antioxidative activity of the drugs tested was evaluated spectrophotometrically by the use of the DPPH radical. We studied the potential protective ex vivo effect of the plant origin compound arbutin as well as of the pyridoindole stobadine and its derivative SMe1EC2. I/R induced pronounced haemorrhagic intestinal injury accompanied by increase of myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGA) activity. Compared to sham operated (control) rats, there was only a slight increase of CL response after I/R, probably in association with neutrophil increase, indicated by enhanced MPO activity. All compounds significantly reduced the peak values of CL responses of the ileal samples ex vivo, thus reducing the I/R induced increase of free radical production. The antioxidants studied showed a similar inhibitory effect on the CL response influenced by mesenteric I/R. If proved in vivo, these compounds would represent potentially useful therapeutic antioxidants. PMID:21217883

  7. 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.

  8. Nematicidal Activity of Cassia and Cinnamon Oil Compounds and Related Compounds toward Bursaphelenchus xylophilus (Nematoda: Parasitaphelenchidae)

    PubMed Central

    Kong, Jeong-Ok; Lee, Sang-Myung; Moon, Yil-Seong; Lee, Sang-Gil; Ahn, Young-Joon

    2007-01-01

    The nematicidal activity of two cassia, Cinnamomum cassia, oils (Especial and true), four cinnamon, Cinnamomum zey-lanicum, oils (technical, #500, bark and green leaf), and their compounds (e.g., trans-cinnamaldehyde and trans-cinnamic acid) toward adult Bursaphelenchus xylophilus was examined by a direct contact bioassay. Results were compared with those of 34 related compounds. As judged by 24-hour LC50 values, two cassia oils (0.084–0.085 mg/ml) and four cinnamon oils (0.064–0.113 mg/ml) were toxic toward adult B. xylophilus. Of 45 test compounds, trans-cinnamaldehyde (0.061 mg/ml) was the most active nematicide, followed by ethyl cinnamate, α-methyl-trans-cinnamaldehyde, methyl cinnamate and allyl cinnamate (0.114–0.195 mg/ml). Potent nematicidal activity was also observed with 4-methoxycinnamonitrile, trans-4-methoxycinnamaldehyde, trans-2-methoxy-cinnamaldehyde, ethyl α-cyanocinnamate, cinnamonitrile and cinnamyl bromide (0.224–0.502 mg/ml). Structure-activity relationships indicate that structural characteristics, such as types of functional groups, saturation and carbon skeleton, appear to play a role in determining the toxicities to adult B. xylophilus. Cassia and cinnamon oils and test compounds described merit further study as potential nematicides or leads for the control of pine wilt disease caused by B. xylophilus. PMID:19259472

  9. Antimicrobial activity of extractable conifer heartwood compounds toward Phytophthora ramorum.

    PubMed

    Manter, Daniel K; Kelsey, Rick G; Karchesy, Joseph J

    2007-11-01

    Ethyl acetate extracts from heartwood of seven western conifer trees and individual volatile compounds in the extracts were tested for antimicrobial activity against Phytophthora ramorum. Extracts from incense and western redcedar exhibited the strongest activity, followed by yellow-cedar, western juniper, and Port-Orford-cedar with moderate activity, and no activity for Douglas-fir and redwood extracts. Chemical composition of the extracts varied both qualitatively and quantitatively among the species with a total of 37 compounds identified by mass spectrometry. Of the 13 individual heartwood compounds bioassayed, three showed strong activity with a Log(10) EC(50) less than or equal to 1.0 ppm (hinokitiol, thymoquinone, and nootkatin), three expressed moderate activity ranging from 1.0-2.0 ppm (nootkatol, carvacrol, and valencene-11,12-diol), four compounds had weak activity at 2.0-3.0 ppm [alpha-terpineol, valencene-13-ol, (+)-beta-cedrene, (-)-thujopsene], and three had no activity [(+)-cedrol, delta-cadinene, and methyl carvacrol]. All of the most active compounds contained a free hydroxyl group, except thymoquinone. The importance of a free hydroxyl was demonstrated by the tremendous difference in activity between carvacrol (Log(10) EC(50) 1.81 +/- 0.08 ppm) and methyl carvacrol (Log(10) EC(50) >3.0 ppm). A field trial in California, showed that heartwood chips from redcedar placed on the forest floor for 4 months under Umbellularia californica (California bay laurel) with symptoms of P. ramorum leaf blight significantly limited the accumulation of P. ramorum DNA in the litter layer, compared with heartwood chips from redwood.

  10. Biological activities of phenolic compounds present in virgin olive oil.

    PubMed

    Cicerale, Sara; Lucas, Lisa; Keast, Russell

    2010-02-02

    The Mediterranean diet is associated with a lower incidence of atherosclerosis, cardiovascular disease, neurodegenerative diseases and certain types of cancer. The apparent health benefits have been partially ascribed to the dietary consumption of virgin olive oil by Mediterranean populations. Much research has focused on the biologically active phenolic compounds naturally present in virgin olive oils to aid in explaining reduced mortality and morbidity experienced by people consuming a traditional Mediterranean diet. Studies (human, animal, in vivo and in vitro) have demonstrated that olive oil phenolic compounds have positive effects on certain physiological parameters, such as plasma lipoproteins, oxidative damage, inflammatory markers, platelet and cellular function, antimicrobial activity and bone health. This paper summarizes current knowledge on the bioavailability and biological activities of olive oil phenolic compounds.

  11. Bactericidal activity of glutaraldehyde-like compounds from olive products.

    PubMed

    Medina, Eduardo; Brenes, Manuel; García, Aranzazu; Romero, Concepción; de Castro, Antonio

    2009-12-01

    The bactericidal effects of several olive compounds (nonenal, oleuropein, tyrosol, the dialdehydic form of decarboxymethyl elenolic acid either free [EDA] or linked to tyrosol [TyEDA] or to hydroxytyrosol [HyEDA]), other food phenolic compounds (catechin, epicatechin, eugenol, thymol, carvacrol, and carnosic acid), and commercial disinfectants (glutaraldehyde [GTA] and ortho-phthalaldehyde [OPA]), were tested against strains of Pseudomonas fluorescens, Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli. It was found that the bactericidal activities of olive GTA-like compounds (EDA, HyEDA, and TyEDA) were greater than those exerted by several food phenolic substances. Surprisingly, these olive antimicrobials were as active as the synthetic biocides GTA and OPA against the four bacteria studied. Thus, it has been proposed that the bactericidal activity of the main olive antimicrobials is primarily due to their dialdehydic structure, which is similar to that of the commercial biocides GTA and OPA. Our results clearly reveal that olive GTA-like compounds possess a strong bactericidal activity even greater than that of other food phenolic compounds or synthetic biocides.

  12. Aspartate and glutamate mimetic structures in biologically active compounds.

    PubMed

    Stefanic, Peter; Dolenc, Marija Sollner

    2004-04-01

    Glutamate and aspartate are frequently recognized as key structural elements for the biological activity of natural peptides and synthetic compounds. The acidic side-chain functionality of both the amino acids provides the basis for the ionic interaction and subsequent molecular recognition by specific receptor sites that results in the regulation of physiological or pathophysiological processes in the organism. In the development of new biologically active compounds that possess the ability to modulate these processes, compounds offering the same type of interactions are being designed. Thus, using a peptidomimetic design approach, glutamate and aspartate mimetics are incorporated into the structure of final biologically active compounds. This review covers different bioisosteric replacements of carboxylic acid alone, as well as mimetics of the whole amino acid structure. Amino acid analogs presented include those with different distances between anionic moieties, and analogs with additional functional groups that result in conformational restriction or alternative interaction sites. The article also provides an overview of different cyclic structures, including various cycloalkane, bicyclic and heterocyclic analogs, that lead to conformational restriction. Higher di- and tripeptide mimetics in which carboxylic acid functionality is incorporated into larger molecules are also reviewed. In addition to the mimetic structures presented, emphasis in this article is placed on their steric and electronic properties. These mimetics constitute a useful pool of fragments in the design of new biologically active compounds, particularly in the field of RGD mimetics and excitatory amino acid agonists and antagonists.

  13. 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.

  14. Neural activation during response competition

    NASA Technical Reports Server (NTRS)

    Hazeltine, E.; Poldrack, R.; Gabrieli, J. D.

    2000-01-01

    The flanker task, introduced by Eriksen and Eriksen [Eriksen, B. A., & Eriksen, C. W. (1974). Effects of noise letters upon the identification of a target letter in a nonsearch task. Perception & Psychophysics, 16, 143--149], provides a means to selectively manipulate the presence or absence of response competition while keeping other task demands constant. We measured brain activity using functional magnetic resonance imaging (fMRI) during performance of the flanker task. In accordance with previous behavioral studies, trials in which the flanking stimuli indicated a different response than the central stimulus were performed significantly more slowly than trials in which all the stimuli indicated the same response. This reaction time effect was accompanied by increases in activity in four regions: the right ventrolateral prefrontal cortex, the supplementary motor area, the left superior parietal lobe, and the left anterior parietal cortex. The increases were not due to changes in stimulus complexity or the need to overcome previously learned associations between stimuli and responses. Correspondences between this study and other experiments manipulating response interference suggest that the frontal foci may be related to response inhibition processes whereas the posterior foci may be related to the activation of representations of the inappropriate responses.

  15. Reduction of the secretory response to Escherichia coli heat-stable enterotoxin by thiol and disulfide compounds. [Mice

    SciTech Connect

    Greenberg, R.N.; Dunn, J.A.; Guerrant, R.L.

    1983-07-01

    We examined the effects of disulfide and thiol compounds on Escherichia coli heat-stable enterotoxin (ST) and cyclic GMP-induced secretion. Both cystamine and cystine (disulfide compounds) reduced the secretory responses to submaximal doses of ST in suckling mice (at 0.5 mumol per mouse) and reduced ST activation of guanylate cyclase (by 33 to 73% at 1 mM). In higher doses, cystamine completely eradicated a maximally effective ST dose as well. In addition, the sulfhydryl (thiol) compounds cysteamine, cysteine, and acetylcysteine strikingly reduced the secretory response and the guanylate cyclase response to ST. Neither the disulfide nor the thiol compounds tested reduced cyclic GMP-induced secretion. These studies suggest that disulfide and thiol compounds both block ST-induced secretion before its activation of guanylate cyclase. Taken with the work of others, these findings suggest that disulfide compounds may alter the oxidation reduction state of a cell or act directly on the guanylate cyclase enzyme, whereas thiol compounds may inactivate ST itself by breaking its disulfide bridges, or it may alter guanylate cyclase activation by ST. Both families of compounds deserve further consideration among potential antisecretory agents for application in the control of ST-induced diarrhea.

  16. Giant dielectric response of Haldane gap compound Y2BaNiO5

    NASA Astrophysics Data System (ADS)

    Chen, J. W.; Narsinga Rao, G.; Li, K. W.

    2012-03-01

    The dielectric properties of the Haldane gap compound Y2BaNiO5 were studied in the frequency range from 20 Hz to 1 MHz between 20 K and room temperature. This compound exhibits a high dielectric permittivity (ɛ' ˜ 104) at room temperature below 100 kHz. Both dielectric relaxation and dc resistivity ρ follow the thermally activated process with similar value of the activation energy. This indicates the close correlation between the electric conduction and the dielectric polarization. The modulus spectra reveal evidence for both grain and grain boundary relaxation times. The grain relaxation time follows thermally activated process, whereas the grain boundary relaxation time exhibits variable range hopping (VRH) behavior. The observed giant dielectric response were explained in terms of internal (grain boundary) barrier layer capacitance (IBLC) effects.

  17. Geomagnetic response to solar activity.

    NASA Technical Reports Server (NTRS)

    Mead, G. D.

    1972-01-01

    The relationship between solar activity and geomagnetic variations is discussed in the light of spacecraft data obtained during the last decade. The effects of centers of solar activity responsible for producing geomagnetic activity on earth are believed to be transmitted through the solar wind, and there is usually a delay of two or three days before the onset of magnetic activity. Attempts to make a one-to-one correspondence between specific solar events and specific magnetic storms, however, are usually unsuccessful, because of the complex and indirect processes linking the two phenomena. Normally, only statistical tendencies can be shown.

  18. 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.

  19. Screening SIRT1 Activators from Medicinal Plants as Bioactive Compounds against Oxidative Damage in Mitochondrial Function

    PubMed Central

    Wang, Yi; Liang, Xinying; Chen, Yaqi; Zhao, Xiaoping

    2016-01-01

    Sirtuin type 1 (SIRT1) belongs to the family of NAD+ dependent histone deacetylases and plays a critical role in cellular metabolism and response to oxidative stress. Traditional Chinese medicines (TCMs), as an important part of natural products, have been reported to exert protective effect against oxidative stress in mitochondria. In this study, we screened SIRT1 activators from TCMs and investigated their activities against mitochondrial damage. 19 activators were found in total by in vitro SIRT1 activity assay. Among those active compounds, four compounds, ginsenoside Rb2, ginsenoside F1, ginsenoside Rc, and schisandrin A, were further studied to validate the SIRT1-activation effects by liquid chromatography-mass spectrometry and confirm their activities against oxidative damage in H9c2 cardiomyocytes exposed to tert-butyl hydroperoxide (t-BHP). The results showed that those compounds enhanced the deacetylated activity of SIRT1, increased ATP content, and inhibited intracellular ROS formation as well as regulating the activity of Mn-SOD. These SIRT1 activators also showed moderate protective effects on mitochondrial function in t-BHP cells by recovering oxygen consumption and increasing mitochondrial DNA content. Our results suggested that those compounds from TCMs attenuated oxidative stress-induced mitochondrial damage in cardiomyocytes through activation of SIRT1. PMID:26981165

  20. Byrsonima fagifolia Niedenzu Apolar Compounds with Antitubercular Activity

    PubMed Central

    Higuchi, C. T.; Sannomiya, M.; Pavan, F. R.; Leite, S. R. A.; Sato, D. N.; Franzblau, S. G.; Sacramento, L. V. S.; Vilegas, W.; Leite, C. Q. F.

    2011-01-01

    Bioassay-guided fractionation of the chloroform extract of Byrsonima fagifolia leaves led to the isolation of active antitubercular compounds alkane dotriacontane (Minimal Inhibitory Concentration—MIC, 62.5 μg mL−1), triterpenoids as bassic acid (MIC = 2.5 μg mL−1), α-amyrin acetate (MIC = 62.5 μg mL−1), a mixture of lupeol, α- and β-amyrin (MIC = 31.5 μg mL−1) and a mixture of lupeol, and acetates of α- and β-amyrin (MIC = 31.5 μg mL−1). The antimycobacterial activity was determined by the Microplate Alamar Blue Assay (MABA) and the structures of promising compounds were determined by spectroscopic analysis. This investigation constitutes the first report of a chemical and antitubercular study of apolar compounds from B. fagifolia Niedenzu (IK). PMID:19091782

  1. [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.

  2. Compounds active against cell walls of medically important fungi.

    PubMed Central

    Hector, R F

    1993-01-01

    A number of substances that directly or indirectly affect the cell walls of fungi have been identified. Those that actively interfere with the synthesis or degradation of polysaccharide components share the property of being produced by soil microbes as secondary metabolites. Compounds specifically interfering with chitin or beta-glucan synthesis have proven effective in studies of preclinical models of mycoses, though they appear to have a restricted spectrum of coverage. Semisynthetic derivatives of some of the natural products have offered improvements in activity, toxicology, or pharmacokinetic behavior. Compounds which act on the cell wall indirectly or by a secondary mechanism of action, such as the azoles, act against diverse fungi but are usually fungistatic in nature. Overall, these compounds are attractive candidates for further development. PMID:8457977

  3. Anti-Salmonella Activity of Volatile Compounds of Vietnam Coriander.

    PubMed

    Fujita, Ken-Ichi; Chavasiri, Warinthorn; Kubo, Isao

    2015-07-01

    Essential oil derived from the fresh leaves of Polygonum odoratum Lour was tested for their effects on a foodborne bacterium Salmonella choleraesuis subsp. choleraesuis ATCC 35640 using a broth dilution method. This essential oil showed a significant antibacterial activity against S. choleraesuis at the concentration of 200 µg/mL. Twenty-five volatile compounds were characterized from this essential oil by GC-MS, and aldehyde compounds were found abundant and accounted for more than three-fourths of the essential oil. Among the compounds characterized, dodecanal (C12 ) was the most abundant (55.5%), followed by decanal (C10 ) (11.6%). Both alkanals were effective against S. choleraesuis with the minimum growth inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 100 µg/mL. The most potent antibacterial activity against this bacterium was found with two minor compounds, dodecanol (lauryl alcohol) and 2E-dodecenal, both with each MBC of 6.25 µg/mL. Their primary antibacterial action against S. choleraesuis provably comes from their ability to function as nonionic surface-active agents (surfactants), disrupting the native function of integral membrane proteins nonspecifically. Thus, the antibacterial activity is mediated by biophysical processes. In the case of 2E-alkenals, a biochemical mechanism is also somewhat involved, depending on their alkyl chain length.

  4. Biological and chemical investigation of Allium cepa L. response to selenium inorganic compounds.

    PubMed

    Michalska-Kacymirow, M; Kurek, E; Smolis, A; Wierzbicka, M; Bulska, E

    2014-06-01

    The aim of this study was to evaluate the biological and chemical response of Allium cepa L. exposed to inorganic selenium compounds. Besides the investigation of the total content of selenium as well as its chemical speciation, the Allium test was used to evaluate the growth of onion roots and mitotic activity in the roots' meristem. The total content of selenium was determined by inductively coupled plasma mass spectrometry (ICP MS). High-performance liquid chromatography (HPLC), coupled to ICP MS, was used for the selenium chemical speciation. Results indicated that A. cepa plants are able to biotransform inorganic selenium compounds into their organic derivatives, e.g., Se-methylselenocysteine from the Se(IV) inorganic precursor. Although the differences in the biotransformation of selenium are due mainly to the oxidation state of selenium, the experiment has also shown a fine effect of counter ions (H(+), Na(+), NH4 (+)) on the response of plants and on the specific metabolism of selenium.

  5. Natural compounds with aromatase inhibitory activity: an update.

    PubMed

    Balunas, Marcy J; Kinghorn, A Douglas

    2010-08-01

    Several synthetic aromatase inhibitors are currently in clinical use for the treatment of postmenopausal women with hormone-receptor positive breast cancer. However, these treatments may lead to untoward side effects and so the search for new aromatase inhibitors continues, especially those for which the activity is promoter-specific, targeting the breast-specific promoters I.3 and II. Recently, numerous natural compounds have been found to inhibit aromatase in noncellular, cellular, and IN VIVO studies. These investigations, covering the last two years, as well as additional studies that have focused on the evaluation of natural compounds as promoter-specific aromatase inhibitors or as aromatase inducers, are described in this review.

  6. Synthesis and antitumor activity of natural compound aloe emodin derivatives.

    PubMed

    Thimmegowda, Naraganahalli R; Park, Chanmi; Shwetha, Bettaswamigowda; Sakchaisri, Krisada; Liu, Kangdong; Hwang, Joonsung; Lee, Sangku; Jeong, Sook J; Soung, Nak K; Jang, Jae H; Ryoo, In-Ja; Ahn, Jong S; Erikson, Raymond L; Kim, Bo Y

    2015-05-01

    In this study, we have synthesized novel water soluble derivatives of natural compound aloe emodin 4(a-j) by coupling with various amino acid esters and substituted aromatic amines, in an attempt to improve the anticancer activity and to explore the structure-activity relationships. The structures of the compounds were determined by (1) H NMR and mass spectroscopy. Cell growth inhibition assays revealed that the aloe emodin derivatives 4d, 4f, and 4i effectively decreased the growth of HepG2 (human liver cancer cells) and NCI-H460 (human lung cancer cells) and some of the derivatives exhibited comparable antitumor activity against HeLa (Human epithelial carcinoma cells) and PC3 (prostate cancer cells) cell lines compared to that of the parent aloe emodin at low micromolar concentrations.

  7. Antioxidant activity of compounds from the medicinal herb Aster tataricus.

    PubMed

    Ng, T B; Liu, Fang; Lu, Yanhua; Cheng, C H K; Wang, Zhengtao

    2003-10-01

    A number of compounds were isolated from the medicinal plant Aster tataricus including shionone, epifriedelinol, quercetin, kaempferol, scopoletin, emodin, aurantiamide acetate and 1,7-dihydroxy-6-methyl-anthraquinone. The compounds were compared with regard to their ability in inhibiting hemolysis of rat erythrocytes induced by 2'-2' azobis (2-amidinopropane) dihydrochloride, lipid peroxidation using the FeSO(4)-ascorbic acid system, and generation of superoxide radicals using a phenazine methosulfate-nicotinamide adenine dinucleotide system. The effects on the Fe-bleomycin-induced DNA damage reflected pro-oxidant activity. Quercetin and kaempferol were most potent in inhibiting hemolysis, lipid peroxidation and superoxide radical generation. Scopoletin and emodin were similar to quercetin and kaempferol in inhibiting superoxide radical generation and second to them in inhibiting lipid peroxidation. Aurantiamide acetate exhibited some inhibitory activity toward superoxide radical generation. 1,7-dihydroxy-6-methyl-anthraquinone exerted an inhibitory activity only on superoxide radical generation. Shionone and epifriedelinol did not display any antioxidant activity. Quercetin and kaempferol, but not the remaining compounds, exhibited some pro-oxidant activity.

  8. 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.

  9. Hybrid energy storage systems utilizing redox active organic compounds

    SciTech Connect

    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.

  10. Anti-allergic inflammatory activities of compounds of amomi fructus.

    PubMed

    Choi, Hyun Gyu; Je, In-Gyu; Kim, Geum Jin; Choi, Hyukjae; Kim, Sang Hyun; Kim, Jeong Ah; Lee, Kim Seung Ho

    2015-04-01

    Activity-guided isolation of compounds from the fruits of Amomum xanthioides resulted in the purification of fourteen phenolic compounds, 4-hydroxy-benzaldehyde (1), 3,4-dihydroxybenzaldehyde (2), 3,5-dimethoxy-4-methylbenzaldehyde (3), syringic aldehyde (4), benzoic acid (5), 3,4-dihydroxy benzoic acid (6), vanillic acid (7), 3-hydroxy-2-methoxybenzoic acid (8), o-vanillic acid (9), phenylacetic acid (10), tyrosol (11), pyrocatechol (12), 1,2,4,5-tetramethoxybenzene (13), and 3,3',5,5'-tetramethoxybiphenyl-4,4'-diol (14). To evaluate the anti-allergic inflammatory activities of these compounds, we examined the inhibitory effects of the isolates (1-14) on histamine release and on the expressions of tumor necrosis factor (TNF)-ca and interleukin (IL)-6 genes by using human mast cells. Of the tested compounds, 9, 11, and 13 suppressed histamine release from mast cells, and all isolates attenuated the expressions of the pro-inflammatory cytokines, TNF-α and IL-6 genes in human mast cells.

  11. Natural products as a resource for biologically active compounds

    SciTech Connect

    Hanke, F.J.

    1986-01-01

    The goal of this study was to investigate various sources of biologically active natural products in an effort to identify the active pesticidal compounds involved. The study is divided into several parts. Chapter 1 contains a discussion of several new compounds from plant and animal sources. Chapter 2 introduces a new NMR technique. In section 2.1 a new technique for better utilizing the lanthanide relaxation agent Gd(fod)/sub 3/ is presented which allows the predictable removal of resonances without line broadening. Section 2.2 discusses a variation of this technique for use in an aqueous solvent by applying this technique towards identifying the binding sites of metals of biological interest. Section 2.3 presents an unambiguous /sup 13/C NMR assignment of melibiose. Chapter 3 deals with work relating to the molting hormone of most arthropods, 20-hydroxyecdysone. Section 3.1 discusses the use of two-dimensional NMR (2D NMR) to assign the /sup 1/H NMR spectrum of this biologically important compound. Section 3.2 presents a new application for Droplet countercurrent chromatography (DCCC). Chapter 4 presents a basic improvement to the commercial DCCC instrument that is currently being applied to future commercial instruments. Chapter 5 discusses a curious observation of the effects that two previously known compounds, nagilactone C and (-)-epicatechin, have on lettuce and rice and suggest a possible new role for the ubiquitous flavanol (-)-epicatechin in plants.

  12. Antimicrobial active herbal compounds against Acinetobacter baumannii and other pathogens

    PubMed Central

    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. PMID:26150810

  13. Simultaneous Activation of Iron- and Thiol-Based Sensor-Regulator Systems by Redox-Active Compounds

    PubMed Central

    Lee, Kang-Lok; Yoo, Ji-Sun; Oh, Gyeong-Seok; Singh, Atul K.; Roe, Jung-Hye

    2017-01-01

    Bacteria in natural habitats are exposed to myriad redox-active compounds (RACs), which include producers of reactive oxygen species (ROS) and reactive electrophile species (RES) that alkylate or oxidize thiols. RACs can induce oxidative stress in cells and activate response pathways by modulating the activity of sensitive regulators. However, the effect of a certain compound on the cell has been investigated primarily with respect to a specific regulatory pathway. Since a single compound can exert multiple chemical effects in the cell, its effect can be better understood by time-course monitoring of multiple sensitive regulatory pathways that the compound induces. We investigated the effect of representative RACs by monitoring the activity of three sensor-regulators in the model actinobacterium Streptomyces coelicolor; SoxR that senses reactive compounds directly through oxidation of its [2Fe–2S] cluster, CatR/PerR that senses peroxides through bound iron, and an anti-sigma factor RsrA that senses RES via disulfide formation. The time course and magnitude of induction of their target transcripts were monitored to predict the chemical activities of each compound in S. coelicolor. Phenazine methosulfate (PMS) was found to be an effective RAC that directly activated SoxR and an effective ROS-producer that induced CatR/PerR with little thiol-perturbing activity. p-Benzoquinone was an effective RAC that directly activated SoxR, with slower ROS-producing activity, and an effective RES that induced the RsrA-SigR system. Plumbagin was an effective RAC that activated SoxR, an effective ROS-producer, and a less agile but effective RES. Diamide was an RES that effectively formed disulfides and a weak RAC that activated SoxR. Monobromobimane was a moderately effective RES and a slow producer of ROS. Interestingly, benzoquinone induced the SigR system by forming adducts on cysteine thiols in RsrA, revealing a new pathway to modulate RsrA activity. Overall, this study showed

  14. Antiandrogenic activity and metabolism of the organophosphorus pesticide fenthion and related compounds.

    PubMed Central

    Kitamura, Shigeyuki; Suzuki, Tomoharu; Ohta, Shigeru; Fujimoto, Nariaki

    2003-01-01

    We investigated the endocrine-disrupting actions of the organophosphorus pesticide fenthion and related compounds and the influence of metabolic transformation on the activities of these compounds. Fenthion acted as an antagonist of the androgenic activity of dihydrotestosterone (10(-7)M) in the concentration range of 10(-6)-10(-4)M in an androgen-responsive element-luciferase reporter-responsive assay using NIH3T3 cells. The antiandrogenic activity of fenthion was similar in magnitude to that of flutamide. Fenthion also tested positive in the Hershberger assay using castrated male rats. Marked estrogenic and antiestrogenic activities of fenthion and related compounds were not observed in MCF-7 cells. When fenthion was incubated with rat liver microsomes in the presence of NADPH, the antiandrogenic activity markedly decreased, and fenthion sulfoxide was detected as a major metabolite. The oxidase activity toward fenthion was exhibited by cytochrome P450 and flavin-containing monooxygenase. Fenthion sulfoxide was negative in the screening test for antiandrogens, as was fenthion sulfone. However, when fenthion sulfoxide was incubated with liver cytosol in the presence of 2-hydroxypyrimidine, an electron donor of aldehyde oxidase, the extract of the incubation mixture exhibited antiandrogenic activity. In this case, fenthion was detected as a major metabolite of the sulfoxide. Metabolic interconversion between fenthion and fenthion sulfoxide in the body seems to maintain the antiandrogenic activity. PMID:12676606

  15. Molecular Adaptation Mechanisms Employed by Ethanologenic Bacteria in Response to Lignocellulose-derived Inhibitory Compounds

    PubMed Central

    Ibraheem, Omodele; Ndimba, Bongani K.

    2013-01-01

    Current international interest in finding alternative sources of energy to the diminishing supplies of fossil fuels has encouraged research efforts in improving biofuel production technologies. In countries which lack sufficient food, the use of sustainable lignocellulosic feedstocks, for the production of bioethanol, is an attractive option. In the pre-treatment of lignocellulosic feedstocks for ethanol production, various chemicals and/or enzymatic processes are employed. These methods generally result in a range of fermentable sugars, which are subjected to microbial fermentation and distillation to produce bioethanol. However, these methods also produce compounds that are inhibitory to the microbial fermentation process. These compounds include products of sugar dehydration and lignin depolymerisation, such as organic acids, derivatised furaldehydes and phenolic acids. These compounds are known to have a severe negative impact on the ethanologenic microorganisms involved in the fermentation process by compromising the integrity of their cell membranes, inhibiting essential enzymes and negatively interact with their DNA/RNA. It is therefore important to understand the molecular mechanisms of these inhibitions, and the mechanisms by which these microorganisms show increased adaptation to such inhibitors. Presented here is a concise overview of the molecular adaptation mechanisms of ethanologenic bacteria in response to lignocellulose-derived inhibitory compounds. These include general stress response and tolerance mechanisms, which are typically those that maintain intracellular pH homeostasis and cell membrane integrity, activation/regulation of global stress responses and inhibitor substrate-specific degradation pathways. We anticipate that understanding these adaptation responses will be essential in the design of 'intelligent' metabolic engineering strategies for the generation of hyper-tolerant fermentation bacteria strains. PMID:23847442

  16. Molecular adaptation mechanisms employed by ethanologenic bacteria in response to lignocellulose-derived inhibitory compounds.

    PubMed

    Ibraheem, Omodele; Ndimba, Bongani K

    2013-01-01

    Current international interest in finding alternative sources of energy to the diminishing supplies of fossil fuels has encouraged research efforts in improving biofuel production technologies. In countries which lack sufficient food, the use of sustainable lignocellulosic feedstocks, for the production of bioethanol, is an attractive option. In the pre-treatment of lignocellulosic feedstocks for ethanol production, various chemicals and/or enzymatic processes are employed. These methods generally result in a range of fermentable sugars, which are subjected to microbial fermentation and distillation to produce bioethanol. However, these methods also produce compounds that are inhibitory to the microbial fermentation process. These compounds include products of sugar dehydration and lignin depolymerisation, such as organic acids, derivatised furaldehydes and phenolic acids. These compounds are known to have a severe negative impact on the ethanologenic microorganisms involved in the fermentation process by compromising the integrity of their cell membranes, inhibiting essential enzymes and negatively interact with their DNA/RNA. It is therefore important to understand the molecular mechanisms of these inhibitions, and the mechanisms by which these microorganisms show increased adaptation to such inhibitors. Presented here is a concise overview of the molecular adaptation mechanisms of ethanologenic bacteria in response to lignocellulose-derived inhibitory compounds. These include general stress response and tolerance mechanisms, which are typically those that maintain intracellular pH homeostasis and cell membrane integrity, activation/regulation of global stress responses and inhibitor substrate-specific degradation pathways. We anticipate that understanding these adaptation responses will be essential in the design of 'intelligent' metabolic engineering strategies for the generation of hyper-tolerant fermentation bacteria strains.

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

    PubMed Central

    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

    2015-01-01

    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. PMID:25419740

  18. Antileishmanial Activity of Compounds Isolated from Sassafras albidum.

    PubMed

    Pulivarthi, Divya; Steinberg, Kelly Marie; Monzote, Lianet; Piñón, Abel; Setzer, William N

    2015-07-01

    Leishmaniasis is a neglected tropical disease caused by Leishmania parasitic protozoa, which currently lacks efficient treatment. Natural products have shown promise as a potential source for antiprotozoal drugs. This work focuses on the antileishmanial potential of Sassafras albidum (Lauraceae) bark extract. The crude bark extract of S. albidum showed excellent antileishmanial activity with an IC50 value less than 12.5 μg/mL against promastigotes of L. amazonensis. The chloroform stem bark extract of S. albidum was subjected to preparative column chromatography. Five compounds were isolated, purified by recrystallization, and identified as sesamin, spinescin, β-sitosterol, hexatriacontanal, and 1-triacontanol. Antileishmanial and cytotoxic screening were performed on these compounds. Sesamin exhibited the best activity against L. amazonensis with an IC50 of 15.8 μg/mL and was not cytotoxic to mouse macrophage cells (CC50 > 100 μg/mL).

  19. Cooked garlic and antioxidant activity: Correlation with organosulfur compound composition.

    PubMed

    Locatelli, D A; Nazareno, M A; Fusari, C M; Camargo, A B

    2017-04-01

    The antioxidant properties and the main beneficial organosulphur compounds of home-cooked garlic samples were studied in order to establish relationships between them. Antioxidant activity was tested by free radical scavenging against 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and 2,2'-azino-bis-(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS(+)), Fe(III) reducing ability (FRAP) and linoleic acid co-oxidation initiated by soybean lipoxygenase in a micelle system. DPPH, ABTS and FRAP assays showed the highest activity for raw garlic samples, while β-carotene bleaching assay yielded the highest activity for stir-fried garlic. Pure organosulphur compounds tested by DPPH, FRAP and β-carotene bleaching assays showed that allicin had an antiradical action mechanism, as well as iron reducing capacity; while antioxidant activity was the main mechanism for ajoenes and 2-VD. To our knowledge, this study is the first demonstration that home-cooked garlic retains its antioxidant activity, and, at the same time, elucidates the mechanisms involved in this activity.

  20. Antiplatelet and Anticoagulant Activities of Angelica shikokiana Extract and Its Isolated Compounds.

    PubMed

    Mira, Amira; Alkhiary, Wael; Shimizu, Kuniyoshi

    2017-01-01

    Angelica shikokiana is a Japanese medicinal plant that is used traditionally in several ailments of cardiovascular diseases. However, there is no report regarding its anticoagulant or antiplatelet activities. So this study was designed to screen for such activities (anticoagulant by prothrombin time [PT], activated partial thromboplastin time, and thrombin time assays and antiplatelet activities against adenosine 5'-diphosphate [ADP] and arachidonic acid-induced platelet aggregations) for the methanol extract of the aerial part (Angelica methanol extract [AME]), its isolated coumarins, flavonoids, and flavonoid metabolites. The AME had potent anticoagulant and antiplatelet activities, and the flavonoid compounds were evidenced to be responsible for such activities. Among coumarins compounds, hyuganin C showed significant prolongation of only PT, while other coumarins were inactive. Similarly, hyuganin C and bergapten were the only active coumarins against ADP-induced platelet aggregation. Compared to the parent compounds, colonic metabolites of the flavonoids had similar anticoagulant and antiplatelet activities, while glucuronides showed sharp decreases in all studied activities. This is the first report showing that the medicinal plant A shikokiana has potent antiplatelet and anticoagulant activities.

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

    SciTech Connect

    Jacobs, Miriam N. . E-mail: miriam.jacobs@jrc.it; 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 the positive control 10 {mu}M rifampicin ranged from 1.3% (trans-resveratrol) to 152% (ICI 182780). Hydroxylated compounds were marginally more potent than the parent compounds (tamoxifen activation was 74.6% whereas 4 hydroxytamoxifen activation was 84.2%) or significantly greater (vitamin D{sub 3} activation was 1.6%, while hydroxylated vitamin D{sub 3} activation was 55.6%). Enterolactone, the metabolite of common dietary lignans, was a medium activator of PXR (35.6%), compared to the lower activation of a parent lignan, secoisolariciresinol (20%). Two non-hydroxylated PCB congeners (PCB 118 and 153), which present a larger fraction of the PCB contamination of fatty foods, activated hPXR by 26.6% and 17%, respectively. The pesticide trans-nonachlor activation was 53.8%, while the widely used bacteriocide triclosan was a medium activator of hPXR at 46.2%. The responsiveness of PXR to activation by lignan metabolites suggests that dietary intake of these compounds may affect the metabolism of drugs that are CYP3A substrates. Additionally, the evidence that organochlorine chemicals, particularly the ubiquitous triclosan, activate hPXR suggests that these environmental chemicals may, in part, exhibit their endocrine disruptor activities by altering PXR-regulated steroid

  2. Quinolone Amides as Antitrypanosomal Lead Compounds with In Vivo Activity

    PubMed Central

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

    2016-01-01

    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

  3. Factors that influence the response of the LysR type transcriptional regulators to aromatic compounds

    PubMed Central

    2011-01-01

    Background The transcriptional regulators DntR, NagR and NtdR have a high sequence identity and belong to the large family of LysR type transcriptional regulators (LTTRs). These three regulators are all involved in regulation of genes identified in pathways for degradation of aromatic compounds. They activate the transcription of these genes in the presence of an inducer, but the inducer specificity profiles are different. Results The results from this study show that NtdR has the broadest inducer specificity, responding to several nitro-aromatic compounds. Mutational studies of residues that differ between DntR, NagR and NtdR suggest that a number of specific residues are involved in the broader inducer specificity of NtdR when compared to DntR and NagR. The inducer response was also investigated as a function of the experimental conditions and a number of parameters such as the growth media, plasmid arrangement of the LTTR-encoding genes, promoter and gfp reporter gene, and the presence of a His6-tag were shown to affect the inducer response in E.coli DH5α. Furthermore, the response upon addition of both salicylate and 4-nitrobenzoate to the growth media was larger than the sum of responses upon addition of each of the compounds, which suggests the presence of a secondary binding site, as previously reported for other LTTRs. Conclusions Optimization of the growth conditions and gene arrangement resulted in improved responses to nitro-aromatic inducers. The data also suggests the presence of a previously unknown secondary binding site in DntR, analogous to that of BenM. PMID:21884597

  4. Active and responsive polymer surfaces.

    PubMed

    Zhang, Jilin; Han, Yanchun

    2010-02-01

    A central challenge in polymer science today is creating materials that dynamically alter their structures and properties on demand, or in response to changes in their environment. Surfaces represent an attractive area of focus, since they exert disproportionately large effects on properties such as wettability, adhesiveness, optical appearance, and bioactivity, enabling pronounced changes in properties to be accomplished through subtle changes in interfacial structure or chemistry. In this critical review, we review the recent research progress into active and responsive polymer surfaces. The chief purpose of this article is to summarize the advanced preparation techniques and applications in this field from the past decade. This review should be of interest both to new scientists in this field and the interdisciplinary researchers who are working on "intelligent" polymer surfaces (117 references).

  5. Imidazolium compounds are active against all stages of Trypanosoma cruzi.

    PubMed

    Faral-Tello, Paula; Liang, Mary; Mahler, Graciela; Wipf, Peter; Robello, Carlos

    2014-03-01

    Imidazolium salts are best known for their applications in organic synthesis as room-temperature ionic liquids, or as precursors of stable carbenes, but they also show important biological properties such as anti-oxidative effects, induction of mitochondrial membrane permeabilisation and inhibition of the infection cycle of Plasmodium falciparum. For these reasons, and since chemotherapy for Chagas disease is inefficient, the aim of this study was to test the use of imidazolium compounds against the kinetoplastid haemoflagellate aetiological agent for this disease, namely Trypanosoma cruzi. The results show that five of the tested compounds are more effective than the reference drug benznidazole against the epimastigote and trypomastigote forms of T. cruzi. Moreover, intracellular amastigotes were also affected by the compounds, which showed lower toxicity in host cells. Transmission electron microscopy analysis demonstrated that the tested agents induced alterations of the kinetoplast and particularly of the mitochondria, leading to extraordinary swelling of the organelle. These results further demonstrate that the test agents with the best profile are those bearing symmetrical bulky substituents at N(1) and N(3), displaying promising activity against all forms of T. cruzi, interesting selectivity indexes and exceptional activity at low doses. Accordingly, these agents represent promising candidates for the treatment of Chagas disease.

  6. Platelet anti-aggregation activities of compounds from Cinnamomum cassia.

    PubMed

    Kim, Sun Young; Koo, Yean Kyoung; Koo, Ja Yong; Ngoc, Tran Minh; Kang, Sam Sik; Bae, KiHwan; Kim, Yeong Sik; Yun-Choi, Hye Sook

    2010-10-01

    Cinnamomum cassia is a well-known traditional medicine for improvement of blood circulation. An extract of this plant showed both platelet anti-aggregation and blood anti-coagulation effects in preliminary testing. Among the 13 compounds obtained from this plant, eugenol (2), amygdalactone (4), cinnamic alcohol (5), 2-hydroxycinnamaldehyde (7), 2-methoxycinnamaldehyde (8), and coniferaldehyde (9) showed 1.5-73-fold greater inhibitory effects than acetylsalicylic acid (ASA) on arachidonic acid (AA)-induced aggregation (50% inhibitory concentration [IC₅₀] = 3.8, 5.16, 31.2, 40.0, 16.9, and 0.82 μM, respectively, vs. 60.3 μM) and 6.3-730-fold stronger effect than ASA on U46619 (a thromboxane A₂ mimic)-induced aggregation (IC₅₀ = 3.51, 33.9, 31.0, 51.3, 14.6, and 0.44 μM, respectively, vs. 321 μM). The other compounds, coumarin (3), cinnamaldehyde (6), cinnamic acid (10), icariside DC (11), and dihydrocinnacasside (12), also inhibited (2.5 to four times greater than ASA) U46619-induced aggregation. In addition, compounds 2, 4, 5, 6, 7, 8, and 9 were 1.3-87 times more effective than ASA against epinephrine-induced aggregation (IC₅₀ = 1.86, 1.10, 37.7, 25.0, 16.8, 15.3, and 0.57 μM, respectively, vs. 50.0 μM). However, the 13 compounds were only very mildly effective against blood coagulation, if at all. In conclusion, compounds 2, 4, 8, and 9 showed stronger inhibitory potencies than others on AA-, U46619-, and epinephrine-induced platelet aggregation. Eugenol (2) and coniferaldehyde (9) were the two of the most active anti-platelet constituents of C. cassia.

  7. Active Response Gravity Offload System

    NASA Technical Reports Server (NTRS)

    Valle, Paul; Dungan, Larry; Cunningham, Thomas; Lieberman, Asher; Poncia, Dina

    2011-01-01

    The Active Response Gravity Offload System (ARGOS) provides the ability to simulate with one system the gravity effect of planets, moons, comets, asteroids, and microgravity, where the gravity is less than Earth fs gravity. The system works by providing a constant force offload through an overhead hoist system and horizontal motion through a rail and trolley system. The facility covers a 20 by 40-ft (approximately equals 6.1 by 12.2m) horizontal area with 15 ft (approximately equals4.6 m) of lifting vertical range.

  8. Natural Product Compounds with Aromatase Inhibitory Activity: An Update

    PubMed Central

    Balunas, Marcy J.; Kinghorn, A. Douglas

    2010-01-01

    Several synthetic aromatase inhibitors are currently in clinical use for the treatment of postmenopausal women with hormone-receptor positive breast cancer. However, these treatments may lead to untoward side effects and so a search for new aromatase inhibitors continues, especially those for which the activity is promoter-specific, targeting the breast-specific promoters I.3 and II. Recently, numerous natural product compounds have been found to inhibit aromatase in non-cellular, cellular, and in vivo studies. These investigations, covering the last two years, as well as additional studies that have focused on the evaluation of natural product compounds as promoter-specific aromatase inhibitors or as aromatase inducers, are described in this review. PMID:20635310

  9. Pharmacologically active compounds in the environment and their chirality.

    PubMed

    Kasprzyk-Hordern, Barbara

    2010-11-01

    Pharmacologically active compounds including both legally used pharmaceuticals and illicit drugs are potent environmental contaminants. Extensive research has been undertaken over the recent years to understand their environmental fate and toxicity. The one very important phenomenon that has been overlooked by environmental researchers studying the fate of pharmacologically active compounds in the environment is their chirality. Chiral drugs can exist in the form of enantiomers, which have similar physicochemical properties but differ in their biological properties such as distribution, metabolism and excretion, as these processes (due to stereospecific interactions of enantiomers with biological systems) usually favour one enantiomer over the other. Additionally, due to different pharmacological activity, enantiomers of chiral drugs can differ in toxicity. Furthermore, degradation of chiral drugs during wastewater treatment and in the environment can be stereoselective and can lead to chiral products of varied toxicity. The distribution of different enantiomers of the same chiral drug in the aquatic environment and biota can also be stereoselective. Biological processes can lead to stereoselective enrichment or depletion of the enantiomeric composition of chiral drugs. As a result the very same drug might reveal different activity and toxicity and this will depend on its origin and exposure to several factors governing its fate in the environment. In this critical review a discussion of the importance of chirality of pharmacologically active compounds in the environmental context is undertaken and suggestions for directions in further research are made. Several groups of chiral drugs of major environmental relevance are discussed and their pharmacological action and disposition in the body is also outlined as it is a key factor in developing a full understanding of their environmental occurrence, fate and toxicity. This review will be of interest to environmental

  10. Screening for antiviral activities of isolated compounds from essential oils.

    PubMed

    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.

  11. Photoelectrochemical response of some layered chalcogenophosphate compounds /MPX3/

    NASA Technical Reports Server (NTRS)

    Byvik, C. E.; Reichman, B.; Coleman, D. W.

    1982-01-01

    New photoelectrochemical results for the layered chalcogenophosphate compounds MPX3, FePS3, NiPS3, and SnPS3 are presented. The compounds were grown by iodine vapor transport in quartz ampules from a stoichiometric amount of the elements. Crystals of the layered type up to 10 mm x 10 mm x 0.1 mm were grown. The results of the layered compounds from the MPX3 series show good stability in acid solutions under photoelectrolysis condition. The relatively slow increase in the photocurrent with increasing electrode potential suggests high recombination rates for the photogenerated carriers in these layered materials. It is noted that improvements may be possible by, for example, optimizing the preparation of the crystals and the electrode surfaces.

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

    NASA Astrophysics Data System (ADS)

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

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

  13. Influence of redox-active compounds and PXR-activators on human MRP1 and MRP2 gene expression.

    PubMed

    Kauffmann, Hans Martin; Pfannschmidt, Sylvia; Zöller, Heike; Benz, Anke; Vorderstemann, Birgit; Webster, Jeanette I; Schrenk, Dieter

    2002-02-28

    In the present study, we investigated the inducibility of the drug conjugate transporter genes MRP1 and MRP2 by redox-active compounds such as tertiary butylated hydroquinone (tBHQ) and quercetin and by chemicals known to activate the pregnane X receptor (PXR) such as rifampicin and clotrimazol and by the metalloid compound arsenite. The human MRP2 gene was found to be inducible in HepG2 cells by rifampicin, clotrimazol, arsenite and tBHQ. As MRP1 expression is extremely low in HepG2 cells, its inducibility was studied in MCF-7 cells. However, only tBHQ and quercetin acted as inducers, but not the other compounds investigated. Reporter gene assays demonstrated that proximal promoter regions of the genes contribute to the induction by tBHQ, quercetin (MRP1) and clotrimazol (MRP2). However, the deletion of binding sites supposed to mediate the induction process (a PXR-binding element-like sequence for the clotrimazol effect and an ARE (antioxidative response element) for the tBHQ/quercetin effect) did not result in a significant decrease in the induction factor indicating that other parts of the promoter are probably involved in the induction process. In summary, expression of both genes can be up-regulated by redox-active compounds, while the other compounds tested induced only MRP2 but not MRP1 expression.

  14. ULTRAVIOLET PROTECTIVE COMPOUNDS AS A RESPONSE TO ULTRAVIOLET RADIATION EXPOSURE

    EPA Science Inventory

    Life on Earth has evolved adaptations to many environmental stresses over the epochs. One consistent stress has been exposure to ultraviolet radiation. In response to UVR organisms have adapted myriad responses; behavioral, morphological and physiological. Behaviorally, some orga...

  15. Novel Antiproliferative Chimeric Compounds with Marked Histone Deacetylase Inhibitory Activity

    PubMed Central

    2014-01-01

    Given our interest in finding potential antitumor agents and in view of the multifactorial mechanistic nature of cancer, in the present work, taking advantage of the multifunctional ligands approach, new chimeric molecules were designed and synthesized by combining in single chemical entities structural features of SAHA, targeting histone deacetylases (HDACs), with substituted stilbene or terphenyl derivatives previously obtained by us and endowed with antiproliferative and pro-apoptotic activity. The new chimeric derivatives were characterized with respect to their cytotoxic activity and their effects on cell cycle progression on different tumor cell lines, as well as their HDACs inhibition. Among the other, trans-6 showed the most interesting biological profile, as it exhibited a strong pro-apoptotic activity in tumor cell lines in comparison with both of its parent compounds and a marked HDAC inhibition. PMID:25221651

  16. Endophytic fungal compounds active against Cryptococcus neoformans and C. gattii.

    PubMed

    Pereira, Cristiane B; de Oliveira, Djalma M; Hughes, Alice Fs; Kohlhoff, Markus; LA Vieira, Mariana; Martins Vaz, Aline B; Ferreira, Mariana C; Carvalho, Camila R; Rosa, Luiz H; Rosa, Carlos A; Alves, Tânia Ma; Zani, Carlos L; Johann, Susana; Cota, Betania B

    2015-07-01

    Infections with Cryptococcus are invasive mycoses associated with significant morbidity and mortality, mainly in immunosuppressed patients. Several drugs have been introduced to combat these opportunistic infections. However, resistance of this organism to antifungal drugs has increased, causing difficulties in the treatment. The goal of this work was to evaluate the antifungal activity of ethanol extracts from endophytic fungi isolated from plants collected from different Brazilian ecosystems and to perform the fractionation of the most promising extract. Four-hundred fungal extracts were investigated by microdilution broth assays against Cryptococcus neoformans and Cryptococcus gattii at a concentration of 500 μg ml(-1). Among them, the extract of Mycosphaerella sp. UFMGCB 2032, an endophytic fungus isolated from the plant Eugenia bimarginata DC. (Myrtaceae) exhibited outstanding antifungal activity against C. neoformans and C. gattii, with MIC values of 31.2 μg ml(-1) and 7.8 μg ml(-1), respectively. The fractionation of this extract using liquid-liquid partitioning and semi-preparative HPLC afforded two eicosanoic acids with antifungal activity, compound 1, (2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-(hydroxymethyl)-14-oxoeicos-6,12-dienoic acid with MIC values ranging from 1.3-2.50 μg ml(-1), and compound 2, known as myriocin, with MIC values of 0.5 μg ml(-1) against C. neoformans and C. gattii. These compounds are reported for the first time in the Mycosphaerella genus.

  17. Extremely Randomized Machine Learning Methods for Compound Activity Prediction.

    PubMed

    Czarnecki, Wojciech M; Podlewska, Sabina; Bojarski, Andrzej J

    2015-11-09

    Speed, a relatively low requirement for computational resources and high effectiveness of the evaluation of the bioactivity of compounds have caused a rapid growth of interest in the application of machine learning methods to virtual screening tasks. However, due to the growth of the amount of data also in cheminformatics and related fields, the aim of research has shifted not only towards the development of algorithms of high predictive power but also towards the simplification of previously existing methods to obtain results more quickly. In the study, we tested two approaches belonging to the group of so-called 'extremely randomized methods'-Extreme Entropy Machine and Extremely Randomized Trees-for their ability to properly identify compounds that have activity towards particular protein targets. These methods were compared with their 'non-extreme' competitors, i.e., Support Vector Machine and Random Forest. The extreme approaches were not only found out to improve the efficiency of the classification of bioactive compounds, but they were also proved to be less computationally complex, requiring fewer steps to perform an optimization procedure.

  18. Large-scale assessment of activity landscape feature probabilities of bioactive compounds.

    PubMed

    Kayastha, Shilva; Dimova, Dilyana; Iyer, Preeti; Vogt, Martin; Bajorath, Jürgen

    2014-02-24

    Activity landscape representations integrate pairwise compound similarity and potency relationships and provide direct access to characteristic structure-activity relationship features in compound data sets. Because pairwise compound comparisons provide the foundation of activity landscape design, the assessment of specific landscape features such as activity cliffs has generally been confined to the level of compound pairs. A conditional probability-based approach has been applied herein to assign most probable activity landscape features to individual compounds. For example, for a given data set compound, it was determined if it would preferentially engage in the formation of activity cliffs or other landscape features. In a large-scale effort, we have determined conditional activity landscape feature probabilities for more than 160,000 compounds with well-defined activity annotations contained in 427 different target-based data sets. These landscape feature probabilities provide a detailed view of how different activity landscape features are distributed over currently available bioactive compounds.

  19. Catalytic activities of zeolite compounds for decomposing aqueous ozone.

    PubMed

    Kusuda, Ai; Kitayama, Mikito; Ohta, Yoshio

    2013-12-01

    The advanced oxidation process (AOP), chemical oxidation using aqueous ozone in the presence of appropriate catalysts to generate highly reactive oxygen species, offers an attractive option for removing poorly biodegradable pollutants. Using the commercial zeolite powders with various Si/Al ratios and crystal structures, their catalytic activities for decomposing aqueous ozone were evaluated by continuously flowing ozone to water containing the zeolite powders. The hydrophilic zeolites (low Si/Al ratio) with alkali cations in the crystal structures were found to possess high catalytic activity for decomposing aqueous ozone. The hydrophobic zeolite compounds (high Si/Al ratio) were found to absorb ozone very well, but to have no catalytic activity for decomposing aqueous ozone. Their catalytic activities were also evaluated by using the fixed bed column method. When alkali cations were removed by acid rinsing or substituted by alkali-earth cations, the catalytic activities was significantly deteriorated. These results suggest that the metal cations on the crystal surface of the hydrophilic zeolite would play a key role for catalytic activity for decomposing aqueous ozone.

  20. 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

  1. Bioactive compounds and antioxidant activity of wolfberry infusion.

    PubMed

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

    2017-01-19

    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.

  2. Influence of plasma-activated compounds on melanogenesis and tyrosinase activity

    NASA Astrophysics Data System (ADS)

    Ali, Anser; Ashraf, Zaman; Kumar, Naresh; Rafiq, Muhammad; Jabeen, Farukh; Park, Ji Hoon; Choi, Ki Hong; Lee, Seunghyun; Seo, Sung-Yum; Choi, Eun Ha; Attri, Pankaj

    2016-03-01

    Many organic chemists around the world synthesize medicinal compounds or extract multiple compounds from plants in order to increase the activity and quality of medicines. In this work, we synthesized new eugenol derivatives (ED) and then treated them with an N2 feeding gas atmospheric pressure plasma jet (APPJ) to increase their utility. We studied the tyrosinase-inhibition activity (activity test) and structural changes (circular dichroism) of tyrosinase with ED and plasma activated eugenol derivatives (PAED) in a cell-free environment. Later, we used docking studies to determine the possible interaction sites of ED and PAED compounds with tyrosinase enzyme. Moreover, we studied the possible effect of ED and PAED on melanin synthesis and its mechanism in melanoma (B16F10) cells. Additionally, we investigated the structural changes that occurred in activated ED after plasma treatment using nuclear magnetic resonance (NMR). Hence, this study provides a new perspective on PAED for the field of plasma medicine.

  3. Influence of plasma-activated compounds on melanogenesis and tyrosinase activity.

    PubMed

    Ali, Anser; Ashraf, Zaman; Kumar, Naresh; Rafiq, Muhammad; Jabeen, Farukh; Park, Ji Hoon; Choi, Ki Hong; Lee, SeungHyun; Seo, Sung-Yum; Choi, Eun Ha; Attri, Pankaj

    2016-03-02

    Many organic chemists around the world synthesize medicinal compounds or extract multiple compounds from plants in order to increase the activity and quality of medicines. In this work, we synthesized new eugenol derivatives (ED) and then treated them with an N2 feeding gas atmospheric pressure plasma jet (APPJ) to increase their utility. We studied the tyrosinase-inhibition activity (activity test) and structural changes (circular dichroism) of tyrosinase with ED and plasma activated eugenol derivatives (PAED) in a cell-free environment. Later, we used docking studies to determine the possible interaction sites of ED and PAED compounds with tyrosinase enzyme. Moreover, we studied the possible effect of ED and PAED on melanin synthesis and its mechanism in melanoma (B16F10) cells. Additionally, we investigated the structural changes that occurred in activated ED after plasma treatment using nuclear magnetic resonance (NMR). Hence, this study provides a new perspective on PAED for the field of plasma medicine.

  4. Influence of plasma-activated compounds on melanogenesis and tyrosinase activity

    PubMed Central

    Ali, Anser; Ashraf, Zaman; Kumar, Naresh; Rafiq, Muhammad; Jabeen, Farukh; Park, Ji Hoon; Choi, Ki Hong; Lee, SeungHyun; Seo, Sung-Yum; Choi, Eun Ha; Attri, Pankaj

    2016-01-01

    Many organic chemists around the world synthesize medicinal compounds or extract multiple compounds from plants in order to increase the activity and quality of medicines. In this work, we synthesized new eugenol derivatives (ED) and then treated them with an N2 feeding gas atmospheric pressure plasma jet (APPJ) to increase their utility. We studied the tyrosinase-inhibition activity (activity test) and structural changes (circular dichroism) of tyrosinase with ED and plasma activated eugenol derivatives (PAED) in a cell-free environment. Later, we used docking studies to determine the possible interaction sites of ED and PAED compounds with tyrosinase enzyme. Moreover, we studied the possible effect of ED and PAED on melanin synthesis and its mechanism in melanoma (B16F10) cells. Additionally, we investigated the structural changes that occurred in activated ED after plasma treatment using nuclear magnetic resonance (NMR). Hence, this study provides a new perspective on PAED for the field of plasma medicine. PMID:26931617

  5. A novel dicyclodextrinyl ditelluride compound with antioxidant activity.

    PubMed

    Ren, X; Xue, Y; Zhang, K; Liu, J; Luo, G; Zheng, J; Mu, Y; Shen, J

    2001-11-02

    Reactive oxygen species (ROS) primarily arise from products of normal metabolic activities and are thought to be the etiology of many diseases. A novel dicyclodextrinyl ditelluride (2-TeCD) compound was designed to be a functional mimic of the glutathione peroxidase that normally removes ROS. 2-TeCD exhibited highly catalytic efficiency and good water solubility. Antioxidant activity was studied by using ferrous sulfate/ascorbate-induced mitochondria damage model system. 2-TeCD protected the mitochondria against oxidative damage in a dose-dependent manner and exhibited also great antioxidant ability in comparison with 2-phenyl-1,2-benziososelenazol-3(2H)-one. The mimic may result in better clinical therapies for the treatment of ROS-mediated diseases.

  6. [Estrogenic activity of ultraviolet absorbers and the related compounds].

    PubMed

    Matsumoto, Hisashi; Adachi, Shinichi; Suzuki, Yasuhiko

    2005-08-01

    The estrogenic activities of ultraviolet absorbers and their related compounds were investigated using MCF-7 cell proliferation assay. Nine of 33 chemicals (benzophenone, 2,4-dihydroxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 4-hydroxybenzophenone, 3-(4-methylbenzylidene) camphor, ethyl 2-cyano-3,3-diphenylacrylate (etocrylene) and 2-ethylhexyl-2-cyano-3,3-diphenylacrylate (octocrylene)) were positive compared with the vehicle control. Benzhydrol, ethyl cinnamate and 2,2'-dihydroxy-4-methoxybenzophenone were weakly active. When each xenoestrogen was added to the cells along with ICI 182780, an estrogen receptor (ER) antagonist, the cell growth was reduced according to its doses. Therefore, the cell proliferation was suggested to generate through ER. Most of these chemicals were also positive using CHOOSER assay, a new method of testing estrogenic activity of xenoestrogen. Each xenoestrogen was also confirmed to bind to ERalpha and ERbeta using a human ER competitive binding assay against 17beta-estradiol. The concentration order of the strength of its inhibitory effect using both ERalpha and ERbeta was similar to that of MCF-7 cell proliferation assay, except for benzyl 4-hydroxybenzoate (B4HB). B4HB showed a stronger activity on CHOOSER assay and the competitive binding assay using both ERalpha and ERbeta, although there was no activity observed on MCF-7 cell proliferation assay. Our findings were to detect the estrogenic activity of etocrylene and octocrylene in vitro, in addition to confirming the activities of some ultraviolet absorbers as previously reported.

  7. Targeting prostate cancer with compounds possessing dual activity as androgen receptor antagonists and HDAC6 inhibitors.

    PubMed

    Jadhavar, Pradeep S; Ramachandran, Sreekanth A; Riquelme, Eduardo; Gupta, Ashu; Quinn, Kevin P; Shivakumar, Devleena; Ray, Soumya; Zende, Dnyaneshwar; Nayak, Anjan K; Miglani, Sandeep K; Sathe, Balaji D; Raja, Mohd; Farias, Olivia; Alfaro, Ivan; Belmar, Sebastián; Guerrero, Javier; Bernales, Sebastián; Chakravarty, Sarvajit; Hung, David T; Lindquist, Jeffrey N; Rai, Roopa

    2016-11-01

    While enzalutamide and abiraterone are approved for treatment of metastatic castration-resistant prostate cancer (mCRPC), approximately 20-40% of patients have no response to these agents. It has been stipulated that the lack of response and the development of secondary resistance to these drugs may be due to the presence of AR splice variants. HDAC6 has a role in regulating the androgen receptor (AR) by modulating heat shock protein 90 (Hsp90) acetylation, which controls the nuclear localization and activation of the AR in androgen-dependent and independent scenarios. With dual-acting AR-HDAC6 inhibitors it should be possible to target patients who don't respond to enzalutamide. Herein, we describe the design, synthesis and biological evaluation of dual-acting compounds which target AR and are also specific towards HDAC6. Our efforts led to compound 10 which was found to have potent dual activity (HDAC6 IC50=0.0356μM and AR binding IC50=<0.03μM). Compound 10 was further evaluated for antagonist and other cell-based activities, in vitro stability and pharmacokinetics.

  8. Biological Activities of Phenolic Compounds of Extra Virgin Olive Oil.

    PubMed

    Servili, Maurizio; Sordini, Beatrice; Esposto, Sonia; Urbani, Stefania; Veneziani, Gianluca; Di Maio, Ilona; Selvaggini, Roberto; Taticchi, Agnese

    2013-12-20

    Over the last few decades, multiple biological properties, providing antioxidant, anti-inflammatory, chemopreventive and anti-cancer benefits, as well as the characteristic pungent and bitter taste, have been attributed to Extra Virgin Olive Oil (EVOO) phenols. In particular, growing efforts have been devoted to the study of the antioxidants of EVOO, due to their importance from health, biological and sensory points of view. Hydrophilic and lipophilic phenols represent the main antioxidants of EVOO, and they include a large variety of compounds. Among them, the most concentrated phenols are lignans and secoiridoids, with the latter found exclusively in the Oleaceae family, of which the drupe is the only edible fruit. In recent years, therefore, we have tackled the study of the main properties of phenols, including the relationships between their biological activity and the related chemical structure. This review, in fact, focuses on the phenolic compounds of EVOO, and, in particular, on their biological properties, sensory aspects and antioxidant capacity, with a particular emphasis on the extension of the product shelf-life.

  9. Biological Activities of Phenolic Compounds of Extra Virgin Olive Oil

    PubMed Central

    Servili, Maurizio; Sordini, Beatrice; Esposto, Sonia; Urbani, Stefania; Veneziani, Gianluca; Maio, Ilona Di; Selvaggini, Roberto; Taticchi, Agnese

    2013-01-01

    Over the last few decades, multiple biological properties, providing antioxidant, anti-inflammatory, chemopreventive and anti-cancer benefits, as well as the characteristic pungent and bitter taste, have been attributed to Extra Virgin Olive Oil (EVOO) phenols. In particular, growing efforts have been devoted to the study of the antioxidants of EVOO, due to their importance from health, biological and sensory points of view. Hydrophilic and lipophilic phenols represent the main antioxidants of EVOO, and they include a large variety of compounds. Among them, the most concentrated phenols are lignans and secoiridoids, with the latter found exclusively in the Oleaceae family, of which the drupe is the only edible fruit. In recent years, therefore, we have tackled the study of the main properties of phenols, including the relationships between their biological activity and the related chemical structure. This review, in fact, focuses on the phenolic compounds of EVOO, and, in particular, on their biological properties, sensory aspects and antioxidant capacity, with a particular emphasis on the extension of the product shelf-life. PMID:26784660

  10. Antibacterial Activity of Alanine-Derived Gemini Quaternary Ammonium Compounds.

    PubMed

    Piecuch, Agata; Obłąk, Ewa; Guz-Regner, Katarzyna

    The antibacterial activity of alanine-derived gemini quaternary ammonium salts (chlorides and bromides) with various spacer and alkyl chain lengths was investigated. The studied compounds exhibited a strong bactericidal effect, especially bromides with 10 and 12 carbon alkyl chains and 3 carbon spacer groups (TMPAL-10 Br and TMPAL-12 Br), with a short contact time. Both salts dislodged biofilms of Pseudomonas aeruginosa and Staphylococcus epidermidis, and were lethal to adherent cells of S. epidermidis. Bromide with 2 carbon spacer groups and 12 carbon alkyl chains (TMEAL-12 Br) effectively reduced microbial adhesion by coating polystyrene and silicone surfaces. The results obtained suggest that, after further studies, gemini QAS might be considered as antimicrobial agents in medicine or industry.

  11. Irreversible adsorption of phenolic compounds by activated carbons

    SciTech Connect

    Grant, T.M.; King, C.J.

    1988-12-01

    Studies were undertaken to determine the reasons why phenolic sorbates can be difficult to remove and recover from activated carbons. The chemical properties of the sorbate and the adsorbent surface, and the influences of changes in the adsorption and desorption conditions were investigated. Comparison of isotherms established after different contact times or at different temperatures indicated that phenolic compounds react on carbon surfaces. The reaction rate is a strong function of temperature. Regeneration of carbons by leaching with acetone recovered at least as much phenol as did regeneration with other solvents or with displacers. The physiochemical properties of adsorbents influences irreversible uptakes. Sorbates differed markedly in their tendencies to undergo irreversible adsorption. 64 refs., 47 figs., 32 tabs.

  12. [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.

  13. Radioprotective effects of active compounds from Acanthopanax senticosus of Lesser Khingan Mountain in China

    NASA Astrophysics Data System (ADS)

    Lu, Weihong; Sun, Yeqing; Shi, Jinming

    Bioactive compounds including polysaccharides, flavones, syringin and eleutheroside E were extracted from wild Acanthopanax senticosus and purified by chromatography. In vitro and in vivo anti-radiation activities of the compounds were compared. In vitro radical scavenging results showed that polysaccharides and flavones were more effective than syringin and eleutheroside E in In vivo study proved that polysaccharides and flavones were effective in protecting mice from heavy ion radiation induced oxidative damages. Also, the activity of polysaccharides and flavones in repressing expression changes of radiation response proteins including heat shock protein, disulfide-isomerase and glutathione S-transferase were also found by our results. Moreover, the radioprotective effects were more significant when polysaccharides and flavones were used together.

  14. Refractory Organic Compounds in Enceladus' Ice Grains and Hydrothermal Activity

    NASA Astrophysics Data System (ADS)

    Postberg, F.; Khawaja, N.; Hsu, H. W.; Sekine, Y.; Shibuya, T.

    2015-12-01

    Cassini's Cosmic Dust Analyzer (CDA) generates time-of-flight mass spectra of individual grains impinging on the instruments target-plate. Following the analysis of salt rich ice grains emitted by Enceladus that indicated a salt-water ocean in contact with the moon's rocky core [1,2] a recent CDA analysis of nano-phase silica particles pointed at hydrothermal activity at the moon's rock/water interface [3]. The results imply temperatures above 80 - 90°C and alkaline pH values around 10 reminiscent of alkaline hydrothermal vents on Earth like the Lost City Hydrothermal Field. In this context the compositional analysis of organic components in CDA mass spectra of the ejected ice grains is of particular relevance. A multitude of volatile organic species has already been identified in the gas component of the plume [4]. As expected, we find more complex organic molecules in ice grains than in the gas indicating aromatic species, amines, and carbonyl group species. The composition of organic-bearing ice grains displays a great diversity indicating a variety of different organic species in varying concentrations. Recent spatially resolved CDA in situ measurements inside Enceladus' plume indicate that these organic compounds are especially frequent in 'young' ice grains that have just been ejected by high velocity jets. We investigate the implications of our findings with respect to ice grain formation at the water surface and inside the icy vents. We constrain the generation of organic compounds at the rock/water interface in the light of hydrothermal activity and the potential for the formation of life precursor molecules in Enceladus' ocean. Ref:[1] Postberg et al., Nature 459, 1098-1101 (2009). [2] Postberg et al., Nature 474, 620-622 (2011). [3]. Hsu, Postberg, Sekine et al., Nature, 519, 207-210 (2015). [4] Waite et al., Nature 460, 487-490 (2009).

  15. Queen signals in a stingless bee: suppression of worker ovary activation and spatial distribution of active compounds

    PubMed Central

    Nunes, Túlio M.; Mateus, Sidnei; Favaris, Arodi P.; Amaral, Mônica F. Z. J.; von Zuben, Lucas G.; Clososki, Giuliano C.; Bento, José M. S.; Oldroyd, Benjamin P.; Silva, Ricardo; Zucchi, Ronaldo; Silva, Denise B.; Lopes, Norberto P.

    2014-01-01

    In most species of social insect the queen signals her presence to her workers via pheromones. Worker responses to queen pheromones include retinue formation around the queen, inhibition of queen cell production and suppression of worker ovary activation. Here we show that the queen signal of the Brazilian stingless bee Friesella schrottkyi is a mixture of cuticular hydrocarbons. Stingless bees are therefore similar to ants, wasps and bumble bees, but differ from honey bees in which the queen's signal mostly comprises volatile compounds originating from the mandibular glands. This shows that cuticular hydrocarbons have independently evolved as the queen's signal across multiple taxa, and that the honey bees are exceptional. We also report the distribution of four active queen-signal compounds by Matrix-assisted laser desorption/ionization (MALDI) imaging. The results indicate a relationship between the behavior of workers towards the queen and the likely site of secretion of the queen's pheromones. PMID:25502598

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

    PubMed Central

    2014-01-01

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

  17. 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.

  18. Bronchial responsiveness in active steelworkers.

    PubMed

    Corhay, J L; Bury, T; Louis, R; Delavignette, J P; Kayembe, J M; Weber, G; Albert, A; Radermecker, M F

    1998-02-01

    Coke-oven workers are exposed to dust and irritant gases. Therefore they are at risk of developing lung diseases including chronic bronchitis. Nonspecific bronchial hyperresponsiveness (BHR) has been advocated as a potential risk factor predisposing to the development of chronic bronchitis. In a previous study, we showed that prevalence of BHR was higher in retired coke-oven workers than in retired blast furnace workers. The present study was carried out to determine the prevalence of BHR in active steelworkers. Thus, 137 coke-oven workers and 150 blast furnace workers underwent clinical examination, a standardized questionnaire for the study of respiratory symptoms, pulmonary function testing and methacholine aerosol challenge. The study demonstrates a higher prevalence and degree of BHR [provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) < or = 8 mg x mL(-1)] in coke-oven workers than in blast furnace workers (31.4 versus 6.7%; p<0.001). Moreover, the frequency of respiratory symptoms and basal bronchial obstruction were greater among coke-oven workers with BHR in nonresponders. The basal maximum expiratory flow from 25-75% of forced vital capacity and the respiratory symptoms were correlated with bronchial responsiveness. The lack of correlation observed between BHR and the intensity of smoking or years spent in coke-oven environment may be explained by the high proportion of smokers, the worker turnover in the steel plant, and the "healthy worker effect". In conclusion, the higher prevalence and degree of bronchial hyperresponsiveness in coke-oven workers suggests that coke-oven pollutants are more intense irritants than those that escape from blast furnaces.

  19. 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.

  20. 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.

  1. 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

  2. Data-Driven Derivation of an "Informer Compound Set" for Improved Selection of Active Compounds in High-Throughput Screening.

    PubMed

    Paricharak, Shardul; IJzerman, Adriaan P; Jenkins, Jeremy L; Bender, Andreas; Nigsch, Florian

    2016-09-26

    Despite the usefulness of high-throughput screening (HTS) in drug discovery, for some systems, low assay throughput or high screening cost can prohibit the screening of large numbers of compounds. In such cases, iterative cycles of screening involving active learning (AL) are employed, creating the need for smaller "informer sets" that can be routinely screened to build predictive models for selecting compounds from the screening collection for follow-up screens. Here, we present a data-driven derivation of an informer compound set with improved predictivity of active compounds in HTS, and we validate its benefit over randomly selected training sets on 46 PubChem assays comprising at least 300,000 compounds and covering a wide range of assay biology. The informer compound set showed improvement in BEDROC(α = 100), PRAUC, and ROCAUC values averaged over all assays of 0.024, 0.014, and 0.016, respectively, compared to randomly selected training sets, all with paired t-test p-values <10(-15). A per-assay assessment showed that the BEDROC(α = 100), which is of particular relevance for early retrieval of actives, improved for 38 out of 46 assays, increasing the success rate of smaller follow-up screens. Overall, we showed that an informer set derived from historical HTS activity data can be employed for routine small-scale exploratory screening in an assay-agnostic fashion. This approach led to a consistent improvement in hit rates in follow-up screens without compromising scaffold retrieval. The informer set is adjustable in size depending on the number of compounds one intends to screen, as performance gains are realized for sets with more than 3,000 compounds, and this set is therefore applicable to a variety of situations. Finally, our results indicate that random sampling may not adequately cover descriptor space, drawing attention to the importance of the composition of the training set for predicting actives.

  3. Pseudoalteromonas haloplanktis produces methylamine, a volatile compound active against Burkholderia cepacia complex strains.

    PubMed

    Sannino, Filomena; Parrilli, Ermenegilda; Apuzzo, Gennaro Antonio; de Pascale, Donatella; Tedesco, Pietro; Maida, Isabel; Perrin, Elena; Fondi, Marco; Fani, Renato; Marino, Gennaro; Tutino, Maria Luisa

    2017-03-25

    The Antarctic marine bacterium Pseudoalteromonas haloplanktis TAC125 has been reported to produce several Volatile Organic Compounds (VOCs), which are able to inhibit the growth of Burkholderia cepacia complex (Bcc) strains, opportunistic pathogens responsible for the infection of immune-compromised patients. However, no specific antibacterial VOCs have been identified to date. The purpose of the present study was to identify specific VOCs that contribute to Bcc inhibition by the Antarctic strain. When grown on defined medium containing D-gluconate and L-glutamate as carbon, nitrogen and energy sources, P. haloplanktis TAC125 is unable to inhibit the growth of Bcc strains. However, single addition of several amino acids to the defined medium restores the P. haloplanktis TAC125 inhibition ability. With the aim of identifying specific volatile compound/s responsible for Bcc inhibition, we set up an apparatus for VOC capture, accumulation, and storage. P. haloplanktis TAC125 was grown in an automatic fermenter which was connected to a cooling system to condense VOCs present in the exhaust air outlet. Upon addition of methionine to the growth medium, the VOC methylamine was produced by P. haloplanktis TAC125. Methylamine was found to inhibit the growth of several Bcc strains in a dose-dependent way. Although it was reported that P. haloplanktis TAC125 produces VOCs endowed with antimicrobial activity, this is the first demonstration that methylamine probably contributes to the anti-Bcc activity of P. haloplanktis TAC125 VOCs.

  4. Compound

    NASA Astrophysics Data System (ADS)

    Suzumura, Akitoshi; Watanabe, Masaki; Nagasako, Naoyuki; Asahi, Ryoji

    2014-06-01

    Recently, Cu-based chalcogenides such as Cu3SbSe4, Cu2Se, and Cu2SnSe3 have attracted much attention because of their high thermoelectric performance and their common feature of very low thermal conductivity. However, for practical use, materials without toxic elements such as selenium are preferable. In this paper, we report Se-free Cu3SbS4 thermoelectric material and improvement of its figure of merit ( ZT) by chemical substitutions. Substitutions of 3 at.% Ag for Cu and 2 at.% Ge for Sb lead to significant reductions in the thermal conductivity by 37% and 22%, respectively. These substitutions do not sacrifice the power factor, thus resulting in enhancement of the ZT value. The sensitivity of the thermal conductivity to chemical substitutions in these compounds is discussed in terms of the calculated phonon dispersion and previously proposed models for Cu-based chalcogenides. To improve the power factor, we optimize the hole carrier concentration by substitution of Ge for Sb, achieving a power factor of 16 μW/cm K2 at 573 K, which is better than the best reported for Se-based Cu3SbSe4 compounds.

  5. Allergy-Inducing Chromium Compounds Trigger Potent Innate Immune Stimulation Via ROS-Dependent Inflammasome Activation.

    PubMed

    Adam, Christian; Wohlfarth, Jonas; Haußmann, Maike; Sennefelder, Helga; Rodin, Annette; Maler, Mareike; Martin, Stefan F; Goebeler, Matthias; Schmidt, Marc

    2017-02-01

    Chromium allergy is a common occupational skin disease mediated by chromium (VI)-specific T cells that induce delayed-type hypersensitivity in sensitized individuals. Additionally, chromium (VI) can act as an irritant. Both responses critically require innate immune activation, but if and how chromium (VI) elicits this signal is currently unclear. Using human monocytes, primary human keratinocytes, and murine dendritic cells we show that chromium (VI) compounds fail to trigger direct proinflammatory activation but potently induce processing and secretion of IL-1β. IL-1β release required priming by phorbol-ester or toll-like receptor stimulation and was prevented by inhibition of K(+) efflux, NLRP3 depletion or caspase-1 inhibition, identifying chromium (VI) as a hapten activator of the NLRP3 inflammasome. Inflammasome activation was initiated by mitochondrial reactive oxygen species production triggered by chromium (VI), as indicated by sensitivity to treatment with the ROS scavenger N-acetyl cysteine and a coinciding failure of K(+) efflux, caspase-1, or NLRP3 inhibition to prevent mitochondrial reactive oxygen species accumulation. IL-1β release further correlated with cytotoxicity that was secondary to reactive oxygen species, K(+) efflux, and NLRP3 activation. Trivalent chromium was unable to induce mitochondrial reactive oxygen species production, inflammasome activation, and cytotoxicity, suggesting that oxidation state-specific differences in mitochondrial reactivity may determine inflammasome activation and allergic/irritant capacity of different chromium compounds.

  6. Phenolic compounds and biological activity of Kitaibelia vitifolia.

    PubMed

    Mašković, Pavle; Solujić, Slavica; Mihailović, Vladimir; Mladenović, Milan; Cvijović, Milica; Mladenović, Jelena; Aćamović-Đoković, Gordana; Kurćubić, Vladimir

    2011-12-01

    This study was aimed at evaluating the antioxidant activity and efficacy of the ethanolic extract of the endemic plant species Kitaibelia vitifolia in inhibiting the growth of selected fungi and bacteria. Antimicrobial activity was tested using the broth dilution procedure for determination of minimum inhibitory concentration (MIC). MICs were determined for eight selected indicator strains. The highest susceptibility to K. vitifolia ethanolic extract among the bacteria tested was exhibited by Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 25923, and Klebsiella pneumoniae ATCC 13883 (MIC=15.62 μg/mL), followed by Escherichia coli ATCC 25922 and Proteus mirabilis ATCC 14153 (MIC=31.25 μg/mL), and Proteus vulgaris ATCC 13315 (MIC=62.50 μg/mL). Of the fungi, Candida albicans ATCC 10231 (MIC=15.62 μg/mL) showed the highest susceptibility, and Aspergillus niger ATCC 16404 (MIC=31.25 μg/mL) had the lowest. Results showed that K. vitifolia extract possesses antioxidant activity, with total antioxidant capacity of 75.45±0.68 μg of ascorbic acid/g and 50% inhibition concentration values of 47.45±0.55 μg/mL for 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity, 35.35±0.68 μg/mL for inhibitory activity against lipid peroxidation, 95.25±0.52 μg/mL for hydroxyl radical scavenging activity, and 31.50±0.35 μg/mL for metal chelating activity. Total phenolics, flavonoids, condensed tannins, and gallotannins were 85.25±0.69 mg of gallic acid (GA)/g, 45.32±0.55 mg of rutin/g, 54.25±0.75 mg of GA/g, and 41.74±0.55 mg of GA/g, respectively. The phenolic composition of K. vitifolia extract was determined by high-performance liquid chromatography. Rosmarinic acid was found to be the dominant phenolic compound of the extract.

  7. Phenolic Compounds and Antioxidant Activity of Phalaenopsis Orchid Hybrids

    PubMed Central

    Minh, Truong Ngoc; Khang, Do Tan; Tuyen, Phung Thi; Minh, Luong The; Anh, La Hoang; Quan, Nguyen Van; Ha, Pham Thi Thu; Quan, Nguyen Thanh; Toan, Nguyen Phu; Elzaawely, Abdelnaser Abdelghany; Xuan, Tran Dang

    2016-01-01

    Phalaenopsis spp. is the most commercially and economically important orchid, but their plant parts are often left unused, which has caused environmental problems. To date, reports on phytochemical analyses were most available on endangered and medicinal orchids. The present study was conducted to determine the total phenolics, total flavonoids, and antioxidant activity of ethanol extracts prepared from leaves and roots of six commercial hybrid Phalaenopsis spp. Leaf extracts of “Chian Xen Queen” contained the highest total phenolics with a value of 11.52 ± 0.43 mg gallic acid equivalent per g dry weight and the highest total flavonoids (4.98 ± 0.27 mg rutin equivalent per g dry weight). The antioxidant activity of root extracts evaluated by DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging assay and β-carotene bleaching method was higher than those of the leaf extracts. Eleven phenolic compounds were identified, namely, protocatechuic acid, p-hydroxybenzoic acid, vanillic acid, caffeic acid, syringic acid, vanillin, ferulic acid, sinapic acid, p-coumaric acid, benzoic acid, and ellagic acid. Ferulic, p-coumaric and sinapic acids were concentrated largely in the roots. The results suggested that the root extracts from hybrid Phalaenopsis spp. could be a potential source of natural antioxidants. This study also helps to reduce the amount of this orchid waste in industrial production, as its roots can be exploited for pharmaceutical purposes. PMID:27649250

  8. Platinum (II) Compounds With Antitumor Activity Studied by Molecular Mechanics

    PubMed Central

    Georgieva, Ivelina; Nikolov, George St.

    1998-01-01

    A series of Pt(ll) complexes with antitumor properties: [1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]PtL2 (meso-1-PtL2) and [erythro-1-(2,6-dichloro-4-hydroxyphenyl)-2-(2-halo-4-hydroxyphenyl)ethylenediamine]PtL2, [2L=2Cl−,2I−,SO42−; halo = F (erythro-8-PtL2),halo = Cl (erythro-9-PtL2)] has been modelled by molecular mechanics (MM). The MM calculations were carried out for different isomers and ligand conformations meso-δ, meso-λ, d,l-δ, d,I-λ. The compounds with the lowest MM energies have the same geometries as those obtained by X-ray analysis. The calculated MMX energy orders: meso-1-PtL2 < erythro-9-PtL2 < erythro-8-PtL2 for L=I−, Cl− and SO42− are reverse to the known antitumor activity order - the lowest energy complex (the most stable one)is the one with the highest estrogen activity (meso-1-PtL2). The type of the leaving group (L) does not alter the energy order, which is in agreement with the biological experiments that show a slight dependence of the estrogen properties on the leaving group type. PMID:18475828

  9. Platinum (II) Compounds With Antitumor Activity Studied by Molecular Mechanics.

    PubMed

    Trendafilova, N; Georgieva, I; Nikolov, G S

    1998-01-01

    A SERIES OF PT(LL) COMPLEXES WITH ANTITUMOR PROPERTIES: [1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]PtL(2) (meso-1-PtL(2)) and [erythro-1-(2,6-dichloro-4-hydroxyphenyl)-2-(2-halo-4-hydroxyphenyl)ethylenediamine]PtL(2), [2L=2Cl-,2I-,SO(4) (2)-; halo = F (erythro-8-PtL(2)),halo = Cl (erythro-9-PtL(2))] has been modelled by molecular mechanics (MM). The MM calculations were carried out for different isomers and ligand conformations meso-delta, meso-lambda, d,l-delta, d,I-lambda. The compounds with the lowest MM energies have the same geometries as those obtained by X-ray analysis. The calculated MMX energy orders: meso-1-PtL(2) < erythro-9-PtL(2) < erythro-8-PtL(2) for L=I-, Cl- and SO(4) (2-) are reverse to the known antitumor activity order - the lowest energy complex (the most stable one)is the one with the highest estrogen activity (meso-1-PtL(2)). The type of the leaving group (L) does not alter the energy order, which is in agreement with the biological experiments that show a slight dependence of the estrogen properties on the leaving group type.

  10. Variations in essential oil, phenolic compounds, and antioxidant activity of tunisian cultivated Salvia officinalis L.

    PubMed

    Ben Farhat, Mouna; Jordán, María J; Chaouech-Hamada, Rym; Landoulsi, Ahmed; Sotomayor, Jose A

    2009-11-11

    The variation in the chemical composition of the essential oil of Salvia officinalis , growing in different habitats, was studied. GC-MS analysis revealed 57 compounds representing 94.68-96.80% of total oils. The major components were alpha-thujone (11.55-19.23%), viridiflorol (9.94-19.46%), 1,8-cineole (8.85-15.60%), camphor (5.08-15.06%), manool (5.52-13.06%), beta-caryophyllene (2.63-9.24%), alpha-humulene (1.93-8.94%), and beta-thujone (5.45-6.17%), showing significant differences between different collection sites. Analysis of some representative polyphenolic compounds and antioxidant activity was performed using postdistilled dry samples. Rosmarinic acid, carnosol, and carnosic acid were the prevalent compounds of S. officinalis methanolic extracts. The results revealed differences in the polyphenolic composition and also exhibited antioxidant and radical-scavenging activities at different magnitudes of potency. However, within the used methods, only the DPPH(*) assay showed significant differences (p < 0.05) in free radical scavenging activity among samples collected in different regions. Plants collected in the coastal regions Soliman and Kelibia accumulate more polyphenolic compounds, known to be responsible for the main antioxidant activity of sage (rosmarinic acid, carnosol, and carnosic acid), than those growing inland at Bou Arada and Sers. Moreover, the former presented a higher radical-scavenging activity. The methanolic extracts of postdistilled S. officinalis might be valuable antioxidant natural sources and seemed to be applicable in both the health medicine and food industries.

  11. Identification of new compounds with high activity against stationary phase Borrelia burgdorferi from the NCI compound collection

    PubMed Central

    Feng, Jie; Shi, Wanliang; Zhang, Shuo; Zhang, Ying

    2015-01-01

    Lyme disease is the leading tick-borne disease in the USA. Whereas the majority of Lyme disease patients with early disease can be cured with standard treatment, some patients suffer from chronic fatigue and joint and muscular pain despite treatment, a syndrome called posttreatment Lyme disease syndrome. Although the cause is unclear, ineffective killing of Borrelia burgdorferi persisters by current Lyme disease antibiotics is one possible explanation. We took advantage of our recently developed high-throughput viability assay and screened the National Cancer Institute compound library collection consisting of 2526 compounds against stationary phase B. burgdorferi. We identified the top 30 new active hits, including the top six anthracycline antibiotics daunomycin 3-oxime, dimethyldaunomycin, daunomycin, NSC299187, NSC363998 and nogalamycin, along with other compounds, including prodigiosin, mitomycin, nanaomycin and dactinomycin, as having excellent activity against B. burgdorferi stationary phase culture. The anthracycline or anthraquinone compounds, which are known to have both anti-cancer and antibacterial activities, also had high activity against growing B. burgdorferi with low minimum inhibitory concentration. Future studies on the structure–activity relationship and mechanisms of action of anthracyclines/anthraquinones are warranted. In addition, drug combination studies with the anthracycline class of compounds and the current Lyme antibiotics to eradicate B. burgdorferi persisters in vitro and in animal models are needed to determine if they improve the treatment of Lyme disease. PMID:26954881

  12. Identification of new compounds with high activity against stationary phase Borrelia burgdorferi from the NCI compound collection.

    PubMed

    Feng, Jie; Shi, Wanliang; Zhang, Shuo; Zhang, Ying

    2015-06-03

    Lyme disease is the leading tick-borne disease in the USA. Whereas the majority of Lyme disease patients with early disease can be cured with standard treatment, some patients suffer from chronic fatigue and joint and muscular pain despite treatment, a syndrome called posttreatment Lyme disease syndrome. Although the cause is unclear, ineffective killing of Borrelia burgdorferi persisters by current Lyme disease antibiotics is one possible explanation. We took advantage of our recently developed high-throughput viability assay and screened the National Cancer Institute compound library collection consisting of 2526 compounds against stationary phase B. burgdorferi. We identified the top 30 new active hits, including the top six anthracycline antibiotics daunomycin 3-oxime, dimethyldaunomycin, daunomycin, NSC299187, NSC363998 and nogalamycin, along with other compounds, including prodigiosin, mitomycin, nanaomycin and dactinomycin, as having excellent activity against B. burgdorferi stationary phase culture. The anthracycline or anthraquinone compounds, which are known to have both anti-cancer and antibacterial activities, also had high activity against growing B. burgdorferi with low minimum inhibitory concentration. Future studies on the structure-activity relationship and mechanisms of action of anthracyclines/anthraquinones are warranted. In addition, drug combination studies with the anthracycline class of compounds and the current Lyme antibiotics to eradicate B. burgdorferi persisters in vitro and in animal models are needed to determine if they improve the treatment of Lyme disease.

  13. Emergency Response and Management Activities

    EPA Pesticide Factsheets

    This quarterly report, highlighting accomplishments over the past several months, showcases EPA’s unique emergency response capabilities through the use of cutting-edge technologies and innovative cleanup strategies.

  14. A single N-terminal cysteine in TRPV1 determines activation by pungent compounds from onion and garlic.

    PubMed

    Salazar, Héctor; Llorente, Itzel; Jara-Oseguera, Andrés; García-Villegas, Refugio; Munari, Mika; Gordon, Sharona E; Islas, León D; Rosenbaum, Tamara

    2008-03-01

    Some members of the transient receptor potential (TRP) family of cation channels mediate sensory responses to irritant substances. Although it is well known that TRPA1 channels are activated by pungent compounds found in garlic, onion, mustard and cinnamon extracts, activation of TRPV1 by these extracts remains controversial. Here we establish that TRPV1 is activated by pungent extracts from onion and garlic, as well as by allicin, the active compound in these preparations, and participates together with TRPA1 in the pain-related behavior induced by this compound. We found that in TRPV1 these agents act by covalent modification of cysteine residues. In contrast to TRPA1 channels, modification of a single cysteine located in the N-terminal region of TRPV1 was necessary and sufficient for all the effects we observed. Our findings point to a conserved mechanism of activation in TRP channels, which provides new insights into the molecular basis of noxious stimuli detection.

  15. Antifungal properties of ethanolic extract and its active compounds from Calocedrus macrolepis var. formosana (Florin) heartwood.

    PubMed

    Yen, Tsair-Bor; Chang, Hui-Ting; Hsieh, Chun-Chun; Chang, Shang-Tzen

    2008-07-01

    The ethanolic extract of Calocedrus macrolepis var. formosana heartwood was screened for antifungal compounds by agar dilution assay and liquid chromatography. Two compounds, beta-thujaplicin and gamma-thujaplicin, responsible for the antifungal property of C. macrolepis var. formosana heartwood were isolated by high performance liquid chromatography (HPLC), and identified by 1H NMR and 13C NMR. The antifungal activities of these two compounds were further evaluated against total 15 fungi, including wood decay fungi, tree pathogenic fungi and molds. The hexane soluble fraction showed the strongest antifungal activities among all fractions. beta-Thujaplicin and gamma-thujaplicin exhibited not only very strong antifungal activity, but also broad antifungal spectrum. The MIC values of beta-thujaplicin and gamma-thujaplicin were in the range of 5.0-50.0 microg/ml. In addition, scanning electron microscopy (SEM) was carried out to study the structural change of fungal hyphae induced by beta-thujaplicin. Strong cell wall shrinkage indicated the fungicidal effect could be attributed to the combined actions of metal chelating and cytoplasm leakage. It also suggests that the role of metal chelating is indispensable in the design of environmental-friendly fungicides.

  16. Response of Nodularia spumigena to pCO2 - Part 3: Turnover of phosphorus compounds

    NASA Astrophysics Data System (ADS)

    Unger, J.; Endres, S.; Wannicke, N.; Engel, A.; Voss, M.; Nausch, G.; Nausch, M.

    2013-03-01

    Diazotrophic cyanobacteria form extensive summer blooms in the Baltic Sea driving the surrounding surface waters into phosphate limitation. One of the main bloom-forming species is the heterocystous cyanobacterium Nodularia spumigena. N. spumigena exhibits accelerated uptake of phosphate through the release of the extracellular enzyme alkaline phosphatase whose activity also serves as an indicator of the hydrolysis of dissolved organic phosphorus (DOP). The present study investigated the utilisation of DOP and its compounds (e.g., ATP) by N. spumigena during growth under different CO2 concentrations, in order to estimate potential consequences of ocean acidification on the cell's supply with phosphorus (P). Cell growth, the phosphorus pool, and four DOP compounds (ATP, DNA, RNA, and phospholipids) were determined in three setups with different CO2 concentrations (average 341 μatm, 399 μatm, and 508 μatm) during a 15-day batch experiment. The results showed stimulated growth of N. spumigena and a rapid depletion of dissolved inorganic phosphorus (DIP) in all pCO2 treatments. DOP uptake was enhanced by a factor of 1.32 at 399 μatm and of 2.25 at 508 μatm compared to the lowest CO2 concentration. Among the measured DOP compounds, none was found to accumulate preferentially during the incubation or in response to a specific pCO2 treatment. However, at the beginning 61.9 ± 4.3% of total DOP were not characterised but comprised the most utilised fraction. This is demonstrated by the decrement of this fraction to 27.4 ± 9.9% of total DOP during the growth phase with a preference at high pCO2. Our results indicate a stimulated growth of diazotrophic cyanobacteria at increasing CO2 concentrations which is accompanied by increasing utilisation of DOP as an alternative P source.

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

    PubMed

    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.

  18. Persistence of biologically active compounds in aquatic systems: Final report

    SciTech Connect

    Boelter, A.M.; Fernandez, J.D.; Meyer, J.S.; Sanchez, D.A.; Bergman, H.L.

    1986-11-01

    Waters collected from two study sites were tested for persistence of biologically active compounds as the waters percolated through experimental media. At the first site, the Paraho Lysimeter in Anvil Points, Colorado, two leachate samples (early and late flow in Spring 1983) were collected from each of four piles of processed oil shale overlain by different thicknesses of soil. Although water quality differed among samples, six of eight lysimeter leachates tested were acutely toxic to an aquatic invertebrate, Daphnia magna, and five were acutely toxic to fathead minnows (Pimephales promelas). Water collected from a modified in situ (MIS) retort was percolated through columns containing three different types of soil. Raw leachate from the MIS spent shale was acutely toxic to an aquatic invertebrate, Ceriodaphnia dubia. The toxicity of samples from nine pore volumes of retort water percolating through a column containing a sandy soil increased with successive pore volumes, but leachate toxicity never equaled the toxicity of the retort water. In contrast, the first pore volumes of retort water or reconstituted water leached through a sandy loam soil were more toxic than the retort water; however, the second pore volumes of leachates were not toxic. First pore volume leachates of retort water percolating through a sandy clay loam soil were much less toxic than the retort water; second pore volume leachates were not toxic.

  19. Study of the volatile compounds and odor-active compounds of dry-cured Iberian ham extracted by SPME.

    PubMed

    del Pulgar, José Sánchez; García, Carmen; Reina, Raquel; Carrapiso, Ana I

    2013-06-01

    The volatile compounds and the most odor-active compounds of dry-cured Iberian ham were investigated by extracting them using a solid phase microextraction technique with a 2 cm Carboxen/PDMS/DVB fiber. The detection frequency method was applied to estimate the potential contribution of each compound to the odor of hams. Twenty-one volatile compounds were tentatively identified for the first time in dry-cured ham by gas chromatography-mass spectrometry, and eight in dry-cured Iberian ham. Gas chromatography-olfactometry allowed the identification for the first time of six compounds not previously reported as odorants of Iberian ham, and also two odorants were newly identified in dry-cured ham. According to the detection frequency method, the most odor active compounds found were 3-methylbutanoic acid (dirty sock-like smelling), hexanal (cut grass-like odor), 3-methylbutanal (sweaty and bitter almond-like odor), 2-methyl-3-furanthiol (toasted nuts-like odor) and 1-octen-3-one (mushroom-like odor).

  20. 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

  1. A strategy for screening active lead compounds and functional compound combinations from herbal medicines based on pharmacophore filtering and knockout/knockin chromatography.

    PubMed

    Song, Hui-Peng; Wu, Si-Qi; Qi, Lian-Wen; Long, Fang; Jiang, Li-Feng; Liu, Ke; Zeng, Hao; Xu, Zhi-Meng; Li, Ping; Yang, Hua

    2016-07-22

    Screening and deciphering active natural products of herbal medicines are of great importance for modern drug discovery. In this study, a novel strategy was proposed to rapidly filter ineffective compounds and target the most potential leads. The aim is to answer the key question of what components are responsible for the holistic bioactivity of an herbal product. To support the strategy, the pharmacophore-guided knockout/knockin chromatography was established for the first time. The greatest advantage of this method is that any interesting components could be automatically fished or knocked out. The method validation shows that the herbal extract was accurately reconstructed according to the experimental design. By combining with bioactivity assays, we demonstrated that "functional compound combination (FCC)", which is the core and indispensable effective part, could be discovered from an herbal medicine and suitable as marker compounds for quality control. The applicable objects of the strategy include single herbs, herbal formulas and commercially herbal preparations. As an illustrative case study, the strategy was successfully applied to simultaneously determine active leads and the FCC in Dan-Qi formula which shows excellent free radical scavenging activity. The potential mechanisms of compounds in Dan-Qi formula reacting with three different free radicals were systematically reported for the first time. This strategy was expected to unveil the mystery of herbal medicines and inspire a natural product-based drug discovery.

  2. Improved absorption and bioactivity of active compounds from an anti-diabetic extract of Artemisia dracunculus L

    PubMed Central

    Ribnicky, David M; Kuhn, Peter; Poulev, Alexander; Logendra, Sithes; Zuberi, Aamir; Cefalu, William T; Raskin, Ilya

    2010-01-01

    An ethanolic extract of Artemisia dracunculus L. (PMI-5011) was shown to be hypoglycemic in animal models for Type 2 diabetes and contain at least 6 bioactive compounds responsible for its anti-diabetic properties. To evaluate the bioavailability of the active compounds, high fat dietary induced obese C57BL/6J male mice were gavaged with PMI-5011 at 500 mg/kg body weight, after 4 h of food restriction. Blood plasma samples (200 uL) were obtained after ingestion, and the concentrations of the active compound in the blood sera were measured by electrospray LC-MS and determined to be maximal 4–6 h after gavage. Formulations of the extract with bioenhancers/solubilizers were evaluated in vivo for hypoglycemic activity and their effect on the abundance of active compounds in blood sera. At doses of 50–500 mg/kg/day, the hypoglycemic activity of the extract was enhanced 3–5 fold with the bioenhancer Labrasol, making it comparable to the activity of the anti-diabetic drug metformin. When combined with Labrasol, one of the active compounds, 2′, 4′-dihydroxy-4-methoxydihydrochalcone, was at least as effective as metformin at doses of 200–300 mg/kg/day. Therefore, bioenhancing agents like Labrasol can be used with multi-component botanical therapeutics such as PMI-5011 to increase their efficacy and/or to reduce the effective dose. PMID:19084584

  3. A review on antifungal activity of mushroom (basidiomycetes) extracts and isolated compounds.

    PubMed

    Alves, Maria José; Ferreira, Isabel C F R; Dias, Joana; Teixeira, Vânia; Martins, Anabela; Pintado, Manuela

    2013-01-01

    The present review reports the antifungal activity of mushroom extracts and isolated compounds including high (e.g. peptides and proteins) and low (e.g. sesquiterpenes and other terpenes, steroids, organic acids, acylcyclopentenediones and quinolines) molecular weight compounds. Most of the studies available on literature focused on screening of antifungal activity of mushroom extracts, rather than of isolated compounds. Data indicate that mushroom extracts are mainly tested against different Candida species, while mushroom compounds are mostly tested upon other fungi. Therefore, the potential of these compounds might be more useful in food industry than in clinics. Oudemansiella canarii and Agaricus bisporus methanolic extracts proved to be the most active mushroom extracts against Candida spp. Grifolin, isolated from Albatrellus dispansus, seemed to be the most active compound against phytopathogenic fungi. Further studies should be performed in order to better understand the mechanism of action of this and other antifungal compounds as well as safety issues.

  4. Formation and emission of volatile polonium compound by microbial activity and polonium methylation with methylcobalamin.

    PubMed

    Momoshima, N; Song, L X; Osaki, S; Maeda, Y

    2001-07-15

    We observed biologically mediated emission of Po from culture solution inoculated sea sediment extract and incubated under natural light/dark cycle condition or dark condition the emitted Po compound would be lipophilic because of effective collection in organic solvent. Sterilization of the culture medium with antibiotics or CuSO4 completely suppressed growth of microorganisms and resulted in no emission of Po, indicating biological activity of microorganisms is responsible for formation and emission of volatile Po compound. Po emission also occurred when seawater was used as a culture medium. Our finding indicates a possibility of biotic source for atmospheric Po in the environment, which has been believed to be originated from abiotic sources. We compared emission behavior of Po and S in the culture experiments, the elements belong to XVI group in the Periodical Table, and consider that their emission mechanisms involved would be different though the emission of both elements is supported by biological activity of microorganisms. One of the chemical forms of S emitted was confirmed to be dimethyl sulfide (DMS) but that of Po is not known. Methylation experiments of Po with methylcobalamin demonstrated a formation and emission of volatile Po compound. The methylation of Po with methylcobalamin might be related to the observed Po emission in the culture experiments.

  5. Human Health Relevance of Pharmaceutically Active Compounds in Drinking Water.

    PubMed

    Khan, Usman; Nicell, Jim

    2015-05-01

    In Canada, as many as 20 pharmaceutically active compounds (PhACs) have been detected in samples of treated drinking water. The presence of these PhACs in drinking water raises important questions as to the human health risk posed by their potential appearance in drinking water supplies and the extent to which they indicate that other PhACs are present but have not been detected using current analytical methods. Therefore, the goal of the current investigation was to conduct a screening-level assessment of the human health risks posed by the aquatic release of an evaluation set of 335 selected PhACs. Predicted and measured concentrations were used to estimate the exposure of Canadians to each PhAC in the evaluation set. Risk evaluations based on measurements could only be performed for 17 PhACs and, of these, all were found to pose a negligible risk to human health when considered individually. The same approach to risk evaluation, but based on predicted rather than measured environmental concentrations, suggested that 322 PhACs of the evaluation set, when considered individually, are expected to pose a negligible risk to human health due to their potential presence in drinking waters. However, the following 14 PhACs should be prioritized for further study: triiodothyronine, thyroxine, ramipril and its metabolite ramiprilat, candesartan, lisinopril, atorvastatin, lorazepam, fentanyl, atenolol, metformin, enalaprilat, morphine, and irbesartan. Finally, the currently available monitoring data for PhACs in Canadian surface and drinking waters was found to be lacking, irrespective of whether their suitability was assessed based on risk posed, predicted exposure concentrations, or potency.

  6. SYNTHESIZING ORGANIC COMPOUNDS USING LIGHT-ACTIVATED TIO2

    EPA Science Inventory

    High-value organic compounds have been synthesized successfully from linear and cyclic hydrocarbons, by photocatalytic oxidation using a semiconductor material, titanium dioxide (TiO2). Various hydrocarbons were partially oxgenated in both liquid and gaseous phase reactors usi...

  7. 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…

  8. Imperanene, a novel phenolic compound with platelet aggregation inhibitory activity from Imperata cylindrica.

    PubMed

    Matsunaga, K; Shibuya, M; Ohizumi, Y

    1995-01-01

    Imperanene, a novel phenolic compound [1] has been isolated from Imperata cylindrica. Its structure was elucidated by spectroscopic evidence. Imperanene showed platelet aggregation inhibitory activity.

  9. Compositions comprising a polypeptide having cellulolytic enhancing activity and a bicycle compound and uses thereof

    DOEpatents

    Xu, Feng; Sweeney, Matthew; Quinlan, Jason

    2015-06-16

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a bicyclic compound. The present invention also relates to methods of using the compositions.

  10. Compositions comprising a polypeptide having cellulolytic enhancing activity and a bicyclic compound and uses thereof

    DOEpatents

    Quinlan, Jason; Xu, Feng; Sweeney, Matthew

    2016-10-04

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a bicyclic compound. The present invention also relates to methods of using the compositions.

  11. Compositions comprising a polypeptide having cellulolytic enhancing activity and a quinone compound and uses thereof

    DOEpatents

    Quinlan, Jason; Xu, Feng; Sweeney, Matthew

    2016-03-01

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a quinone compound. The present invention also relates to methods of using the compositions.

  12. Compositions comprising a polypeptide having cellulolytic enhancing activity and a heterocyclic compound and uses thereof

    DOEpatents

    Xu, Feng; Sweeney, Matthew; Quinlan, Jason

    2016-08-02

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a heterocyclic compound. The present invention also relates to methods of using the compositions.

  13. Compositions comprising a polypeptide having cellulolytic enhancing activity and a dioxy compound and uses thereof

    DOEpatents

    Sweeney, Matthew; Xu, Feng; Quinlan, Jason

    2016-07-19

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a dioxy compound. The present invention also relates to methods of using the compositions.

  14. Antiproliferative activity of New Zealand propolis and phenolic compounds vs human colorectal adenocarcinoma cells.

    PubMed

    Catchpole, Owen; Mitchell, Kevin; Bloor, Stephen; Davis, Paul; Suddes, Amanda

    2015-10-01

    New Zealand propolis is a "European" type propolis obtained by honey bees mainly from exudates of poplar. European type propolis is known to have anti-inflammatory and anti-cancer properties and this activity has been attributed to some of the main constituents such as chrysin and CAPE (caffeic acid phenethyl ester). As part of our studies on how New Zealand propolis might benefit gastro-intestinal health, we carried out in vitro bioactivity-guided fractionation of "Bio30™" propolis using both anti-inflammatory (TNF-α, COX-1, COX-2) and anti-colon cancer (DLD-1 colon cancer cell viability) assays; and determined the phenolic compounds responsible for the activity. The New Zealand wax-free Bio30™ propolis tincture solids had very high levels of the dihydroflavonoids pinocembrin and pinobanksin-3-O-acetate, and high levels of the dimethylallyl, benzyl and 3-methyl-3-butenyl caffeates relative to CAPE. The DLD-1 assays identified strong anti-proliferative activity associated with these components as well as chrysin, galangin and CAPE and a number of lesser known or lower concentration compounds including benzyl ferulate, benzyl isoferulate, pinostrobin, 5-phenylpenta-2,4-dienoic acid and tectochrysin. The phenolic compounds pinocembrin, pinobanksin-3-O-acetate, tectochrysin, dimethylallyl caffeate, 3-methyl-3-butenyl caffeate, benzyl ferulate and benzyl isoferulate also showed good broad spectrum activity in anti-proliferative assays against three other gastro-intestinal cancer cell lines; HCT-116 colon carcinoma, KYSE-30 oesophageal squamous cancer, and NCI-N87 gastric carcinoma. Activity is also observed in anti-inflammatory assays although it appears to be limited to one of the first cytokines in the inflammatory cascade, TNF-α.

  15. 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.

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

    SciTech Connect

    Boehme, Kathleen; Simon, Stephanie

    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 by 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.

  17. Cytochrome P450-mediated activation of the fragrance compound geraniol forms potent contact allergens

    SciTech Connect

    Hagvall, Lina; Baron, Jens Malte; Boerje, Anna; Weidolf, Lars; Merk, Hans; Karlberg, Ann-Therese

    2008-12-01

    Contact sensitization is caused by low molecular weight compounds which penetrate the skin and bind to protein. In many cases, these compounds are activated to reactive species, either by autoxidation on exposure to air or by metabolic activation in the skin. Geraniol, a widely used fragrance chemical, is considered to be a weak allergen, although its chemical structure does not indicate it to be a contact sensitizer. We have shown that geraniol autoxidizes and forms allergenic oxidation products. In the literature, it is suggested but not shown that geraniol could be metabolically activated to geranial. Previously, a skin-like CYP cocktail consisting of cutaneous CYP isoenzymes, was developed as a model system to study cutaneous metabolism. In the present study, we used this system to investigate CYP-mediated activation of geraniol. In incubations with the skin-like CYP cocktail, geranial, neral, 2,3-epoxygeraniol, 6,7-epoxygeraniol and 6,7-epoxygeranial were identified. Geranial was the main metabolite formed followed by 6,7-epoxygeraniol. The allergenic activities of the identified metabolites were determined in the murine local lymph node assay (LLNA). Geranial, neral and 6,7-epoxygeraniol were shown to be moderate sensitizers, and 6,7-epoxygeranial a strong sensitizer. Of the isoenzymes studied, CYP2B6, CYP1A1 and CYP3A5 showed high activities. It is likely that CYP1A1 and CYP3A5 are mainly responsible for the metabolic activation of geraniol in the skin, as they are expressed constitutively at significantly higher levels than CYP2B6. Thus, geraniol is activated through both autoxidation and metabolism. The allergens geranial and neral are formed via both oxidation mechanisms, thereby playing a large role in the sensitization to geraniol.

  18. Prediction of human population responses to toxic compounds by a collaborative competition

    PubMed Central

    Eduati, Federica; Mangravite, Lara M.; Wang, Tao; Tang, Hao; Bare, J. Christopher; Huang, Ruili; Norman, Thea; Kellen, Mike; Menden, Michael P.; Yang, Jichen; Zhan, Xiaowei; Zhong, Rui; Xiao, Guanghua; Xia, Menghang; Abdo, Nour; Kosyk, Oksana; Friend, Stephen; Dearry, Allen; Simeonov, Anton; Tice, Raymond; Rusyn, Ivan; Wright, Fred A.; Stolovitzky, Gustavo; Xie, Yang; Saez-Rodriguez, Julio

    2015-01-01

    The ability to computationally predict the effects of toxic compounds on humans could help address the deficiencies of current chemical safety testing. Here, we report the results from a community-based DREAM challenge to predict toxicities of environmental compounds with potential adverse health effects for human populations. We measured the cytotoxicity of 156 compounds in 884 lymphoblastoid cell lines for which genotype and transcriptional data are available as part of the Tox21 1000-Genomes Project. The challenge participants developed algorithms to predict inter-individual variability of toxic response from genomic profiles and population-level cytotoxicity data from structural attributes of the compounds. 179 submitted predictions were evaluated against a blinded experimental dataset. Individual cytotoxicity predictions were better than random, with modest correlations (Pearson’s r<0.28), consistent with complex trait genomic prediction. In contrast, predictions of population-level response to different compounds were higher (r<0.66). The results highlight the possibility of predicting health risks associated with unknown compounds, although risk estimation accuracy remains suboptimal. PMID:26258538

  19. Prediction of human population responses to toxic compounds by a collaborative competition.

    PubMed

    Eduati, Federica; Mangravite, Lara M; Wang, Tao; Tang, Hao; Bare, J Christopher; Huang, Ruili; Norman, Thea; Kellen, Mike; Menden, Michael P; Yang, Jichen; Zhan, Xiaowei; Zhong, Rui; Xiao, Guanghua; Xia, Menghang; Abdo, Nour; Kosyk, Oksana; Friend, Stephen; Dearry, Allen; Simeonov, Anton; Tice, Raymond R; Rusyn, Ivan; Wright, Fred A; Stolovitzky, Gustavo; Xie, Yang; Saez-Rodriguez, Julio

    2015-09-01

    The ability to computationally predict the effects of toxic compounds on humans could help address the deficiencies of current chemical safety testing. Here, we report the results from a community-based DREAM challenge to predict toxicities of environmental compounds with potential adverse health effects for human populations. We measured the cytotoxicity of 156 compounds in 884 lymphoblastoid cell lines for which genotype and transcriptional data are available as part of the Tox21 1000 Genomes Project. The challenge participants developed algorithms to predict interindividual variability of toxic response from genomic profiles and population-level cytotoxicity data from structural attributes of the compounds. 179 submitted predictions were evaluated against an experimental data set to which participants were blinded. Individual cytotoxicity predictions were better than random, with modest correlations (Pearson's r < 0.28), consistent with complex trait genomic prediction. In contrast, predictions of population-level response to different compounds were higher (r < 0.66). The results highlight the possibility of predicting health risks associated with unknown compounds, although risk estimation accuracy remains suboptimal.

  20. Effects of polyhydroxy compounds on beetle antifreeze protein activity

    PubMed Central

    Amornwittawat, Natapol; Wang, Sen; Banatlao, Joseph; Chung, Melody; Velasco, Efrain; Duman, John G.; Wen, Xin

    2016-01-01

    Antifreeze proteins (AFPs) noncolligatively depress the nonequilibrium freezing point of a solution and produce a difference between the melting and freezing points termed thermal hysteresis (TH). Some low-molecular-mass solutes can affect the TH values. The TH enhancement effects of selected polyhydroxy compounds including polyols and carbohydrates on an AFP from the beetle Dendroides canadensis were systematically investigated using differential scanning calorimetry (DSC). The number of hydroxyl groups dominates the molar enhancement effectiveness of polyhydroxy compounds having one to five hydroxyl groups. However, the above rule does not apply for polyhydroxy compounds having more than five hydroxyl groups. The most efficient polyhydroxy enhancer identified is trehalose. In a combination of enhancers the strongest enhancer plays the major role in determining the TH enhancement. Mechanistic insights into identification of highly efficient AFP enhancers are discussed. PMID:19038370

  1. 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.

  2. Effects of active hexose correlated compound on the seasonal variations of immune competence in healthy subjects.

    PubMed

    Takanari, Jun; Hirayama, Yosuke; Homma, Kohei; Miura, Takehito; Nishioka, Hiroshi; Maeda, Takahiro

    2015-01-01

    The aim of this study was to evaluate the effects of active hexose correlated compound intake on the immune competence in healthy volunteers. Thirty-four subjects were randomized to receive placebo or active hexose correlated compound at 1.0 g/d for 4 weeks in early winter. Natural killer cell activity was significantly increased in both groups during the study period, the natural killer cell number, however, was not altered in the active hexose correlated compound group while placebo group showed remarkable decline. In addition, the score of immunological vigor, an index of total immune competence, was maintained in the active hexose correlated compound group although that of placebo group lowered during the test period. These results suggested that the continuous active hexose correlated compound intake maintained the immune competence against the seasonal change.

  3. Growth promotion of Lactuca sativa in response to volatile organic compounds emitted from diverse bacterial species.

    PubMed

    Fincheira, Paola; Venthur, Herbert; Mutis, Ana; Parada, Maribel; Quiroz, Andrés

    2016-12-01

    Agrochemicals are currently used in horticulture to increase crop production. Nevertheless, their indiscriminate use is a relevant issue for environmental and legal aspects. Alternative tools for reducing fertilizers and synthetic phytohormones are being investigated, such as the use of volatile organic compounds (VOCs) as growth inducers. Some soil bacteria, such as Pseudomonas and Bacillus, stimulate Arabidopsis and tobacco growth by releasing VOCs, but their effects on vegetables have not been investigated. Lactuca sativa was used as model vegetable to investigate bacterial VOCs as growth inducers. We selected 10 bacteria strains, belonging to Bacillus, Staphylococcus and Serratia genera that are able to produce 3-hydroxy-2-butanone (acetoin), a compound with proven growth promoting activity. Two-day old-seedlings of L. sativa were exposed to VOCs emitted by the selected bacteria grown in different media cultures for 7 days. The results showed that the VOCs released from the bacteria elicited an increase in the number of lateral roots, dry weight, root growth and shoot length, depending on the media used. Three Bacillus strains, BCT53, BCT9 and BCT4, were selected according to its their growth inducing capacity. The BCT9 strain elicited the greatest increases in dry weight and primary root length when L. sativa seedlings were subjected to a 10-day experiment. Finally, because acetoin only stimulated root growth, we suggest that other volatiles could be responsible for the growth promotion of L. sativa. In conclusion, our results strongly suggest that bacteria volatiles can be used as growth-inducers as alternative or complementary strategies for application in horticulture species.

  4. Optimisation of ultrasonic-assisted extraction of antioxidant compounds from Artemisia absinthium using response surface methodology.

    PubMed

    Sahin, Saliha; Aybastıer, Onder; Işık, Esra

    2013-11-15

    Response surface methodology was used to optimise experimental conditions for ultrasonic-assisted extraction of phenolic compounds from Artemisia absinthium. The central composite design was employed, the extracts were characterised by the determination of total phenolic content and antioxidant capacity. The total phenolic contents of extracts were determined by Folin method and also total antioxidant capacities of extracts were determined by ABTS and CUPRAC methods. The phenolic compounds of A. absinthium at optimum extraction conditions were determined by HPLC-DAD. The optimum conditions were determined as HCl concentration between 0.41 and 0.44mol/L, methanol volume between 55% and 59% (v/v), extraction temperature between 64 and 70°C, extraction time between 101 and 107min. The experimental values agreed with those predicted within a 95% confidence level, thus indicating the suitability of response surface methodology in optimising the ultrasound-assisted extraction of phenolic compounds from A. absinthium.

  5. 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.

  6. Overexpectation: Response Loss during Sustained Stimulus Compounding in the Rabbit Nictitating Membrane Preparation

    ERIC Educational Resources Information Center

    Kehoe, E. James; White, Natasha E.

    2004-01-01

    Rabbits were given reinforced training of the nictitating membrane (NM) response using separate conditioned stimuli (CSs), which were a tone, light, and/or tactile vibration. Then, two CSs were compounded and given further pairings with the unconditioned stimulus (US). Evidence of both overexpectation and summation effects appeared. That is,…

  7. Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar

    USGS Publications Warehouse

    Duffy, Tara A.; Iwanowicz, Luke R.; McCormick, Stephen D.

    2014-01-01

    Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (four day) exposures using three doses each of 17α-ethinylestradiol (EE2), 17β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and one year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embyos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting this is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2 and plasma T3 decreased at the highest dose of EE2. Our results indicate that all life stages after hatching are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild.

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

    DOEpatents

    DiSpirito, Alan A.; Zahn, James A.; Graham, David W.; Kim, Hyung J.; Alterman, Michail; Larive, Cynthia

    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.

  9. Computational modeling of serum-binding proteins and clearance in extrapolations across life stages and species for endocrine active compounds.

    PubMed

    Teeguarden, Justin G; Barton, Hugh A

    2004-06-01

    One measure of the potency of compounds that lead to the effects through ligand-dependent gene transcription is the relative affinity for the critical receptor. Endocrine active compounds that are presumed to act principally through binding to the estrogen receptor (e.g., estradiol, genistein, bisphenol A, and octylphenol) comprise one class of such compounds. For making simple comparisons, receptor-binding affinity has been equated to in vivo potency, which consequently defines the dose-response characteristics for the compound. Direct extrapolation of in vitro estimated affinities to the corresponding in vivo system and to specific species or life stages (e.g., neonatal, pregnancy) can be misleading. Accurate comparison of the potency of endocrine active compounds requires characterization of biochemical and pharmacokinetic factors that affect their free concentration. Quantitative in vitro and in vivo models were developed for integrating pharmacokinetics factors (e.g., serum protein and receptor-binding affinities, clearance) that affect potency. Data for parameterizing these models for several estrogenic compounds were evaluated and the models exercised. While simulations of adult human or rat sera were generally successful, difficulties in describing early life stages were identified. Exogenous compounds were predicted to be largely ineffective at competing estradiol off serum-binding proteins, suggesting this was unlikely to be physiologically significant. Discrepancies were identified between relative potencies based upon modeling in vitro receptor-binding activity versus in vivo activity in the presence of clearance and serum-binding proteins. The examples illustrate the utility of this approach for integrating available experimental data from in vitro and in vivo studies to estimate the relative potency of these compounds.

  10. 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)

  11. Ovicidal and adulticidal activities of Cinnamomum zeylanicum bark essential oil compounds and related compounds against Pediculus humanus capitis (Anoplura: Pediculicidae).

    PubMed

    Yang, Young-Cheol; Lee, Hoi-Seon; Lee, Si Hyeock; Clark, J Marshall; Ahn, Young-Joon

    2005-12-01

    The toxicity of cinnamon, Cinnamomum zeylanicum, bark essential oil compounds against eggs and adult females of human head louse, Pediculus humanus capitis, was examined using direct contact and vapour phase toxicity bioassays and compared with the lethal activity of their related compounds, benzyl alcohol, cinnamic acid, cinnamyl acetate, 4-hydroxybenzaldehyde and salicylaldehyde, as well as two widely used pediculicides, d-phenothrin and pyrethrum. In a filter-paper contact toxicity bioassay with female lice at 0.25 mg/cm(2), benzaldehyde was 29- and 27-fold more toxic than pyrethrum and d-phenothrin, respectively, as judged by median lethal time (LT(50)) values. Salicylaldehyde was nine and eight times more active than pyrethrum and d-phenothrin, respectively. Pediculicidal activity of linalool was comparable with that of d-phenothrin and pyrethrum. Cinnamomum bark essential oil was slightly less effective than either d-phenothrin or pyrethrum. Benzyl alcohol and (E)-cinnamaldehyde exhibited moderate pediculicidal activity. After 24h of exposure, no hatching was observed with 0.063 mg/cm(2) salicylaldehyde, 0.125 mg/cm(2) benzaldehyde, 0.5mg/cm(2)Cinnamomum bark essential oil, 1.0 mg/cm(2) (E)-cinnamaldehyde, and 1.0 mg/cm(2) benzyl cinnamate. Little or no ovicidal activity was observed with d-phenothrin or pyrethrum. In vapour phase toxicity tests with female lice, benzaldehyde and salicylaldehyde were much more effective in closed containers than in open ones, indicating that the mode of delivery of these compounds was largely due to action in the vapour phase. Neither d-phenothrin nor pyrethrum exhibited fumigant toxicity. Cinnamomum bark essential oil and test compounds described merit further study as potential pediculicides or ovicides for the control of P. h. capitis.

  12. Nematicidal activity of natural ester compounds and their analogues against pine wood nematode, Bursaphelenchus xylophilus.

    PubMed

    Seo, Seon-Mi; Kim, Junheon; Koh, Sang-Hyun; Ahn, Young-Joon; Park, Il-Kwon

    2014-09-17

    In this study, we evaluated the nematicidal activity of natural ester compounds against the pine wood nematode, Bursaphelenchus xylophilus, to identify candidates for the development of novel, safe nematicides. We also tested the nematicidal activity of synthesized analogues of these ester compounds to determine the structure-activity relationship. Among 28 ester compounds tested, isobutyl 2-methylbutanoate, 3-methylbutyl 2-methylbutanoate, 3-methylbutyl tiglate, 3-methyl-2-butenyl 2-methylbutanoate, and pentyl 2-methylbutanoate showed strong nematicidal activity against the pine wood nematode at a 1 mg/mL concentration. The other ester compounds showed weak nematicidal activity. The LC50 values of 3-methylbutyl tiglate, isobutyl 2-methylbutanoate, 3-methylbutyl 2-methylbutanoate, 3-methyl-2-butenyl 2-methylbutanoate, and pentyl 2-methylbutanoate were 0.0218, 0.0284, 0.0326, 0.0402, and 0.0480 mg/mL, respectively. The ester compounds described herein merit further study as potential nematicides for pine wood nematode control.

  13. The removal of endocrine disrupting compounds, pharmaceutically activated compounds and cyanobacterial toxins during drinking water preparation using activated carbon--a review.

    PubMed

    Delgado, Luis F; Charles, Philippe; Glucina, Karl; Morlay, Catherine

    2012-10-01

    This paper provides a review of recent scientific research on the removal by activated carbon (AC) in drinking water (DW) treatment of 1) two classes of currently unregulated trace level contaminants with potential chronic toxicity-pharmaceutically activate compounds (PhACs) and endocrine disrupting compounds (EDCs); 2) cyanobacterial toxins (CyBTs), which are a group of highly toxic and regulated compounds (as microcystin-LR); and 3) the above mentioned compounds by the hybrid system powdered AC/membrane filtration. The influence of solute and AC properties, as well as the competitive effect from background natural organic matter on the adsorption of such trace contaminants, are also considered. In addition, a number of adsorption isotherm parameters reported for PhACs, EDCs and CyBTs are presented herein. AC adsorption has proven to be an effective removal process for such trace contaminants without generating transformation products. This process appears to be a crucial step in order to minimize PhACs, EDCs and CyBTs in finished DW, hence calling for further studies on AC adsorption removal of these compounds. Finally, a priority chart of PhACs and EDCs warranting further study for the removal by AC adsorption is proposed based on the compounds' structural characteristics and their low removal by AC compared to the other compounds.

  14. Leishmanicidal and cytotoxic activities of extracts and naturally-occurring compounds from two Lauraceae species.

    PubMed

    Sánchez-Suárez, Jeysson; Coy-Barrera, Ericsson; Cuca, Luis Enrique; Delgado, Gabriela

    2011-02-01

    The in vitro leishmanicidal effects of ethanolic extracts and fifteen naturally-occurring compounds (five lignans, eight neolignans, a diterpene and a dihydrochalcone), obtained from Pleurothyrium cinereum and Ocotea macrophylla, were evaluated on promastigotes of Leishmania panamensis and L. braziliensis. In addition, in order to determine the selective action on Leishmania species as a safety principle, in vitro cytotoxicity on J774 cells was also evaluated for test compounds and extracts. One extract and seven compounds showed activity against Leishmania parasites at different levels. Dihydroflavokawin B (8) was found to be the most potent antileishmanial compound on both parasites, whilst (+)-otobaphenol (14), was found to be the most selective compound on L. panamensis.

  15. Plant compounds enhance the assay sensitivity for detection of active Bacillus cereus toxin.

    PubMed

    Rasooly, Reuven; Hernlem, Bradley; He, Xiaohua; Friedman, Mendel

    2015-03-11

    Bacillus cereus is an important food pathogen, producing emetic and diarrheal syndromes, the latter mediated by enterotoxins. The ability to sensitively trace and identify this active toxin is important for food safety. This study evaluated a nonradioactive, sensitive, in vitro cell-based assay, based on B. cereus toxin inhibition of green fluorescent protein (GFP) synthesis in transduced monkey kidney Vero cells, combined with plant extracts or plant compounds that reduce viable count of B. cereus in food. The assay exhibited a dose dependent GFP inhibition response with ~25% inhibition at 50 ng/mL toxin evaluated in culture media or soy milk, rice milk or infant formula, products associated with food poisonings outbreak. The plant extracts of green tea or bitter almond and the plant compounds epicatechin or carvacrol were found to amplify the assay response to ~90% inhibition at the 50 ng/mL toxin concentration greatly increasing the sensitivity of this assay. Additional studies showed that the test formulations also inhibited the growth of the B. cereus bacteria, likely through cell membrane disruption. The results suggest that the improved highly sensitive assay for the toxin and the rapid inactivation of the pathogen producing the toxin have the potential to enhance food safety.

  16. Plant Compounds Enhance the Assay Sensitivity for Detection of Active Bacillus cereus Toxin

    PubMed Central

    Rasooly, Reuven; Hernlem, Bradley; He, Xiaohua; Friedman, Mendel

    2015-01-01

    Bacillus cereus is an important food pathogen, producing emetic and diarrheal syndromes, the latter mediated by enterotoxins. The ability to sensitively trace and identify this active toxin is important for food safety. This study evaluated a nonradioactive, sensitive, in vitro cell-based assay, based on B. cereus toxin inhibition of green fluorescent protein (GFP) synthesis in transduced monkey kidney Vero cells, combined with plant extracts or plant compounds that reduce viable count of B. cereus in food. The assay exhibited a dose dependent GFP inhibition response with ~25% inhibition at 50 ng/mL toxin evaluated in culture media or soy milk, rice milk or infant formula, products associated with food poisonings outbreak. The plant extracts of green tea or bitter almond and the plant compounds epicatechin or carvacrol were found to amplify the assay response to ~90% inhibition at the 50 ng/mL toxin concentration greatly increasing the sensitivity of this assay. Additional studies showed that the test formulations also inhibited the growth of the B. cereus bacteria, likely through cell membrane disruption. The results suggest that the improved highly sensitive assay for the toxin and the rapid inactivation of the pathogen producing the toxin have the potential to enhance food safety. PMID:25767986

  17. Composition and topology of activity cliff clusters formed by bioactive compounds.

    PubMed

    Stumpfe, Dagmar; Dimova, Dilyana; Bajorath, Jürgen

    2014-02-24

    The assessment of activity cliffs has thus far mostly focused on compound pairs, although the majority of activity cliffs are not formed in isolation but in a coordinated manner involving multiple active compounds and cliffs. However, the composition of coordinated activity cliff configurations and their topologies are unknown. Therefore, we have identified all activity cliff configurations formed by currently available bioactive compounds and analyzed them in network representations where activity cliff configurations occur as clusters. The composition, topology, frequency of occurrence, and target distribution of activity cliff clusters have been determined. A limited number of large cliff clusters with unique topologies were identified that were centers of activity cliff formation. These clusters originated from a small number of target sets. However, most clusters were of small to moderate size. Three basic topologies were sufficient to describe recurrent activity cliff cluster motifs/topologies. For example, frequently occurring clusters with star topology determined the scale-free character of the global activity cliff network and represented a characteristic activity cliff configuration. Large clusters with complex topology were often found to contain different combinations of basic topologies. Our study provides a first view of activity cliff configurations formed by currently available bioactive compounds and of the recurrent topologies of activity cliff clusters. Activity cliff clusters of defined topology can be selected, and from compounds forming the clusters, SAR information can be obtained. The SAR information of activity cliff clusters sharing a/one specific activity and topology can be compared.

  18. Physiological Response to Physical Activity in Children.

    ERIC Educational Resources Information Center

    Gilliam, Thomas B.

    This is a report on research in the field of physical responses of children to strenuous activity. The paper is divided into three subtopics: (1) peak performance measure in children; (2) training effects on children; and (3) importance of physical activity for children. Measurements used are oxygen consumption, ventilation, heart rate, cardiac…

  19. [Activity of digestive enzymes during intraperitoneal intake of metal compounds].

    PubMed

    Zdol'nik, T D

    2001-01-01

    Digestive function was studied when three compounds from Group VIB of the Mendeleev periodic system of elements were intraperitoneally administered during 100 days. Potassium bichromate, ammonium molybdate in a dose of 0.2 mg/kg and sodium tungstate in a dose of 5.0 mg/kg (in terms of metal) were found to have a resorptive effect on pancreatic function and a local effect on the small intestinal mucosa.

  20. Bioactive compounds and antioxidant activity analysis of Malaysian pineapple cultivars

    NASA Astrophysics Data System (ADS)

    Chiet, Chong Hang; Zulkifli, Razauden Mohamed; Hidayat, Topik; Yaakob, Harisun

    2014-03-01

    Pineapple industry is one of the important agricultural sectors in Malaysia with 76 cultivars planted throughout the country. This study aims to generate useful nutritional information as well as evaluating antioxidant properties of different pineapple commercial cultivars in Malaysia. The bioactive compound content and antioxidant capacity of `Josapine', `Morris' and `Sarawak' pineapple (Ananas comosus) were studied. The pineapple varieties were collected at commercial maturity stage (20-40% yellowish of fruit peel) and the edible portion of the fruit was used as sample for evaluation. The bioactive compound of the fruit extracts were evaluated by total phenolic and tannin content assay while the antioxidant capacity was determined by ferric reducing antioxidant power (FRAP). From the results obtained, total phenolic and tannin content was highest for `Josapine' followed by `Morris' and `Sarawak'. With respect to FRAP, `Josapine' showed highest reducing capacity, followed by `Morris' and then `Sarawak' having the least value. The bioactive compounds content are positively correlated with the antioxidant capacities of the pineapple extracts. This result indicates that the total phenolics and tannin content present in the pineapples may contribute to the antioxidant capacity of the pineapples.

  1. Radiosensitization of Escherichia coli and Salmonella typhi in presence of active compounds

    NASA Astrophysics Data System (ADS)

    Lacroix, M.; Chiasson, F.; Borsa, J.; Ouattara, B.

    2004-09-01

    The radiosensitization of Escherichia coli and Salmonella typhi in ground beef was evaluated in the presence of 18 active compounds. Medium fat ground beef (23% fat) was inoculated with E. coli or S. typhi and each active compound was added separately at various concentrations. For E. coli, the most efficient compounds were trans-cinnamaldehyde, thymol and thyme. For S. typhi, the most efficient compounds was trans-cinnamaldehyde, carvacrol and thymol. The addition of tetrasodium pyrophosphate, carvacrol and ascorbic acid had no effect on the irradiation sensitivity of E. coli. For S. typhi, only ascorbic acid had no effect.

  2. Antibacterial and antifungal activity of sulfur-containing compounds from Petiveria alliacea L.

    PubMed

    Kim, Seokwon; Kubec, Roman; Musah, Rabi A

    2006-03-08

    A total of 18 organosulfur compounds originating from Petiveria alliacea L. roots have been tested for their antibacterial and antifungal activities. These represent compounds occurring in fresh homogenates as well as those present in various macerates, extracts and other preparations made from Petiveria alliacea. Of the compounds assayed, the thiosulfinates, trisulfides and benzylsulfinic acid were observed to be the most active, with the benzyl-containing thiosulfinates exhibiting the broadest spectrum of antimicrobial activity. The effect of plant sample preparation conditions on the antimicrobial activity of the extract is discussed.

  3. The chalcone compound isosalipurposide (ISPP) exerts a cytoprotective effect against oxidative injury via Nrf2 activation

    SciTech Connect

    Han, Jae Yun; Cho, Seung Sik; Yang, Ji Hye; Kim, Kyu Min; Jang, Chang Ho; Park, Da Eon; Bang, Joon Seok; Jung, Young Suk; Ki, Sung Hwan

    2015-08-15

    The chalcone compound isosalipurposide (ISPP) has been successfully isolated from the native Korean plant species Corylopsis coreana Uyeki (Korean winter hazel). However, the therapeutic efficacy of ISPP remains poorly understood. This study investigated whether ISPP has the capacity to activate NF-E2-related factor (Nrf2)-antioxidant response element (ARE) signaling and induce its target gene expression, and to determined the protective role of ISPP against oxidative injury of hepatocytes. In HepG2 cells, nuclear translocation of Nrf2 is augmented by ISPP treatment. Consistently, ISPP increased ARE reporter gene activity and the protein levels of glutamate cysteine ligase (GCL) and hemeoxygenase (HO-1), resulting in increased intracellular glutathione levels. Cells pretreated with ISPP were rescued from tert-butylhydroperoxide-induced reactive oxygen species (ROS) production and glutathione depletion and consequently, apoptotic cell death. Moreover, ISPP ameliorated the mitochondrial dysfunction and apoptosis induced by rotenone which is an inhibitor of complex 1 of the mitochondrial respiratory chain. The specific role of Nrf2 activation by ISPP was demonstrated using an ARE-deletion mutant plasmid and Nrf2-knockout cells. Finally, we observed that extracellular signal-regulated kinase (ERK) and AMP-activated protein kinase (AMPK), but not protein kinase C (PKC)-δ or other mitogen-activated protein kinases (MAPKs), are involved in the activation of Nrf2 by ISPP. Taken together, our results demonstrate that ISPP has a cytoprotective effect against oxidative damage mediated through Nrf2 activation and induction of its target gene expression in hepatocytes. - Highlights: • We investigated the effect of ISPP on Nrf2 activation. • ISPP increased Nrf2 activity and its target gene expression. • ISPP inhibited the mitochondrial dysfunction and ROS production. • Nrf2 activation by ISPP is dependent on ERK1/2 and AMPK phosphorylation. • ISPP may be a promising

  4. 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

  5. Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors.

    PubMed

    Goto, Tsuyoshi; Kim, Young-Il; Takahashi, Nobuyuki; Kawada, Teruo

    2013-01-01

    Obesity causes excess fat accumulation in various tissues, most notoriously in the adipose tissue, along with other insulin-responsive organs such as skeletal muscle and the liver, which predisposes an individual to the development of metabolic abnormalities. The molecular mechanisms underlying obesity-induced metabolic abnormalities have not been completely elucidated; however, in recent years, the search for therapies to prevent the development of obesity and obesity-associated metabolic disorders has increased. It is known that several nuclear receptors, when activated by specific ligands, regulate carbohydrate and lipid metabolism at the transcriptional level. The expression of lipid metabolism-related enzymes is directly regulated by the activity of various nuclear receptors via their interaction with specific response elements in promoters of those genes. Many natural compounds act as ligands of nuclear receptors and regulate carbohydrate and lipid metabolism by regulating the activities of these nuclear receptors. In this review, we describe our current knowledge of obesity, the role of lipid-sensing nuclear receptors in energy metabolism, and several examples of food factors that act as agonists or antagonists of nuclear receptors, which may be useful for the management of obesity and the accompanying energy metabolism abnormalities.

  6. Multiple microbial activities for volatile organic compounds reduction by biofiltration.

    PubMed

    Civilini, Marcello

    2006-07-01

    In the northeast of Italy, high volatile organic carbon (VOC) emissions originate from small-medium companies producing furniture. In these conditions it is difficult to propose a single, efficient, and economic system to reduce pollution. Among the various choices, the biofiltration method could be a good solution, because microbial populations possess multiple VOC degradation potentials used to oxidize these compounds to CO2. Starting from the air emissions of a typical industrial wood-painting plant, a series of experiments studied in vitro microbial degradation of each individual VOC. Isolated strains were then added to a laboratory-scale biofiltration apparatus filled with an organic matrix, and the different VOC behavior demonstrated the potential of single and/or synergic microbial removal actions. When a single substrate was fed, the removal efficiency of a Pseudomonas aeruginosa inoculated reactor was 1.1, 1.17, and 0.33 g m(-3) hr(-1), respectively, for xylene, toluene, and ethoxy propyl acetate. A VOC mixture composed of butyl acetate, ethyl acetate, diacetin alcohol, ethoxy propanol acetate, methyl ethyl ketone, methyl isobutyl ketone, toluene, and xylene was then fed into a 2-m(3) reactor treating 100 m3 hr(-1) of contaminated air. The reactor was filled with the same mixture of organic matrix, enriched with all of the isolated strains together. During reactor study, different VOC loading rates were used, and the behavior was evaluated continuously. After a short acclimation period, the removal efficiency was > 65% at VOC load of 150-200 g m(-3) hr(-1). Quantification of removal efficiencies and VOC speciation confirmed the relationship among removal efficiencies, compound biodegradability, and the dynamic transport of each mixture component within the organic matrix. Samples of the fixed bed were withdrawn at different intervals and the heterogeneous microbial community evaluated for both total and differential compound counts.

  7. Review on Natural Coumarin Lead Compounds for Their Pharmacological Activity

    PubMed Central

    Venugopala, K. N.; Rashmi, V.; Odhav, B.

    2013-01-01

    Coumarin (2H-1-benzopyran-2-one) is a plant-derived natural product known for its pharmacological properties such as anti-inflammatory, anticoagulant, antibacterial, antifungal, antiviral, anticancer, antihypertensive, antitubercular, anticonvulsant, antiadipogenic, antihyperglycemic, antioxidant, and neuroprotective properties. Dietary exposure to benzopyrones is significant as these compounds are found in vegetables, fruits, seeds, nuts, coffee, tea, and wine. In view of the established low toxicity, relative cheapness, presence in the diet, and occurrence in various herbal remedies of coumarins, it appears prudent to evaluate their properties and applications further. PMID:23586066

  8. Review on natural coumarin lead compounds for their pharmacological activity.

    PubMed

    Venugopala, K N; Rashmi, V; Odhav, B

    2013-01-01

    Coumarin (2H-1-benzopyran-2-one) is a plant-derived natural product known for its pharmacological properties such as anti-inflammatory, anticoagulant, antibacterial, antifungal, antiviral, anticancer, antihypertensive, antitubercular, anticonvulsant, antiadipogenic, antihyperglycemic, antioxidant, and neuroprotective properties. Dietary exposure to benzopyrones is significant as these compounds are found in vegetables, fruits, seeds, nuts, coffee, tea, and wine. In view of the established low toxicity, relative cheapness, presence in the diet, and occurrence in various herbal remedies of coumarins, it appears prudent to evaluate their properties and applications further.

  9. Determination of phenolic compounds and antioxidant activity in leaves from wild Rubus L. species.

    PubMed

    Oszmiański, Jan; Wojdyło, Aneta; Nowicka, Paulina; Teleszko, Mirosława; Cebulak, Tomasz; Wolanin, Mateusz

    2015-03-18

    Twenty-six different wild blackberry leaf samples were harvested from various localities throughout southeastern Poland. Leaf samples were assessed regarding their phenolic compound profiles and contents by LC/MS QTOF, and their antioxidant activity by ABTS and FRAP. Thirty-three phenolic compounds were detected (15 flavonols, 13 hydroxycinnamic acids, three ellagic acid derivatives and two flavones). Ellagic acid derivatives were the predominant compounds in the analyzed leaves, especially sanguiin H-6, ellagitannins, lambertianin C, and casuarinin. The content of phenolic compounds was significantly correlated with the antioxidant activity of the analyzed samples. The highest level of phenolic compounds was measured for R. perrobustus, R. wimmerianus, R. pedemontanus and R. grabowskii. The study showed that wild blackberry leaves can be considered a good source of antioxidant compounds. There is clear potential for the utilization of blackberry leaves as a food additive, medicinal source or herbal tea.

  10. Optimisation of the extraction of phenolic compounds from apples using response surface methodology.

    PubMed

    Alberti, Aline; Zielinski, Acácio Antonio Ferreira; Zardo, Danianni Marinho; Demiate, Ivo Mottin; Nogueira, Alessandro; Mafra, Luciana Igarashi

    2014-04-15

    The extraction of phenolic compounds from apples was optimised using response surface methodology (RSM). A Box-Behnken design was conducted to analyse the effects of solvent concentration (methanol or acetone), temperature and time on the extraction of total phenolic content, total flavonoids and antioxidant capacity (FRAP and DPPH). Analysis of the individual phenolics was performed by HPLC in optimal extraction conditions. The optimisation suggested that extraction with 84.5% methanol for 15 min, at 28 °C and extraction with 65% acetone for 20 min, at 10 °C were the best solutions for this combination of variables. RSM was shown to be an adequate approach for modelling the extraction of phenolic compounds from apples. Most of the experiments with acetone solutions extracted more bioactive compounds, and hence they had more antioxidant capacity, however, chlorogenic acid and phloridzin had higher yields (32.4% and 48.4%, respectively) in extraction with methanol.

  11. Cigarette smoke-mediated perturbations of the immune response: A new therapeutic approach with natural compounds.

    PubMed

    Magrone, Thea; Jirillo, Emilio

    2016-09-27

    Cigarette smoke (CS) accounts for the outcome of several pathologies, even including lung cancer, cardiovascular disease and chronic obstructive pulmonary disease (COPD). Under healthy conditions, lung immune system becomes tolerant in response to various external stimuli. CS exposure alters the pulmonary immune equilibrium, thus leading to a condition of hyper activation of the local innate and adaptive immunity. COPD is one of the major complications of chronic CS exposure where a pro-inflammatory profile of the pulmonary and systemic immunity is predominant. In this review, alternative treatments with natural products to mitigate CS-mediated pulmonary inflammation are proposed. In particular, polyphenols, a class of natural compounds largely present in fruits and vegetables, have been shown to act as anti-inflammatory agents. Accordingly, recent experimental and clinical evidences support polyphenol-mediated potential health benefits in smokers. For instance, pomegranate juice is able to attenuate the damage provoked by CS on cultured human alveolar macrophages. In addition, maqui beery extract has been proven to normalize H2O2 and interleukin-6 levels in exhaled breath condensate in healthy smokers. However, some limitations of alternative treatments are represented by a better knowledge of the mechanism(s) of action exerted by polyphenols and by the lack of animal models of COPD. In any case, the potential targets of polyphenols in the course of COPD will be outlined with special reference to the activation of T regulatory cells as well as to the inhibition of the polymorphonuclear cell and monocyte respiratory burst and of the NF-kB pathway, respectively.

  12. Thiazole compounds with activity against Cryptococcus gattii and Cryptococcus neoformans in vitro.

    PubMed

    Pereira de Sá, Nívea; Lino, Cleudiomar Inácio; Fonseca, Nayara Cristina; Borelli, Beatriz Martins; Ramos, Jonas Pereira; Souza-Fagundes, Elaine Maria; Rosa, Carlos Augusto; Santos, Daniel Assis; Barbosa de Oliveira, Renata; Johann, Susana

    2015-09-18

    Human cryptococcosis can occur as a primary or opportunistic infection and develop as an acute, subacute, or chronic, systemic infection involving different host organs. We evaluated the antifungal activity of thirteen compounds against Cryptococcus gattii and Cryptococcus neoformans in vitro, by assessing the toxicity of the compounds showing the greatest antifungal activity in VERO cells and murine macrophages. From these results, four compounds were considered promising for further studies because they displayed low cytotoxicity and significant antifungal activity. The heterocyclic compounds 1b, 1c, 1d, and 1m have antifungal activity levels between that of amphotericin B and fluconazole in vitro. The death curve of Cryptococcus spp. treated with these four compounds was similar to the curve obtained for amphotericin B, in that we observed a significant reduction in cell viability within the first 24 h of treatment. Additionally, we found that there was no effect when these compounds were combined with amphotericin and fluconazole, except for 1c, which antagonized the effect of amphotericin B against C. gattii, also reflected in the reduction of the post-antifungal effect (PAFE); however, this interaction did not alter the ergosterol content. The results shown in this paper reveal the discovery of novel thiazole compounds, which are easy to synthesize, and with potentially exhibit antifungal activity, and display low cytotoxicity in normal mammalian cells. These compounds can be used as prototypes for the design of new antifungal drugs against C. gattii and C. neoformans.

  13. 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.

  14. Analysis of volatile compounds responsible for kiwifruit aroma by desiccated headspace gas chromatography-mass spectrometry.

    PubMed

    Zhang, Chun-Yun; Zhang, Qiong; Zhong, Cai-Hong; Guo, Ming-Quan

    2016-04-01

    A new method for desiccated headspace (DHS) sampling of aqueous sample to GC-MS for the analysis of volatile compounds responsible for kiwifruit aroma in different kiwifruit cultivars has been developed based on the complete hydrate formation between the sample solvent (water) with anhydrous salt (calcium chloride) at an elevated temperature (above the boiling point of the aqueous sample) in a non-contact format, which overcame the water-effect challenge to directly introduce aqueous sample into GC-MS analysis. By means of DHS, the volatile compounds in three different kiwifruit cultivars were analyzed and compared under the optimized operating conditions, mainly time and temperature for headspace equilibration, column temperature program for GC-MS measurement. As a result, 20 peaks of volatile compounds responsible for kiwifruit aroma were detected and remarkable differences were found in the relative contents of three major volatile compounds among the three different kiwifruit cultivars, i.e., acetaldehyde, ethanol and furfural. The DHS sampling technique used in the present method can make the GC-MS analysis of volatile compounds in the aqueous sample within complex matrix possible without contaminating the GC-MS instrument. In terms of the analysis of volatile compounds in kiwifruit, the present method enabled a direct measurement on the filtrate of the aqueous kiwifruit pulp, without intermediate trap phase for the extraction of analytes, which will be more reliable and simpler as compared with any other headspace method in use. Thus, DHS coupled with GC-MS will be a new valuable tool available for the kiwifruit related research and organoleptic quality control.

  15. In vitro neuroprotective activities of compounds from Angelica shikokiana Makino.

    PubMed

    Mira, Amira; Yamashita, Shuntaro; Katakura, Yoshinori; Shimizu, Kuniyoshi

    2015-03-16

    Angelica shikokiana is widely marketed in Japan as a dietary food supplement. With a focus on neurodegenerative conditions such as Alzheimer's disease, the aerial part was extracted and through bio-guided fractionation, fifteen compounds [α-glutinol, β-amyrin, kaempferol, luteolin, quercetin, kaempferol-3-O-glucoside, kaempferol-3-O-rutinoside, methyl chlorogenate, chlorogenic acid, hyuganin E, 5-(hydroxymethyl)-2-furaldehyde, β-sitosterol-3-O-glucoside, adenosine (isolated for the first time from A. shikokiana), isoepoxypteryxin and isopteryxin] were isolated. Isolated compounds were evaluated for in vitro neuroprotection using acetylcholine esterase inhibitory, protection against hydrogen peroxide and amyloid β peptide (Aβ25-35)-induced neurotoxicity in neuro-2A cells, scavenging of hydroxyl radicals and intracellular reactive oxygen species and thioflavin T assays. Quercetin showed the strongest AChE inhibition (IC50 value = 35.5 µM) through binding to His-440 and Tyr-70 residues at the catalytic and anionic sites of acetylcholine esterase, respectively. Chlorogenic acid, its methyl ester, quercetin and luteolin could significantly protect neuro-2A cells against H2O2-induced neurotoxicity and scavenge hydroxyl radical and intracellular reactive oxygen species. Kaempferol-3-O-rutinoiside, hyuganin E and isoepoxypteryxin significantly decreased Aβ25-35-induced neurotoxicity and Th-T fluorescence. To the best of our knowledge, this is the first report about neuroprotection of hyuganin E and isoepoxypteryxin against Aβ25-35-induced neurotoxicity.

  16. Two new phenolic compounds and antitumor activities of asparinin A from Asparagus officinalis.

    PubMed

    Li, Xue-Mei; Cai, Jin-Long; Wang, Le; Wang, Wen-Xiang; Ai, Hong-Lian; Mao, Zi-Chao

    2017-02-01

    Two new phenolic acid compounds, asparoffin C (1) and asparoffin D (2), together with four known compounds, asparenyol (3), gobicusin B (4), 1-methoxy-2-hydroxy-4-[5-(4-hydroxyphenoxy)-3-penten-1-ynyl] phenol (5), and asparinin A (6), have been isolated from the stems of Asparagus officinalis. The structures were established by extensive spectroscopic methods (MS and 1D and 2D NMR). Compound 6 has obvious antitumor activities both in vitro and in vivo.

  17. Effect of polyphenolic compounds on the growth and cellulolytic activity of a strain of Trichoderma viride

    SciTech Connect

    Arrieta-Escobar, A.; Belin, J.M.

    1982-04-01

    Polyphenolic compounds are often regarded as inhibitors of microorganism growth. However, polyphenolic compounds can also induce stimulating effects on the growth, respiration, fermentation and excretion of amino acids. Depending on the concentration of polyphenolic compounds in the medium, opposed effects (inhibition, stimulation) can be observed. The purpose of this article is to study the effects of condensed tannins and some monomers on the growth and cellulolytic activity of Trichoderma viride. (Refs. 30).

  18. Antioxidant Activity of Novel Fused Heterocyclic Compounds Derived from Tetrahydropyrimidine Derivative.

    PubMed

    Salem, Marwa Sayed; Farhat, Mahmoud; Errayes, Asma Omar; Madkour, Hassan Mohamed Fawzy

    2015-01-01

    6-(Benzo[d][1,3]dioxol-5-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile has been utilized for synthesis of the fused heterocyclic compounds namely thiazolopyrimidines, tetrazolopyrimidine, pyrimidoquinazoline, pyrimidothiazolopyrimidine, pyrimidothiazolotriazine and pyrrolothiazolopyrimidine derivatives. The newly synthesized compounds were characterized by IR, (1)H-NMR, (13)C-NMR, and mass spectral data. Antioxidant activities of all synthesized compounds were investigated.

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

    SciTech Connect

    Satoh, Takumi Saitoh, Sachie; Hosaka, Manami; Kosaka, Kunio

    2009-02-06

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

  20. Synergistic activation of human pregnane X receptor by binary cocktails of pharmaceutical and environmental compounds

    PubMed Central

    Delfosse, Vanessa; Dendele, Béatrice; Huet, Tiphaine; Grimaldi, Marina; Boulahtouf, Abdelhay; Gerbal-Chaloin, Sabine; Beucher, Bertrand; Roecklin, Dominique; Muller, Christina; Rahmani, Roger; Cavaillès, Vincent; Daujat-Chavanieu, Martine; Vivat, Valérie; Pascussi, Jean-Marc; Balaguer, Patrick; Bourguet, William

    2015-01-01

    Humans are chronically exposed to multiple exogenous substances, including environmental pollutants, drugs and dietary components. Many of these compounds are suspected to impact human health, and their combination in complex mixtures could exacerbate their harmful effects. Here we demonstrate that a pharmaceutical oestrogen and a persistent organochlorine pesticide, both exhibiting low efficacy when studied separately, cooperatively bind to the pregnane X receptor, leading to synergistic activation. Biophysical analysis shows that each ligand enhances the binding affinity of the other, so the binary mixture induces a substantial biological response at doses at which each chemical individually is inactive. High-resolution crystal structures reveal the structural basis for the observed cooperativity. Our results suggest that the formation of ‘supramolecular ligands' within the ligand-binding pocket of nuclear receptors contributes to the synergistic toxic effect of chemical mixtures, which may have broad implications for the fields of endocrine disruption, toxicology and chemical risk assessment. PMID:26333997

  1. Candidate pheromone receptors provide the basis for the response of distinct antennal neurons to pheromonal compounds.

    PubMed

    Grosse-Wilde, Ewald; Gohl, Thomas; Bouché, Elisabeth; Breer, Heinz; Krieger, Jürgen

    2007-04-01

    Males of the moth species Heliothis virescens are able to detect the female-released pheromone with remarkable sensitivity and specificity, distinguishing between highly related pheromonal compounds. In the past, electrophysiological studies succeeded in assigning sensory hairs to identified compounds revealing three functional types of long sensilla trichodea housing neurons specifically responding to distinct semiochemicals. The specific responsiveness implies that the sensory neurons express different receptor types tuned to pheromone components. In this study we demonstrate that heterologously expressed candidate pheromone receptors from Heliothis responded to several pheromonal compounds, including the major sex-pheromone component Z-11-hexadecenal indicating a limited specificity of each receptor type. Nonetheless, based on functional analysis and in situ hybridization studies the analysed receptor types could tentatively be assigned to types of long sensilla trichodea, containing the pheromone-binding proteins (PBPs) HvirPBP1 and HvirPBP2 in the sensillum lymph. Substituting organic solvent with PBPs to solubilize the hydrophobic pheromone compounds in functional assays revealed an increase in sensitivity and especially specificity. It was found that in the presence of HvirPBP2, cells expressing the receptor type HR13 specifically responded to the main component of the sex pheromone blend only. The data provide further evidence that a combination of a distinct receptor type and binding protein underlie the specific response observed in the detection of a pheromone component in vivo.

  2. Derivatives of Procaspase-Activating Compound 1 (PAC-1) and Anticancer Activities

    PubMed Central

    Roth, Howard S.; Hergenrother, Paul J.

    2016-01-01

    PAC-1 induces the activation of procaspase-3 in vitro and in cell culture by chelation of inhibitory labile zinc ions via its ortho-hydroxy-N-acylhydrazone moiety. First reported in 2006, PAC-1 has shown promise in cell culture and animal models of cancer, and a Phase I clinical trial in cancer patients began in March 2015 (NCT02355535). Because of the considerable interest in this compound and a well-defined structure-activity relationship, over 1000 PAC-1 derivatives have been synthesized in an effort to vary pharmacological properties such as potency and pharmacokinetics. This article provides a comprehensive examination of all PAC-1 derivatives reported to date. A survey of PAC-1 derivative libraries is provided, with an in-depth discussion of four derivatives on which extensive studies have been performed. PMID:26630918

  3. Derivatives of Procaspase-Activating Compound 1 (PAC-1) and their Anticancer Activities.

    PubMed

    Roth, Howard S; Hergenrother, Paul J

    2016-01-01

    PAC-1 induces the activation of procaspase-3 in vitro and in cell culture by chelation of inhibitory labile zinc ions via its ortho-hydroxy-N-acylhydrazone moiety. First reported in 2006, PAC-1 has shown promise in cell culture and animal models of cancer, and a Phase I clinical trial in cancer patients began in March 2015 (NCT02355535). Because of the considerable interest in this compound and a well-defined structure-activity relationship, over 1000 PAC-1 derivatives have been synthesized in an effort to vary pharmacological properties such as potency and pharmacokinetics. This article provides a comprehensive examination of all PAC-1 derivatives reported to date. A survey of PAC-1 derivative libraries is provided, with an indepth discussion of four derivatives on which extensive studies have been performed.

  4. 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.

  5. Synthesis, antimicrobial activity of Schiff base compounds of cinnamaldehyde and amino acids.

    PubMed

    Wang, Hui; Yuan, Haijian; Li, Shujun; Li, Zhuo; Jiang, Mingyue

    2016-02-01

    The purpose of this study was to synthesize hydrophilic cinnamaldehyde Schiff base compounds and investigate those bioactivity. A total of 24 Schiff base compounds were synthesized using a simple approach with 3 cinnamaldehyde derivates and 8 amino acids as raw materials. The structures of synthesized compounds were confirmed using FTIR, (1)HNMR, HRMS purity and melting point. The antimicrobial activities of new compounds were evaluated with fluconazole and ciprofloxacin as the control against Aspergillus niger, Penicillium citrinum, Escherichia coli and Staphylococcus aureus. Findings show that major compounds exhibited significant bioactivity. Results from the structure-activity relationship suggest that both -p-Cl on benzene ring of cinnamaldehyde and the number of -COOK of amino acid salts significantly contributed to antimicrobial activity.

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

    NASA Astrophysics Data System (ADS)

    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.

  7. Pomegranate Ellagitannin-Derived Compounds Exhibit Anti-proliferative and Anti-aromatase Activity in Breast Cancer Cells In Vitro

    PubMed Central

    Adams, Lynn S.; Zhang, Yanjun; Seeram, Navindra P.; Heber, David; Chen, Shiuan

    2009-01-01

    Estrogen stimulates the proliferation of breast cancer cells and the growth of estrogen-responsive tumors. The aromatase enzyme, which converts androgen to estrogen, plays a key role in breast carcinogenesis. The pomegranate fruit, a rich source of ellagitannins (ETs), has attracted recent attention due to its anti-cancer and anti-atherosclerotic properties. On consumption, pomegranate ETs hydrolyze, releasing ellagic acid (EA) which is then converted to 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one (‘urolithin’) derivatives by gut microflora. The purpose of this study was to investigate the anti-aromatase activity and inhibition of testosterone-induced breast cancer cell proliferation by ellagitannin (ET)-derived compounds isolated from pomegranates. A panel of ten ET-derived compounds including EA, gallagic acid (GA), and urolithins A and B (and their acetylated, methylated and sulfated analogs prepared in our laboratory) were examined for ability to inhibit aromatase activity and testosterone-induced breast cancer cell proliferation. Using a microsomal aromatase assay, we screened the panel of ET-derived compounds and identified six with anti-aromatase activity. Among these, urolithin B (UB) was shown to most effectively inhibit aromatase activity in a live-cell assay. Kinetic analysis of UB demonstrated mixed inhibition, suggesting more than one inhibitory mechanism. Proliferation assays also determined that UB significantly inhibited testosterone-induced MCF-7aro cell proliferation. The remaining test compounds also exhibited anti-proliferative activity, but to a lesser degree than UB. These studies suggest that pomegranate ET-derived compounds have potential for the prevention of estrogen-responsive breast cancers. PMID:20051378

  8. Design, synthesis and cytotoxic activities of novel hybrid compounds between 2-phenylbenzofuran and imidazole.

    PubMed

    Yang, Xiao-Dong; Wan, Wei-Chao; Deng, Xiao-Yan; Li, Yan; Yang, Li-Juan; Li, Liang; Zhang, Hong-Bin

    2012-04-15

    A series of novel hybrid compounds between 2-phenylbenzofuran and imidazole have been prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that substitution of the imidazolyl-3-position with a naphthylacyl or bromophenacyl group, were vital for modulating cytotoxic activity. In particular, hybrid compound 15 was found to be the most potent compound against 4 strains human tumor cell lines and more active than cisplatin (DDP), and exhibited cytotoxic activity selectively against liver carcinoma (SMMC-7721).

  9. Screening of Panamanian Plant Extracts for Pesticidal Properties and HPLC-Based Identification of Active Compounds

    PubMed Central

    Guldbrandsen, Niels; De Mieri, Maria; Gupta, Mahabir; Seiser, Tobias; Wiebe, Christine; Dickhaut, Joachim; Reingruber, Rüdiger; Sorgenfrei, Oliver; Hamburger, Matthias

    2015-01-01

    A library of 600 taxonomically diverse Panamanian plant extracts was screened for fungicidal, insecticidal, and herbicidal activities. A total of 19 active extracts were submitted to HPLC-based activity profiling, and extracts of Bocconia frutescens, Miconia affinis, Myrcia splendens, Combretum aff. laxum, and Erythroxylum macrophyllum were selected for the isolation of compounds. Chelerythrine (2), macarpine (3), dihydrosanguinarine (5), and arjunolic acid (8) showed moderate-to-good fungicidal activity. Myricetin-3-O-(6’’-O-galloyl)-β-galactopyranoside (13) showed moderate insecticidal activity, but no compound with herbicidal activity was identified. PMID:26839818

  10. Active thermal isolation for temperature responsive sensors

    NASA Technical Reports Server (NTRS)

    Martinson, Scott D. (Inventor); Gray, David L. (Inventor); Carraway, Debra L. (Inventor); Reda, Daniel C. (Inventor)

    1994-01-01

    A temperature responsive sensor is located in the airflow over the specified surface of a body and is maintained at a constant temperature. An active thermal isolator is located between this temperature responsive sensor and the specified surface of the body. The temperature of this isolator is controlled to reduce conductive heat flow from the temperature responsive sensor to the body. This temperature control includes: (1) operating the isolator at the same temperature as the constant temperature of the sensor and (2) establishing a fixed boundary temperature which is either less than or equal to or slightly greater than the sensor constant temperature.

  11. 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.

  12. A glimpse on biological activities of tellurium compounds.

    PubMed

    Cunha, Rodrigo L O R; Gouvea, Iuri E; Juliano, Luiz

    2009-09-01

    Tellurium is a rare element which has been regarded as a toxic, non-essential trace element and its biological role is not clearly established to date. Besides of that, the biological effects of elemental tellurium and some of its inorganic and organic derivatives have been studied, leading to a set of interesting and promising applications. As an example, it can be highlighted the uses of alkali-metal tellurites and tellurates in microbiology, the antioxidant effects of organotellurides and diorganoditellurides and the immunomodulatory effects of the non-toxic inorganic tellurane, named AS-101, and the plethora of its uses. Inasmuch, the nascent applications of organic telluranes (organotelluranes) as protease inhibitors and its applications in disease models are the most recent contribution to the scenario of the biological effects and applications of tellurium and its compounds discussed in this manuscript.

  13. Antipoliovirus Activity of the Organic Extract of Eupatorium buniifolium: Isolation of Euparin as an Active Compound

    PubMed Central

    Visintini Jaime, María Florencia; Campos, Rodolfo H.; Martino, Virginia S.; Cavallaro, Lucía V.; Muschietti, Liliana V.

    2013-01-01

    The antiviral activity of the organic extract (OE) of Eupatorium buniifolium against poliovirus type 1 was determined by in vitro assays with an effective concentration 50 (EC50) of 23.3 ± 3.3 µg/mL. Bioassay-guided fractionation of the OE allowed the isolation of an active principle that was identified by spectroscopic methods (1H- and 13C-NMR, EI-MS, UV, and IR spectroscopy) as the benzofuran euparin. The plaque reduction assay in Vero cells was used to assess the antiviral activity of euparin against poliovirus types 1, 2, and 3 with EC50 values of 0.47, 0.12, and 0.15 µg/mL, respectively. Moreover, this compound showed high selectivity indexes of 284.9, 1068, and 854.7, respectively. In order to identify the mechanism by which euparin exerts its antiviral activity, the virucidal effect, the pretreatment of Vero cells, and the time of action on one viral replication cycle were evaluated. Results obtained demonstrated that euparin exerts its effect during the early events of the replication cycle, from the virus adsorption to cells up to the first twenty minutes after infection. This is the first report on the presence of euparin in E. buniifolium and its antiviral activity. PMID:23956770

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  15. Volatile sulfur compounds responsible for an offensive odor of the flat-head, Calliurichthys doryssus.

    PubMed

    Shiomi, K; Noguchi, A; Yamanaka, H; Kikuchi, T; Iida, H

    1982-01-01

    1. The volatiles of a flat-head, Calliurichthys doryssus, which gives out a characteristic offensive odor in living time, were analyzed by gas chromatography. 2. A large quantity of volatile sulfur compounds was detected in the flat-head; of which methyl mercaptan and/or dimethyl disulfide were judged to be responsible for the offensive odor. 3. The contents of methyl mercaptan and dimethyl disulfide were much higher in skin than in muscle and viscera.

  16. Efficacy and Mode of Action of Immune Response Modifying Compounds against Alphaviruses and Flaviviruses

    DTIC Science & Technology

    1987-12-01

    UTJC RE F mnpv Lfl AD _ _ _ _ _ _ _ 0 N Efficacy and Node of A-tion of Imune Response Modifying Compounds Against Alphaviruses and Flaviviruses...Against Alphaviruses and Flaviviruses 12. PERSONAL AUTHOR(S) Page S. Morahan, Margo Brinton, Angelo J. Pinto 13a. TYPE OF REPORT 13b. TIME COVERED 14...prophylactic and/or therapeutic treatment with immunomodulators alone and in combination with antiviral drugs against alphavirus , flavivirus, bunyavirus and

  17. Effect of Cytotoxic Compounds on Activity of Antioxidant Enzyme System in MCF-7 and H1299 Cells.

    PubMed

    Mumyatova, V A; Balakina, A A; Filatova, N V; Sen', V D; Korepin, A G; Terentev, A A

    2016-05-01

    We studied the function of the antioxidant system in tumor cell lines MCF-7 and H1299 that differ by the state of tumor suppressor gene p53. Exposure to different classes of cytotoxic compounds induced several types of antioxidant system responses that depend on the type of cell line. The effects of platinum(II) and platinum(IV) complexes on activity of antioxidant enzymes vary, which can be explained by differences in their accumulation and biotransformation in tumor cells. Triazole and oxazolidinone derivatives had little effect on activity of superoxide dismutase and catalase in H1299 cells, but increased superoxide dismutase activity in MCF-7 cells.

  18. Growth inhibitory activity of extracts and compounds from Cimicifuga species on human breast cancer cells.

    PubMed

    Einbond, Linda Saxe; Wen-Cai, Ye; He, Kan; Wu, Hsan-au; Cruz, Erica; Roller, Marc; Kronenberg, Fredi

    2008-06-01

    The purpose of this report is to explore the growth inhibitory effect of extracts and compounds from black cohosh and related Cimicifuga species on human breast cancer cells and to determine the nature of the active components. Black cohosh fractions enriched for triterpene glycosides and purified components from black cohosh and related Asian species were tested for growth inhibition of the ER(-) Her2 overexpressing human breast cancer cell line MDA-MB-453. Growth inhibitory activity was assayed using the Coulter Counter, MTT and colony formation assays. Results suggested that the growth inhibitory activity of black cohosh extracts appears to be related to their triterpene glycoside composition. The most potent Cimicifuga component tested was 25-acetyl-7,8-didehydrocimigenol 3-O-beta-d-xylopyranoside, which has an acetyl group at position C-25. It had an IC(50) of 3.2microg/ml (5microM) compared to 7.2microg/ml (12.1microM) for the parent compound 7,8-didehydrocimigenol 3-O-beta-d-xylopyranoside. Thus, the acetyl group at position C-25 enhances growth inhibitory activity. The purified triterpene glycoside actein (beta-d-xylopyranoside), with an IC(50) equal to 5.7microg/ml (8.4microM), exhibited activity comparable to cimigenol 3-O-beta-d-xyloside. MCF7 (ER(+)Her2 low) cells transfected for Her2 are more sensitive than the parental MCF7 cells to the growth inhibitory effects of actein from black cohosh, indicating that Her2 plays a role in the action of actein. The effect of actein on Her2 overexpressing MDA-MB-453 and MCF7 (ER(+)Her2 low) human breast cancer cells was examined by fluorescent microscopy. Treatment with actein altered the distribution of actin filaments and induced apoptosis in these cells. These findings, coupled with our previous evidence that treatment with the triterpene glycoside actein induced a stress response and apoptosis in human breast cancer cells, suggest that compounds from Cimicifuga species may be useful in the prevention and

  19. Essential oils and isolated compounds from Lippia alba leaves and flowers: antimicrobial activity and osteoclast apoptosis.

    PubMed

    Juiz, Paulo José Lima; Lucchese, Angelica Maria; Gambari, Roberto; Piva, Roberta; Penolazzi, Letizia; Di Ciano, Martina; Uetanabaro, Ana Paula Trovatti; Silva, Franceli; Avila-Campos, Mario Julio

    2015-01-01

    In the present study, essential oils extracted from the leaves and flowers of Lippia alba (Mill.) N.E.Br. (L. alba) were analyzed for their antimicrobial activity and their effects on osteoclasts. The periodontal pathogens, Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans; ATCC 43717), Fusobacterium nucleatum (F. nucleatum; ATCC 25586) and Porphyromonas gingivalis (P. gingivalis); ATCC 33277) were used in antimicrobial activity assays for determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC), whereas Bacteroides fragilis (B. fragilis; ATCC 25285) was used as the control microorganism. Osteoclast (OC) apoptosis was assessed by TUNEL assay and Fas receptor expression was detected by immunocytochemistry. The analysis of antimicrobial activity revealed that P. gingivalis had the lowest MIC values, whereas A. actinomycetemcomitans had the highest. L. alba essential oils were found to be toxic to human cells, although the compounds, carvone, limonene and citral, were non-toxic and induced apoptosis in the OCs. This study demonstrates that L. alba has potential biotechnological application in dentistry. In fact periodontal disease has a multifactorial etiology, and the immune response to microbial challenge leads to osteoclast activation and the resorption of the alveolar bone, resulting in tooth loss.

  20. An Activation Threshold Model for Response Inhibition

    PubMed Central

    MacDonald, Hayley J.; McMorland, Angus J. C.; Stinear, Cathy M.; Coxon, James P.; Byblow, Winston D.

    2017-01-01

    Reactive response inhibition (RI) is the cancellation of a prepared response when it is no longer appropriate. Selectivity of RI can be examined by cueing the cancellation of one component of a prepared multi-component response. This substantially delays execution of other components. There is debate regarding whether this response delay is due to a selective neural mechanism. Here we propose a computational activation threshold model (ATM) and test it against a classical “horse-race” model using behavioural and neurophysiological data from partial RI experiments. The models comprise both facilitatory and inhibitory processes that compete upstream of motor output regions. Summary statistics (means and standard deviations) of predicted muscular and neurophysiological data were fit in both models to equivalent experimental measures by minimizing a Pearson Chi-square statistic. The ATM best captured behavioural and neurophysiological dynamics of partial RI. The ATM demonstrated that the observed modulation of corticomotor excitability during partial RI can be explained by nonselective inhibition of the prepared response. The inhibition raised the activation threshold to a level that could not be reached by the original response. This was necessarily followed by an additional phase of facilitation representing a secondary activation process in order to reach the new inhibition threshold and initiate the executed component of the response. The ATM offers a mechanistic description of the neural events underlying RI, in which partial movement cancellation results from a nonselective inhibitory event followed by subsequent initiation of a new response. The ATM provides a framework for considering and exploring the neuroanatomical constraints that underlie RI. PMID:28085907

  1. Global transcriptomic responses of Escherichia coli K-12 to volatile organic compounds

    PubMed Central

    Yung, Pui Yi; Grasso, Letizia Lo; Mohidin, Abeed Fatima; Acerbi, Enzo; Hinks, Jamie; Seviour, Thomas; Marsili, Enrico; Lauro, Federico M.

    2016-01-01

    Volatile organic compounds (VOCs) are commonly used as solvents in various industrial settings. Many of them present a challenge to receiving environments, due to their toxicity and low bioavailability for degradation. Microorganisms are capable of sensing and responding to their surroundings and this makes them ideal detectors for toxic compounds. This study investigates the global transcriptomic responses of Escherichia coli K-12 to selected VOCs at sub-toxic levels. Cells grown in the presence of VOCs were harvested during exponential growth, followed by whole transcriptome shotgun sequencing (RNAseq). The analysis of the data revealed both shared and unique genetic responses compared to cells without exposure to VOCs. Results suggest that various functional gene categories, for example, those relating to Fe/S cluster biogenesis, oxidative stress responses and transport proteins, are responsive to selected VOCs in E. coli. The differential expression (DE) of genes was validated using GFP-promoter fusion assays. A variety of genes were differentially expressed even at non-inhibitory concentrations and when the cells are at their balanced-growth. Some of these genes belong to generic stress response and others could be specific to VOCs. Such candidate genes and their regulatory elements could be used as the basis for designing biosensors for selected VOCs. PMID:26818886

  2. Isolation and Antimicrobial Activity of Flavonoid Compounds from Mahagony Seeds (Swietenia macrophylla, King)

    NASA Astrophysics Data System (ADS)

    Mursiti, S.; Supartono

    2017-02-01

    Flavonoid is one of the secondary metabolites compounds in mahogany seeds. Mahogany seeds can be used as an antimicrobial. This study aims to determine the antimicrobial activity of flavonoid compounds from mahogany seeds against Escherichia coli (E.coli) and Bacillus cereus (B.cereus). Isolation of flavonoid compounds done step by step. First, the maceration using n-hexane, then with methanol. The methanol extract was dissolved in ethyl acetate and aquadest, then separated. Ethyl acetate extract evaporated Flavonoid compounds were. The testing of antimicrobial activity of flavonoid compounds using the absorption method. The results showed that the antimicrobial activity of flavonoid compounds from mahogany seeds shows the inhibitory activity and provide clear zone against bacteria E.coli with value Inhibitory Regional Diameter 18.50 mm respectively, and 14.50 mm to the bacteria. Based on the results of the study, it can be concluded that flavonoid compounds from mahogany seeds have antimicrobial activity against E.coli and B.cereus.

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

    PubMed

    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.

  4. INT-dehydrogenase activity test for assessing anaerobic biodegradability of organic compounds.

    PubMed

    Hongwei, Yang; Zhanpeng, Jiang; Shaoqi, Shi; Tang, W Z

    2002-11-01

    This study assessed anaerobic biodegradability of organic compounds from microorganism activity. Dehydrogenase activity can be a good parameter characterizing the microorganism activity. A modified method of 2-(p-iodophenyl-3-(p-nitrophenyl)-5-pheny tetrazolium chloride-dehydrogenase activity determination was proposed in anaerobic biodegradability assessment. Cubic spline curves were adopted to link the data points. This curve was integrated twice to calculate areas. The microorganism activity index in anaerobic biodegradability assessment was calculated by standardizing the integral. According to the results of the activity index, 14 kinds of organic compounds were classified into readily, partially, and poorly biodegradable under anaerobic conditions, respectively. As a result, some conclusions for anaerobic biodegradability of organic compounds were reached, based on the activity index value.

  5. Rigor and Responsiveness in Classroom Activity

    ERIC Educational Resources Information Center

    Thomspon, Jessica; Hagenah, Sara; Kang, Hosun; Stroupe, David; Braaten, Melissa; Colley, Carolyn; Windschitl, Mark

    2016-01-01

    Background/Context: There are few examples from classrooms or the literature that provide a clear vision of teaching that simultaneously promotes rigorous disciplinary activity and is responsive to all students. Maintaining rigorous and equitable classroom discourse is a worthy goal, yet there is no clear consensus of how this actually works in a…

  6. Enhancing Engagement through Active Student Response

    ERIC Educational Resources Information Center

    Tincani, Matt; Twyman, Janet S.

    2016-01-01

    Student engagement is critical to academic success. High-Active Student Response (ASR) teaching techniques are an effective way to improve student engagement and are an important component of evidence-based practice. High-ASR teaching strategies accompany important assumptions: (1) ASR is an alterable variable; (2) teachers can increase ASR in…

  7. Teaching Responsibility through Physical Activity. Second Edition.

    ERIC Educational Resources Information Center

    Hellison, Don

    This book guides teachers in using physical activity to foster personal and social responsibility. Focusing on teaching in school settings, the book features comments from real students to motivate teachers to apply the concept; take-aways that summarize each chapter and help teachers consider their own situations; new chapters on the lesson plan…

  8. Phenolic compounds and antioxidant activity of red wine made from grapes treated with different fungicides.

    PubMed

    Mulero, J; Martínez, G; Oliva, J; Cermeño, S; Cayuela, J M; Zafrilla, P; Martínez-Cachá, A; Barba, A

    2015-08-01

    The effect of treating grapes with six fungicides, applied under critical agricultural practices (CAP) on levels of phenolic compounds and antioxidant activity of red wines of Monastrell variety was studied. Vinifications were performed through addition of active dry yeast (ADY). Measurement of phenolic compounds was made with HPLC-DAD. Determination of antioxidant activity was through reaction of the wine sample with the DPPH radical. The wine prepared from grapes treated with quinoxyfen shows a greater increase of phenolic compounds than the control wine. In contrast, the wine obtained from grapes treated with trifloxystrobin showed lower total concentration of phenolic compounds, including stilbenes, whilst treatments with kresoxim-methyl, fluquinconazole, and famoxadone slightly reduced their content. Hence, the use of these last four fungicides could cause a decrease in possible health benefits to consumers. Antioxidant activity hardly varied in the assays with quinoxyfen, fluquinconazole and famoxadone, and decreased in the other wines.

  9. The phenolic compounds of olive oil: structure, biological activity and beneficial effects on human health.

    PubMed

    Tripoli, Elisa; Giammanco, Marco; Tabacchi, Garden; Di Majo, Danila; Giammanco, Santo; La Guardia, Maurizio

    2005-06-01

    The Mediterranean diet is rich in vegetables, cereals, fruit, fish, milk, wine and olive oil and has salutary biological functions. Epidemiological studies have shown a lower incidence of atherosclerosis, cardiovascular diseases and certain kinds of cancer in the Mediterranean area. Olive oil is the main source of fat, and the Mediterranean diet's healthy effects can in particular be attributed not only to the high relationship between unsaturated and saturated fatty acids in olive oil but also to the antioxidant property of its phenolic compounds. The main phenolic compounds, hydroxytyrosol and oleuropein, which give extra-virgin olive oil its bitter, pungent taste, have powerful antioxidant activity both in vivo and in vitro. The present review focuses on recent works analysing the relationship between the structure of olive oil polyphenolic compounds and their antioxidant activity. These compounds' possible beneficial effects are due to their antioxidant activity, which is related to the development of atherosclerosis and cancer, and to anti-inflammatory and antimicrobial activity.

  10. 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.

  11. Acaricidal Activity of Eugenol Based Compounds against Scabies Mites

    PubMed Central

    Pasay, Cielo; Mounsey, Kate; Stevenson, Graeme; Davis, Rohan; Arlian, Larry; Morgan, Marjorie; Vyszenski-Moher, DiAnn; Andrews, Kathy; McCarthy, James

    2010-01-01

    Backgound Human scabies is a debilitating skin disease caused by the “itch mite” Sarcoptes scabiei. Ordinary scabies is commonly treated with topical creams such as permethrin, while crusted scabies is treated with topical creams in combination with oral ivermectin. Recent reports of acaricide tolerance in scabies endemic communities in Northern Australia have prompted efforts to better understand resistance mechanisms and to identify potential new acaricides. In this study, we screened three essential oils and four pure compounds based on eugenol for acaricidal properties. Methodology/Principal Findings Contact bioassays were performed using live permethrin-sensitive S. scabiei var suis mites harvested from pigs and permethrin-resistant S. scabiei var canis mites harvested from rabbits. Results of bioassays showed that clove oil was highly toxic against scabies mites. Nutmeg oil had moderate toxicity and ylang ylang oil was the least toxic. Eugenol, a major component of clove oil and its analogues –acetyleugenol and isoeugenol, demonstrated levels of toxicity comparable to benzyl benzoate, the positive control acaricide, killing mites within an hour of contact. Conclusions The acaricidal properties demonstrated by eugenol and its analogues show promise as leads for future development of alternative topical acaricides to treat scabies. PMID:20711455

  12. Methylation Landscape of Human Breast Cancer Cells in Response to Dietary Compound Resveratrol

    PubMed Central

    Medina-Aguilar, Rubiceli; Pérez-Plasencia, Carlos; Marchat, Laurence A.; Gariglio, Patricio; García Mena, Jaime; Rodríguez Cuevas, Sergio; Ruíz-García, Erika; Astudillo-de la Vega, Horacio; Hernández Juárez, Jennifer; Flores-Pérez, Ali; López-Camarillo, César

    2016-01-01

    Aberrant DNA methylation is a frequent epigenetic alteration in cancer cells that has emerged as a pivotal mechanism for tumorigenesis. Accordingly, novel therapies targeting the epigenome are being explored with the aim to restore normal DNA methylation patterns on oncogenes and tumor suppressor genes. A limited number of studies indicate that dietary compound resveratrol modulates DNA methylation of several cancer-related genes; however a complete view of changes in methylome by resveratrol has not been reported yet. In this study we performed a genome-wide survey of DNA methylation signatures in triple negative breast cancer cells exposed to resveratrol. Our data showed that resveratrol treatment for 24 h and 48 h decreased gene promoter hypermethylation and increased DNA hypomethylation. Of 2476 hypermethylated genes in control cells, 1,459 and 1,547 were differentially hypomethylated after 24 h and 48 h, respectively. Remarkably, resveratrol did not induce widespread non-specific DNA hyper- or hypomethylation as changes in methylation were found in only 12.5% of 27,728 CpG loci. Moreover, resveratrol restores the hypomethylated and hypermethylated status of key tumor suppressor genes and oncogenes, respectively. Importantly, the integrative analysis of methylome and transcriptome profiles in response to resveratrol showed that methylation alterations were concordant with changes in mRNA expression. Our findings reveal for the first time the impact of resveratrol on the methylome of breast cancer cells and identify novel potential targets for epigenetic therapy. We propose that resveratrol may be considered as a dietary epidrug as it may exert its anti-tumor activities by modifying the methylation status of cancer -related genes which deserves further in vivo characterization. PMID:27355345

  13. Characterization of nitrated phenolic compounds for their anti-oxidant, pro-oxidant, and nitration activities.

    PubMed

    Iwasaki, Yusuke; Nomoto, Maki; Oda, Momoko; Mochizuki, Keisuke; Nakano, Yuki; Ishii, Yuji; Ito, Rie; Saito, Koichi; Umemura, Takashi; Nishikawa, Akiyoshi; Nakazawa, Hiroyuki

    2011-09-01

    Coffee is one of the most widely consumed beverages worldwide. Evidence of the health benefits and the important contribution of coffee brew to the intake of anti-oxidants in the diet has increased coffee consumption. Chlorogenic acid (ChA) and caffeic acid (CaA) are the major phenolic compounds in coffee. However, phenolic compounds, which are generally effective anti-oxidants, can become pro-oxidants in the presence of Cu(2+) to induce DNA damage under certain conditions. On the other hand, sodium nitrite (NaNO(2)) is widely used as a food additive to preserve and tinge color on cured meat and fish. It is possible that phenolic compounds react with NaNO(2) under acidic conditions, such as gastric juice. In this study, we identified compounds produced by the reaction between ChA or CaA in coffee and NaNO(2) in artificial gastric juice. The identified phenolic compounds and nitrated phenolic compounds were assessed for their anti-oxidant, pro-oxidant, and nitration activities by performing an in vitro assay. The nitrated phenolic compounds seemed to show increased anti-oxidant activity and decreased pro-oxidant activity. However, one nitrated CaA compound that has a furoxan ring showed the ability to release NO(2)(-) in the neutral condition.

  14. A Quantum Chemical and Statistical Study of Cytotoxic Activity of Compounds Isolated from Curcuma zedoaria

    PubMed Central

    Hamdi, Omer Abdalla Ahmed; Anouar, El Hassane; Shilpi, Jamil A.; Trabolsy, Zuhra Bashir Khalifa Al; Zain, Sharifuddin Bin Md; Zakaria, Nur Shahidatul Shida; Zulkefeli, Mohd; Weber, Jean-Frédéric F.; Malek, Sri Nurestri A.; Rahman, Syarifah Nur Syed Abdul; Awang, Khalijah

    2015-01-01

    A series of 21 compounds isolated from Curcuma zedoaria was subjected to cytotoxicity test against MCF7; Ca Ski; PC3 and HT-29 cancer cell lines; and a normal HUVEC cell line. To rationalize the structure–activity relationships of the isolated compounds; a set of electronic; steric and hydrophobic descriptors were calculated using density functional theory (DFT) method. Statistical analyses were carried out using simple and multiple linear regressions (SLR; MLR); principal component analysis (PCA); and hierarchical cluster analysis (HCA). SLR analyses showed that the cytotoxicity of the isolated compounds against a given cell line depend on certain descriptors; and the corresponding correlation coefficients (R2) vary from 0%–55%. MLR results revealed that the best models can be achieved with a limited number of specific descriptors applicable for compounds having a similar basic skeleton. Based on PCA; HCA and MLR analyses; active compounds were classified into subgroups; which was in agreement with the cell based cytotoxicity assay. PMID:25923077

  15. 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.

  16. Fractionation of Phenolic Compounds Extracted from Propolis and Their Activity in the Yeast Saccharomyces cerevisiae

    PubMed Central

    Petelinc, Tanja; Polak, Tomaž; Demšar, Lea; Jamnik, Polona

    2013-01-01

    We have here investigated the activities of Slovenian propolis extracts in the yeast Saccharomyces cerevisiae, and identified the phenolic compounds that appear to contribute to these activities. We correlated changes in intracellular oxidation and cellular metabolic energy in these yeasts with the individual fractions of the propolis extracts obtained following solid-phase extraction. The most effective fraction was further investigated according to its phenolic compounds. PMID:23409133

  17. Pulmonary metabolism of foreign compounds: Its role in metabolic activation

    SciTech Connect

    Cohen, G.M. )

    1990-04-01

    The lung has the potential of metabolizing many foreign chemicals to a vast array of metabolites with different pharmacological and toxicological properties. Because many chemicals require metabolic activation in order to exert their toxicity, the cellular distribution of the drug-metabolizing enzymes in a heterogeneous tissue, such as the lung, and the balance of metabolic activation and deactivation pathways in any particular cell are key factors in determining the cellular specificity of many pulmonary toxins. Environmental factors such as air pollution, cigarette smoking, and diet markedly affect the pulmonary metabolism of some chemicals and, thereby, possibly affect their toxicity.

  18. 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.

  19. Three new resin glycosides compounds from Argyreia acuta and their α-glucosidase inhibitory activity.

    PubMed

    Wang, Li; Yan, You-Shao; Cui, Hong-Hua; Yin, Yong-Qin; Pan, Jie-Tao; Yu, Bang-Wei

    2017-03-01

    Three new phenolic compounds, acutacoside C (1), acutacoside D (2) and acutacoside E (3) were isolated from the aerial part of Argyreia acuta. The oligosaccharide chain was composed of two glucoses and three rhamnoses, and the aglycone was (11S)-hydroxyhexadecanoic acid (jalapinolic acid). The core of the three compounds was operculinic acid B, which was rare in resin glycosides. Their structures were established by a combination of spectroscopic and chemical methods. Compounds 1-3 have been evaluated for inhibitory activity against α-glucosidase, which all showed weak inhibitory activities.

  20. 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.

  1. Correlation of antimutagenic activity and suppression of CYP1A with the lipophilicity of alkyl gallates and other phenolic compounds.

    PubMed

    Feng, Qing; Kumagai, Takeshi; Nakamura, Yoshimasa; Uchida, Koji; Osawa, Toshihiko

    2003-05-09

    Alkyl gallates are widely used as food antioxidants. Methyl, ethyl, propyl, lauryl, and cetyl gallates showed antimutagenicity to activated 2-aminoanthracene (2AA)-induced SOS responses in Salmonella typhimurium TA1535/pSK1002. They also exhibited a suppressive effect on 3-methylcholanthrene (3-MC)-induced cytochrome P450 1A (CYP1A) in human hepatoma HepG2 cells, as indexed by the 7-ethoxyresorufin-O-deethylase (EROD) activity, and on CYP1A protein level. Both antimutagenicity and suppression of CYP1A appeared to be dependent on alkyl chain lengths, which suggested lipophilicity dependence. Based on those results, we investigated 26 other phenolic compounds for their lipophilicity, antimutagenicity and inhibition of EROD activity. The lipophilicity correlated well with the inhibition of EROD activity (r=0.78), and the inhibition of EROD activity correlated with the antimutagenicity of those compounds (r=0.71). The results suggest that the lipophilicity of the phenolic compounds may be an important factor in their ability to inhibit EROD activity.

  2. Characteristic aroma-active compounds of Korean perilla (Perilla frutescens Britton) leaf.

    PubMed

    Seo, Won Ho; Baek, Hyung Hee

    2009-12-23

    Aroma-active compounds from Korean perilla (Perilla frutescens Britton) leaf were extracted by solvent-assisted flavor evaporation (SAFE), liquid-liquid continuous extraction (LLCE), and hydrodistillation (HD) and analyzed by gas chromatography-mass spectrometry (GC-MS) and gas chromatography-olfactometry (GC-O). Thirty-three volatile compounds were identified by GC-MS. 1-(3-Furyl)-4-methyl-1-pentanone (perilla ketone) was found to be the most abundant volatile compound, followed in order by (Z)-3-hexenol and 1-octen-3-ol. Perilla ketone comprised 81% (93 ppm), 84% (120 ppm), and 95% (490 ppm) of the volatile compounds obtained from SAFE, LLCE, and HD, respectively. Thirteen aroma-active compounds were detected by GC-O. Perilla ketone, 1-(3-furyl)-4-methyl-3-penten-1-one (egoma ketone), and 1-(3-furyl)-4-methyl-2-penten-1-one (isoegoma ketone) were considered to be the characteristic aroma-active compounds of Korean perilla leaf. Perilla ketone, (Z)-3-hexenal (green), egoma ketone, and isoegoma ketone were the most intense aroma-active compounds in Korean perilla leaf. Other relatively intense odorants included (Z)-3-hexenol (green), (E)-2-hexenal (green), benzaldehyde (almond), 1-octen-3-one (metallic), 1-octen-3-ol (mushroom), phenylacetaldehyde (honeysuckle), linalool (lemon), and beta-caryophyllene (woody).

  3. Prediction of compounds in different local structure-activity relationship environments using emerging chemical patterns.

    PubMed

    Namasivayam, Vigneshwaran; Gupta-Ostermann, Disha; Balfer, Jenny; Heikamp, Kathrin; Bajorath, Jürgen

    2014-05-27

    Active compounds can participate in different local structure-activity relationship (SAR) environments and introduce different degrees of local SAR discontinuity, depending on their structural and potency relationships in data sets. Such SAR features have thus far mostly been analyzed using descriptive approaches, in particular, on the basis of activity landscape modeling. However, compounds in different local SAR environments have not yet been predicted. Herein, we adapt the emerging chemical patterns (ECP) method, a machine learning approach for compound classification, to systematically predict compounds with different local SAR characteristics. ECP analysis is shown to accurately assign many compounds to different local SAR environments across a variety of activity classes covering the entire range of observed local SARs. Control calculations using random forests and multiclass support vector machines were carried out and a variety of statistical performance measures were applied. In all instances, ECP calculations yielded comparable or better performance than controls. The approach presented herein can be applied to predict compounds that complement local SARs or prioritize compounds with different SAR characteristics.

  4. Supercritical Carbon Dioxide Extraction of Bioactive Compounds from Ampelopsis grossedentata Stems: Process Optimization and Antioxidant Activity

    PubMed Central

    Wang, Yuefei; Ying, Le; Sun, Da; Zhang, Shikang; Zhu, Yuejin; Xu, Ping

    2011-01-01

    Supercritical carbon dioxide (SC-CO2) extraction of bioactive compounds including flavonoids and phenolics from Ampelopsis grossedentata stems was carried out. Extraction parameters such as pressure, temperature, dynamic time and modifier, were optimized using an orthogonal array design of L9 (34), and antioxidant activities of the extracts were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay and ferrous ion chelating (FIC) assay. The best conditions obtained for SC-CO2 extraction of flavonoids was 250 bar, 40 °C, 50 min, and with a modifier of methanol/ethanol (1:3, v/v), and that for phenolics extraction was 250 bar, 40 °C, 50 min, and with a modifier of methanol/ethanol (1:1, v/v). Meantime, flavonoids and phenolics were found to be mainly responsible for the DPPH scavenging activity of the extracts, but not for the chelating activity on ferrous ion according to Pearson correlation analysis. Furthermore, several unreported flavonoids such as apigenin, vitexin, luteolin, etc., have been detected in the extracts from A. grossedentata stems. PMID:22072923

  5. Phenolic compounds and antioxidant activity of olive leaf extracts.

    PubMed

    Kontogianni, Vassiliki G; Gerothanassis, Ioannis P

    2012-01-01

    The total phenolic content and antioxidant activities of olive leaf extracts were determined. Plant material was extracted with methanol and fractionated with solvents of increasing polarity, giving certain extracts. The qualitative changes in the composition of the extracts were determined after the storage of leaves for 22 h at 37°C, before the extraction. Total polyphenol contents in extracts were determined by the Folin-Ciocalteu procedure. They were also analysed by liquid chromatography-mass spectrometry. Their antioxidant activities were evaluated using the diphenyl picrylhydrazyl method and the β-carotene linoleate model assay. Moreover, the effects of different crude olive leaf extracts on the oxidative stability of sunflower oil at 40°C and sunflower oil-in-water emulsions (10% o/w) at 37°C, at a final concentration of crude extract 200 mg kg(-1) oil, were tested and compared with butylated hydroxyl toluene.

  6. Global emissions and models of photochemically active compounds

    SciTech Connect

    Penner, J.E.; Atherton, C.S.; Graedel, T.E.

    1993-05-20

    Anthropogenic emissions from industrial activity, fossil fuel combustion, and biomass burning are now known to be large enough (relative to natural sources) to perturb the chemistry of vast regions of the troposphere. A goal of the IGAC Global Emissions Inventory Activity (GEIA) is to provide authoritative and reliable emissions inventories on a 1{degree} {times} 1{degree} grid. When combined with atmospheric photochemical models, these high quality emissions inventories may be used to predict the concentrations of major photochemical products. Comparison of model results with measurements of pertinent species allows us to understand whether there are major shortcomings in our understanding of tropospheric photochemistry, the budgets and transport of trace species, and their effects in the atmosphere. Through this activity, we are building the capability to make confident predictions of the future consequences of anthropogenic emissions. This paper compares IGAC recommended emissions inventories for reactive nitrogen and sulfur dioxide to those that have been in use previously. We also present results from the three-dimensional LLNL atmospheric chemistry model that show how emissions of anthropogenic nitrogen oxides might potentially affect tropospheric ozone and OH concentrations and how emissions of anthropogenic sulfur increase sulfate aerosol loadings.

  7. Solubility Prediction of Active Pharmaceutical Compounds with the UNIFAC Model

    NASA Astrophysics Data System (ADS)

    Nouar, Abderrahim; Benmessaoud, Ibtissem; Koutchoukali, Ouahiba; Koutchoukali, Mohamed Salah

    2016-03-01

    The crystallization from solution of an active pharmaceutical ingredient requires the knowledge of the solubility in the entire temperature range investigated during the process. However, during the development of a new active ingredient, these data are missing. Its experimental determination is possible, but tedious. UNIFAC Group contribution method Fredenslund et al. (Vapor-liquid equilibria using UNIFAC: a group contribution method, 1977; AIChE J 21:1086, 1975) can be used to predict this physical property. Several modifications on this model have been proposed since its development in 1977, modified UNIFAC of Dortmund Weidlich et al. (Ind Eng Chem Res 26:1372, 1987), Gmehling et al. (Ind Eng Chem Res 32:178, 1993), Pharma-modified UNIFAC Diedrichs et al. (Evaluation und Erweiterung thermodynamischer Modelle zur Vorhersage von Wirkstofflöslichkeiten, PhD Thesis, 2010), KT-UNIFAC Kang et al. (Ind Eng Chem Res 41:3260, 2002), ldots In this study, we used UNIFAC model by considering the linear temperature dependence of interaction parameters as in Pharma-modified UNIFAC and structural groups as defined by KT-UNIFAC first-order model. More than 100 binary datasets were involved in the estimation of interaction parameters. These new parameters were then used to calculate activity coefficient and solubility of some molecules in various solvents at different temperatures. The model gives better results than those from the original UNIFAC and shows good agreement between the experimental solubility and the calculated one.

  8. Modulation of aromatase activity by diet polyphenolic compounds.

    PubMed

    Monteiro, Rosário; Azevedo, Isabel; Calhau, Conceição

    2006-05-17

    Estrogens are involved in physiological actions related to reproduction, body fat distribution, and maintenance of bone mass and are also related to the pathogenesis of estrogen-dependent cancers. The aim of this work was to study the effect of polyphenols on estrogen synthesis. The effect of polyphenols and polyphenolic-rich beverages on aromatase activity was tested in JAR cells (a choriocarcinoma cell line) through the tritiated water release assay. Some of the tested polyphenols inhibited estrogen production, chrysin being the most potent. Additionally, we observed that red wine, alcohol-free red wine, green tea, and black tea (200 microL/mL) significantly decreased aromatase activity. No effect on aromatase expression, as assessed by western blotting and RT-PCR, has been detected after 24 h of treatment with any of the flavonoids under study. In conclusion, polyphenols are able to modulate aromatase activity and, consequently, estrogen synthesis. The knowledge of such interference may help to clarify some of the biological properties attributed to polyphenols and may be useful in prevention/treatment of estrogen-dependent disorders.

  9. Charge Trapping in Photovoltaically Active Perovskites and Related Halogenoplumbate Compounds.

    PubMed

    Shkrob, Ilya A; Marin, Timothy W

    2014-04-03

    Halogenoplumbate perovskites (MeNH3PbX3, where X is I and/or Br) have emerged as promising solar panel materials. Their limiting photovoltaic efficiency depends on charge localization and trapping processes that are presently insufficiently understood. We demonstrate that in halogenoplumbate materials the holes are trapped by organic cations (that deprotonate from their oxidized state) and Pb(2+) cations (as Pb(3+) centers), whereas the electrons are trapped by several Pb(2+) cations, forming diamagnetic lead clusters that also serve as color centers. In some cases, paramagnetic variants of these clusters can be observed. We suggest that charge separation in the halogenoplumbates resembles latent image formation in silver halide photography. Electron and hole trapping by lead clusters in extended dislocations in the bulk may be responsible for accumulation of trapped charge observed in this photovoltaic material.

  10. In vitro antitrypanosomal activity of some phenolic compounds from propolis and lactones from Fijian Kawa (Piper methysticum).

    PubMed

    Otoguro, Kazuhiko; Iwatsuki, Masato; Ishiyama, Aki; Namatame, Miyuki; Nishihara-Tsukashima, Aki; Kiyohara, Hiroaki; Hashimoto, Toshihiro; Asakawa, Yoshinori; Omura, Satoshi; Yamada, Haruki

    2012-07-01

    During our search to discover new antitrypanosomal compounds, eight known plant compounds (three phenolic compounds and five kawa lactones) were evaluated for in vitro activity against Trypanosoma brucei brucei. Among them, we found two phenolic compounds and three kawa lactones possessing an α-pyrone influenced antitrypanosomal property. In particular, β-phenethyl caffeate, farnesyl caffeate and dihydrokawain exhibited high or moderate selective and potent antitrypanosomal activity in vitro. We detail here the antitrypanosomal activity and cytotoxicities of the compounds, in comparison with two commonly used antitrypanosomal drugs (eflornithine and suramin). Our findings represent the first report of the promising trypanocidal activity of these compounds.

  11. Enzyme activity in the flesh fly Parasarcophaga dux Thomson influenced by dill compounds, myristicin and apiol.

    PubMed

    Khalaf, Abdel-Fattah A

    2004-04-01

    The newly emerged adults of Parasarcophaga dux were treated topically with various doses of myristicin and apiol isolated from roots of dill plant, Anethum graveolus. The compounds toxicity and the dehydrogenase activities of the treated stage and its subsequent developmental stages were studied. The results indicated that apiol more toxic than myristicin. The spectrophotometric evaluation exhibited changes in dehydrogenase activities after treatments. Compounds increased the activities of both alpha-GPDH and MDH in first half of metamorphosis (immature stages). But, the level of ME activities of the various stages was obviously decreased.

  12. Responses of marine unicellular algae to brominated organic compounds in six growth media

    SciTech Connect

    Walsh, G.E.; Yoder, M.J.; McLaughlin, L.L.; Lores, E.M.

    1987-12-01

    Marine unicellular algae, Skeletonema costatum, Thalassiosira pseudonana, and Chlorella sp. were exposed to the industrial brominated compounds tetrabromobisphenol A, decabromobiphenyloxide (DBBO), hexabromocyclododecane (HBCD), pentabromomethylbenzene (PBMB), pentabromoethylbenzene (PBEB), and the herbicide bromoxynil (BROM), in six algal growth media. High concentrations of DBBO (1 mg liter-1), PBMB (1 mg liter-1), and PBEB (0.5 mg liter-1) reduced growth by less than 50%. EC50s of the other compounds varied with growth medium, with high EC50/low EC50 ratios between 1.3 and 9.9. Lowest EC50s, 9.3 to 12.0 micrograms liter-1, were obtained with S. costatum and HBCD. It is concluded that responses to toxicants in different media are the results of interactions among algae, growth medium, toxicant, and solvent carrier.

  13. Screening of Pharmacologically Active Small Molecule Compounds Identifies Antifungal Agents Against Candida Biofilms

    PubMed Central

    Watamoto, Takao; Egusa, Hiroshi; Sawase, Takashi; Yatani, Hirofumi

    2015-01-01

    Candida species have emerged as important and common opportunistic human pathogens, particularly in immunocompromised individuals. The current antifungal therapies either have toxic side effects or are insufficiently effect. The aim of this study is develop new small-molecule antifungal compounds by library screening methods using Candida albicans, and to evaluate their antifungal effects on Candida biofilms and cytotoxic effects on human cells. Wild-type C. albicans strain SC5314 was used in library screening. To identify antifungal compounds, we screened a small-molecule library of 1,280 pharmacologically active compounds (LOPAC1280TM) using an antifungal susceptibility test (AST). To investigate the antifungal effects of the hit compounds, ASTs were conducted using Candida strains in various growth modes, including biofilms. We tested the cytotoxicity of the hit compounds using human gingival fibroblast (hGF) cells to evaluate their clinical safety. Only 35 compounds were identified by screening, which inhibited the metabolic activity of C. albicans by >50%. Of these, 26 compounds had fungistatic effects and nine compounds had fungicidal effects on C. albicans. Five compounds, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate, ellipticine and CV-3988, had strong fungicidal effects and could inhibit the metabolic activity of Candida biofilms. However, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine were cytotoxic to hGF cells at low concentrations. CV-3988 showed no cytotoxicity at a fungicidal concentration. Four of the compounds identified, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine, had toxic effects on Candida strains and hGF cells. In contrast, CV-3988 had fungicidal effects on Candida strains, but low cytotoxic effects on hGF cells. Therefore, this screening reveals agent, CV-3988 that was previously unknown to be antifungal agent, which could be a novel therapies for superficial mucosal candidiasis. PMID

  14. Cell extraction combined with off-line HPLC for screening active compounds from Coptis chinensis.

    PubMed

    Tang, Cheng; Wu, Xiao-Dan; Yu, Ya-Ming; Duan, Hongquan; Zhou, Jing; Xu, Liang

    2016-04-01

    Cell membrane chromatography is a useful tool for screening active compounds from natural products. As the reason of separation mechanism, traditional cell membrane chromatography could not be used for screening the active compounds absorbed through the cell membrane and influencing the cell signal transduction pathway. In this work, we establish a new method named cell extraction combined with off-line HPLC for screening the compounds penetrating the cell membrane. This is the first time 3 T3-L1 adipocyte culture has been combined with HPLC technology. Compared with other cell membrane chromatography methods, there is good resolution and no further analysis by other chromatographic steps is required. On co-incubating crude extracts of Coptis chinensis with cells and analyzing the compounds extracted by the cells, active compounds such as berberine were detected. Glucose consumption tests showed that berberine could increase glucose consumption by insulin-resistant 3 T3-L1 adipocytes. The levels of intracellular berberine correlated with its activity. The results indicate that the developed method could be an alternative method for screening active compounds from natural products.

  15. Comparison of antioxidant activity of compounds isolated from guava leaves and a stability study of the most active compound.

    PubMed

    Nantitanon, W; Okonogi, S

    2012-02-01

    In the present study, quercetin (QT), morin (MR), and quercetin-3-O-glucopyranoside (QG) isolated from guava leaves were comparatively tested for antioxidant activity using DPPH, ABTS, and FRAP methods. QT was the most active among them. The free radical scavenging activity of QT was approximately four times higher than MR and two times higher than QG. The reducing power of QT was eight times higher than MR and two times higher than QG. A mixture of QT with MR or QG showed interesting combination effect. The synergistic antioxidant activity was obtained when QT was mixed with MR whereas the antagonistic effect was found when mixed with QG. The stability study of QT in liquid preparations indicated that the decomposition reaction rate of QT could be explained by a kinetic model assuming a first-order chemical reaction. The aqueous solution of QT was rapidly decomposed with t1/2 of approximately five days whereas QT entrapped in chitosan nanoparticles was five times longer. It was concluded that QT was the most active antioxidant from guava leaves. Entrapment of QT in chitosan nanoparticles could significantly enhance its stability.

  16. Impact of estrogenic compounds on DNA integrity in human spermatozoa: evidence for cross-linking and redox cycling activities.

    PubMed

    Bennetts, L E; De Iuliis, G N; Nixon, B; Kime, M; Zelski, K; McVicar, C M; Lewis, S E; Aitken, R J

    2008-05-10

    A great deal of circumstantial evidence has linked DNA damage in human spermatozoa with adverse reproductive outcomes including reduced fertility and high rates of miscarriage. Although oxidative stress is thought to make a significant contribution to DNA damage in the male germ line, the factors responsible for creating this stress have not been elucidated. One group of compounds that are thought to be active in this context are the estrogens, either generated as a result of the endogenous metabolism of androgens within the male reproductive tract or gaining access to the latter as a consequence of environmental exposure. In this study, a wide variety of estrogenic compounds were assessed for their direct effects on human spermatozoa in vitro. DNA integrity was assessed using the Comet and TUNEL assays, lesion frequencies were quantified by QPCR using targets within the mitochondrial and nuclear (beta-globin) genomes, DNA adducts were characterized by mass spectrometry and redox activity was monitored using dihydroethidium (DHE) as the probe. Of the estrogenic and estrogen analogue compounds evaluated, catechol estrogens, quercetin, diethylstilbestrol and pyrocatechol stimulated intense redox activity while genistein was only active at the highest doses tested. Other estrogens and estrogen analogues, such as 17beta-estradiol, nonylphenol, bisphenol A and 2,3-dihydroxynaphthalene were inactive. Estrogen-induced redox activity was associated with a dramatic loss of motility and, in the case of 2-hydroxyestradiol, the induction of significant DNA fragmentation. Mass spectrometry also indicated that catechol estrogens were capable of forming dimers that can cross-link the densely packed DNA strands in sperm chromatin, impairing nuclear decondensation. These results highlight the potential importance of estrogenic compounds in creating oxidative stress and DNA damage in the male germ line and suggest that further exploration of these compounds in the aetiology of male

  17. Antioxidant activity and phytochemical compounds of snake fruit (Salacca Zalacca)

    NASA Astrophysics Data System (ADS)

    Suica-Bunghez, I. R.; Teodorescu, S.; Dulama, I. D.; Voinea, O. C.; imionescu, S.; Ion, R. M.

    2016-06-01

    Snake fruit (Salacca zalacca) is a palm tree species, which is found in Malaysia and Indonesia. This study was conducted to investigate and compare the composition, total phenolic, flavonoid, tanins and monoterpenoids contents in the core and shell fruits. Concentration values of extracts were obtained from standard curves obtained. Antioxidant activity was determined using DPPH method. For all methods it was used the UV-VIS Specord M40, using different wavelength. The infrared spectral analysis was carried out to caracterized the type of functional group existent in snake fruit parts (shell and core).

  18. Activated phosphors having matrices of yttrium-transition metal compound

    DOEpatents

    De Kalb, E.L.; Fassel, V.A.

    1975-07-01

    A method is described for preparing a phosphor composition containing a lanthanide activator element with a host matrix having a transition element as a major component. The host matrix is composed of certain rare earth phosphates or vanadates such as YPO$sub 4$ with a portion of the rare earth replaced with one or more of the transition elements. On x-ray or other electromagnetic excitation, trace lanthanide impurities or additives within the phosphor are spectrometrically determined from their characteristic luminescence. (auth)

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

    NASA Astrophysics Data System (ADS)

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

    2002-11-01

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

  20. Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines.

    PubMed

    Macpherson, Lindsey J; Dubin, Adrienne E; Evans, Michael J; Marr, Felix; Schultz, Peter G; Cravatt, Benjamin F; Patapoutian, Ardem

    2007-02-01

    The nervous system senses peripheral damage through nociceptive neurons that transmit a pain signal. TRPA1 is a member of the Transient Receptor Potential (TRP) family of ion channels and is expressed in nociceptive neurons. TRPA1 is activated by a variety of noxious stimuli, including cold temperatures, pungent natural compounds, and environmental irritants. How such diverse stimuli activate TRPA1 is not known. We observed that most compounds known to activate TRPA1 are able to covalently bind cysteine residues. Here we use click chemistry to show that derivatives of two such compounds, mustard oil and cinnamaldehyde, covalently bind mouse TRPA1. Structurally unrelated cysteine-modifying agents such as iodoacetamide (IA) and (2-aminoethyl)methanethiosulphonate (MTSEA) also bind and activate TRPA1. We identified by mass spectrometry fourteen cytosolic TRPA1 cysteines labelled by IA, three of which are required for normal channel function. In excised patches, reactive compounds activated TRPA1 currents that were maintained at least 10 min after washout of the compound in calcium-free solutions. Finally, activation of TRPA1 by disulphide-bond-forming MTSEA is blocked by the reducing agent dithiothreitol (DTT). Collectively, our data indicate that covalent modification of reactive cysteines within TRPA1 can cause channel activation, rapidly signalling potential tissue damage through the pain pathway.

  1. Trisomy 21 consistently activates the interferon response.

    PubMed

    Sullivan, Kelly D; Lewis, Hannah C; Hill, Amanda A; Pandey, Ahwan; Jackson, Leisa P; Cabral, Joseph M; Smith, Keith P; Liggett, L Alexander; Gomez, Eliana B; Galbraith, Matthew D; DeGregori, James; Espinosa, Joaquín M

    2016-07-29

    Although it is clear that trisomy 21 causes Down syndrome, the molecular events acting downstream of the trisomy remain ill defined. Using complementary genomics analyses, we identified the interferon pathway as the major signaling cascade consistently activated by trisomy 21 in human cells. Transcriptome analysis revealed that trisomy 21 activates the interferon transcriptional response in fibroblast and lymphoblastoid cell lines, as well as circulating monocytes and T cells. Trisomy 21 cells show increased induction of interferon-stimulated genes and decreased expression of ribosomal proteins and translation factors. An shRNA screen determined that the interferon-activated kinases JAK1 and TYK2 suppress proliferation of trisomy 21 fibroblasts, and this defect is rescued by pharmacological JAK inhibition. Therefore, we propose that interferon activation, likely via increased gene dosage of the four interferon receptors encoded on chromosome 21, contributes to many of the clinical impacts of trisomy 21, and that interferon antagonists could have therapeutic benefits.

  2. Competitive adsorption of furfural and phenolic compounds onto activated carbon in fixed bed column.

    PubMed

    Sulaymon, Abbas H; Ahmed, Kawther W

    2008-01-15

    For a multicomponent competitive adsorption of furfural and phenolic compounds, a mathematical model was builtto describe the mass transfer kinetics in a fixed bed column with activated carbon. The effects of competitive adsorption equilibrium constant, axial dispersion, external mass transfer, and intraparticle diffusion resistance on the breakthrough curve were studied for weakly adsorbed compound (furfural) and strongly adsorbed compounds (parachlorophenol and phenol). Experiments were carried out to remove the furfural and phenolic compound from aqueous solution. The equilibrium data and intraparticle diffusion coefficients obtained from separate experiments in a batch adsorber, by fitting the experimental data with theoretical model. The results show that the mathematical model includes external mass transfer and pore diffusion using nonlinear isotherms and provides a good description of the adsorption process for furfural and phenolic compounds in a fixed bed adsorber.

  3. Compounds from Polyphaga plancyi and their inhibitory activities against JAK3 and DDR1 kinases.

    PubMed

    Zhu, Hong-Jie; Yan, Yong-Ming; Tu, Zheng-Chao; Luo, Jin-Feng; Liang, Rui; Yang, Tong-Hua; Cheng, Yong-Xian; Wang, Shu-Mei

    2016-10-01

    Plancyamides A (1) and B (3), plancypyrazine A (2), and plancyols A (4) and B (5), five new compounds (1-5), and three known ones (6-8), were isolated from the whole bodies of Polyphaga plancyi Bolivar. Their structures were elucidated by a combination of spectroscopic analyses including 1D and 2D NMR, and HRESIMS. Among them, compound 3 is racemic, chiral HPLC separation afforded its respective enantiomers. The absolute configuration of 1 was assigned by computational methods. Biological evaluation of all the compounds with exception of 7 and 8 discloses that compounds 2 and 4 could inhibit JAK3 kinase with IC50 values of 12.6 and 5.0μM, respectively. In addition, compound 4 exhibit inhibitory activity towards DDR1 kinase with IC50 value of 4.87μM.

  4. Overcoming Chloroquine Resistance in Malaria: Design, Synthesis, and Structure-Activity Relationships of Novel Hybrid Compounds

    PubMed Central

    Boudhar, Aicha; Ng, Xiao Wei; Loh, Chiew Yee; Chia, Wan Ni; Tan, Zhi Ming; Nosten, Francois

    2016-01-01

    Resistance to antimalarial therapies, including artemisinin, has emerged as a significant challenge. Reversal of acquired resistance can be achieved using agents that resensitize resistant parasites to a previously efficacious therapy. Building on our initial work describing novel chemoreversal agents (CRAs) that resensitize resistant parasites to chloroquine (CQ), we herein report new hybrid single agents as an innovative strategy in the battle against resistant malaria. Synthetically linking a CRA scaffold to chloroquine produces hybrid compounds with restored potency toward a range of resistant malaria parasites. A preferred compound, compound 35, showed broad activity and good potency against seven strains resistant to chloroquine and artemisinin. Assessment of aqueous solubility, membrane permeability, and in vitro toxicity in a hepatocyte line and a cardiomyocyte line indicates that compound 35 has a good therapeutic window and favorable drug-like properties. This study provides initial support for CQ-CRA hybrid compounds as a potential treatment for resistant malaria. PMID:26953199

  5. 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.

  6. Terpenoid bioactive compound from Streptomyces rochei (M32): taxonomy, fermentation and biological activities.

    PubMed

    Pazhanimurugan, Raasaiyah; Radhakrishnan, Manikkam; Shanmugasundaram, Thangavel; Gopikrishnan, Venugopal; Balagurunathan, Ramasamy

    2016-10-01

    The present study emphasized the production of biologically active terpenoid compound from Streptomyces rochei M32, which was isolated from Western Ghats ecosystem, South India. The presence of resistant genes like mecA, vanA of Staphylococcus aureus and bla SHV, bla TEM of Pseudomonas aeruginosa was confirmed by molecular studies. The isolated compound from Streptomyces rochei M32 inhibited wide range of standard and clinical drug resistant pathogens and enteric pathogens. The rice bran supplemented basal medium influenced the active compound production on 8th day of fermentation and yielded 1875 mg of crude extract from 10 g of rice bran substrate. Purification and characterization of crude ethyl acetate extract was achieved by preparative thin layer chromatography. The active fraction was identified as terpenoid class compound by chemical screening. Based on the results of spectral studies (NMR, LC-MS, FTIR, etc.), the active compound was tentatively identified as 1, 19-bis (3-hydroxyazetidin-1-yl) nonadeca-5, 14-diene-1, 8, 12, 19-tetraone with molecular weight 462.41 g/mol. Minimum inhibitory concentration value ranges between 7.6 and 31.2 µg/mL against test organisms was observed. The cytotoxicity results on cervical cancer (HeLa) cell line showed IC50 value of 2.034 µg/mL. The corresponding compound is not previously reported from any microbial resources.

  7. 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

  8. Antioxidant activity and bioactive compounds of tea seed (Camellia oleifera Abel.) oil.

    PubMed

    Lee, Chia-Pu; Yen, Gow-Chin

    2006-02-08

    The oil of tea seed (Camellia oleifera Abel.) is used extensively in China as cooking oil. The objectives of this study were to investigate the antioxidant activity of tea seed oil and its active compounds. Of the five solvent extracts, methanol extract of tea seed oil exhibited the highest yield and the strongest antioxidant activity as determined by DPPH scavenging activity and Trolox equivalent antioxidant capacity (TEAC). Two peaks separated from the methanol extract by HPLC contributed the most significant antioxidant activity. These two peaks were further identified as sesamin and a novel compound: 2,5-bis-benzo[1,3]dioxol-5-yl-tetrahydro-furo [3,4-d][1,3]dioxine (named compound B) by UV absorption and characterized by MS, IR, 1H NMR, and 13C NMR techniques. Sesamin and compound B decreased H2O2-mediated formation of reactive oxygen species in red blood cells (RBCs), inhibited RBCs hemolysis induced by AAPH, and increased the lag time of conjugated dienes formation in human low-density lipoprotein. The results indicate that both compounds isolated from tea seed oil exhibit remarkable antioxidant activity. Apart from the traditional pharmacological effects of Camellia oleifera, the oil of tea seed may also act as a prophylactic agent to prevent free radical related diseases.

  9. Isolation and identification of compounds responsible for antioxidant capacity of Euryale ferox seeds.

    PubMed

    Song, Chang-Wei; Wang, Shu-Mei; Zhou, Li-Li; Hou, Fan-Fan; Wang, Kai-Jin; Han, Quan-Bin; Li, Ning; Cheng, Yong-Xian

    2011-02-23

    Euryale ferox seed is consumed medicinally or for food in China. The present study revealed it to contain significant antioxidant activity, which may be associated with its medical applications as a proteinuria inhibitor of diabetic nephropathy. This study resulted in the identification of 3 new sesquineolignans, named euryalins A-C (1-3), and 16 known compounds, which were all first isolated from this plant apart from 5,7,4-trihydroxy-flavanone. The antioxidant potential of the partial isolates was evaluated using the DPPH radical scavenging assay and mesangial cellular assay. Compounds 2, rel-(2α,3β)-7-O-methylcedrusin (4), syringylglycerol-8-O-4-(sinapyl alcohol) ether (5), and (+)-syringaresinol (7) were found to be most active on DPPH assay, whereas compounds 2, 4, 7, (1R,2R,5R,6S)-2-(3,4-dimethoxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3.3.0]octane, and buddlenol E could significantly inhibit high glucose-stimulated reactive oxygen species production in mesangial cells. The results suggested that E. ferox seed could be considered as an excellent source of natural antioxidants and is useful in the prevention of diabetic nephropathy.

  10. Essential requirement of cytochrome c release for caspase activation by procaspase-activating compound defined by cellular models

    PubMed Central

    Seervi, M; Joseph, J; Sobhan, P K; Bhavya, B C; Santhoshkumar, T R

    2011-01-01

    Mitochondrial cytochrome c (cyt. c) release and caspase activation are often impaired in tumors with Bcl-2 overexpression or Bax and Bak-defective status. Direct triggering of cell death downstream of Bax and Bak is an attractive strategy to kill such cancers. Small molecule compounds capable of direct caspase activation appear to be the best mode for killing such tumors. However, there is no precise model to screen such compounds. The currently employed cell-free systems possess the inherent drawback of lacking cellular contents and organelles that operate in integrating cell death signaling. We have developed highly refined cell-based approaches to validate direct caspase activation in cancer cells. Using this approach, we show that PAC-1 (first procaspase-activating compound), the first direct activator of procaspases identified in a cell-free system, in fact requires mitochondrial cyt. c release for triggering caspase activation similar to other antitumor agents. It can induce significant caspase activation and cell death in the absence of Bax and Bak, and in cells overexpressing Bcl-2 and Bcl-xL. This study for the first time defines precise criteria for the validation of direct caspase-activating compounds using specialized cellular models that is expected to accelerate the discovery of potential direct caspase activators. PMID:21900958

  11. Selective Small Molecule Compounds Increase BMP-2 Responsiveness by Inhibiting Smurf1-mediated Smad1/5 Degradation

    PubMed Central

    Cao, Yu; Wang, Cheng; Zhang, Xueli; Xing, Guichun; Lu, Kefeng; Gu, Yongqing; He, Fuchu; Zhang, Lingqiang

    2014-01-01

    The ubiquitin ligase Smad ubiquitination regulatory factor-1 (Smurf1) negatively regulates bone morphogenetic protein (BMP) pathway by ubiquitinating certain signal components for degradation. Thus, it can be an eligible pharmacological target for increasing BMP signal responsiveness. We established a strategy to discover small molecule compounds that block the WW1 domain of Smurf1 from interacting with Smad1/5 by structure based virtual screening, molecular experimental examination and cytological efficacy evaluation. Our selected hits could reserve the protein level of Smad1/5 from degradation by interrupting Smurf1-Smad1/5 interaction and inhibiting Smurf1 mediated ubiquitination of Smad1/5. Further, these compounds increased BMP-2 signal responsiveness and the expression of certain downstream genes, enhanced the osteoblastic activity of myoblasts and osteoblasts. Our work indicates targeting Smurf1 for inhibition could be an accessible strategy to discover BMP-sensitizers that might be applied in future clinical treatments of bone disorders such as osteopenia. PMID:24828823

  12. The structure-activity relationship of various YO compounds, novel plasmin inhibitors, in the apoptosis induction.

    PubMed

    Enomoto, Riyo; Sugahara, Chiyoko; Komai, Tomoe; Suzuki, Chie; Kinoshita, Noriko; Hosoda, Akiko; Yoshikawa, Asa; Tsuda, Yuko; Okada, Yoshio; Lee, Eibai

    2004-11-01

    We have previously reported that YO-2, a selective plasmin inhibitor, induces thymocyte apoptosis. To elucidate the mechanism of YO-2-induced apoptosis, other YO compounds with different plasmin inhibitory action were tested for the pro-apoptotic activity in this study. The treatment of rat thymocytes with the YO compounds which had the hydrophobic but not the hydrophilic moiety at the C-terminal increased DNA fragmentation, the number of condensed nuclei and caspase-3-like activity. All pro-apoptotic YO compounds not only were potent plasmin inhibitors but also had the hydrophobic C-terminal as the common structure. Therefore, the target molecule of the YO compounds may be located not on the cell surface but rather inside the cells.

  13. 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.

  14. [Antibacterial activity of polyphenolic compounds isolated from plants of Geraniaceae and Rosaceae families].

    PubMed

    Nikitina, V S; Kuz'mina, L Iu; Melent'ev, A I; Shendel', G V

    2007-01-01

    Polyphenolic compounds present in extracts of plants belonging to the families Geraniaceae (blood-red cranesbill, wood cranesbill, meadow cranesbill, and alfilaria) and Rosaceae (red raspberry, European dewberry, and tormentil) have been tested for their activity against gram-positive and gram-negative bacteria of the genera Azotobacter, Bacillus, and Pseudomonas. The bacteriostatic activity exhibited some species-related features and depended on the polarity of the extracting agent. The bacteriostatic activity of plant-derived phenolic compounds correlated with their antioxidant potential. The plants of the families Geraniaceae and Rosaceae offer promise as a source of raw material for isolation of polyphenolic compounds exhibiting bactericidal activity, including against opportunistic pathogens (B. cereus, E. coli, P. aeruginosa, and S. aureus strains).

  15. SYNTHESIS AND BIOLOGICAL ACTIVITY OF SULFUR COMPOUNDS SHOWING STRUCTURAL ANALOGY WITH COMBRETASTATIN A-4

    PubMed Central

    dos Santos, Edson dos A.; Prado, Paulo C.; de Carvalho, Wanderley R.; de Lima, Ricardo V.; Beatriz e, Adilson; de Lima, Dênis P.; Hamel, Ernest; Dyba, Marzena A.; Albuquerque, Sergio

    2013-01-01

    We extended our previous exploration of sulfur bridges as bioisosteric replacements for atoms forming the bridge between the aromatic rings of combretastatin A-4. Employing coupling reactions between 5-iodo-1,2,3-trimethoxybenzene and substituted thiols, followed by oxidation to sulfones with m-CPBA, different locations for attaching the sulfur atom to ring A through the synthesis of nine compounds were examined. Antitubulin activity was performed with electrophoretically homogenous bovine brain tubulin, and activity occurred with the 1,2,3-trimethoxy-4-[(4-methoxyphenyl)thio]benzene (12), while the other compounds were inactive. The compounds were also tested for leishmanicidal activity using promastigote forms of Leishmania braziliensis (MHOM/BR175/M2904), and the greatest activity was observed with 1,2,3-trimethoxy-4-(phenylthio)benzene (10) and 1,2,3-trimethoxy-4-[(4-methoxyphenyl) sulfinyl]benzene (15). PMID:23766547

  16. SYNTHESIS AND BIOLOGICAL ACTIVITY OF SULFUR COMPOUNDS SHOWING STRUCTURAL ANALOGY WITH COMBRETASTATIN A-4.

    PubMed

    Dos Santos, Edson Dos A; Prado, Paulo C; de Carvalho, Wanderley R; de Lima, Ricardo V; Beatriz E, Adilson; de Lima, Dênis P; Hamel, Ernest; Dyba, Marzena A; Albuquerque, Sergio

    2013-02-01

    We extended our previous exploration of sulfur bridges as bioisosteric replacements for atoms forming the bridge between the aromatic rings of combretastatin A-4. Employing coupling reactions between 5-iodo-1,2,3-trimethoxybenzene and substituted thiols, followed by oxidation to sulfones with m-CPBA, different locations for attaching the sulfur atom to ring A through the synthesis of nine compounds were examined. Antitubulin activity was performed with electrophoretically homogenous bovine brain tubulin, and activity occurred with the 1,2,3-trimethoxy-4-[(4-methoxyphenyl)thio]benzene (12), while the other compounds were inactive. The compounds were also tested for leishmanicidal activity using promastigote forms of Leishmania braziliensis (MHOM/BR175/M2904), and the greatest activity was observed with 1,2,3-trimethoxy-4-(phenylthio)benzene (10) and 1,2,3-trimethoxy-4-[(4-methoxyphenyl) sulfinyl]benzene (15).

  17. An expedient synthesis and screening for antiacetylcholinesterase activity of piperidine embedded novel pentacyclic cage compounds.

    PubMed

    Kumar, Raju Suresh; Almansour, Abdulrahman I; Arumugam, Natarajan; Osman, Hasnah; Ali, Mohamed Ashraf; Basiri, Alireza; Kia, Yalda

    2014-03-01

    The aim of this study was to synthesize and evaluate diazapentacyclic analogs for their acetylcholinesterase (AChE) inhibitory activity. The pentacyclic analogs were synthesized by one-pot three-component domino reactions in a microwave synthesizer. Most of the compounds exhibited moderate to good AChE inhibitory activity, compound 5i showed potent inhibitory activity with IC50 1.12 ± 0.01 µM and this may provide a new lead for developing potential inhibitors for Alzheimer's disease.

  18. Defence response of tomato seedlings to oxidative stress induced by phenolic compounds from dry olive mill residue.

    PubMed

    García-Sánchez, Mercedes; Garrido, Inmaculada; Casimiro, Ilda de Jesús; Casero, Pedro Joaquín; Espinosa, Francisco; García-Romera, Inmaculada; Aranda, Elisabet

    2012-10-01

    ADOR is an aqueous extract obtained from the dry olive mill residue (DOR) which contains the majority of its soluble phenolic compounds, which are responsible for its phytotoxic properties. Some studies have shown that ADOR negatively affects seed germination. However, to date, few studies have been carried out on the effect of ADOR on the oxidative stress of the plant. It is well known that saprobe fungi can detoxify these phenolic compounds and reduce the potential negative effects of ADOR on plants. To gain a better understanding of the phytotoxic effects and oxidative stress caused by this residue, tomato seeds were germinated in the presence of ADOR, treated and untreated with Coriolopsis rigida, Trametes versicolor, Pycnoporus cinnabarinus and Penicillium chrysogenum-10 saprobe fungi. ADOR sharply reduced tomato seed germination and also generated high levels of malondialdehyde (MDA), O(2)(-) and H(2)O(2). However, bioremediated ADOR did not negatively affect germination and reduced MDA, O(2)(-) and H(2)O(2) content in different ways depending on the fungus used. In addition, the induced defense response was studied by analyzing the activity of both antioxidant enzymes (superoxide dismutase (SOD), catalase, ascorbate peroxidasa, glutathione reductase (GR), peroxidases and coniferil alcohol peroxidasa) and detoxification enzymes (glutathione-S-transferase (GST)). Our findings suggest that, because ADOR is capable of inducing oxidative stress, tomato seedlings trigger a defense response through SOD, GR, and GST activity and through antioxidant and lignification processes. On the other hand, the bioremediation of ADOR plays an important role in counteracting the oxidative stress induced by the untreated residue.

  19. Dose-Dependent Behavioral Response of the Mosquito Aedes albopictus to Floral Odorous Compounds

    PubMed Central

    Hao, Huiling; Sun, Jingcheng; Dai, Jianqing

    2013-01-01

    The value of using plant volatiles as attractants for trapping and spatial repellents to protect hosts against mosquitoes has been widely recognized. The current study characterized behavioral responses of Aedes albopictus (Skuse) (Diptera: Culicidae) to different concentrations, ranging from 6 to 96%, of several common floral odorous compounds, including linalool, geraniol, citronellal, eugenol, anisaldehyde, and citral, using a wind tunnel olfactometer system. The results indicated that female mosquitoes reacted differently to different concentrations of the tested compounds, and the reactions also were different when those chemicals were tested alone or in the presence of human host odor. When tested alone, anisaldehyde was attractive at all tested concentrations, eugenol was attractive only at concentrations of 48–96%, while citronellal, linalool, citral, and geraniol were attractive at lower concentrations and repellent at higher concentrations. When tested in the presence of a human host, all compounds except for anisaldehyde at all tested concentrations showed host-seeking inhibition to certain degrees. Based on the results, it was concluded that anisaldehyde was effective in attracting Ae. albopictus when used alone but could also remarkably inhibit the host-seeking ability at a concentration of 96%, while citral, geraniol, linalool, citronellal, and eugenol are suitable as spatial repellents. PMID:24779928

  20. Dose-dependent behavioral response of the mosquito Aedes albopictus to floral odorous compounds.

    PubMed

    Hao, Huiling; Sun, Jingcheng; Dai, Jianqing

    2013-01-01

    The value of using plant volatiles as attractants for trapping and spatial repellents to protect hosts against mosquitoes has been widely recognized. The current study characterized behavioral responses of Aedes albopictus (Skuse) (Diptera: Culicidae) to different concentrations, ranging from 6 to 96%, of several common floral odorous compounds, including linalool, geraniol, citronellal, eugenol, anisaldehyde, and citral, using a wind tunnel olfactometer system. The results indicated that female mosquitoes reacted differently to different concentrations of the tested compounds, and the reactions also were different when those chemicals were tested alone or in the presence of human host odor. When tested alone, anisaldehyde was attractive at all tested concentrations, eugenol was attractive only at concentrations of 48-96%, while citronellal, linalool, citral, and geraniol were attractive at lower concentrations and repellent at higher concentrations. When tested in the presence of a human host, all compounds except for anisaldehyde at all tested concentrations showed host-seeking inhibition to certain degrees. Based on the results, it was concluded that anisaldehyde was effective in attracting Ae. albopictus when used alone but could also remarkably inhibit the host-seeking ability at a concentration of 96%, while citral, geraniol, linalool, citronellal, and eugenol are suitable as spatial repellents.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. Occurrence of pharmaceutically active and non-steroidal estrogenic compounds in three different wastewater recycling schemes in Australia.

    PubMed

    Al-Rifai, Jawad H; Gabelish, Candace L; Schäfer, Andrea I

    2007-10-01

    The discovery that natural and synthetic chemicals, in the form of excreted hormones and pharmaceuticals, as well as a vast array of compounds with domestic and industrial applications, can enter the environment via wastewater treatment plants and cause a wide variety of environmental and health problems even at very low concentrations, suggests the need for improvement of water recycling. Three Australian wastewater recycling schemes, two of which employ reverse osmosis (RO) technology, the other applying ozonation and biological activated carbon filtration, have been studied for their ability to remove trace organic contaminants including 11 pharmaceutically active compounds and two non-steroidal estrogenic compounds. Contaminant concentrations were determined using a sensitive analytical method comprising solid phase extraction, derivatization and GC with MS using selected ion monitoring. In raw wastewater, concentrations of analgesics and non-steroidal anti-inflammatory medications were comparable to those found in wastewaters around the world. Remarkably, removal efficiencies for the three schemes were superior to literature values and RO was responsible for the greatest proportion of contaminant removal. The ability of RO membranes to concentrate many of the compounds was demonstrated and highlights the need for continued research into monitoring wastewater treatment, concentrate disposal, improved water recycling schemes and ultimately, safer water and a cleaner environment.

  6. [Biosynthesis of biologically active low-molecular weight compounds by fungi of the genus Penicillium (review)].

    PubMed

    Kozlovskii, A G; Antipova, T V; Zhelifonova, V P

    2015-01-01

    The recent data on exometabolite biosynthesis in fungi of the genus Penicillium is summarized. The study of creative species, as well as those isolated from extreme ecotopes, resulted in the identification of a number of novel, biologically active compounds. Alkaloid biosynthesis has been shown to begin on.the first day of fungus cultivation and to proceed throughout the cultivation period. Idiophase kinetics was observed for the biosynthesis of polyketide metabolites. The mechanisms of regulation of biosynthesis of promising bioactive compounds are discussed.

  7. Structure-activity of antifungal compounds inspired by aminobisabolenes from the sponge Halichondria sp.

    PubMed

    Jamison, Matthew T; Macho, Jocelyn; Molinski, Tadeusz F

    2016-11-01

    Structure-activity relationships of the antifungal aminobisabolene natural product, 1 isolated from Halichondria sp., and synthetic analogs were explored, in parallel with the antidermatophytic allylamine, Terbinafine®, against a panel of pathogenic fungi: Candida spp., Cryptococcus spp. and Trichophyton rubrum. Interpretation of the results suggest different modes of action in antifungal activity for the two classes of compounds.

  8. Structure-activity relationship of benzoxazinones and related compounds with respect to the growth inhibition and alpha-amylase activity in cress seedlings.

    PubMed

    Kato-Noguchi, Hisashi; Macías, Francisco A; Molinillo, José M G

    2010-10-15

    Benzoxazinones and their degradation compounds inhibited root growth and alpha-amylase activity in cress seedlings. The inhibitory activity of these compounds was divided into three groups: the high active group; 2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one, 2,4-dihydroxy-(2H)-1,4-benzoxazin-3(4H)-one, 4-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one, 4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one, the moderate active group; 7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one, (2H)-1,4-benzoxazin-3(4H)-one, 6-methoxy-benzoxazolin-2(3H)-one, benzoxazolin-2(3H)-one and 2-amino-phenoxazine-3-one, and the low active group; 2-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one, 2-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one, 2-amino-7-hydroxyphenoxazine-3-one and 2-amino-7-methoxyphenoxazine-3-one. The structure-activity of these compounds suggests that compounds that have benzoxazinone skeletons are the most active structure, and a hydroxyl group at position C-2 on the benzoxazinone skeleton may not affect inhibitory activity, whereas a hydroxyl group at position N-4 on the skeleton is essential for inhibitory activity. However, the concentration-response curves of these compounds and the I(50) values (the concentrations required for 50% inhibition) for root growth and alpha-amylase indicated that root growth was positively correlated with the alpha-amylase activity in the seedlings. alpha-Amylase is required not only for seed germination, but also subsequent seedling growth until photosynthesis is sufficient to support seedling growth. Therefore, these results suggest that the compounds studied here may inhibit the root growth of cress seedlings by inhibiting alpha-amylase activity.

  9. Identification of orthologous target pairs with shared active compounds and comparison of organism-specific activity patterns.

    PubMed

    Dimova, Dilyana; Stumpfe, Dagmar; Bajorath, Jürgen

    2015-11-01

    A systematic search for active small molecules shared by orthologous targets was carried out, leading to the identification of 803 compound-based orthologous target pairs covering a total of 938 orthologues, 358 unique targets and 98 organisms. Many orthologous target pairs were found to have substantial compound coverage, enabling the introduction of an orthologous target pairs classification including 'organism cliffs' and 'potency-retaining' pairs. A total of 158 orthologous target pairs involving human orthologues were identified, which were typically associated with drug discovery-relevant targets, organism combinations and compound data. Orthologous target pairs with human orthologues included 83 potency-retaining orthologous target pairs covering a variety of targets and organisms. On the basis of these orthologous target pairs, the compound search was further extended and 1149 potent compounds were identified that only had reported activities for non-human orthologues of 48 therapeutic targets, but not their human counterparts, hence providing a large pool of candidate compounds for further evaluation. The complete set of orthologous target pairs identified in our analysis, the orthologous target pairs classification including associated data and all candidate compounds are made freely available.

  10. Cancer Stem Cells: The Potential Targets of Chinese Medicines and Their Active Compounds

    PubMed Central

    Hong, Ming; Tan, Hor Yue; Li, Sha; Cheung, Fan; Wang, Ning; Nagamatsu, Tadashi; Feng, Yibin

    2016-01-01

    The pivotal role of cancer stem cells (CSCs) in the initiation and progression of malignancies has been rigorously validated, and the specific methods for identifying and isolating the CSCs from the parental cancer population have also been rapidly developed in recent years. This review aims to provide an overview of recent research progress of Chinese medicines (CMs) and their active compounds in inhibiting tumor progression by targeting CSCs. A great deal of CMs and their active compounds, such as Antrodia camphorate, berberine, resveratrol, and curcumin have been shown to regress CSCs, in terms of reversing drug resistance, inducing cell death and inhibiting cell proliferation as well as metastasis. Furthermore, one of the active compounds in coptis, berbamine may inhibit tumor progression by modulating microRNAs to regulate CSCs. The underlying molecular mechanisms and related signaling pathways involved in these processes were also discussed and concluded in this paper. Overall, the use of CMs and their active compounds may be a promising therapeutic strategy to eradicate cancer by targeting CSCs. However, further studies are needed to clarify the potential of clinical application of CMs and their active compounds as complementary and alternative therapy in this field. PMID:27338343

  11. Multifunctional activity of polyphenolic compounds associated with a potential for Alzheimer's disease therapy from Ecklonia cava.

    PubMed

    Choi, Byoung Wook; Lee, Hye Sook; Shin, Hyeon-Cheol; Lee, Bong Ho

    2015-04-01

    Five polyphenols were isolated and purified from a brown alga Ecklonia cava. These compounds showed diverse biological activities such as antioxidative, antiinflammatory, and enzyme inhibitory activities. This led us to investigate the potential of these compounds as Alzheimer's disease drugs. All of the compounds showed moderate acetylcholinesterase inhibitory activity in a micromolar range (IC50 from 16.0 to 96.3 μM). For butyrylcholinesterase, a new target for the treatment of Alzheimer's disease, phlorofucofuroeckol-A (PFF-A), showed a particularly potent inhibitory activity (IC50 0.95 μM), which is over 100-fold greater than for acetylcholinesterase. These compounds inhibited glycogen synthase kinase 3 beta, which is related to the formation of hyperphosphorylated tau and generation Aβ. Bieckol and PFF-A inhibited amyloid precursor protein biosynthesis. PFF-A also showed very strong β-secretase inhibitory activity with IC50 of submicromole. These results render these compounds as interesting potential drug candidates for Alzheimer's disease.

  12. 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

  13. 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.

  14. Effects of organochlorine compounds on cytochrome P450 aromatase activity in an immortal sea turtle cell line.

    PubMed

    Keller, Jennifer M; McClellan-Green, Patricia

    2004-01-01

    Many classes of environmental contaminants affect the reproductive function of animals through interactions with the endocrine system. The primary components affected by endocrine active compounds (EACs) are the steroid receptors and the enzymes responsible for steroidogenesis. This study sought to develop an in vitro model for assessing EAC effects in sea turtles by examining their ability to alter cytochrome P450 aromatase (CYP19) activity. Aromatase is the enzyme responsible for the conversion of testosterone to estradiol. This enzyme is critical in the sexual differentiation of reptiles which demonstrate temperature-dependent sex determination. An immortal testis cell line GST-TS from a green sea turtle was grown in culture at 30 degrees C in RPMI 1640 media. The cells were exposed to three known aromatase inducers; dexamethasone (Dex), 8Br-cyclic AMP, or human chronic gonadotropin (HCG) and one aromatase inhibitor 4-androstenol-dione (4-OHA). In addition, the GST-TS cells were exposed to 0.1-30 microM atrazine and 3-100 microM 4,4'-DDE. The inducing compounds that have been shown to increase aromatase activity in other systems failed to induce aromatase activity in the GST-TS cells, yet exposure to the inhibiting compound, 4-OHA, did result in a significant reduction. Atrazine (0.1, 1.0 and 10 microM) significantly induced aromatase activity following a 24 h exposure, and 4,4'-DDE inhibited the activity but only at cytotoxic concentrations (100 microM). Based on these results, this in vitro model can be useful in examining the endocrine effects of EACs in sea turtles.

  15. Laccase Production and Differential Transcription of Laccase Genes in Cerrena sp. in Response to Metal Ions, Aromatic Compounds, and Nutrients

    PubMed Central

    Yang, Jie; Wang, Guozeng; Ng, Tzi Bun; Lin, Juan; Ye, Xiuyun

    2016-01-01

    Laccases can oxidize a wide range of aromatic compounds and are industrially valuable. Laccases often exist in gene families and may differ from each other in expression and function. Quantitative real-time polymerase chain reaction (qPCR) was used for transcription profiling of eight laccase genes in Cerrena sp. strain HYB07 with validated reference genes. A high laccase activity of 280.0 U/mL was obtained after submerged fermentation for 5 days. Laccase production and laccase gene transcription at different fermentation stages and in response to various environmental cues were revealed. HYB07 laccase activity correlated with transcription levels of its predominantly expressed laccase gene, Lac7. Cu2+ ions were indispensable for efficient laccase production by HYB07, mainly through Lac7 transcription induction, and no aromatic compounds were needed. HYB07 laccase synthesis and biomass accumulation were highest with non-limiting carbon and nitrogen. Glycerol and inorganic nitrogen sources adversely impacted Lac7 transcription, laccase yields, and fungal growth. The present study would further our understanding of transcription regulation of laccase genes, which may in turn facilitate laccase production as well as elucidation of their physiological roles. PMID:26793186

  16. Canine postradiation histamine levels and subsequent response to Compound 48/80

    SciTech Connect

    Cockerham, L.G.; Doyle, T.F.; Donlon, M.A.; Helgeson, E.A.

    1984-11-01

    Radiation-induced hypotension in the beagle is accompanied by increased intestinal blood flow (IBF) and hematocrit (HCT). This study was performed to correlate these radiation-induced changes with plasma histamine (PH) levels following radiation. The histamine (H) levels were monitored in the systemic arterial circulation (SA) and the hepatic portal vein (HPV) before and after radiation. To examine the effect of radiation on the mobilization of total body H stores, Compound 48/80 was given I.V., and H responses were monitored in both control and radiated animals. Data obtained indicated that 100 Gy, whole-body, gamma-radiation produced a decrease in systemic mean blood pressure (BP), an increase in IBF and an increase in HCT. Concurrently, the mean PH/SA values increased and the PH/HPV levels decreased. Compound 48/80 produced a marked increase in PH levels in both control and radiated animals however, the levels found in the radiated animals were consistently lower than those in the controls, although not statistically different. This implies that H may mediate these observed intestinal responses and that the mobility of histamine is decreased in radiated animals. 19 references.

  17. Bioregeneration of activated carbon and activated rice husk loaded with phenolic compounds: Kinetic modeling.

    PubMed

    Ng, S L; Seng, C E; Lim, P E

    2010-01-01

    A kinetic model consisting of first-order desorption and biodegradation processes was developed to describe the bioregeneration of phenol- and p-nitrophenol-loaded powdered activated carbon (PAC) and pyrolyzed rice husk (PRH), respectively. Different dosages of PAC and PRH were loaded with phenol or p-nitrophenol by contacting with the respective phenolic compound at various concentrations. The kinetic model was used to fit the phenol or p-nitrophenol concentration data in the bulk solution during the bioregeneration process to determine the rate constants of desorption, k(d), and biodegradation, k. The results showed that the kinetic model fitted relatively well (R(2)>0.9) to the experimental data for the phenol- and p-nitrophenol-loaded PAC as well as p-nitrophenol-loaded PRH. Comparison of the values of k(d) and k shows that k is much greater than k(d). This indicates clearly that the desorption process is the rate-determining step in bioregeneration and k(d) can be used to characterize the rate of bioregeneration. The trend of the variation of the k(d) values with the dosages of PAC or PRH used suggests that higher rate of bioregeneration can be achieved under non-excess adsorbent dosage condition.

  18. Novel ruthenium(II) cyclopentadienyl thiosemicarbazone compounds with antiproliferative activity on pathogenic trypanosomatid parasites.

    PubMed

    Fernández, Mariana; Arce, Esteban Rodríguez; Sarniguet, Cynthia; Morais, Tânia S; Tomaz, Ana Isabel; Azar, Claudio Olea; Figueroa, Roberto; Diego Maya, J; Medeiros, Andrea; Comini, Marcelo; Helena Garcia, M; Otero, Lucía; Gambino, Dinorah

    2015-12-01

    Searching for new prospective antitrypanosomal agents, three novel Ru(II)-cyclopentadienyl compounds, [Ru(η(5)-C5H5)(PPh3)L], with HL=bioactive 5-nitrofuryl containing thiosemicarbazones were synthesized and characterized in the solid state and in solution. The compounds were evaluated in vitro on the blood circulating trypomastigote form of Trypanosoma cruzi (Dm28c strain), the infective form of Trypanosoma brucei brucei (strain 427) and on J774 murine macrophages and human-derived EA.hy926 endothelial cells. The compounds were active against both parasites with IC50 values in the micromolar or submicromolar range. Interestingly, they are much more active on T. cruzi than previously developed Ru(II) classical and organometallic compounds with the same bioactive ligands. The new compounds showed moderate to very good selectivity towards the parasites in respect to mammalian cells. The global results point at [RuCp(PPh3)L2] (L2=N-methyl derivative of 5-nitrofuryl containing thiosemicarbazone and Cp=cyclopentadienyl) as the most promising compound for further developments (IC50T. cruzi=0.41μM; IC50T. brucei brucei=3.5μM). Moreover, this compound shows excellent selectivity towards T. cruzi (SI>49) and good selectivity towards T. brucei brucei (SI>6). In order to get insight into the mechanism of antiparasitic action, the intracellular free radical production capacity of the new compounds was assessed by ESR. DMPO (5,5-dimethyl-1-pirroline-N-oxide) spin adducts related to the bioreduction of the complexes and to redox cycling processes were characterized. In addition, DNA competitive binding studies with ethidium bromide by fluorescence measurements showed that the compounds interact with this biomolecule.

  19. Active thermal isolation for temperature responsive sensors

    NASA Technical Reports Server (NTRS)

    Martinson, Scott D. (Inventor); Gray, David L. (Inventor); Carraway, Debra L. (Inventor); Reda, Daniel C. (Inventor)

    1994-01-01

    The detection of flow transition between laminar and turbulent flow and of shear stress or skin friction of airfoils is important in basic research for validation of airfoil theory and design. These values are conventionally measured using hot film nickel sensors deposited on a polyimide substrate. The substrate electrically insulates the sensor and underlying airfoil but is prevented from thermally isolating the sensor by thickness constraints necessary to avoid flow contamination. Proposed heating of the model surface is difficult to control, requires significant energy expenditures, and may alter the basic flow state of the airfoil. A temperature responsive sensor is located in the airflow over the specified surface of a body and is maintained at a constant temperature. An active thermal isolator is located between this temperature responsive sensor and the specific surface of the body. The total thickness of the isolator and sensor avoid any contamination of the flow. The temperature of this isolator is controlled to reduce conductive heat flow from the temperature responsive sensor to the body. This temperature control includes (1) operating the isolator at the same temperature as the constant temperature of the sensor; and (2) establishing a fixed boundary temperature which is either less than or equal to, or slightly greater than the sensor constant temperature. The present invention accordingly thermally isolates a temperature responsive sensor in an energy efficient, controllable manner while avoiding any contamination of the flow.

  20. Effective anti-leishmanial activity of minimalist squaramide-based compounds.

    PubMed

    Marín, Clotilde; Ximenis, Marta; Ramirez-Macías, Inmaculada; Rotger, Carmen; Urbanova, Kristina; Olmo, Francisco; Martín-Escolano, Rubén; Rosales, María José; Cañas, Rocio; Gutierrez-Sánchez, Ramón; Costa, Antonio; Sánchez-Moreno, Manuel

    2016-11-01

    In order to evaluate the in vitro leishmanicidal activity of N,N'-Squaramides derivatives, compounds that feature both hydrogen bond donor and acceptor groups and are capable of multiple interactions with complementary sites, against Leishmania infantum, Leishmania braziliensis and Leishmania donovani a series of 18compounds was prepared and assayed on extracellular and intracellular parasite forms. Infectivity and cytotoxicity tests were performed on J774.2 macrophage cells using meglumine antimoniate (Glucantime) as the reference drug. Changes in metabolite excretion by (1)H-NMR and the ultrastructural alterations occurring in the parasites treated using transmission electron microscopy (TEM), was analyzed. Compounds 1, 7, 11, 14 and 17 were the more active and less toxic. Infection rates showed that the order of effectiveness was 17 > 11 > 14 > 7 for both L. infantum and L. braziliensis and in the same way, the compound 1 for L. donovani. All these compounds have altered the typical structure of the promastigotes, glycosomes and mitochondria. These severe modifications by the compounds are the ultimate reasons for the alterations observed in the excretion products. The Squaramide 17 (3-(butylamino)-4-((3-(dimetilamino)propyl)(methyl)amino)cyclobut-3-en-1,2-dione) was clearly the most efficient of all compounds. The data appear to confirm that the severe modifications generated in organelles such as glycosomes or mitochondria by the compounds are the ultimate reasons for the alterations observed in the excretion products of all species. The activity, stability, low cost of starting materials, and straightforward synthesis make amino squaramides appropriate molecules for the development of an affordable anti-leishmanial agent.

  1. Antitumor and antiparasitic activity of novel ruthenium compounds with polycyclic aromatic ligands.

    PubMed

    Miserachs, Helena Guiset; Cipriani, Micaella; Grau, Jordi; Vilaseca, Marta; Lorenzo, Julia; Medeiros, Andrea; Comini, Marcelo A; Gambino, Dinorah; Otero, Lucía; Moreno, Virtudes

    2015-09-01

    Five novel ruthenium(II)-arene complexes with polycyclic aromatic ligands were synthesized, comprising three compounds of the formula [RuCl(η(6)-p-cym)(L)][PF6], where p-cym = 1-isopropyl-4-methylbenzene and L are the bidentate aromatic ligands 1,10-phenanthroline-5,6-dione, 1, 5-amine-1,10-phenanthroline, 4, or 5,6-epoxy-5,6-dihydro-phenanthroline, 5. In the other two complexes [RuCl2(η(6)-p-cym)(L')], the metal is coordinated to a monodentate ligand L', where L' is phenanthridine, 2, or 9-carbonylanthracene, 3. All compounds were fully characterized by mass spectrometry and elemental analysis, as well as NMR and IR spectroscopic techniques. Obtained ruthenium compounds as well as their respective ligands were tested for their antiparasitic and antitumoral activities. Even though all compounds showed lower Trypanosoma brucei activity than the free ligands, they also resulted less toxic on mammalian cells. Cytotoxicity assays on HL60 cells showed a moderate antitumoral activity for all ruthenium compounds. Compound 1 was the most potent antitumoral (IC50 = 1.26±0.78 μM) and antiparasitic (IC50 = 0.19 ± 0.05 μM) agent, showing high selectivity towards the parasites (selectivity index >100). As complex 1 was the most promising antitumoral compound, its interaction with ubiquitin as potential target was also studied. In addition, obtained ruthenium compounds were found to bind DNA, and they are thought to interact with this macromolecule mainly through intercalation of the aromatic ligand.

  2. Microbial community response to addition of polylactate compounds to stimulate hexavalent chromium reduction in groundwater.

    PubMed

    Brodie, Eoin L; Joyner, Dominique C; Faybishenko, Boris; Conrad, Mark E; Rios-Velazquez, Carlos; Malave, Josue; Martinez, Ramon; Mork, Benjamin; Willett, Anna; Koenigsberg, Steven; Herman, Donald J; Firestone, Mary K; Hazen, Terry C

    2011-10-01

    To evaluate the efficacy of bioimmobilization of Cr(VI) in groundwater at the Department of Energy Hanford site, we conducted a series of microcosm experiments using a range of commercial electron donors with varying degrees of lactate polymerization (polylactate). These experiments were conducted using Hanford Formation sediments (coarse sand and gravel) immersed in Hanford groundwater, which were amended with Cr(VI) and several types of lactate-based electron donors (Hydrogen Release Compound, HRC; primer-HRC, pHRC; extended release HRC) and the polylactate-cysteine form (Metal Remediation Compound, MRC). The results showed that polylactate compounds stimulated an increase in bacterial biomass and activity to a greater extent than sodium lactate when applied at equivalent carbon concentrations. At the same time, concentrations of headspace hydrogen and methane increased and correlated with changes in the microbial community structure. Enrichment of Pseudomonas spp. occurred with all lactate additions, and enrichment of sulfate-reducing Desulfosporosinus spp. occurred with almost complete sulfate reduction. The results of these experiments demonstrate that amendment with the pHRC and MRC forms result in effective removal of Cr(VI) from solution most likely by both direct (enzymatic) and indirect (microbially generated reductant) mechanisms.

  3. Screening of novel chemical compounds as possible inhibitors of carbonic anhydrase and photosynthetic activity of photosystem II.

    PubMed

    Karacan, Mehmet Sayım; Zharmukhamedov, Sergei K; Mamaş, Serhat; Kupriyanova, Elena V; Shitov, Alexandr V; Klimov, Vyacheslav V; Özbek, Neslihan; Özmen, Ümmühan; Gündüzalp, Ayla; Schmitt, Franz-Josef; Karacan, Nurcan; Friedrich, Thomas; Los, Dmitry A; Carpentier, Robert; Allakhverdiev, Suleyman I

    2014-08-01

    Thirty novel chemical compounds were designed and synthesized expecting that they would be possible inhibitors. From this number eleven were organic bases, twenty-four were their organic derivatives and fourteen were metal complexes. Screening of these chemicals by their action on photosynthetic electron transfer (PET) and carbonic anhydrase (CA) activity (CAA) of photosystem II (PSII), α-CA, as well as β-CA was done. Several groups were revealed among them. Some of them are capable to suppress either one, two, three, or even all of the measured activities. As example, one of the Cu(II)-phenyl sulfonylhydrazone complexes (compound 25) suppresses CAA of α-CA by 88%, CAA of β-CA by 100% inhibition; CAA of PSII by 100% and the PSII photosynthetic activity by 66.2%. The Schiff base compounds (12, 15) and Cu(II)-phenyl sulfonylhydrazone complexes (25, 26) inhibited the CAA and PET of PSII significantly. The obtained data indicate that the PSII donor side is a target of the inhibitory action of these agents. Some physico- or electrochemical properties such as diffusion coefficient, number of transferred electrons, peak potential and heterogeneous standard rate constants of the compounds were determined in nonaqueous media. pKa values were also determined in nonaqueous and aqueous media. Availability in the studied group of novel chemical agents possessing different inhibitory activity allow in future to isolate the "active part" in the structure of the inhibitors responsible for different inhibitory mechanisms, as well as to determine the influence of side substituters on its inhibitory efficiency.

  4. Monitoring the Activation of the DNA Damage Response Pathway in a 3D Spheroid Model.

    PubMed

    Mondesert, Odile; Frongia, Céline; Clayton, Olivia; Boizeau, Marie-Laure; Lobjois, Valérie; Ducommun, Bernard

    2015-01-01

    Monitoring the DNA-Damage Response (DDR) activated pathway in multicellular tumor spheroid models is an important challenge as these 3D models have demonstrated their major relevance in pharmacological evaluation. Herein we present DDR-Act-FP, a fluorescent biosensor that allows detection of DDR activation through monitoring of the p21 promoter p53-dependent activation. We show that cells expressing the DDR-Act-FP biosensor efficiently report activation of the DDR pathway after DNA damage and its pharmacological manipulation using ATM kinase inhibitors. We also report the successful use of this assay to screen a small compound library in order to identify activators of the DDR response. Finally, using multicellular spheroids expressing the DDR-Act-FP we demonstrate that DDR activation and its pharmacological manipulation with inhibitory and activatory compounds can be efficiently monitored in live 3D spheroid model. This study paves the way for the development of innovative screening and preclinical evaluation assays.

  5. Sorghum flour fractions: correlations among polysaccharides, phenolic compounds, antioxidant activity and glycemic index.

    PubMed

    Moraes, Érica Aguiar; Marineli, Rafaela da Silva; Lenquiste, Sabrina Alves; Steel, Caroline Joy; de Menezes, Cícero Beserra; Queiroz, Valéria Aparecida Vieira; Maróstica Júnior, Mário Roberto

    2015-08-01

    Nutrients composition, phenolic compounds, antioxidant activity and estimated glycemic index (EGI) were evaluated in sorghum bran (SB) and decorticated sorghum flour (DSF), obtained by a rice-polisher, as well as whole sorghum flour (WSF). Correlation between EGI and the studied parameters were determined. SB presented the highest protein, lipid, ash, β-glucan, total and insoluble dietary fiber contents; and the lowest non-resistant and total starch contents. The highest carbohydrate and resistant starch contents were in DSF and WSF, respectively. Phenolic compounds and antioxidant activities were concentrated in SB. The EGI values were: DSF 84.5 ± 0.41; WSF 77.2 ± 0.33; and SB 60.3 ± 0.78. Phenolic compounds, specific flavonoids and antioxidant activities, as well as total, insoluble and soluble dietary fiber and β-glucans of sorghum flour samples were all negatively correlated to EGI. RS content was not correlated to EGI.

  6. 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.

  7. [Synthesis and antitumor activity of 5-substituted-2-(pyridyl)benzothiazole compounds].

    PubMed

    Liu, Wen-Hu; Chang, Jin-Xia; Liu, Yi

    2013-01-01

    Fifteen novel 5-substituted-2-(pyridyl)benzothiazole compounds were designed and synthesized by simple hydrolization and condensation reaction of the 2-amino-5-substituent benzothiazole. Activities of these synthesized compounds were evaluated on Bcap-37, HCT-15 and HepG2 tumor cells in vitro by standard MTT assay. 5-Fluorouracil (5-FU) was used as the positive control. The results revealed that most of the new compounds had potent effects on Bcap-37, HCT-15 and HepG2 tumor cells, and had no or less effect on 293T and L02 normal cells. Particularly, compounds 1c and 2e exhibited better activities on HCT-15 and HepG2 cells with IC50 values of 41.59 and 38.65 micromol x L(-1), and 1i showed excellent activities on Bcap-37 and HepG2 cells with IC50 values of 46.63 and 23.51 micromol x L(-1), respectively. The structure-activity relationship of 5-substituted-2-(pyridyl)benzothiazole compounds were also discussed preliminarily.

  8. Developmental toxicity of thyroid-active compounds in a zebrafish embryotoxicity test.

    PubMed

    Jomaa, Barae; Hermsen, Sanne A B; Kessels, Maurijn Y; van den Berg, Johannes H J; Peijnenburg, Ad A C M; Aarts, Jac M M J G; Piersma, Aldert H; Rietjens, Ivonne M C M

    2014-01-01

    Zebrafish embryos were exposed to concentration ranges of selected thyroid-active model compounds in order to assess the applicability of zebrafish-based developmental scoring systems withinan alternative testing strategy to detect the developmental toxicity ofthyroid-active compounds. Model compounds tested included triiodothyronine (T3), propylthiouracil (PTU), methimazole (MMI), sodium perchlorate (NaClO4) and amiodarone hydrochloride (AMI), selected to represent different modes of action affecting thyroid activity. Tested time windows included 48-120 hours post fertilization (hpf), 0-72 hpf and 0-120 hpf. All tested compounds resulted in developmental changes, with T3 being the most potent. The developmental parameters affected included reflective iridophores, beat and glide swimming, inflated swim bladders, as well as resorbed yolk sacs. These effects are only evident by 120 hpf and therefore an existing General Morphology Score (GMS) system was extended to create a General Developmental Score(GDS) that extends beyond the 72 hpfscoring limit of GMS and includes additional parameters that are affected by exposure to model thyroid-active compounds. Moreover, the GDS is cumulative as it includes not only the scoring of developmental morphologies but also integrates developmental dysmorphologies. Exposures from 48-120 hpf did not provide additional information to exposures from 0-120 hpf. The results indicate that the zebrafish GDS can detect the developmental toxicity of thyroid toxicants and may be of use in an integrated testing strategy to reduce, refine and in certain cases replace animal testing.

  9. 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

  10. Prenylated polyphenolic compounds from Glycyrrhiza iconica and their antimicrobial and antioxidant activities.

    PubMed

    Kırmızıbekmez, Hasan; Uysal, Görkem Berk; Masullo, Milena; Demirci, Fatih; Bağcı, Yavuz; Kan, Yüksel; Piacente, Sonia

    2015-06-01

    A new prenylated isoflavan, iconisoflavan (1), and a new prenylated isoflav-3-ene, iconisoflaven (2) were isolated from the roots of Glycyrrhiza iconica together with four known ones namely (3S)-licoricidin (3), licorisoflavan A (4), topazolin (5) and glycycoumarin (6). The structures were elucidated on the basis of extensive spectroscopic analysis including 1D and 2D NMR as well as HR-MS. Furthermore, the absolute configurations of compounds 1, 3 and 4 were established by electronic circular dichroism (ECD). All the isolated compounds (1-6) were evaluated for their in vitro antimicrobial activities against five pathogenic bacteria and one yeast (Candida albicans) using an in vitro microdilution method. Compounds 1 and 3-5 displayed significant activity against Salmonella typhimurium ATCC 13311 with MIC values ranging from 2 to 8 μg/mL. Additionally, all compounds were screened for their in vitro free radical scavenging activities using an in vitro microdilution DPPH assay spectrofotometrically. The tested compounds exhibited IC50 values in the range of 0.18-0.56 mg/mL, suggesting an activity comparable with that of ascorbic acid (IC50: 0.07 mg/mL). To the best of our knowledge, the present study constitutes the first phytochemical and bioactivity investigation on G. iconica.

  11. 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.

  12. In vitro antifungal activity of organic compounds derived from amino alcohols against onychomycosis.

    PubMed

    Caneschi, César Augusto; Almeida, Angelina Maria de; Martins, Francislene Juliana; Hyaric, Mireille Le; Oliveira, Manoel Marques Evangelista; Macedo, Gilson Costa; Almeida, Mauro Vieira de; Raposo, Nádia Rezende Barbosa

    2017-02-09

    Onychomycosis is a fungal infection of the nail caused by high densities of filamentous fungi and yeasts. Treatment for this illness is long-term, and recurrences are frequently detected. This study evaluated in vitro antifungal activities of 12 organic compounds derived from amino alcohols against standard fungal strains, such as Trichophyton rubrum CCT 5507 URM 1666, Trichophyton mentagrophytes ATCC 11481, and Candida albicans ATCC 10231. The antifungal compounds were synthesized from p-hydroxybenzaldehyde (4a-4f) and p-hydroxybenzoic acid (9a-9f). Minimum inhibitory concentrations and minimum fungicidal concentrations were determined according to Clinical and Laboratory Standards Institute protocols M38-A2, M27-A3, and M27-S4. The amine series 4b-4e, mainly 4c and 4e compounds, were effective against filamentous fungi and yeast (MIC from 7.8 to 312μg/mL). On the other hand, the amide series (9a-9f) did not present inhibitory effect against fungi, except amide 9c, which demonstrated activity only against C. albicans. This allowed us to infer that the presence of amine group and intermediate carbon number (8C-11C) in its aliphatic side chain seems to be important for antifungal activity. Although these compounds present cytotoxic activity on macrophages J774, our results suggest that these aromatic compounds might constitute potential as leader molecules in the development of more effective and less toxic analogs that could have considerable implications for future therapies of onychomycosis.

  13. Activity Profile of an FDA-Approved Compound Library against Schistosoma mansoni

    PubMed Central

    Panic, Gordana; Vargas, Mireille; Scandale, Ivan; Keiser, Jennifer

    2015-01-01

    Background As plans to expand mass drug treatment campaigns to fight schistosomiasis form, worries about reliance on praziquantel as the sole available treatment motivate the investigation for novel antischistosomal compounds. Drug repurposing might be an inexpensive and effective source of novel antischistosomal leads. Methodology 1600 FDA approved compounds were first assayed against Schistosoma mansoni schistosomula at a concentration of 10 µM. Active compounds identified from this screen were advanced to the adult worm screen at 33.33 µM, followed by hit characterization. Leads with complementary pharmacokinetic and toxicity profiles were then selected for in vivo studies. Principal Findings The in vitro screen identified 121 and 36 compounds active against the schistosomula and adult stage, respectively. Further, in vitro characterization and comparison with already available pharmacokinetic and toxicity data identified 11 in vivo candidates. Doramectin (10 mg/kg) and clofazimine (400 mg/kg) were found to be active in vivo with worm burden reductions of 60.1% and 82.7%, respectively. Conclusions/Significance The work presented here expands the knowledge of antischistosomal properties of already approved compounds and underscores variations observed between target-based and phenotypic approaches and among laboratories. The two in vivo-active drugs identified in this study, doramectin and clofazimine are widely available and present as novel drug classes as starting points for further investigation. PMID:26230921

  14. Overexpression of Pto activates defense responses and confers broad resistance.

    PubMed Central

    Tang, X; Xie, M; Kim, Y J; Zhou, J; Klessig, D F; Martin, G B

    1999-01-01

    The tomato disease resistance (R) gene Pto specifies race-specific resistance to the bacterial pathogen Pseudomonas syringae pv tomato carrying the avrPto gene. Pto encodes a serine/threonine protein kinase that is postulated to be activated by a physical interaction with the AvrPto protein. Here, we report that overexpression of Pto in tomato activates defense responses in the absence of the Pto-AvrPto interaction. Leaves of three transgenic tomato lines carrying the cauliflower mosaic virus 35S::Pto transgene exhibited microscopic cell death, salicylic acid accumulation, and increased expression of pathogenesis-related genes. Cell death in these plants was limited to palisade mesophyll cells and required light for induction. Mesophyll cells of 35S::Pto plants showed the accumulation of autofluorescent compounds, callose deposition, and lignification. When inoculated with P. s. tomato without avrPto, all three 35S::Pto lines displayed significant resistance and supported less bacterial growth than did nontransgenic lines. Similarly, the 35S::Pto lines also were more resistant to Xanthomonas campestris pv vesicatoria and Cladosporium fulvum. These results demonstrate that defense responses and general resistance can be activated by the overexpression of an R gene. PMID:9878629

  15. Metabolic responses to simulated extravehicular activity

    NASA Technical Reports Server (NTRS)

    Williamson, Rebecca C.; Sharer, Peter J.; Webbon, Bruce W.; Rendon, Lisa R.

    1992-01-01

    Automatic control of the liquid cooling garment (LCG) worn by astronauts during extravehicular activity (EVA) would more efficiently regulate astronaut thermal comfort and improve astronaut productivity. An experiment was conducted in which subjects performed exercise profiles on a unique, supine upper body ergometer to elicit physiological and thermal responses similar to those achieved during zero-g EVAs. Results were analyzed to quantify metabolic rate, various body temperatures, and other heat balance parameters. Such data may lead to development of a microprocessor-based system to automatically maintain astronaut heat balance during extended EVAs.

  16. Comamonas testosteroni uses a chemoreceptor for tricarboxylic acid cycle intermediates to trigger chemotactic responses towards aromatic compounds.

    PubMed

    Ni, Bin; Huang, Zhou; Fan, Zheng; Jiang, Cheng-Ying; Liu, Shuang-Jiang

    2013-11-01

    Bacterial chemotaxis towards aromatic compounds has been frequently observed; however, knowledge of how bacteria sense aromatic compounds is limited. Comamonas testosteroni CNB-1 is able to grow on a range of aromatic compounds. This study investigated the chemotactic responses of CNB-1 to 10 aromatic compounds. We constructed a chemoreceptor-free, non-chemotactic mutant, CNB-1Δ20, by disruption of all 19 putative methyl-accepting chemotaxis proteins (MCPs) and the atypical chemoreceptor in strain CNB-1. Individual complementation revealed that a putative MCP (tagged MCP2201) was involved in triggering chemotaxis towards all 10 aromatic compounds. The recombinant sensory domain of MCP2201 did not bind to 3- or 4-hydroxybenzoate, protocatechuate, catechol, benzoate, vanillate and gentisate, but bound oxaloacetate, citrate, cis-aconitate, isocitrate, α-ketoglutarate, succinate, fumarate and malate. The mutant CNB-1ΔpmdF that lost the ability to metabolize 4-hydroxybenzoate and protocatechuate also lost its chemotactic response to these compounds, suggesting that taxis towards aromatic compounds is metabolism-dependent. Based on the ligand profile, we proposed that MCP2201 triggers taxis towards aromatic compounds by sensing TCA cycle intermediates. Our hypothesis was further supported by the finding that introduction of the previously characterized pseudomonad chemoreceptor (McpS) for TCA cycle intermediates into CNB-1Δ20 likewise triggered chemotaxis towards aromatic compounds.

  17. Synthesis, characterization, investigation of biological activity and theoretical studies of hydrazone compounds containing choloroacetyl group

    NASA Astrophysics Data System (ADS)

    Cukurovali, Alaaddin; Yilmaz, Engin

    2014-10-01

    In this study, three new hydrazide-hydrazone derivative compounds which contain choloroacetyl group have been synthesized and characterized. In the characterization, spectral techniques such as IR, 1H NMR, 13C NMR and UV-Vis spectroscopy techniques were used. Antibacterial effects of the synthesized compounds were investigated against Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853. In the theoretical calculations Gaussian 09 software was used with the DFT/6-311+(d,p) basis set. Experimental X-ray analysis of compounds has not been studied. Theoretical bond lengths of synthesized compounds were compared with experimental bond lengths of a similar compound. Theoretical and experimental bond lengths are in good agreement with R2: 0.896, 0.899 and 0.900 for compounds 1, 2, and 3, respectively. For antibacterial activity, the most effective one was found to be N‧-(4-bromobenzylidene)-2-chloro-N-(4-(3-methyl-3-phenylcyclobutyl)-thiazol-2-yl) acetohydrazide against P.aeroginaosa ATTC 27853, among the studied compounds.

  18. 3-Hydroxy-2-phenyl-4(1H)-quinolinones as promising biologically active compounds.

    PubMed

    Hradil, P; Hlavác, J; Soural, M; Hajdúch, M; Kolár, M; Vecerová, R

    2009-06-01

    2-Phenyl-3-hydroxy-4(1H)-quinolinones can be considered as aza-analogues of flavones, compounds which are known for the wide-range of their biological activity. These quinolinones were studied as inhibitors of topoisomerase, gyrase and IMPDH. They were tested for anticancer activity in-vitro and were also shown to possess immunosuppressive properties. This review is the first summarizing the synthesis and activity of the mentioned quinolinones.

  19. Pathways for tailoring the magnetostructural response of FeRh-based compounds

    NASA Astrophysics Data System (ADS)

    Barua, Radhika

    Materials systems that undergo magnetostructural phase transitions (simultaneous magnetic and structural phase changes) have the capability of providing exceptional functional effects (example: colossal magnetoresistance effect (CMR), giant magnetocaloric (GMCE) and giant volume magnetostriction effects) in response to small physical inputs such as magnetic field, temperature and pressure. It is envisioned that magnetostructural materials may have significant potential for environmental and economic impact as they can be incorporated into a wide array of devices ranging from sensors for energy applications to actuators for tissue engineering constructs. From the standpoint of fundamental scientific research, these materials are interesting as they serve as model systems for understanding basic spin-lattice interactions. In this work, the near-equiatomic phase of FeRh serves as a test bed for understanding the magnetostructural phenomena in intermetallic alloys due to its relatively simple crystal structure (cubic with B2 (CsCl)-type ordering) and its reported ability to undergo a first-order magnetic phase change from antiferromagnetic (AF) to ferromagnetic (FM) ordering, with an accompanying 1 % volume expansion in the unit cell near room temperature ( Tt ~ 350 K). Overall, three interrelated but largely unexplored aspects concerning the FeRh system have been examined here: (1) influence of nanostructuring on the magnetostructural response; (2) influence of simultaneous application of pressure and magnetic field on the magnetostructural response; (3) correlations between chemical modification of the lattice and the magnetostructural response. Bulk FeRh-based samples in this study were synthesized using the arc-melting technique and nanostructuring of the system was achieved via rapid solidification processing (melt-spinning) of the arc-melted precursor. Structure-property correlations between the parent equiatomic FeRh compound and its nanostructured

  20. Inhibition of NADPH oxidase activation by 4-(2-aminoethyl)-benzenesulfonyl fluoride and related compounds.

    PubMed

    Diatchuk, V; Lotan, O; Koshkin, V; Wikstroem, P; Pick, E

    1997-05-16

    The elicitation of an oxidative burst in phagocytes rests on the assembly of a multicomponental complex (NADPH oxidase) consisting of a membrane-associated flavocytochrome (cytochrome b559), representing the redox element responsible for the NADPH-dependent reduction of oxygen to superoxide (O-2), two cytosolic components (p47(phox), p67(phox)), and the small GTPase Rac (1 or 2). We found that 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), an irreversible serine protease inhibitor, prevented the elicitation of O-2 production in intact macrophages and the amphiphile-dependent activation of NADPH oxidase in a cell-free system, consisting of solubilized membrane or purified cytochrome b559 combined with total cytosol or a mixture of recombinant p47(phox), p67(phox), and Rac1. AEBSF acted at the activation step and did not interfere with the ensuing electron flow. It did not scavenge oxygen radicals and did not affect assay reagents. Five other serine protease inhibitors (three irreversible and two reversible) were found to lack an inhibitory effect on cell-free activation of NADPH oxidase. A structure-function study of AEBSF analogues demonstrated that the presence of a sulfonyl fluoride group was essential for inhibitory activity and that compounds containing an aminoalkylbenzene moiety were more active than amidinobenzene derivatives. Exposure of the membrane fraction or of purified cytochrome b559, but not of cytosol or recombinant cytosolic components, to AEBSF, in the presence of a critical concentration of the activating amphiphile lithium dodecyl sulfate, resulted in a marked impairment of their ability to support cell-free NADPH oxidase activation upon complementation with untreated cytosol or cytosolic components. Kinetic analysis of the effect of varying the concentration of each of the three cytosolic components on the inhibitory potency of AEBSF indicated that this was inversely related to the concentrations of p47(phox) and, to a lesser degree, p67

  1. Highly efficient antiviral and antibacterial activities of solid-state cuprous compounds.

    PubMed

    Sunada, Kayano; Minoshima, Masafumi; Hashimoto, Kazuhito

    2012-10-15

    We found that several solid-state cuprous compounds, including cuprous oxide (Cu(2)O), sulfide (Cu(2)S), iodide (CuI), and chloride (CuCl), have highly efficient antiviral activities, whereas those of solid-state silver and cupric compounds are markedly lower. On a Cu(2)O-loaded glass substrate, for example, the infectious activity of bacteriophages was reduced by 5-orders of magnitude within 30 min and by 3-orders of magnitude within 1h for bacteria. In contrast, the infectious activities of both phages and bacteria were not markedly reduced on CuO-loaded substrates within a similar time frame. To determine the origin of this inhibitory activity, we investigated the effects of reactive oxygen species (ROS), leached copper ions, and the solid-state compound itself against bacteriophages, and concluded that infectious activity is lost following direct contact with the solid-state surface of cuprous compounds, but not ROS or copper ions. Furthermore, we found that Cu(2)O adsorbed and denatured more proteins than CuO, which suggests the difference of the inhibitory activity between Cu(2)O and CuO.

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

    PubMed

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

    2017-08-15

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

  3. Parallel synthesis and biological evaluation of 837 analogues of procaspase-activating compound 1 (PAC-1).

    PubMed

    Hsu, Danny C; Roth, Howard S; West, Diana C; Botham, Rachel C; Novotny, Chris J; Schmid, Steven C; Hergenrother, Paul J

    2012-01-09

    Procaspase-Activating Compound 1 (PAC-1) is an ortho-hydroxy N-acyl hydrazone that enhances the enzymatic activity of procaspase-3 in vitro and induces apoptosis in cancer cells. An analogue of PAC-1, called S-PAC-1, was evaluated in a veterinary clinical trial in pet dogs with lymphoma and found to have considerable potential as an anticancer agent. With the goal of identifying more potent compounds in this promising class of experimental therapeutics, a combinatorial library based on PAC-1 was created, and the compounds were evaluated for their ability to induce death of cancer cells in culture. For library construction, 31 hydrazides were condensed in parallel with 27 aldehydes to create 837 PAC-1 analogues, with an average purity of 91%. The compounds were evaluated for their ability to induce apoptosis in cancer cells, and through this work, six compounds were discovered to be substantially more potent than PAC-1 and S-PAC-1. These six hits were further evaluated for their ability to relieve zinc-mediated inhibition of procaspase-3 in vitro. In general, the newly identified hit compounds are two- to four-fold more potent than PAC-1 and S-PAC-1 in cell culture, and thus have promise as experimental therapeutics for treatment of the many cancers that have elevated expression levels of procaspase-3.

  4. Effect of resveratrol, a natural polyphenolic compound, on platelet activation induced by endotoxin or thrombin.

    PubMed

    Olas, Beata; Wachowicz, Barbara; Saluk-Juszczak, Joanna; Zieliński, Tomasz

    2002-08-15

    Resveratrol (3, 4', 5-trihydroxystilbene), a natural polyphenol, is found in some plants that are used in human nutrition. Grapes are a major source for resveratrol, and a significant amount can also be found in red wine. Several experimental studies have demonstrated biological properties of resveratrol, especially its anti-inflammatory, antioxidant, anti-platelet and antitumor effects. In the present study, we investigated the first step of platelet activation-platelet adhesion stimulated by lipopolysaccharide (LPS) from Proteus mirabilis (weak stimulator) and thrombin (strong activator) in the presence of resveratrol. Our studies show that endotoxin (0.3 microg/10(8) platelets), like thrombin (0.2 U/10(8) platelets), induced the adhesion of platelets (expressed as absorbance of cell attached proteins) to collagen and fibrinogen. Preincubation of washed platelets with resveratrol at physiological plasma concentrations (25-100 microg/ml, 30 min, 37 degrees C) had an inhibitory effect on adhesion of platelets to collagen after activation by LPS alone or LPS with thrombin. The strongest effect on this process was caused by resveratrol at the concentration of 100 microg/ml. Pretreatment of platelets with resveratrol (25-100 microg/ml, 30 min, 37 degrees C) had also inhibitory effects on adhesion of platelets to fibrinogen after stimulation of these cells by LPS alone or by LPS with thrombin at the same concentration. In conclusion, we suggest that resveratrol present in human diet may be an important compound responsible for the reduction of platelet adhesion and changed reactivity of blood platelets in inflammatory process.

  5. Allyl isothiocyanate from mustard seed is effective in reducing the levels of volatile sulfur compounds responsible for intrinsic oral malodor.

    PubMed

    Tian, Minmin; Hanley, A Bryan; Dodds, Michael W J

    2013-06-01

    Oral malodor is a major social and psychological issue that affects general populations. Volatile sulfur compounds (VSCs), particularly hydrogen sulfide (H₂S) and methyl mercaptan (CH₃SH), are responsible for most oral malodor. The objectives for this study were to determine whether allyl isothiocyanate (AITC) at an organoleptically acceptable level can eliminate VSCs containing a free thiol moiety and further to elucidate the mechanism of action and reaction kinetics. The study revealed that gas chromatograph with a sulfur detector demonstrated a good linearity, high accuracy and sensitivity on analysis of VSCs. Zinc salts eliminate the headspace level of H₂S but not CH₃SH. AITC eliminates both H₂S and CH₃SH via a nucleophilic addition reaction. In addition, a chemical structure-activity relationship study revealed that the presence of unsaturated group on the side chain of the isothiocyanate accelerates the elimination of VSCs.

  6. Use of response biomarkers in milk for assessing exposure to environmental contaminants: the case for dioxin-like compounds.

    PubMed

    Diehl-Jones, W L; Bols, N C

    2000-01-01

    Screening for environmental contaminants in milk is generally conducted by chemical analysis, yet such an approach may be time-consuming and expensive, and is not indicative of the physiological consequences of such exposure. The focus of this review is to summarize those constituents of milk that may be altered by maternal exposure to one of the most biologically active environmental pollutants, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and to develop the case for their use as biomarkers of response. Several chemical and/or cellular components of milk are potentially useful as biomarkers, and may be developed as convenient, biologically relevant indicators of maternal exposure to dioxin-like compounds.

  7. Evaluation of antiviral activity of compounds isolated from Ranunculus sieboldii and Ranunculus sceleratus.

    PubMed

    Li, Haibo; Zhou, Changxin; Pan, Yunxue; Gao, Xiaozhong; Wu, Xiumei; Bai, Hua; Zhou, Linfu; Chen, Zhi; Zhang, Shuili; Shi, Shuyun; Luo, Jiali; Xu, Juanhua; Chen, Liurong; Zheng, Xiaoxiang; Zhao, Yu

    2005-12-01

    Nineteen compounds isolated from Ranunculus sieboldii and Ranunculus sceleratus were tested for inhibitory effects on hepatitis B virus (HBV) and Herpes simplex virus type-1 (HSV-1). The results showed that apigenin 4'- O- alpha-rhamnopyranoside, apigenin 7- O- beta-glucopyranosyl-4'- O- alpha-rhamnopyranoside, tricin 7- O- beta-glucopyranoside, tricin, and isoscopoletin possessed inhibitory activity against HBV replication. Protocatechuyl aldehyde exhibited an inhibiting activity on HSV-1 replication. It is therefore suggested that further investigations on these bioactive compounds might be needed to discover and develop new antiviral agents.

  8. New compound with DNA Topo I inhibitory activity purified from Penicillium oxalicum HSY05.

    PubMed

    Liu, Bing; Wang, Hai-Feng; Zhang, Li-Hua; Liu, Fang; He, Feng-Jun; Bai, Jiao; Hua, Hui-Ming; Chen, Gang; Pei, Yue-Hu

    2015-01-01

    Strain HSY05 was isolated from sea sediment collected from the South China Sea and was later identified as Penicillium oxalicum by 16S rDNA sequence analysis. Various chromatographic processes led to the isolation and purification of two metabolites from the fermentation culture of HSY05, including one new compound, 2,2',4,4'-tetrahyoxy-8'-methyl-6-methoxy-acyl-ethyl-diphenylmethanone (1), and a known compound secalonic acid D (SAD, 2), as characterised by UV, IR, 1D, 2D-NMR and MS data. The inhibitory activities against topoisomerase I of these two compounds were evaluated. The result showed that in addition to the known topo I inhibitor SAD (2), compound 1 also exhibited a moderate inhibitory effect.

  9. Trisomy 21 consistently activates the interferon response

    PubMed Central

    Sullivan, Kelly D; Lewis, Hannah C; Hill, Amanda A; Pandey, Ahwan; Jackson, Leisa P; Cabral, Joseph M; Smith, Keith P; Liggett, L Alexander; Gomez, Eliana B; Galbraith, Matthew D; DeGregori, James; Espinosa, Joaquín M

    2016-01-01

    Although it is clear that trisomy 21 causes Down syndrome, the molecular events acting downstream of the trisomy remain ill defined. Using complementary genomics analyses, we identified the interferon pathway as the major signaling cascade consistently activated by trisomy 21 in human cells. Transcriptome analysis revealed that trisomy 21 activates the interferon transcriptional response in fibroblast and lymphoblastoid cell lines, as well as circulating monocytes and T cells. Trisomy 21 cells show increased induction of interferon-stimulated genes and decreased expression of ribosomal proteins and translation factors. An shRNA screen determined that the interferon-activated kinases JAK1 and TYK2 suppress proliferation of trisomy 21 fibroblasts, and this defect is rescued by pharmacological JAK inhibition. Therefore, we propose that interferon activation, likely via increased gene dosage of the four interferon receptors encoded on chromosome 21, contributes to many of the clinical impacts of trisomy 21, and that interferon antagonists could have therapeutic benefits. DOI: http://dx.doi.org/10.7554/eLife.16220.001 PMID:27472900

  10. Cerebral blood flow response to functional activation

    PubMed Central

    Paulson, Olaf B; Hasselbalch, Steen G; Rostrup, Egill; Knudsen, Gitte Moos; Pelligrino, Dale

    2010-01-01

    Cerebral blood flow (CBF) and cerebral metabolic rate are normally coupled, that is an increase in metabolic demand will lead to an increase in flow. However, during functional activation, CBF and glucose metabolism remain coupled as they increase in proportion, whereas oxygen metabolism only increases to a minor degree—the so-called uncoupling of CBF and oxidative metabolism. Several studies have dealt with these issues, and theories have been forwarded regarding the underlying mechanisms. Some reports have speculated about the existence of a potentially deficient oxygen supply to the tissue most distant from the capillaries, whereas other studies point to a shift toward a higher degree of non-oxidative glucose consumption during activation. In this review, we argue that the key mechanism responsible for the regional CBF (rCBF) increase during functional activation is a tight coupling between rCBF and glucose metabolism. We assert that uncoupling of rCBF and oxidative metabolism is a consequence of a less pronounced increase in oxygen consumption. On the basis of earlier studies, we take into consideration the functional recruitment of capillaries and attempt to accommodate the cerebral tissue's increased demand for glucose supply during neural activation with recent evidence supporting a key function for astrocytes in rCBF regulation. PMID:19738630

  11. Electroantennogram response of the parasitoid, Microplitis croceipes to host-related odors: The discrepancy between relative abundance and level of antennal responses to volatile compound

    PubMed Central

    Morawo, Tolulope; Burrows, Matthew; Fadamiro, Henry

    2017-01-01

    Herbivores emit volatile organic compounds (VOCs) after feeding on plants. Parasitoids exploit these VOCs as odor cues to locate their hosts. In nature, host-related odors are emitted as blends of various compounds occurring in different proportions, and minor blend components can sometimes have profound effects on parasitoid responses. In a previous related study, we identified and quantified VOCs emitted by cotton plant-fed Heliothis virescens (Lepidoptera: Noctuidae) larvae, an herbivore host of the parasitoid Microplitis croceipes (Hymenoptera: Braconidae). In the present study, the olfactory response of female M. croceipes to synthetic versions of 15 previously identified compounds was tested in electroantennogram (EAG) bioassays. Using M. croceipes as a model species, we further asked the question: does the relative abundance of a volatile compound match the level of antennal response in parasitoids? Female M. croceipes showed varying EAG responses to test compounds, indicating different levels of bioactivity in the insect antenna. Eight compounds, including decanal, 1-octen-3-ol, 3-octanone, 2-ethylhexanol, tridecane, tetradecane, α-farnesene and bisabolene, elicited EAG responses above or equal to the 50 th percentile rank of all responses. Interestingly, decanal, which represented only 1% of the total amount of odors emitted by cotton-fed hosts, elicited the highest (0.82 mV) EAG response in parasitoids. On the other hand, ( E)-β-caryophyllene, the most abundant (29%) blend component, elicited a relatively low (0.17 mV) EAG response. The results suggest that EAG response to host-related volatiles in parasitoids is probably more influenced by the ecological relevance or functional role of the compound in the blend, rather than its relative abundance. PMID:28232862

  12. Electroantennogram response of the parasitoid, Microplitis croceipes to host-related odors: The discrepancy between relative abundance and level of antennal responses to volatile compound.

    PubMed

    Morawo, Tolulope; Burrows, Matthew; Fadamiro, Henry

    2016-01-01

    Herbivores emit volatile organic compounds (VOCs) after feeding on plants. Parasitoids exploit these VOCs as odor cues to locate their hosts. In nature, host-related odors are emitted as blends of various compounds occurring in different proportions, and minor blend components can sometimes have profound effects on parasitoid responses. In a previous related study, we identified and quantified VOCs emitted by cotton plant-fed Heliothis virescens (Lepidoptera: Noctuidae) larvae, an herbivore host of the parasitoid Microplitis croceipes (Hymenoptera: Braconidae). In the present study, the olfactory response of female M. croceipes to synthetic versions of 15 previously identified compounds was tested in electroantennogram (EAG) bioassays. Using M. croceipes as a model species, we further asked the question: does the relative abundance of a volatile compound match the level of antennal response in parasitoids? Female M. croceipes showed varying EAG responses to test compounds, indicating different levels of bioactivity in the insect antenna. Eight compounds, including decanal, 1-octen-3-ol, 3-octanone, 2-ethylhexanol, tridecane, tetradecane, α-farnesene and bisabolene, elicited EAG responses above or equal to the 50 (th) percentile rank of all responses. Interestingly, decanal, which represented only 1% of the total amount of odors emitted by cotton-fed hosts, elicited the highest (0.82 mV) EAG response in parasitoids. On the other hand, ( E)-β-caryophyllene, the most abundant (29%) blend component, elicited a relatively low (0.17 mV) EAG response. The results suggest that EAG response to host-related volatiles in parasitoids is probably more influenced by the ecological relevance or functional role of the compound in the blend, rather than its relative abundance.

  13. New quinoline di-Mannich base compounds with greater antimalarial activity than chloroquine, amodiaquine, or pyronaridine.

    PubMed Central

    Kotecka, B M; Barlin, G B; Edstein, M D; Rieckmann, K H

    1997-01-01

    We have compared the ex vivo antimalarial activity of 12 new quinoline di-Mannich base compounds containing the 7-dichloroquinoline or 7-trifluoromethylquinoline nucleus with amodiaquine, chloroquine, and pyronaridine using the Saimiri-bioassay model. Each compound was administered orally (30 mg/kg of body weight) to three or more noninfected Saimiri sciureus monkeys, and serum samples were collected at various times after drug administration and serially diluted with drug-free (control) serum. In vitro activity against the multidrug-resistant K1 isolate of Plasmodium falciparum was determined in serum samples by measuring the maximum inhibitory dilution at which the treated monkey serum inhibited schizont maturation in vitro. Of the 12 Mannich bases tested, 8 were associated with levels of ex vivo antimalarial activity in serum greater than those of amodiaquine, chloroquine, or pyronaridine 1 to 7 days after drug administration. Further studies were carried out with four of these compounds, and the results showed that the areas under the serum drug concentration-time curves for the four compounds were between 7- and 26-fold greater than that obtained for pyronaridine. Activity against four multidrug-resistant strains of P. falciparum was also much greater in serum samples collected from monkeys after administration of these four compounds than in serum samples collected after administration of pyronaridine or chloroquine. These findings suggest that these four quinoline Mannich base compounds possess a very marked and prolonged antimalarial activity and that further studies should be performed to determine their value as antimalarial drugs. PMID:9174201

  14. 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.

  15. Flavonoids, Antioxidant Activity and Aroma Compounds Analysis from Different Kinds of Tartary Buckwheat Tea

    PubMed Central

    Peng, L. X.; Zou, L.; Wang, J. B.; Zhao, J. L.; Xiang, D. B.; Zhao, G.

    2015-01-01

    The rutin, quercetin concentrations, antioxidant activity, and aroma compounds in different commercial tartary buckwheat tea were analyzed in our study. Results revealed that the materials and the processing protocol affected the chemical composition and activity of tartary buckwheat tea. Rutin and quercetin concentrations, antioxidant activity were significantly different in various kinds of tartary buckwheat tea, where the whole bran tea and the whole plant tea had the lower rutin, but higher quercetin concentrations and higher antioxidant activity. The whole embryo tea had the converse results. There was strong correlation between quercetin concentration and antioxidant activity (r>0.98, P<0.05). Meanwhile, Twenty eight different aroma compounds in tartary buckwheat tea were identified by gas chromatography-mass spectrometry. Those compounds were mainly composed of pyrazine, aldehydes, fatty acids and ketones. The main type of aroma compounds in different tartary buckwheat tea were similar, but their relative contents were different. The implications to the quality control of buckwheat tea were extensively discussed. PMID:26997692

  16. Antifungal compounds from turmeric and nutmeg with activity against plant pathogens.

    PubMed

    Radwan, Mohamed M; Tabanca, Nurhayat; Wedge, David E; Tarawneh, Amer H; Cutler, Stephen J

    2014-12-01

    The antifungal activity of twenty-two common spices was evaluated against plant pathogens using direct-bioautography coupled Colletotrichum bioassays. Turmeric, nutmeg, ginger, clove, oregano, cinnamon, anise, fennel, basil, black cumin, and black pepper showed antifungal activity against the plant pathogens Colletotrichum acutatum, Colletotrichum fragariae, and Colletotrichum gloeosporioides. Among the active extracts, turmeric and nutmeg were the most active and were chosen for further investigation. The bioassay-guided fractionation led to the isolation of three compounds from turmeric (1-3) and three compounds from nutmeg (4-6). Their chemical structures were elucidated by spectroscopic analysis including HR-MS, 1D, and 2D NMR as curcumin (1), demethoxycurcumin (2) and bisdemethoxy-curcumin (3), erythro-(7R,8R)-Δ(8')-4,7-dihydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan (4), erythro-(7R,8R)-Δ8'-7-acetoxy-3,4,3',5'-tetra-methoxy-8-O-4'-neolignan (5), and 5-hydroxy-eugenol (6). The isolated compounds were subsequently evaluated using a 96-well microbioassay against plant pathogens. At 30 μM, compounds 2 and 3 possessed the most antifungal activity against Phomopsis obscurans and Phomopsis viticola, respectively.

  17. Identification of Volatile Organic Compounds (VOCs) From Photochemical Activity in Snow Samples

    NASA Astrophysics Data System (ADS)

    Kos, G.; Ariya, P. A.

    2004-05-01

    The occurrence of VOCs in snow has been observed and can be related to anthropogenic emissions and biological activity. Photochemistry and microorganisms play a major role in the transformation of compounds in different compartments of the global ecosystem. Studies so far focused on the determination of single analytes or a class of compounds - mainly of anthropogenic origin (e.g. halogenated aromatic hydrocarbons) - that were considered important with regard to health and environmental concerns. Broader studies that describe a range of different compounds with different functionalities are relatively rare, especially for those of biological origin. The presented study investigated the formation of VOCs in snow samples and their connection with microbiological activity. The main aim was to pre-concentrate, identify and quantify volatile organic compounds. Snow samples were collected in an urban environment (Montreal, Canada) with sterilized containers. Samples were transferred into a heated reaction flask, where the sample was melted. A two-trap system was employed for pre-concentration: The first trap was used for water removal. The second trap was used for the collection of expected analytes by removing volatiles from the circulating air. Circulation was maintained with a pump at atmospheric pressure. Adsorption to glass walls of the reaction flask was prevented with halocarbon wax coating. Different sterilization methods were employed to suppress microbiological activity in order to collect background data and identify compounds of biological origin. VOC concentration and compound identification was performed with gas chromatography and mass spectrometric detection (GC-MS) by taking a sample with a gas-tight syringe through a septum-port. The sample was directly injected into the GC system. Compounds were identified by their respective mass spectra and included aldehydes and alcohols.

  18. 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

  19. Structure-activity relationships for a series of quinoline-based compounds active against replicating and nonreplicating Mycobacterium tuberculosis.

    PubMed

    Lilienkampf, Annamaria; Mao, Jialin; Wan, Baojie; Wang, Yuehong; Franzblau, Scott G; Kozikowski, Alan P

    2009-04-09

    Tuberculosis (TB) remains as a global pandemic that is aggravated by a lack of health care, the spread of HIV, and the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains. New anti-TB drugs are urgently required to shorten the long 6-12 month treatment regimen and to battle drug-resistant Mtb strains. We have identified several potent quinoline-based anti-TB compounds, bearing an isoxazole containing side-chain. The most potent compounds, 7g and 13, exhibited submicromolar activity against the replicating bacteria (R-TB), with minimum inhibitory concentrations (MICs) of 0.77 and 0.95 microM, respectively. In general, these compounds also had micromolar activity against the nonreplicating persistent bacteria (NRP-TB) and did not show toxicity on Vero cells up to 128 microM concentration. Compounds 7g and 13 were shown to retain their anti-TB activity against rifampin, isoniazid, and streptomycin resistant Mtb strains. The results suggest that quinoline-isoxazole-based anti-TB compounds are promising leads for new TB drug development.

  20. Antileishmanial Activity and Structure-Activity Relationship of Triazolic Compounds Derived from the Neolignans Grandisin, Veraguensin, and Machilin G.

    PubMed

    Costa, Eduarda C; Cassamale, Tatiana B; Carvalho, Diego B; Bosquiroli, Lauriane S S; Ojeda, Mariáh; Ximenes, Thalita V; Matos, Maria F C; Kadri, Mônica C T; Baroni, Adriano C M; Arruda, Carla C P

    2016-06-20

    Sixteen 1,4-diaryl-1,2,3-triazole compounds 4-19 derived from the tetrahydrofuran neolignans veraguensin 1, grandisin 2, and machilin G 3 were tested against Leishmania (Leishmania) amazonensis intracellular amastigotes. Triazole compounds 4-19 were synthetized via Click Chemistry strategy by 1,3-dipolar cycloaddition between terminal acetylenes and aryl azides containing methoxy and methylenedioxy groups as substituents. Our results suggest that most derivatives were active against intracellular amastigotes, with IC50 values ranging from 4.4 to 32.7 µM. The index of molecular hydrophobicity (ClogP) ranged from 2.8 to 3.4, reflecting a lipophilicity/hydrosolubility rate suitable for transport across membranes, which may have resulted in the potent antileishmanial activity observed. Regarding structure-activity relationship (SAR), compounds 14 and 19, containing a trimethoxy group, were the most active (IC50 values of 5.6 and 4.4 µM, respectively), with low cytotoxicity on mammalian cells (SI = 14.1 and 10.6). These compounds induced nitric oxide production by the host macrophage cells, which could be suggested as the mechanism involved in the intracellular killing of parasites. These results would be useful for the planning of new derivatives with higher antileishmanial activities.

  1. 1998 equivalence of sensory responses to single and mixed volatile organic compounds at equimolar concentrations.

    PubMed Central

    Prah, J D

    1998-01-01

    Exposure to low levels of chemicals indoors is often to a mixture of volatile organic compounds (VOCs). It is of interest to determine if the symptomatic and sensory responses can be attributed to a single chemical or to a mixture of chemicals. To determine if sensory or symptomatic responses differ with exposure to single or mixed VOCs, 100 female subjects participated in a 6-hr exposure study. Subjects were exposed to one of six equimolar concentrations equivalent to 24 mg/m3 toluene, control, m-xylene, n-butyl acetate, m-xylene plus n-butyl acetate, a mixture of 21 chemicals including n-butyl acetate and m-xylene, and to the same mixture of chemicals without n-butyl acetate and m-xylene (19 chemicals). The results indicated that there was no difference in reporting of symptoms or sensory responses between the exposures. When the control group was added, some variables, primarily odor intensity and nasal irritation, attained significance. Images Figure 1 Figure 2 Figure 3 PMID:9799190

  2. Estrogenic activity of isolated compounds and essential oils of Pimpinella species from Turkey, evaluated using a recombinant yeast screen.

    PubMed

    Tabanca, Nurhayat; Khan, Shabana I; Bedir, Erdal; Annavarapu, Srinivas; Willett, Kristine; Khan, Ikhlas A; Kirimer, Nese; Baser, K Husnu Can

    2004-08-01

    Several plants and plant-derived pure compounds, designated as phytoestrogens, have been reported to cause estrogenic effects. They have been used for alleviation of menopausal symptoms, prevention of osteoporosis, heart disease and cancer. There is an increased interest in studying phytoestrogens such as isoflavones and lignans for their use as replacements for synthetic estrogens. In this study, the estrogenic activity of essential oils of eleven Pimpinella species and the compounds isolated from these species were evaluated using the yeast estrogen screen (YES) assay. The essential oils containing (E)-anethole as major compound showed estrogenic activity in the YES assay, except for the aerial parts without fruits of P. anisetum and P. flabellifolia. The percent maximal response produced by most anethole-containing oils was 30-50%. Fruits of P. isaurica and P. peucedanifolia were estrogenic in spite of the absence or trace amount of anethole, respectively. This study indicates that the estrogenic activity of Pimpinella oils is not solely due to the presence of anethole. Components other than anethole may be responsible for contributing towards the estrogenic activity. The essential oils from different species varied in their estrogenic potencies (relative potency from 8.3 x 10(-8) to 1.2 x 10(-6) compared to 17 beta-estradiol) and among the different plant parts, the fruit oils of most species were estrogenic followed by the aerial parts without fruits and the root oils and their EC50 values varied from 45 micrograms/mL to 650 micrograms/mL.

  3. 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.

  4. Cytotoxic activity of C-geranyl compounds from Paulownia tomentosa fruits.

    PubMed

    Smejkal, Karel; Babula, Petr; Slapetová, Tereza; Brognara, Eleonora; Dall'acqua, Stefano; Zemlicka, Milan; Innocenti, Gabbriella; Cvacka, Josef

    2008-10-01

    The newly discovered 5,7-dihydroxy-6-geranylchromone ( 1) was isolated from PAULOWNIA TOMENTOSA fruit and subsequently characterized. The structure of the isolated compound was elucidated on the basis of extensive NMR experiments including HMQC, HMBC, COSY, and NOESY, as well as HR-MS, IR, and UV. The cytotoxicity of 1 was evaluated using a plant cell model represented by tobacco BY-2 cells. The other phytoconstituents ( 2 - 8) previously isolated from P. TOMENTOSA were similarly evaluated together with the known flavanones 10 and 11. The cytotoxicity (human erythro-leukaemia cell line K562) and activity on erythroid differentiation of compounds 2 - 9 and 12 and 13 have also been evaluated. Acteoside ( 2) was determined to be the most toxic of the compounds tested on BY-2 cells, diplacone ( 6) on the K562 cell line. Some aspects of the relationship between the flavanone skeleton substitution and the metabolic activation necessary for a toxic effect are discussed.

  5. Analytic model of energy-absorption response functions in compound X-ray detector materials.

    PubMed

    Yun, Seungman; Kim, Ho Kyung; Youn, Hanbean; Tanguay, Jesse; Cunningham, Ian A

    2013-10-01

    The absorbed energy distribution (AED) in X-ray imaging detectors is an important factor that affects both energy resolution and image quality through the Swank factor and detective quantum efficiency. In the diagnostic energy range (20-140 keV), escape of characteristic photons following photoelectric absorption and Compton scatter photons are primary sources of absorbed-energy dispersion in X-ray detectors. In this paper, we describe the development of an analytic model of the AED in compound X-ray detector materials, based on the cascaded-systems approach, that includes the effects of escape and reabsorption of characteristic and Compton-scatter photons. We derive analytic expressions for both semi-infinite slab and pixel geometries and validate our approach by Monte Carlo simulations. The analytic model provides the energy-dependent X-ray response function of arbitrary compound materials without time-consuming Monte Carlo simulations. We believe this model will be useful for correcting spectral distortion artifacts commonly observed in photon-counting applications and optimal design and development of novel X-ray detectors.

  6. Enhancing production of a 24-membered ring macrolide compound by a marine bacterium using response surface methodology*

    PubMed Central

    Chen, Hua; Wu, Mian-bin; Chen, Zheng-jie; Wang, Ming-lu; Lin, Jian-ping; Yang, Li-rong

    2013-01-01

    A 24-membered ring macrolide compound, macrolactin A has potential applications in pharmaceuticals for its anti-infectious and antiviral activity. In this study, macrolactin A was produced by a marine bacterium, which was identified as Bacillus subtilis by 16S ribosomal RNA (rRNA) sequence analysis. Electrospray ionization mass spectrometry (ESI/MS) and nuclear magnetic resonance (NMR) spectroscopy analyses were used to characterize this compound. To improve the production, response surface methodology (RSM) involving Box-Behnken design (BBD) was employed. Faeces bombycis, the main by-product in sericulture, was used as a nitrogen source in fermentation. The interactions between three significant factors, F. bombycis, soluble starch, and (NH4)2SO4 were investigated. A quadratic model was constructed to fit the production and the factors. Optimum medium composition was obtained by analysis of the model. When cultivated in the optimum medium, the production of macrolactin A was increased to 851 mg/L, 2.7 times as compared to the original. This study is also useful to find another way in utilizing F. bombycis. PMID:23549852

  7. Placebo-Activated Neural Systems are Linked to Antidepressant Responses

    PubMed Central

    Peciña, Marta; Bohnert, Amy S. B.; Sikora, Magdalena; Avery, Erich T.; Langenecker, Scott A.; Mickey, Brian J.; Zubieta, Jon-Kar

    2016-01-01

    Importance High placebo responses have been observed across a wide range of pathologies, severely impacting drug development. Objective Here we examined neurochemical mechanisms underlying the formation of placebo effects in patients with Major Depressive Disorder (MDD). Participants Thirty-five medication-free MDD patients. Design and Intervention We performed a single-blinded two-week cross-over randomized controlled trial of two identical oral placebos (described as having either “active” or “inactive” fast-acting antidepressant-like effects) followed by a 10-week open-label treatment with a selective serotonin reuptake inhibitor (SSRI) or in some cases, another agent as clinically indicated. The volunteers were studied with PET and the μ-opioid receptor (MOR)-selective radiotracer [11C]carfentanil after each 1-week “inactive” and “active” oral placebo treatment. In addition, 1 mL of isotonic saline was administered intravenously (i.v.) within sight of the volunteer during PET scanning every 4 min over 20 min only after the 1-week active placebo treatment, with instructions that the compound may be associated with the activation of brain systems involved in mood improvement. This challenge stimulus was utilized to test the individual capacity to acutely activate endogenous opioid neurotransmision under expectations of antidepressant effect. Setting A University Health System. Main Outcomes and Measures Changes in depressive symptoms in response to “active” placebo and antidepressant. Baseline and activation measures of MOR binding. Results Higher baseline MOR binding in the nucleus accumbens (NAc) was associated with better response to antidepressant treatment (r=0.48; p=0.02). Reductions in depressive symptoms after 1-week of “active” placebo treatment, compared to the “inactive”, were associated with increased placebo-induced μ-opioid neurotransmission in a network of regions implicated in emotion, stress regulation, and the

  8. Genetic and environmental factors affecting host response to drugs and other chemical compounds in our environment.

    PubMed Central

    Vesell, E S; Passananti, G T

    1977-01-01

    Compared to laboratory animals, humans are extremely heterogenous with respect to the many factors that can influence the distribution and biological effects of toxic chemicals. This heterogeneity can prevent an accurate assessment of the impact of a particular toxic compound on the health of an individual subject. Some of the factors that can significantly modify the host response to certain drugs, which serve in this review as a model for environmental chemicals, are enumerated and discussed. Although the mechanisms by which many of these factors modify the biological effects of certain environmental chemicals and drugs have been determined in some cases, better definition of the nature of interactions between these factors and environmental chemicals in a particular individual is required at a biochemical and molecular level. Recommendations are offered for the further development of our knowledge concerning interactions between environmental chemicals and such factors in a particular individual. PMID:598349

  9. Investigation of fruit peel extracts as sources for compounds with antioxidant and antiproliferative activities against human cell lines.

    PubMed

    Khonkarn, Ruttiros; Okonogi, Siriporn; Ampasavate, Chadarat; Anuchapreeda, Songyot

    2010-01-01

    The aim of this study was to evaluate antioxidant activity and cytotoxicity against human cell lines of fruit peel extracts from rambutan, mangosteen and coconut. The highest antioxidant activity was found from rambutan peel crude extract where the highest radical scavenging capacity via ABTS assay was from its ethyl acetate fraction with a TEAC value of 23.0mM/mg and the highest ferric ion reduction activity via FRAP assay was from its methanol fraction with an EC value of 20.2mM/mg. Importantly, using both assays, these fractions had a higher antioxidant activity than butylated hydroxyl toluene and vitamin E. It was shown that the ethyl acetate fraction of rambutan peel had the highest polyphenolic content with a gallic acid equivalent of 2.3mg/mL. The results indicate that the polyphenolic compounds are responsible for the observed antioxidant activity of the extracts. Interestingly, the hexane fraction of coconut peel showed a potent cytotoxic effect on KB cell line by MTT assay (IC(50)=7.7 microg/mL), and no detectable cytotoxicity toward normal cells. We concluded that the ethyl acetate fraction of rambutan peel is a promising resource for potential novel antioxidant agents whereas the hexane fraction of coconut peel may contain novel anticancer compounds.

  10. Cytotoxic Activity and Chemical Composition of the Root Extract from the Mexican Species Linum scabrellum: Mechanism of Action of the Active Compound 6-Methoxypodophyllotoxin

    PubMed Central

    Alejandre-García, Ivonne; Álvarez, Laura; Cardoso-Taketa, Alexandre; González-Maya, Leticia; Antúnez, Mayra; Salas-Vidal, Enrique; Díaz, J. Fernando; Marquina-Bahena, Silvia; Villarreal, María Luisa

    2015-01-01

    The cytotoxic activity and the chemical composition of the dichloromethane/methanol root extract of Linum scabrellum Planchon (Linaceae) were analyzed. Using NMR spectra and mass spectrometry analyses of the extract we identified eight main constituents: oleic acid (1), octadecenoic acid (2), stigmasterol (3), α-amyrin (4), pinoresinol (5), 6 methoxypodophyllotoxin (6), coniferin (7), and 6-methoxypodophyllotoxin-7-O-β-D-glucopyranoside (8). By using the sulforhodamine B assay, an important cytotoxic activity against four human cancer cell lines, HF6 colon (IC50 = 0.57 μg/mL), MCF7 breast (IC50 = 0.56 μg/mL), PC3 prostate (IC50 = 1.60 μg/mL), and SiHa cervical (IC50 = 1.54 μg/mL), as well as toward the normal fibroblasts line HFS-30 IC50 = 1.02 μg/mL was demonstrated. Compound 6 (6-methoxypodophyllotoxin) was responsible for the cytotoxic activity exhibiting an IC50 value range of 0.0632 to 2.7433 µg/mL against the tested cell lines. Cell cycle studies with compound 6 exhibited a cell arrest in G2/M of the prostate PC3 cancer cell line. Microtubule disruption studies demonstrated that compound 6 inhibited the polymerization of tubulin through its binding to the colchicine site (binding constant Kb = 7.6 × 106 M−1). A dose-response apoptotic effect was also observed. This work constitutes the first investigation reporting the chemical composition of L. scabrellum and the first study determining the mechanism of action of compound 6. PMID:26246833

  11. In Vitro and In Vivo Antimalarial Activity Assays of Seeds from Balanites aegyptiaca: Compounds of the Extract Show Growth Inhibition and Activity against Plasmodial Aminopeptidase

    PubMed Central

    Kusch, Peter; Deininger, Susanne; Specht, Sabine; Maniako, Rudeka; Haubrich, Stefanie; Pommerening, Tanja; Lin, Paul Kong Thoo; Hoerauf, Achim; Kaiser, Annette

    2011-01-01

    Balanites aegyptiaca (Balanitaceae) is a widely grown desert plant with multiuse potential. In the present paper, a crude extract from B. aegyptiaca seeds equivalent to a ratio of 1 : 2000 seeds to the extract was screened for antiplasmodial activity. The determined IC50 value for the chloroquine-susceptible Plasmodium falciparum NF54 strain was 68.26 μg/μL ± 3.5. Analysis of the extract by gas chromatography-mass spectrometry detected 6-phenyl-2(H)-1,2,4-triazin-5-one oxime, an inhibitor of the parasitic M18 Aspartyl Aminopeptidase as one of the compounds which is responsible for the in vitro antiplasmodial activity. The crude plant extract had a Ki of 2.35 μg/μL and showed a dose-dependent response. After depletion of the compound, a significantly lower inhibition was determined with a Ki of 4.8 μg/μL. Moreover, two phenolic compounds, that is, 2,6-di-tert-butyl-phenol and 2,4-di-tert-butyl-phenol, with determined IC50 values of 50.29 μM ± 3 and 47.82 μM ± 2.5, respectively, were detected. These compounds may contribute to the in vitro antimalarial activity due to their antioxidative properties. In an in vivo experiment, treatment of BALB/c mice with the aqueous Balanite extract did not lead to eradication of the parasites, although a reduced parasitemia at day 12 p.i. was observed. PMID:21687598

  12. Target Prediction for an Open Access Set of Compounds Active against Mycobacterium tuberculosis

    PubMed Central

    Martínez-Jiménez, Francisco; Papadatos, George; Yang, Lun; Wallace, Iain M.; Kumar, Vinod; Pieper, Ursula; Sali, Andrej; Brown, James R.; Overington, John P.; Marti-Renom, Marc A.

    2013-01-01

    Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), infects an estimated two billion people worldwide and is the leading cause of mortality due to infectious disease. The development of new anti-TB therapeutics is required, because of the emergence of multi-drug resistance strains as well as co-infection with other pathogens, especially HIV. Recently, the pharmaceutical company GlaxoSmithKline published the results of a high-throughput screen (HTS) of their two million compound library for anti-mycobacterial phenotypes. The screen revealed 776 compounds with significant activity against the M. tuberculosis H37Rv strain, including a subset of 177 prioritized compounds with high potency and low in vitro cytotoxicity. The next major challenge is the identification of the target proteins. Here, we use a computational approach that integrates historical bioassay data, chemical properties and structural comparisons of selected compounds to propose their potential targets in M. tuberculosis. We predicted 139 target - compound links, providing a necessary basis for further studies to characterize the mode of action of these compounds. The results from our analysis, including the predicted structural models, are available to the wider scientific community in the open source mode, to encourage further development of novel TB therapeutics. PMID:24098102

  13. Infrared decontamination of oregano: effects on Bacillus cereus spores, water activity, color, and volatile compounds.

    PubMed

    Eliasson, Lovisa; Libander, Patrik; Lövenklev, Maria; Isaksson, Sven; Ahrné, Lilia

    2014-12-01

    Infrared (IR) heating, a novel technology for decontaminating oregano, was evaluated by investigating the reduction of inoculated Bacillus cereus spores and the effect on water activity (a(w)), color, and headspace volatile compounds after exposure to IR treatment. Conditioned oregano (a(w) 0.88) was IR-treated in a closed heating unit at 90 and 100 °C for holding times of 2 and 10 min, respectively. The most successful reduction in B. cereus spore numbers (5.6 log units) was achieved after a holding time of 10 min at 90 °C, while treatment at 100 °C for the same time resulted in a lower reduction efficiency (4.7 log units). The lower reduction at 100 °C was probably due to a reduced aw (aw 0.76) during IR treatment or possibly to the alteration or loss of volatile compounds possessing antimicrobial properties. The green color of oregano was only slightly affected, while the composition of volatile compounds was clearly altered by IR heating. However, two of the key aroma compounds, carvacrol and thymol, were only slightly affected, compared to the effect on the other studied compounds, indicating that the typical oregano aroma can likely be preserved. In conclusion, IR heating shows potential for the successful decontamination of oregano without severe alteration of its color or the key aroma compounds, carvacrol and thymol.

  14. 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.

  15. Auditory Cortex Basal Activity Modulates Cochlear Responses in Chinchillas

    PubMed Central

    León, Alex; Elgueda, Diego; Silva, María A.; Hamamé, Carlos M.; Delano, Paul H.

    2012-01-01

    Background The auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory nerve fibers. The functional role of the cortico-olivocochlear efferent system remains debated. We hypothesized that auditory cortex basal activity modulates cochlear and auditory-nerve afferent responses through the efferent system. Methodology/Principal Findings Cochlear microphonics (CM), auditory-nerve compound action potentials (CAP) and auditory cortex evoked potentials (ACEP) were recorded in twenty anesthetized chinchillas, before, during and after auditory cortex deactivation by two methods: lidocaine microinjections or cortical cooling with cryoloops. Auditory cortex deactivation induced a transient reduction in ACEP amplitudes in fifteen animals (deactivation experiments) and a permanent reduction in five chinchillas (lesion experiments). We found significant changes in the amplitude of CM in both types of experiments, being the most common effect a CM decrease found in fifteen animals. Concomitantly to CM amplitude changes, we found CAP increases in seven chinchillas and CAP reductions in thirteen animals. Although ACEP amplitudes were completely recovered after ninety minutes in deactivation experiments, only partial recovery was observed in the magnitudes of cochlear responses. Conclusions/Significance These results show that blocking ongoing auditory cortex activity modulates CM and CAP responses, demonstrating that cortico-olivocochlear circuits regulate auditory nerve and cochlear responses through a basal efferent tone. The diversity of the obtained effects

  16. Predicting trace organic compound attenuation with spectroscopic parameters in powdered activated carbon processes.

    PubMed

    Ziska, Austin D; Park, Minkyu; Anumol, Tarun; Snyder, Shane A

    2016-08-01

    The removal of trace organic compounds (TOrCs) is of growing interest in water research and society. Powdered activated carbon (PAC) has been proven to be an effective method of removal for TOrCs in water, with the degree of effectiveness depending on dosage, contact time, and activated carbon type. In this study, the attenuation of TOrCs in three different secondary wastewater effluents using four PAC materials was studied in order to elucidate the effectiveness and efficacy of PAC for TOrC removal. With the notable exception of hydrochlorothiazide, all 14 TOrC indicators tested in this study exhibited a positive correlation of removal rate with their log Dow values, demonstrating that the main adsorption mechanism was hydrophobic interaction. As a predictive model, the modified Chick-Watson model, often used for the prediction of microorganism inactivation by disinfectants, was applied. The applied model exhibited good predictive power for TOrC attenuation by PAC in wastewater. In addition, surrogate models based upon spectroscopic measurements including UV absorbance at 254 nm and total fluorescence were applied to predict TOrC removal by PAC. The surrogate model was found to provide an excellent prediction of TOrC attenuation for all combinations of water quality and PAC type included in this study. The success of spectrometric parameters as surrogates in predicting TOrC attenuation by PAC are particularly useful because of their potential application in real-time on-line sensor monitoring and process control at full-scale water treatment plants, which could lead to significantly reduced operator response times and PAC operational optimization.

  17. Phonological and Semantic Activation in Reading Two-Kanji Compound Words.

    ERIC Educational Resources Information Center

    Morita, Aiko; Matsuda, Fumiko

    2000-01-01

    Examined whether phonological information was activated automatically in processing two kanji compound words. In one experiment, participants judged whether pairs of words were homophones, while others judged whether pairs were synonyms. In the second, participants were asked to make one of the two judgments, as in experiment one. Findings support…

  18. COST ANALYSIS OF ACTIVATED CARBON VERSUS PHOTOCATALYTIC OXIDATION FOR REMOVING ORGANIC COMPOUNDS FROM INDOOR AIR

    EPA Science Inventory

    A cost comparison has been conducted of 1 m3/s indoor air cleaners using granular activated carbon (GAC) vs. photocatalytic oxidation (PCO) for treating a steady-state inlet volatile organic compound (VOC) concentration of 0.3 mg/m3. The commercial GAC unit was costed assuming t...

  19. Isolation and characterization of an utero-active compound from Agave americana.

    PubMed

    Basilio, C M; Seyler, L; Bernstein, J; Castro de la Mata, R

    1989-12-01

    Crude extracts of Agave americana contain two utero-active compounds. One of these, tentatively named "Fraction B", has been purified to chromatographic homogeneity. Its pharmacological actions are similar to those of acetylcholine. However its chromatographic and electrophoretic mobilities are different. Some chemical properties of fraction B are compatible with the structure of an acyl derivative of choline different from acetylcholine.

  20. Moooving forward on determining biologically active compounds in milk and their impact on health

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent studies have demonstrated that some of the lesser studied components in milk, known as biologically active compounds (BACs), may provide potential benefits to human health. The added health-value of raw milk and milk from organic and grass-fed herds is strongly debated because of limited, an...

  1. 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...

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

    EPA Science Inventory

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

  3. Development of Novel Repellents Using Structure - Activity Modeling of Compounds in the USDA Archival Database

    DTIC Science & Technology

    2011-01-01

    used in efforts to develop QSAR models. Measurement of Repellent Efficacy Screening for Repellency of Compounds with Unknown Toxicology In screening...CPT) were used to develop Quantitative Structure Activity Relationship ( QSAR ) models to predict repellency. Successful prediction of novel...acylpiperidine QSAR models employed 4 descriptors to describe the relationship between structure and repellent duration. The ANN model of the carboxamides did not

  4. The computational design of test compounds with potentially specific biological activity: Histamine-H2 agonists derived from 5-HT/H2 antagonists

    NASA Astrophysics Data System (ADS)

    Topiol, Sid; Sabio, Michael

    1991-06-01

    The previously proposed models for the recognition and activation of 5-HT and histamine-H2 receptors, which were employed to explain the antagonist activity of LSD at both of these receptors, as well as the selective antagonism for H2 receptors by SKF-10856 and 9,10-dihydro-LSD, are used herein to design a compound to test the H2-receptor model. The design strategy attempts to construct a compound with potentially selective H2 agonism. The design scheme maintains features which were previously used to explain selective recognition of SKF-10856 and 9,10-dihydro-LSD as well as reintroduces the chemical features proposed to be responsible for H2 activation. The existence of the H2 recognition and activation features in the proposed compound is verified, in a previously proposed model, by computational studies of the molecular electrostatic potentials and shifts in the tautomeric preference.

  5. Sigma-1 receptor ligands control a switch between passive and active threat responses

    PubMed Central

    Rennekamp, Andrew J.; Huang, Xi-Ping; Wang, You; Patel, Samir; Lorello, Paul J.; Cade, Lindsay; Gonzales, Andrew P. W.; Yeh, Jing-Ruey Joanna; Caldarone, Barbara J.; Roth, Bryan L.; Kokel, David; Peterson, Randall T.

    2016-01-01

    Humans and many animals exhibit freezing behavior in response to threatening stimuli. In humans, inappropriate threat responses are fundamental characteristics of several mental illnesses. To identify small molecules that modulate threat responses, we developed a high-throughput behavioral assay in zebrafish (Danio rerio) and characterized the effects of 10,000 compounds on freezing behavior. We found three classes of compounds that switch the threat response from freezing to escape-like behavior. We then screened these for binding activity across 45 candidate targets. Using target profile clustering we implicated the sigma-1 receptor in the mechanism of behavioral switching and confirmed that known sigma-1 ligands also disrupt freezing behavior. Furthermore, mutation of the sigma-1 gene prevented the behavioral effect of escape-inducing compounds. The compound ‘finazine’ potently bound mammalian sigma-1 and altered rodent threat response behavior. Thus, pharmacological and genetic interrogation of the freezing response revealed sigma-1 as a mediator of vertebrate threat responses. PMID:27239788

  6. 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.

  7. Therapeutic Uses and Pharmacological Properties of Garlic, Shallot, and Their Biologically Active Compounds

    PubMed Central

    Mikaili, Peyman; Maadirad, Surush; Moloudizargari, Milad; Aghajanshakeri, Shahin; Sarahroodi, Shadi

    2013-01-01

    Objective(s): Garlic (Allium sativum L. family Liliaceae) is well known in Iran and its leaves, flowers, and cloves have been used in traditional medicine for a long time. Research in recent decades has shown widespread pharmacological effects of A. sativum and its organosulfur compounds especially Allicin. Studies carried out on the chemical composition of the plant show that the most important constituents of this plant are organosulfur compounds such as allicin, diallyl disulphide, S-allylcysteine, and diallyl trisulfide. Allicin represents one of the most studied among these naturally occurring compounds. In addition to A. sativum, these compounds are also present in A. hirtifolium (shallot) and have been used to treat various diseases. This article reviews the pharmacological effects and traditional uses of A. sativum, A. hirtifolium, and their active constituents to show whether or not they can be further used as potential natural sources for the development of novel drugs. Materials and Methods: For this purpose, the authors went through a vast number of sources and articles and all needed data was gathered. The findings were reviewed and classified on the basis of relevance to the topic and a summary of all effects were reported as tables. Conclusion: Garlic and shallots are safe and rich sources of biologically active compounds with low toxicity. Further studies are needed to confirm the safety and quality of the plants to be used by clinicians as therapeutic agents. PMID:24379960

  8. Protein Folding Activity of the Ribosome (PFAR) –– A Target for Antiprion Compounds

    PubMed Central

    Banerjee, Debapriya; Sanyal, Suparna

    2014-01-01

    Prion diseases are fatal neurodegenerative diseases affecting mammals. Prions are misfolded amyloid aggregates of the prion protein (PrP), which form when the alpha helical, soluble form of PrP converts to an aggregation-prone, beta sheet form. Thus, prions originate as protein folding problems. The discovery of yeast prion(s) and the development of a red-/white-colony based assay facilitated safe and high-throughput screening of antiprion compounds. With this assay three antiprion compounds; 6-aminophenanthridine (6AP), guanabenz acetate (GA), and imiquimod (IQ) have been identified. Biochemical and genetic studies reveal that these compounds target ribosomal RNA (rRNA) and inhibit specifically the protein folding activity of the ribosome (PFAR). The domain V of the 23S/25S/28S rRNA of the large ribosomal subunit constitutes the active site for PFAR. 6AP and GA inhibit PFAR by competition with the protein substrates for the common binding sites on the domain V rRNA. PFAR inhibition by these antiprion compounds opens up new possibilities for understanding prion formation, propagation and the role of the ribosome therein. In this review, we summarize and analyze the correlation between PFAR and prion processes using the antiprion compounds as tools. PMID:25341659

  9. Compounds from Sorindeia juglandifolia (Anacardiaceae) exhibit potent anti-plasmodial activities in vitro and in vivo

    PubMed Central

    2012-01-01

    Background Discovering new lead compounds against malaria parasites is a crucial step to ensuring a sustainable global pipeline for effective anti-malarial drugs. As far as we know, no previous phytochemical or pharmacological investigations have been carried out on Sorindeia juglandifolia. This paper describes the results of an anti-malarial activity-driven investigation of the fruits of this Cameroonian plant. Methods Air-dried fruits were extracted by maceration using methanol. The extract was fractionated by flash chromatography followed by column chromatography over silica gel, eluting with gradients of hexane-ethyl acetate mixtures. Resulting fractions and compounds were tested in vitro against the Plasmodium falciparum chloroquine-resistant strain W2, against field isolates of P. falciparum, and against the P. falciparum recombinant cysteine protease falcipain-2. Promising fractions were assessed for acute toxicity after oral administration in mice. One of the promising isolated compounds was assessed in vivo against the rodent malaria parasite Plasmodium berghei. Results The main end-products of the activity-guided fractionation were 2,3,6-trihydroxy benzoic acid (1) and 2,3,6-trihydroxy methyl benzoate (2). Overall, nine fractions tested against P. falciparum W2 and falcipain-2 were active, with IC50 values of 2.3-11.6 μg/ml for W2, and 1.1-21.9 μg/ml for falcipain-2. Purified compounds (1) and (2) also showed inhibitory effects against P. falciparum W2 (IC50s 16.5 μM and 13.0 μM) and falcipain-2 (IC50s 35.4 and 6.1 μM). In studies of P. falciparum isolates from Cameroon, the plant fractions demonstrated IC50 values of 0.14-19.4 μg/ml and compounds (1) and (2) values of 6.3 and 36.1 μM. In vivo assessment of compound (1) showed activity against P. berghei strain B, with mean parasitaemia suppressive dose and curative dose of 44.9 mg/kg and 42.2 mg/kg, respectively. Active fractions were found to be safe in mice after oral administration of 7 g

  10. Significance of Cytochrome P450 System Responses and Levels of Bile Fluorescent Aromatic Compounds in Marine Wildlife Following Oil Spills

    SciTech Connect

    Lee, Richard F.; Anderson, Jack W.

    2005-07-01

    The relationships among cytochrome P450 induction in marine wildlife species, levels of fluorescent aromatic compounds (FAC) in their bile, the chemical composition of the inducing compounds, the significance of the exposure pathway, and any resulting injury, as a consequence of exposure to crude oil following a spill, are reviewed. Fish collected after oil spills often show increases in cytochrome P450 system activity, cytochrome P4501A (CYP1A) and bile fluorescent aromatic compounds (FAC), that are correlated with exposure to polycyclic aromatic hydrocarbons (PAH) in the oil. There is also some evidence for increases in bile FAC and induction of cytochrome P450 in marine birds and mammals after oil spills. However, when observed, increases in these exposure indicators are transitory and generally decrease to background levels within one year after the exposure. Laboratory studies have shown induction of cytochrome P450 systems occurs after exposure of fish to crude oil in water, sediment or food. Most of the PAH found in crude oil (dominantly 2- and 3-ring PAH) are not strong inducers of cytochrome P450. Exposure to the 4-ring chrysenes or the photooxidized products of the PAH may account for the cytochrome P450 responses in fish collected from oil-spill sites. The contribution of non-spill background PAH, particularly combustion-derived (pyrogenic) PAH, to bile FAC and cytochrome P450 system responses can be confounding and needs to be considered when evaluating oil spill effects. The ubiquity of pyrogenic PAH makes it important to fully characterize all sources of PAH, including PAH from natural resources, e.g. retene, in oil spill studies. In addition, such parameters as species, sex, age, ambient temperature and season need to be taken into account. While increases in fish bile FAC and cytochrome P450 system responses, can together, be sensitive general indicators of PAH exposure after an oil spill, there is little unequivocal evidence to suggest a linkage to

  11. Significance of cytochrome P450 system responses and levels of bile fluorescent aromatic compounds in marine wildlife following oil spills.

    PubMed

    Lee, Richard F; Anderson, Jack W

    2005-07-01

    The relationships among cytochrome P450 induction in marine wildlife species, levels of fluorescent aromatic compounds (FAC) in their bile, the chemical composition of the inducing compounds, the significance of the exposure pathway, and any resulting injury, as a consequence of exposure to crude oil following a spill, are reviewed. Fish collected after oil spills often show increases in cytochrome P450 system activity, cytochrome P4501A (CYP1A) and bile fluorescent aromatic compounds (FAC), that are correlated with exposure to polycyclic aromatic hydrocarbons (PAH) in the oil. There is also some evidence for increases in bile FAC and induction of cytochrome P450 in marine birds and mammals after oil spills. However, when observed, increases in these exposure indicators are transitory and generally decrease to background levels within one year after the exposure. Laboratory studies have shown induction of cytochrome P450 systems occurs after exposure of fish to crude oil in water, sediment or food. Most of the PAH found in crude oil (dominantly 2- and 3-ring PAH) are not strong inducers of cytochrome P450. Exposure to the 4-ring chrysenes or the photooxidized products of the PAH may account for the cytochrome P450 responses in fish collected from oil-spill sites. The contribution of non-spill background PAH, particularly combustion-derived (pyrogenic) PAH, to bile FAC and cytochrome P450 system responses can be confounding and needs to be considered when evaluating oil spill effects. The ubiquity of pyrogenic PAH makes it important to fully characterize all sources of PAH, including PAH from natural resources, e.g. retene, in oil spill studies. In addition, such parameters as species, sex, age, ambient temperature and season need to be taken into account. While increases in fish bile FAC and cytochrome P450 system responses, can together, be sensitive general indicators of PAH exposure after an oil spill, there is little unequivocal evidence to suggest a linkage to

  12. Assessment of the encapsulation effect of phenolic compounds from Spirulina sp. LEB-18 on their antifusarium activities.

    PubMed

    Pagnussatt, Fernanda Arnhold; de Lima, Vânia Rodrigues; Dora, Cristiana Lima; Costa, Jorge Alberto Vieira; Putaux, Jean-Luc; Badiale-Furlong, Eliana

    2016-11-15

    This study aimed to investigate the antifungal activity of liposomal systems containing Spirulina sp. LEB-18 phenolic extract (PE) against Fusarium graminearum (Fg) isolates. The interaction between PE and phosphatidylcholine-based liposomes was monitored by HATR-FTIR, NMR, DSC, and cryo-TEM. After encapsulation, the active principle was released slower than the free PE, a fact that makes the former very promising as a natural antifungal. The PE encapsulation in the liposomes was responsible for changes in the dynamics of specific regions. These compounds affected the membrane hydration degree, ordered the lipid phosphate region and increased the disorder of the acyl chain methylenes. These physico-chemical effects may be related to the strong inhibition of four Fg isolates. Results were discussed by correlating structural similarities, as well as the membrane effects of the PE under study on antifusarium activities, and those found in the literature, thus enabling the PE mechanisms of action to be analyzed.

  13. Effects of various poisoning compounds on the activity and stereospecificity of heterogeneous Ziegler–Natta catalyst

    PubMed Central

    Tangjituabun, Kitti; Yull Kim, Sang; Hiraoka, Yuichi; Taniike, Toshiaki; Terano, Minoru; Jongsomjit, Bunjerd; Praserthdam, Piyasan

    2008-01-01

    A TiCl4/ethylbenzoate/MgCl2 Ziegler–Natta catalyst was pretreated with chemically different poisoning compounds to investigate their effects on the catalyst activity and stereospecificity for propylene polymerization. The poisoning power on the activity was in the order of methanol > acetone > ethyl acetate. A kinetic analysis using the stopped-flow method revealed that addition of the poisoning materials decreased the activity through the reduction of the number of active sites, whereas the catalyst isospecificity was hardly affected by these materials. PMID:27877969

  14. Rapid, Semiquantitative Assay To Discriminate among Compounds with Activity against Replicating or Nonreplicating Mycobacterium tuberculosis

    PubMed Central

    Roberts, Julia; Ling, Yan; Quezada, Landys Lopez; Glasheen, Jou; Ballinger, Elaine; Somersan-Karakaya, Selin; Warrier, Thulasi; Warren, J. David; Nathan, Carl

    2015-01-01

    The search for drugs that can kill replicating and nonreplicating Mycobacterium tuberculosis faces practical bottlenecks. Measurement of CFU and discrimination of bacteriostatic from bactericidal activity are costly in compounds, supplies, labor, and time. Testing compounds against M. tuberculosis under conditions that prevent the replication of M. tuberculosis often involves a second phase of the test in which conditions are altered to permit the replication of bacteria that survived the first phase. False-positive determinations of activity against nonreplicating M. tuberculosis may arise from carryover of compounds from the nonreplicating stage of the assay that act in the replicating stage. We mitigate these problems by carrying out a 96-well microplate liquid MIC assay and then transferring an aliquot of each well to a second set of plates in which each well contains agar supplemented with activated charcoal. After 7 to 10 days—about 2 weeks sooner than required to count CFU—fluorometry reveals whether M. tuberculosis bacilli in each well have replicated extensively enough to reduce a resazurin dye added for the final hour. This charcoal agar resazurin assay (CARA) distinguishes between bacterial biomasses in any two wells that differ by 2 to 3 log10 CFU. The CARA thus serves as a pretest and semiquantitative surrogate for longer, more laborious, and expensive CFU-based assays, helps distinguish bactericidal from bacteriostatic activity, and identifies compounds that are active under replicating conditions, nonreplicating conditions, or both. Results for 14 antimycobacterial compounds, including tuberculosis (TB) drugs, revealed that PA-824 (pretomanid) and TMC207 (bedaquiline) are largely bacteriostatic. PMID:26239979

  15. 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 Köhler 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. 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

  16. A novel aphrodisiac compound from an orchid that activates nitric oxide synthases.

    PubMed

    Subramoniam, A; Gangaprasad, A; Sureshkumar, P K; Radhika, J; Arun, K B; Arun, B K

    2013-01-01

    Nitric oxide (NO) is known to have roles in several crucial biological functions including vasodilation and penile erection. There are neuronal, endothelial and inducible NO synthases that influence the levels of NO in tissues and blood. NO activates guanylate cyclase and thereby increases the levels of cyclic GMP (cGMP). Viagra (sildenafil), a top selling drug in the world for erectile dysfunction, inhibits phosphodiesterase-5, which hydrolyses cGMP to GMP. Thus, it fosters an NO-mediated increase in the levels of cGMP, which mediates erectile function. Here, we show the aphrodisiac activity of a novel chemical isolate from the flowers of an epiphytic orchid, Vanda tessellata (Roxb.) ex Don, which activates neuronal and endothelial, but not inducible, NO synthases. The aphrodisiac activity is caused by an increase in the level of NO in corpus cavernosum. The drug increases blood levels of NO as early as 30 min after oral administration. The active compound was isolated by column chromatography. Based on the spectral data, the active compound is found to be a new compound, 2,7,7-tri methyl bicyclo [2.2.1] heptane. We anticipate that our findings could lead to the development of a commercially viable and valuable drug for erectile dysfunction.

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

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

    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 Köhler theory to predict the 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. 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.

  18. Optimization of ultrasonic-assisted extraction of antioxidant compounds from Guava (Psidium guajava L.) leaves using response surface methodology

    PubMed Central

    Kong, Fansheng; Yu, Shujuan; Feng, Zeng; Wu, Xinlan

    2015-01-01

    Objective: To optimization of extraction of antioxidant compounds from guava (Psidium guajava L.) leaves and showed that the guava leaves are the potential source of antioxidant compounds. Materials and Methods: The bioactive polysaccharide compounds of guava leaves (P. guajava L.) were obtained using ultrasonic-assisted extraction. Extraction was carried out according to Box-Behnken central composite design, and independent variables were temperature (20–60°C), time (20–40 min) and power (200–350 W). The extraction process was optimized by using response surface methodology for the highest crude extraction yield of bioactive polysaccharide compounds. Results: The optimal conditions were identified as 55°C, 30 min, and 240 W. 1,1-diphenyl-2-picryl-hydrazyl and hydroxyl free radical scavenging were conducted. Conclusion: The results of quantification showed that the guava leaves are the potential source of antioxidant compounds. PMID:26246720

  19. Compounds Released from Biomass Deconstruction: Understanding Their Effect on Cellulose Enzyme Hydrolysis and Their Biological Activity

    NASA Astrophysics Data System (ADS)

    Djioleu, Angele Mezindjou

    The effect of compounds produced during biomass pretreatment on cellulolytic enzyme was investigated. Liquid prehydrolyzates were prepared by pretreating switchgrass using 24 combinations of temperature, time, and sulfuric acid concentration based on a full factorial design. Temperature was varied from 140°C to 180°C; time ranged from 10 to 40 min; and the sulfuric acid concentrations were 0.5% or 1% (v/v). Identified products in the prehydrolyzates included xylose, glucose, hydroxymethylfurfural (HMF), furfural, acetic acid, formic acid, and phenolic compounds at concentration ranging from 0 to 21.4 g/L. Pretreatment conditions significantly affected the concentrations of compounds detected in prehydrolyzates. When assayed in the presence of switchgrass prehydrolyzates against model substrates, activities of cellulase, betaglucosidase, and exoglucanase, were significantly reduced by at least 16%, 31.8%, and 57.8%, respectively, as compared to the control. A strong positive correlation between inhibition of betaglucosidase and concentration of glucose, acetic acid, and furans in prehydrolyzate was established. Exoglucanase inhibition correlated with the presence of phenolic compounds and acetic acid. The prehydrolyzate, prepared at 160°C, 30 min, and 1% acid, was fractionated by centrifugal partition chromatography (CPC) into six fractions; the inhibition effect of these fractions on betaglucosidase and exoglucanase was determined. The initial hydrolysis rate of cellobiose by betaglucosidase was significantly reduced by the CPC sugar-rich fraction; however, exoglucanase was deactivated by the CPC phenolic-rich fraction. Finally, biological activities of water-extracted compounds from sweetgum bark and their effect on cellulase was investigated. It was determined that 12% of solid content of the bark extract could be accounted by phenolic compounds with gallic acid identified as the most concentrated phytochemical. Sweetgum bark extract inhibited Staphylococcus

  20. Applications of organoboron compounds in carbohydrate chemistry and glycobiology: analysis, separation, protection, and activation.

    PubMed

    McClary, Corey A; Taylor, Mark S

    2013-11-15

    The reversible covalent interactions between organoboron compounds and diols have been applied for many years in carbohydrate chemistry. They form the basis of efficient methods for the detection of carbohydrates, and applications in cellular imaging and glycoprotein analysis are beginning to emerge. The interactions are also of widespread utility in carbohydrate synthesis: depending upon the coordination geometry at boron, either protection or activation of a bound diol motif may be achieved. This review article uses recent examples to illustrate the breadth of applications of organoboron compounds in carbohydrate chemistry.

  1. The influence of pine volatile compounds on the olfactory response by Neodiprion sertifer (Geoffroy) females.

    PubMed

    Martini, Antonio; Botti, Federico; Galletti, Guido; Bocchini, Paola; Bazzocchi, Giovanni; Baronio, Piero; Burgio, Giovanni

    2010-10-01

    Females of the pine sawfly Neodiprion sertifer (Hymenoptera Diprionidae) usually avoid Pinus pinea trees as host plants. In contrast, this sawfly species is highly attracted by P. sylvestris and P. nigra trees. Here, we investigated which pine volatiles might mediate this behavior by in situ sampling experiments and olfactometer laboratory tests. Volatiles emitted from P. pinea, P. sylvestris, and P. nigra foliage were sampled by solid-phase microextraction (SPME). Analysis of these volatiles by coupled gaschromatography/mass spectrometry revealed that the relative amounts of the compounds emitted by the three species were significantly different. A discriminant analysis showed that the amounts of limonene and myrcene significantly contributed to the species-specific volatile patterns. Pinus pinea emitted higher relative amounts of limonene than the other pine species. Pinus sylvestris emitted the highest relative amounts of myrcene. When testing the response of N. sertifer females to these pine terpenoids in an olfactometer bioassay, a low amount of limonene was attractive, while a repellent effect was evident when higher amounts were used. The sawfly females showed no significant olfactory response to myrcene. These data suggest that low relative amounts of limonene have a significant function in attracting N. sertifer females, while high amounts might contribute to avoidance of a tree.

  2. Role of the polycarboxylic compounds in the response of Silene vulgaris to chromium.

    PubMed

    Pradas Del Real, Ana E; Silvan, Jose Manuel; de Pascual-Teresa, Sonia; Guerrero, Ana; García-Gonzalo, Pilar; Lobo, M Carmen; Pérez-Sanz, Araceli

    2017-01-03

    This work aims to investigate the nature and the specific mechanisms by which polycarboxylic compounds participate in the tolerance of Silene vulgaris to Cr with special attention given to the rhizosphere system. This knowledge is important to use this species in the implementation of phytoremediation technologies in Cr-polluted soils. According to the results, chromium is chelated and mobilized by the citric and malic acids in plant tissues, while oxalic acid might participate in the reduction and chelation of Cr in the rhizosphere. At the applied doses, the response of both exudation rate and root exudate composition (total polyphenols and quercitin) seems to involve a rearrangement in the lignification of the plant cell wall to immobilize Cr. Quercetin-3-dirhamnosyl-galactoside and apiin (apigenin-7-O-apiosyl-glucoside) have been identified as the major polyphenols in the root exudates of S. vulgaris. The increments found in the apiin concentration in root exudates seem to be related to the protection against Cr toxicity by chelation of Cr or by free radical scavenging. Though earlier response is detected in plant tissues, results from this work together with previous studies in S. vulgaris indicate that exudation might be a regulated mechanism of protection under Cr exposition in S. vulgaris that may involve mainly Cr reduction and chelation.

  3. 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.

  4. 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.

  5. Antiinflammatory and Analgesic Activities of Ethanol Extract and Isolated Compounds from Millettia pulchra.

    PubMed

    Huo, Xiaowei; Zhang, Leilei; Gao, Li; Guo, Yan; Zhang, Lijing; Li, Liyong; Si, Jianyong; Cao, Li

    2015-01-01

    The plant Millettia pulchra was commonly used in folk medicine for the management of inflammation. However, there was no scientific rationale for these effects and the mechanism of action remained incompletely understood. The present study was designed to investigate the antiinflammatory and analgesic activities of an ethanol extract of the stem of M. pulchra (EMP) in vivo, and to explore the antiinflammatory activity of compounds isolated from EMP in vitro. We found that EMP reduced xylene-induced ear edema and relieved both acetic acid-induced pain and pain in the hot plate test. Additionally, a significant decrease in nitric oxide (NO) production was observed in cells treated with the isolated compounds. Lanceolatin B, which showed the greatest inhibition of NO synthesis among the compounds tested, also reduced levels of interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB), and phosphorylation inhibitory kappa B alpha (p-IκBα) in a dose-dependent manner. These findings provide convincing evidence that EMP and the individual isolated compounds possess significant antiinflammatory and analgesic activities.

  6. Antibiofilm Activity, Compound Characterization, and Acute Toxicity of Extract from a Novel Bacterial Species of Paenibacillus

    PubMed Central

    Alasil, Saad Musbah; Omar, Rahmat; Yusof, Mohd Yasim

    2014-01-01

    The effectiveness of many antimicrobial agents is currently decreasing; therefore, it is important to search for alternative therapeutics. Our study was carried out to assess the in vitro antibiofilm activity using microtiter plate assay, to characterize the bioactive compounds using Ultra Performance Liquid Chromatography-Diode Array Detection and Liquid Chromatography-Mass Spectrometry and to test the oral acute toxicity on Sprague Dawley rats of extract derived from a novel bacterial species of Paenibacillus strain 139SI. Our results indicate that the crude extract and its three identified compounds exhibit strong antibiofilm activity against a broad range of clinically important pathogens. Three potential compounds were identified including an amino acid antibiotic C8H20N3O4P (MW 253.237), phospholipase A2 inhibitor C21H36O5 (MW 368.512), and an antibacterial agent C14H11N3O2 (MW 253.260). The acute toxicity test indicates that the mortality rate among all rats was low and that the biochemical parameters, hematological profile, and histopathology examination of liver and kidneys showed no significant differences between experimental groups (P > 0.05). Overall, our findings suggest that the extract and its purified compounds derived from novel Paenibacillus sp. are nontoxic exhibiting strong antibiofilm activity against Gram-positive and Gram-negative pathogens that can be useful towards new therapeutic management of biofilm-associated infections. PMID:24790603

  7. Adsorption of selected pharmaceuticals and an endocrine disrupting compound by granular activated carbon. 2. Model prediction

    SciTech Connect

    Yu, Z.; Peldszus, S.; Huck, P.M.

    2009-03-01

    The adsorption of two representative pharmaceutically active compounds (PhACs) naproxen and carbamazepine and one endocrine disrupting compound (EDC) nonylphenol was studied in pilot-scale granular activated carbon (GAC) adsorbers using post-sedimentation (PS) water from a full-scale drinking water treatment plant. The GAC adsorbents were coal-based Calgon Filtrasorb 400 and coconut shell-based PICA CTIF TE. Acidic naproxen broke through fastest while nonylphenol was removed best, which was consistent with the degree to which fouling affected compound removals. Model predictions and experimental data were generally in good agreement for all three compounds, which demonstrated the effectiveness and robustness of the pore and surface diffusion model (PSDM) used in combination with the time-variable parameter approach for predicting removals at environmentally relevant concentrations (i.e., ng/L range). Sensitivity analyses suggested that accurate determination of film diffusion coefficients was critical for predicting breakthrough for naproxen and carbamazepine, in particular when high removals are targeted. Model simulations demonstrated that GAC carbon usage rates (CURs) for naproxen were substantially influenced by the empty bed contact time (EBCT) at the investigated conditions. Model-based comparisons between GAC CURs and minimum CURs for powdered activated carbon (PAC) applications suggested that PAC would be most appropriate for achieving 90% removal of naproxen, whereas GAC would be more suitable for nonylphenol. 25 refs., 4 figs., 1 tab.

  8. 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.

  9. Biophysical characterization of KV3.1 potassium channel activating compounds.

    PubMed

    Taskin, Bahar; von Schoubye, Nadia Lybøl; Sheykhzade, Majid; Bastlund, Jesper Frank; Grunnet, Morten; Jespersen, Thomas

    2015-07-05

    The effect of two positive modulators, RE1 and EX15, on the voltage-gated K(+) channel Kv3.1 was investigated using the whole-cell patch-clamp technique on HEK293 cells expressing Kv3.1a. RE1 and EX15 increased the Kv3.1 currents in a concentration-dependent manner with an EC50 value of 4.5 and 1.3µM, respectively. However, high compound concentrations caused an inhibition of the Kv3.1 current. The compound-induced activation of Kv3.1 channels showed a profound hyperpolarized shift in activation kinetics. 30µM RE1 shifted V1/2 from 5.63±0.31mV to -9.71±1.00mV and 10µM EX15 induced a shift from 10.77±0.32mV to -15.11±1.57mV. The activation time constant (Tauact) was reduced for both RE1 and EX15, with RE1 being the fastest activator. The deactivation time constant (Taudeact) was also markedly reduced for both RE1 and EX15, with EX15 inducing the most prominent effect. Furthermore, subjected to depolarizing pulses at 30Hz, both compounds were showing a use-dependent effect resulting in a reduction of the compound-mediated effect. However, during these conditions, RE1- and EX15-modified current amplitudes still exceeded the control condition amplitudes by up to 200%. In summary, the present study introduces the first detailed biophysical characterization of two new Kv3.1 channel modifying compounds with different modulating properties.

  10. Evaluation of antioxidant activities of the edible and medicinal Acacia albida organs related to phenolic compounds.

    PubMed

    Karoune, Samira; Falleh, Hanen; Kechebar, Mohamed Seif Allah; Halis, Youcef; Mkadmini, Khaoula; Belhamra, Mohamed; Rahmoune, Chaabane; Ksouri, Riadh

    2015-01-01

    This study compared phenolic contents and antioxidant activity in different organs of Acacia albida (leaves and bark) and focuses on identification of phenolic compounds of leaves by HPLC-DAD. The analysed organs exhibited differences in total polyphenol contents (100 and 59.5 mg GAE g(-1) DW). Phenolic contents of leaves were two times higher than those in bark. Ethanolic extracts exhibited good antioxidant activities with IC50 = 26 μg mL(-1) for DPPH and EC50 = 50 μg mL(-1) for FRAP. Identification by HPLC-DAD revealed the presence of nine phenolic compounds known for their high antioxidant activity. The results suggested that this species can be used as source of natural antioxidants.

  11. Bioassay-Guided Isolation of Compounds from Datura stramonium with TRAIL-Resistance Overcoming Activity.

    PubMed

    Karmakar, Utpal K; Toume, Kazufumi; Ishikawa, Naoki; Arai, Midori A; Sadhu, Samir K; Ahmed, Firoj; Ishibashi, Masami

    2016-02-01

    TRAIL is a potent inducer of apoptosis in most cancer cells, but not in normal cells, and therefore has deserved intense interest as a promising agent for cancer therapy. In the search for bioactive natural products for overcoming TRAIL-resistance, we previously reported a number of active compounds. In our screening program on natural resources targeting overcoming TRAIL-resistance, activity-guided fractionation of the MeOH extract of Datura stramonium leaves led to the isolation of three alkaloids--scopolamine (1), trigonelline (2), and tyramine (3). Compounds 1, 2, and 3 exhibited TRAIL-resistance overcoming activity at 50, 150, and 100 µM, respectively in TRAIL-resistant AGS cells.

  12. Identification of major phenolic compounds of Chinese water chestnut and their antioxidant activity.

    PubMed

    You, Yanli; Duan, Xuewu; Wei, Xiaoyi; Su, Xinguo; Zhao, Mouming; Sun, Jian; Ruenroengklin, Neungnapa; Jiang, Yueming

    2007-04-25

    Chinese water chestnut (CWC) is one of the most popular foods among Asian people due to its special taste and medical function. Experiments were conducted to test the antioxidant activity and then determine the major phenolic compound components present in CWC. CWC phenolic extract strongly inhibited linoleic acid oxidation and exhibited a dose-dependent free-radical scavenging activity against alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radicals, superoxide anions and hydroxyl radicals, which was superior to ascorbic acid and butylated hydroxytoluene (BHT), two commercial used antioxidants. Furthermore, the CWC extract was found to have a relatively higher reducing power, compared with BHT. The major phenolic compounds present in CWC tissues were extracted, purified and identified by high-performance liquid chromatograph (HPLC) as (-)-gallocatechin gallate, (-)-epicatechin gallate and (+)-catechin gallate. This study suggests that CWC tissues exhibit great potential for antioxidant activity and may be useful for their nutritional and medicinal functions.

  13. Antioxidant activities and phenolic compounds of date plum persimmon ( Diospyros lotus L.) fruits.

    PubMed

    Gao, Hui; Cheng, Ni; Zhou, Juan; Wang, Bini; Deng, Jianjun; Cao, Wei

    2014-05-01

    In the present study, phenolic compounds are extracted from the date plum persimmon fruits using water, methanol and acetone as solvents. Antioxidant activities of the phenolic extracts are measured using four different tests, namely, DPPH, hydroxyl radical scavenging activities, chelating and reducing power assays. All the extracts show dose dependent DPPH radical scavenging activity, reducing and chelating powers and moreover, they are well correlated with the total phenolic and total flavonoid substances, suggesting direct contribution of phenolic compounds to these activities. In further, the extracts are identified and quantified by HPLC-ECD. Results show that gallic acid is the most abundant phenolic compound, with amounts ranging between 45.49and 287.47 μg/g dry sample. Myricetin is the dominant flavonoid in all extracts. Its level varied from 2.75 μg/g dry sample in acetone extract to 5.28 μg/g dry sample in water extract. On the basis of the results obtained, the date plum persimmon fruits phenolic extract is a potential source of natural antioxidants owing to its significant antioxidant activities.

  14. Evaluation of leishmanicidal and trypanocidal activities of phenolic compounds from Calea uniflora Less.

    PubMed

    Lima, Tamires C; Souza, Rafaela J; Santos, Alan D C; Moraes, Milene H; Biondo, Nicole E; Barison, Andersson; Steindel, Mário; Biavatti, Maique W

    2016-01-01

    The phytochemical study of Calea uniflora led to the isolation of nine phenolic compounds identified as noreugenin (1), ethyl caffeate (2), a mixture of butein (3) + orobol (4), α-hydroxy-butein (5), caffeic acid (6), butein 4'-O-glucopyranosyl (7), quercetin 3-O-glucopyranosyl (8) and 3,5-di-O-caffeoylquinic acid (9). The chemical identity of the isolates was established on the basis of NMR and physical data. The chemical shifts of 5 and 7 have been reassigned and all the isolates were tested against Leishmania amazonensis and Trypanosoma cruzi amastigotes. None of the metabolites showed promising leishmanicidal activity. However, 2 and the mixture of 3 and 4 demonstrated interesting trypanocidal effect with IC50 values of 18.27 and 26.53 μM, respectively. Besides, these compounds did not present cytotoxic effect towards THP-1 cells, and compound 2 was 3.5-fold more selective than the mixture of 3+4.

  15. Active atmosphere-ecosystem exchange of the vast majority of detected volatile organic compounds.

    PubMed

    Park, J-H; Goldstein, A H; Timkovsky, J; Fares, S; Weber, R; Karlik, J; Holzinger, R

    2013-08-09

    Numerous volatile organic compounds (VOCs) exist in Earth's atmosphere, most of which originate from biogenic emissions. Despite VOCs' critical role in tropospheric chemistry, studies for evaluating their atmosphere-ecosystem exchange (emission and deposition) have been limited to a few dominant compounds owing to a lack of appropriate measurement techniques. Using a high-mass resolution proton transfer reaction-time of flight-mass spectrometer and an absolute value eddy-covariance method, we directly measured 186 organic ions with net deposition, and 494 that have bidirectional flux. This observation of active atmosphere-ecosystem exchange of the vast majority of detected VOCs poses a challenge to current emission, air quality, and global climate models, which do not account for this extremely large range of compounds. This observation also provides new insight for understanding the atmospheric VOC budget.

  16. Two new compounds from the roots of Ilex pubescens and their cytotoxic activity.

    PubMed

    Xiong, Huan; Zhao, Fang; Bi, Jiayi; Zhang, Yang; Zhao, Guiyun; Chen, Xue; Li, Yuncong; Yan, Rui; Zhao, Qiang; Qiao, Hua; Zhang, Guogang

    2016-07-01

    A new phenylethanoid, 1-O-β-D-(4-hydroxyphenyl)-ethyl-6-O-vanilloyl-glucopyranoside (1), and a new furofuran lignan, (7R,7'R,7''S,8S,8'S,8''R)-4', 4''-dihydroxy-3,3',3'',5-tetramethoxy-7,9':7'9-diepoxy-4,8''-oxy-8,8'-sesquineolignan-7'',9''-diol (2), along with five known compounds (3-7) were isolated from the roots of Ilex pubescens. Their chemical structures were elucidated on the basis of extensive spectroscopic analysis, including UV, IR, MS, and NMR experiments. In addition, compounds 2-7 were evaluated in vitro for their cytotoxic effects on human HeLa cells; among them, compounds 2, 3, 6, and 7 showed cytotoxic activity against HeLa cells in the test.

  17. Effect of cultivar and variety on phenolic compounds and antioxidant activity of cherry wine.

    PubMed

    Xiao, Zuobing; Fang, Lingling; Niu, Yunwei; Yu, Haiyan

    2015-11-01

    To compare the influence of cultivar and variety on the phenolic compounds and antioxidant activity (AA) of cherry wines, total phenolic (TP), total flavonoid (TF), total anthocyanin (TA), total tannin (TT), five individual phenolic acids, and AA were determined. An ultra-performance liquid chromatography tandem mass spectrometry (HPLC-DAD/ESI-MS) method was developed for the determination of gallic acid (GAE), p-hydroxybenzoic acid (PHB), chlorogenic acid (CHL), vanillic acid (VAN), and caffeic acid (CAF). A principal component analysis (PCA) and a cluster analysis (CA) were used to analyze differences related to cultivar and variety. The TP, TF, TA, TT, and AA of samples sourced from the Shandong province of China were higher than those from the Jiangsu province. The PCA and CA results showed that phenolic compounds in cherry wines were closely related to cultivar and variety and that cultivar had more influence on the phenolic compounds of cherry wines than variety.

  18. Characterization of the Apoptotic Response Induced by the Cyanine Dye D112: A Potentially Selective Anti-Cancer Compound

    PubMed Central

    Yang, Ning; Gilman, Paul; Mirzayans, Razmik; Sun, Xuejun; Touret, Nicolas; Weinfeld, Michael; Goping, Ing Swie

    2015-01-01

    Chemotherapeutic drugs that are used in anti-cancer treatments often cause the death of both cancerous and noncancerous cells. This non-selective toxicity is the root cause of untoward side effects that limits the effectiveness of therapy. In order to improve chemotherapeutic options for cancer patients, there is a need to identify novel compounds with higher discrimination for cancer cells. In the past, methine dyes that increase the sensitivity of photographic emulsions have been investigated for anti-cancer properties. In the 1970's, Kodak Laboratories initiated a screen of approximately 7000 dye structural variants for selective toxicity. Among these, D112 was identified as a promising compound with elevated toxicity against a colon cancer cell line in comparison to a non-transformed cell line. Despite these results changing industry priorities led to a halt in further studies on D112. We decided to revive investigations on D112 and have further characterized D112-induced cellular toxicity. We identified that in response to D112 treatment, the T-cell leukemia cell line Jurkat showed caspase activation, mitochondrial depolarization, and phosphatidylserine externalization, all of which are hallmarks of apoptosis. Chemical inhibition of caspase enzymatic activity and blockade of the mitochondrial pathway through Bcl-2 expression inhibited D112-induced apoptosis. At lower concentrations, D112 induced growth arrest. To gain insight into the molecular mechanism of D112 induced mitochondrial dysfunction, we analyzed the intracellular localization of D112, and found that D112 associated with mitochondria. Interestingly, in the cell lines that we tested, D112 showed increased toxicity toward transformed versus non-transformed cells. Results from this work identify D112 as a potentially interesting molecule warranting further investigation. PMID:25927702

  19. Synthesis, structural characterization, and anticancer activity of a monobenzyltin compound against MCF-7 breast cancer cells.

    PubMed

    Fani, Somayeh; Kamalidehghan, Behnam; Lo, Kong Mun; Hashim, Najihah Mohd; Chow, Kit May; Ahmadipour, Fatemeh

    2015-01-01

    A new monoorganotin Schiff base compound, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, (compound C1), was synthesized, and its structural features were investigated by spectroscopic techniques and single-crystal X-ray diffractometry. Compound C1 was exposed to several human cancer cell lines, including breast adenocarcinoma cell lines MCF-7 and MDA-MB-231, ovarian adenocarcinoma cell lines Skov3 and Caov3, and prostate cancer cell line PC3, in order to examine its cytotoxic effect for different forms of cancer. Human hepatic cell line WRL-68 was used as a normal cell line. We concentrated on the MCF-7 cell line to detect possible underlying mechanism involvement of compound C1. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed the strongest cytotoxicity of compound C1 against MCF-7 cells, with a half maximal inhibitory concentration (IC50) value of 2.5±0.50 μg/mL after 48 hours treatment. The IC50 value was >30 μg/mL in WRL-68 cells. Induced antiproliferative activity of compound C1 for MCF-7 cells was further confirmed by lactate dehydrogenase, reactive oxygen species, acridine orange/propidium iodide staining, and DNA fragmentation assays. A significant increase of lactate dehydrogenase release in treated cells was observed via fluorescence analysis. Luminescent analysis showed significant growth in intracellular reactive oxygen species production after treatment. Morphological changes of necrosis and early and late apoptosis stages were observed in treated cells after staining with acridine orange/propidium iodide. DNA fragmentation was observed as a characteristic of apoptosis in treated cells. Results of the present study obviously reveal potential cytotoxic effects of compound C1 against human breast cancer MCF-7 cells.

  20. Synthesis, structural characterization, and anticancer activity of a monobenzyltin compound against MCF-7 breast cancer cells

    PubMed Central

    Fani, Somayeh; Kamalidehghan, Behnam; Lo, Kong Mun; Hashim, Najihah Mohd; Chow, Kit May; Ahmadipour, Fatemeh

    2015-01-01

    A new monoorganotin Schiff base compound, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, (compound C1), was synthesized, and its structural features were investigated by spectroscopic techniques and single-crystal X-ray diffractometry. Compound C1 was exposed to several human cancer cell lines, including breast adenocarcinoma cell lines MCF-7 and MDA-MB-231, ovarian adenocarcinoma cell lines Skov3 and Caov3, and prostate cancer cell line PC3, in order to examine its cytotoxic effect for different forms of cancer. Human hepatic cell line WRL-68 was used as a normal cell line. We concentrated on the MCF-7 cell line to detect possible underlying mechanism involvement of compound C1. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed the strongest cytotoxicity of compound C1 against MCF-7 cells, with a half maximal inhibitory concentration (IC50) value of 2.5±0.50 μg/mL after 48 hours treatment. The IC50 value was >30 μg/mL in WRL-68 cells. Induced antiproliferative activity of compound C1 for MCF-7 cells was further confirmed by lactate dehydrogenase, reactive oxygen species, acridine orange/propidium iodide staining, and DNA fragmentation assays. A significant increase of lactate dehydrogenase release in treated cells was observed via fluorescence analysis. Luminescent analysis showed significant growth in intracellular reactive oxygen species production after treatment. Morphological changes of necrosis and early and late apoptosis stages were observed in treated cells after staining with acridine orange/propidium iodide. DNA fragmentation was observed as a characteristic of apoptosis in treated cells. Results of the present study obviously reveal potential cytotoxic effects of compound C1 against human breast cancer MCF-7 cells. PMID:26648695

  1. Rhenium(I) tricarbonyl compounds of bioactive thiosemicarbazones: Synthesis, characterization and activity against Trypanosoma cruzi.

    PubMed

    Rodríguez Arce, Esteban; Machado, Ignacio; Rodríguez, Belén; Lapier, Michel; Zúñiga, María Carolina; Maya, Juan Diego; Olea Azar, Claudio; Otero, Lucía; Gambino, Dinorah

    2017-05-01

    American Trypanosomiasis is a chronic infection discovered and described in 1909 by the Brazilian scientist Carlos Chagas. It is caused by the protozoan parasite Trypanosoma cruzi. Although it affects about 10million people in Latin America, the current chemotherapy is still inadequate. The discovery of new drugs is urgently needed. Our group is focused on the development of prospective metal-based drugs mainly based on bioactive ligands and pharmacologically interesting metal ions. In this work three new rhenium(I) tricarbonyl compounds fac-[Re(I)(CO)3Br(HL)] where HL=5-nitrofuryl containing thiosemicarbazones were synthesized and fully characterized in solution and in the solid state. The in vitro evaluation of the compounds on T. cruzi trypomastigotes (Dm28c strain) showed that the Re(I) compounds are 8 to 15 times more active than the reference drug Nifurtimox and show a 4 to 17 fold increase in activity in respect to the free (HL) ligands. Obtained compounds also show good selectivity indexes (IC50 endothelial cells Ea.hy926/IC50 T. cruzi (Dm28c tripomastigotes)). (1)H NMR and MS studies, performed with time, showed that the fac-[Re(CO)3Br(HL)] species convert into the dimers [Re2(CO)6(L)2] in solution. Crystal structure of [Re(I)2(CO)6(L2)2], the product of complexes' dimerization, was solved. Related to the mechanism of action, the studied compounds do not generate radical oxygen species in the parasite (as 5-nitrofuryl derived thiosemicarbazones do) probably due to the unfavorable nitro reduction potential of the generated dimeric species. On the contrary, the compounds produce a decrease of the oxygen consumption rate of the parasites, maybe inhibiting their mitochondrial respiration.

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

    PubMed

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

    2017-01-23

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

  3. Potential antifertility agents. 6. Synthesis and biological activities of optical isomers of 4 beta-(p-methozyphenyl)-2 beta-methylcyclohexane-alpha-carboxylic acid and related compounds.

    PubMed

    Crenshaw, R R; Jenks, T A; Luke, G M; Bialy, G

    1974-12-01

    The optical isomers of the title compound were synthesized and the biological potencies of the two enantiomers were compared. There was essentially no difference in their hypocholesterolemic activities, as had been predicted, and little or no difference between their uterotropic potencies. The approximately equal uterotropic activities seen with the enantiomers is explained in terms of stereochemical requirements at the receptor level for an estrogenic response. A working model of an estrogenic receptor is proposed. An accompanying paper provides support for the proposed model.

  4. Photo-activated luminescence sensor and method of detecting trichloroethylene and related volatile organochloride compounds

    DOEpatents

    Dinh, T.V.

    1996-06-11

    A sensor for detecting trichloroethylene and related volatile organochloride compounds uses a photo-activator that produces a photo-product complex with the contaminant. Characteristics of the light emitted from the complex will indicate the presence of the contaminant. A probe containing the photo-activator has an excitation light interface and a contaminant interface. One particular embodiment uses a porous membrane as the contaminant interface, so that the contaminant can migrate there through to the photo-activator and thereby form the complex. 23 figs.

  5. Photo-activated luminescence sensor and method of detecting trichloroethylene and related volatile organochloride compounds

    DOEpatents

    Dinh, Tuan V.

    1996-01-01

    A sensor for detecting trichloroethylene and related volatile organochloride compounds uses a photo-activator that produces a photo-product complex with the contaminant. Characteristics of the light emitted from the complex will indicate the presence of the contaminant. A probe containing the photo-activator has an excitation light interface and a contaminant interface. One particular embodiment uses a porous membrane as the contaminant interface, so that the contaminant can migrate therethrough to the photo-activator and thereby form the complex.

  6. Synthesis and antibacterial activities of some novel 17, 18-unsaturated carbonyl compounds derivated from josamycin.

    PubMed

    Zhao, Zhe-Hui; Jin, Long-Long; Xu, Yan-Peng; Liu, Chao; Wang, A-Peng; Lei, Ping-Sheng

    2017-04-01

    Some novel josamycin derivatives bearing an arylalkyl-type side chain were designed and synthesized. By HWE or Wittig reaction, 16-aldehyde group of josamycin analogs were converted into unsaturated carbonyl compounds. They were evaluated for their in vitro antibacterial activities against a panel of respiratory pathogens. 8b and 8e exhibited comparable activities against a panel of respiratory pathogens, especially to resistant ones in the series of desmycarosyl josamycin analogs. Among of all the target molecules, 21 showed the best antibacterial activities.

  7. Geothrix fermentans Secretes Two Different Redox-Active Compounds To Utilize Electron Acceptors across a Wide Range of Redox Potentials

    PubMed Central

    Mehta-Kolte, Misha G.

    2012-01-01

    The current understanding of dissimilatory metal reduction is based primarily on isolates from the proteobacterial genera Geobacter and Shewanella. However, environments undergoing active Fe(III) reduction often harbor less-well-studied phyla that are equally abundant. In this work, electrochemical techniques were used to analyze respiratory electron transfer by the only known Fe(III)-reducing representative of the Acidobacteria, Geothrix fermentans. In contrast to previously characterized metal-reducing bacteria, which typically reach maximal rates of respiration at electron acceptor potentials of 0 V versus standard hydrogen electrode (SHE), G. fermentans required potentials as high as 0.55 V to respire at its maximum rate. In addition, G. fermentans secreted two different soluble redox-active electron shuttles with separate redox potentials (−0.2 V and 0.3 V). The compound with the lower midpoint potential, responsible for 20 to 30% of electron transfer activity, was riboflavin. The behavior of the higher-potential compound was consistent with hydrophilic UV-fluorescent molecules previously found in G. fermentans supernatants. Both electron shuttles were also produced when cultures were grown with Fe(III), but not when fumarate was the electron acceptor. This study reveals that Geothrix is able to take advantage of higher-redox-potential environments, demonstrates that secretion of flavin-based shuttles is not confined to Shewanella, and points to the existence of high-potential-redox-active compounds involved in extracellular electron transfer. Based on differences between the respiratory strategies of Geothrix and Geobacter, these two groups of bacteria could exist in distinctive environmental niches defined by redox potential. PMID:22843516

  8. Diuretic effect of compounds from Hibiscus sabdariffa by modulation of the aldosterone activity.

    PubMed

    Jiménez-Ferrer, Enrique; Alarcón-Alonso, Javier; Aguilar-Rojas, Arturo; Zamilpa, Alejandro; Jiménez-Ferrer C, Itzia; Tortoriello, Jaime; Herrera-Ruiz, Maribel

    2012-12-01

    acetonitrile extract significantly decreased the expression of this protein.The conclusion of this work is that the diuretic, natriuretic, and potassium sparing effects of Hibiscus sabdariffa are due in part to the modulation of aldosterone activity by the presence in the extract of this plant of compounds potentially responsible for this modulation, as anthocyanins, flavonoids, and chlorogenic acid.

  9. Development and validation of quantitative structure-activity relationship models for compounds acting on serotoninergic receptors.

    PubMed

    Zydek, Grażyna; Brzezińska, Elżbieta

    2012-01-01

    A quantitative structure-activity relationship (QSAR) study has been made on 20 compounds with serotonin (5-HT) receptor affinity. Thin-layer chromatographic (TLC) data and physicochemical parameters were applied in this study. RP2 TLC 60F(254) plates (silanized) impregnated with solutions of propionic acid, ethylbenzene, 4-ethylphenol, and propionamide (used as analogues of the key receptor amino acids) and their mixtures (denoted as S1-S7 biochromatographic models) were used in two developing phases as a model of drug-5-HT receptor interaction. The semiempirical method AM1 (HyperChem v. 7.0 program) and ACD/Labs v. 8.0 program were employed to calculate a set of physicochemical parameters for the investigated compounds. Correlation and multiple linear regression analysis were used to search for the best QSAR equations. The correlations obtained for the compounds studied represent their interactions with the proposed biochromatographic models. The good multivariate relationships (R(2) = 0.78-0.84) obtained by means of regression analysis can be used for predicting the quantitative effect of biological activity of different compounds with 5-HT receptor affinity. "Leave-one-out" (LOO) and "leave-N-out" (LNO) cross-validation methods were used to judge the predictive power of final regression equations.

  10. Rapid Diminution in the Level and Activity of DNA-Dependent Protein Kinase in Cancer Cells by a Reactive Nitro-Benzoxadiazole Compound

    PubMed Central

    Silva, Viviane A. O.; Lafont, Florian; Benhelli-Mokrani, Houda; Breton, Magali Le; Hulin, Philippe; Chabot, Thomas; Paris, François; Sakanyan, Vehary; Fleury, Fabrice

    2016-01-01

    The expression and activity of DNA-dependent protein kinase (DNA-PK) is related to DNA repair status in the response of cells to exogenous and endogenous factors. Recent studies indicate that Epidermal Growth Factor Receptor (EGFR) is involved in modulating DNA-PK. It has been shown that a compound 4-nitro-7-[(1-oxidopyridin-2-yl)sulfanyl]-2,1,3-benzoxadiazole (NSC), bearing a nitro-benzoxadiazole (NBD) scaffold, enhances tyrosine phosphorylation of EGFR and triggers downstream signaling pathways. Here, we studied the behavior of DNA-PK and other DNA repair proteins in prostate cancer cells exposed to compound NSC. We showed that both the expression and activity of DNA-PKcs (catalytic subunit of DNA-PK) rapidly decreased upon exposure of cells to the compound. The decline in DNA-PKcs was associated with enhanced protein ubiquitination, indicating the activation of cellular proteasome. However, pretreatment of cells with thioglycerol abolished the action of compound NSC and restored the level of DNA-PKcs. Moreover, the decreased level of DNA-PKcs was associated with the production of intracellular hydrogen peroxide by stable dimeric forms of Cu/Zn SOD1 induced by NSC. Our findings indicate that reactive oxygen species and electrophilic intermediates, generated and accumulated during the redox transformation of NBD compounds, are primarily responsible for the rapid modulation of DNA-PKcs functions in cancer cells. PMID:27187356

  11. Rapid Diminution in the Level and Activity of DNA-Dependent Protein Kinase in Cancer Cells by a Reactive Nitro-Benzoxadiazole Compound.

    PubMed

    Silva, Viviane A O; Lafont, Florian; Benhelli-Mokrani, Houda; Breton, Magali Le; Hulin, Philippe; Chabot, Thomas; Paris, François; Sakanyan, Vehary; Fleury, Fabrice

    2016-05-11

    The expression and activity of DNA-dependent protein kinase (DNA-PK) is related to DNA repair status in the response of cells to exogenous and endogenous factors. Recent studies indicate that Epidermal Growth Factor Receptor (EGFR) is involved in modulating DNA-PK. It has been shown that a compound 4-nitro-7-[(1-oxidopyridin-2-yl)sulfanyl]-2,1,3-benzoxadiazole (NSC), bearing a nitro-benzoxadiazole (NBD) scaffold, enhances tyrosine phosphorylation of EGFR and triggers downstream signaling pathways. Here, we studied the behavior of DNA-PK and other DNA repair proteins in prostate cancer cells exposed to compound NSC. We showed that both the expression and activity of DNA-PKcs (catalytic subunit of DNA-PK) rapidly decreased upon exposure of cells to the compound. The decline in DNA-PKcs was associated with enhanced protein ubiquitination, indicating the activation of cellular proteasome. However, pretreatment of cells with thioglycerol abolished the action of compound NSC and restored the level of DNA-PKcs. Moreover, the decreased level of DNA-PKcs was associated with the production of intracellular hydrogen peroxide by stable dimeric forms of Cu/Zn SOD1 induced by NSC. Our findings indicate that reactive oxygen species and electrophilic intermediates, generated and accumulated during the redox transformation of NBD compounds, are primarily responsible for the rapid modulation of DNA-PKcs functions in cancer cells.

  12. Synthesis and antioxidant activities of some new triheterocyclic compounds containing benzimidazole, thiophene, and 1,2,4-triazole rings.

    PubMed

    Menteşe, Emre; Yılmaz, Fatih; Baltaş, Nimet; Bekircan, Olcay; Kahveci, Bahittin

    2015-06-01

    Various triheterocyclic compounds containing benzimidazole, thiophene, and 1,2,4-triazole rings (3-6) were synthesized and screened for their antioxidant activities. The structures of the synthesized compounds (2-6) were judged by (1)H NMR, (13)C NMR, elemental analysis, and LC-MS spectral data. Antioxidant activities of the synthesized compounds (2-6) were determined with CUPric Reducing Antioxidant Capacity (CUPRAC), ABTS (2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)/persulfate, and DPPH (1,1-diphenyl-2-picrylhydrazyl) assays. Most of the compounds showed a significant antioxidant activity and especially, compound 5c showed very good SC50 value for DPPH method and compound 5h exhibited very high scavenging activity to ABTS method.

  13. 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.

    2017-01-01

    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.

  14. Bioactive Compounds and Antioxidant Activity in Different Grafted Varieties of Bell Pepper

    PubMed Central

    Chávez-Mendoza, Celia; Sanchez, Esteban; Muñoz-Marquez, Ezequiel; Sida-Arreola, Juan Pedro; Flores-Cordova, Maria Antonia

    2015-01-01

    Grafting favors the presence of bioactive compounds in the bell pepper, but many species and varieties have not yet been analyzed in this sense, including commonly grafted varieties. The aim of the present study is to characterize the content in β-carotenes, vitamin C, lycopene, total phenols, and the antioxidant activity of bell pepper (Capsicum annum L) using the cultivar/rootstock combinations: Jeanette/Terrano (yellow), Sweet/Robusto (green), Fascinato/Robusto (red), Orangela/Terrano (orange), and Fascinato/Terrano (red). The plants were grown in a net-shading system and harvested on three sampling dates of the same crop cycle. The results show statistical differences (p ≤ 0.05) between cultivar/rootstock combinations and sampling dates for the content in bioactive compounds and antioxidant activity. Fascinato/Robusto presented the highest concentration of lycopene and total phenols as well as the greatest antioxidant activity of all cultivar/rootstock combinations evaluated. In addition, it was found that the best sampling time for the peppers to have the highest concentrations of bioactive compounds and antioxidant activity was September. PMID:26783714

  15. Bioactive Compounds and Antioxidant Activity in Different Grafted Varieties of Bell Pepper.

    PubMed

    Chávez-Mendoza, Celia; Sanchez, Esteban; Muñoz-Marquez, Ezequiel; Sida-Arreola, Juan Pedro; Flores-Cordova, Maria Antonia

    2015-06-23

    Grafting favors the presence of bioactive compounds in the bell pepper, but many species and varieties have not yet been analyzed in this sense, including commonly grafted varieties. The aim of the present study is to characterize the content in β-carotenes, vitamin C, lycopene, total phenols, and the antioxidant activity of bell pepper (Capsicum annum L.) using the cultivar/rootstock combinations: Jeanette/Terrano (yellow), Sweet/Robusto (green), Fascinato/Robusto (red), Orangela/Terrano (orange), and Fascinato/Terrano (red). The plants were grown in a net-shading system and harvested on three sampling dates of the same crop cycle. The results show statistical differences (p ≤ 0.05) between cultivar/rootstock combinations and sampling dates for the content in bioactive compounds and antioxidant activity. Fascinato/Robusto presented the highest concentration of lycopene and total phenols as well as the greatest antioxidant activity of all cultivar/rootstock combinations evaluated. In addition, it was found that the best sampling time for the peppers to have the highest concentrations of bioactive compounds and antioxidant activity was September.

  16. 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.

  17. 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.

  18. Identification of benzopyrone as a common structural feature in compounds with anti-inflammatory activity in a zebrafish phenotypic screen

    PubMed Central

    Robertson, Anne L.; Ogryzko, Nikolay V.; Henry, Katherine M.; Loynes, Catherine A.; Foulkes, Matthew J.; Meloni, Marco M.; Wang, Xingang; Ford, Christopher; Jackson, Malcolm; Ingham, Philip W.; Wilson, Heather L.; Farrow, Stuart N.; Solari, Roberto; Flower, Roderick J.; Jones, Simon; Whyte, Moira K. B.

    2016-01-01

    ABSTRACT Neutrophils are essential for host defence and are recruited to sites of inflammation in response to tissue injury or infection. For inflammation to resolve, these cells must be cleared efficiently and in a controlled manner, either by apoptosis or reverse migration. If the inflammatory response is not well-regulated, persistent neutrophils can cause damage to host tissues and contribute to the pathogenesis of chronic inflammatory diseases, which respond poorly to current treatments. It is therefore important to develop drug discovery strategies that can identify new therapeutics specifically targeting neutrophils, either by promoting their clearance or by preventing their recruitment. Our recent in vivo chemical genetic screen for accelerators of inflammation resolution identified a subset of compounds sharing a common chemical signature, the bicyclic benzopyrone rings. Here, we further investigate the mechanisms of action of the most active of this chemical series, isopimpinellin, in our zebrafish model of neutrophilic inflammation. We found that this compound targets both the recruitment and resolution phases of the inflammatory response. Neutrophil migration towards a site of injury is reduced by isopimpinellin and this occurs as a result of PI3K inhibition. We also show that isopimpinellin induces neutrophil apoptosis to drive inflammation resolution in vivo using a new zebrafish reporter line detecting in vivo neutrophil caspase-3 activity and allowing quantification of flux through the apoptotic pathway in real time. Finally, our studies reveal that clinically available ‘cromones’ are structurally related to isopimpinellin and have previously undescribed pro-resolution activity in vivo. These findings could have implications for the therapeutic use of benzopyrones in inflammatory disease. PMID:27079522

  19. Bovine chromaffin cells in culture show carboxylesterase activities sensitive to organophosphorus compounds.

    PubMed

    Sogorb, M A; Vilanova, E; Quintanar, J L; Viniegra, S

    1996-09-01

    Carboxylesterase activities are widely distributed in a great variety of tissues; however, the biological function of these enzymes remains unclear. Some organophosphorus compounds induce a neurodegenarative syndrome related to the covalent modification of a carboxylesterase known as neuropathy target esterase. We investigated the expression of neuropathy target esterase and related carboxylesterase in bovine chromaffin cells with the aim of developing a potential in vitro model for studying the cellular function of carboxylesterase enzymes and toxic effects of organophosphorus compounds. Total phenyl valerate esterase exhibited an activity of 1.27 +/- 0.19 mU/10(5) cells (SD, n = 15). From the phenyl valerate esterase paraoxon and mipafox inhibition curves the following activities have been determined: B-activity (resistant to 40 microM paraoxon), 1.05 +/- 0.08 mU/10(5) cells (n = 8); C-activity (resistant to 40 microM paraoxon plus 250 microM mipafox), 0.12 +/- 0.05 mU/10(5) cells (n = 8); and neuropathy target esterase, calculated by the difference between B- and C-activities, 0.93 +/- 0.08 mU/10(5) cells (n = 8). All of these activities increased linearly with the number of cells and time of incubation with the substrate. Most of the phenol product of the reaction was released and detected in the extracellular medium. None of the components of the reaction were shown to affect cell viability when assessed by trypan blue exclusion. The study shows that bovine chromaffin cells possess carboxylesterase activities and respond to inhibition by paraoxon and mipafox, thus facilitating the discrimination of neuropathy target esterase. In conclusion, bovine chromaffin cells are appropriate as an in vitro cell model for studying toxic effects of organophosphorus compounds.

  20. Biological activity of Pinus nigra terpenes--evaluation of FtsZ inhibition by selected compounds as contribution to their antimicrobial activity.

    PubMed

    Sarac, Zorica; Matejić, Jelena S; Stojanović-Radić, Zorica Z; Veselinović, Jovana B; Džamić, Ana M; Bojović, Srdjan; Marin, Petar D

    2014-11-01

    In the current work, in vitro antioxidant, antibacterial, and antifungal activites of the needle terpenes of three taxa of Pinus nigra from Serbia (ssp. nigra, ssp. pallasiana, and var. banatica) were analyzed. The black pine essential oils showed generally weak antioxidative properties tested by two methods (DPPH and ABTS scavenging assays), where the highest activity was identified in P. nigra var. banatica (IC50=25.08 mg/mL and VitC=0.67 mg (vitamin C)/g when tested with the DPPH and ABTS reagents, respectively). In the antimicrobial assays, one fungal (Aspergilus niger) and two bacterial strains (Staphylococcus aureus and Bacillus cereus) showed sensitivity against essential oils of all three P. nigra taxa. The tested oils have been shown to possess inhibitory action in the range from 20.00 to 0.62 mg/mL, where var. banatica exhibited the highest and ssp. nigra the lowest antimicrobial action. In order to determine potential compounds that are responsible for alternative mode of action, molecular docking simulations inside FtsZ (a prokaryotic homolog of tubulin) were performed. Tested compounds were the most abundant terpenoid (germacrene D-4-ol) and its structurally similar terpene (germacrene D), both present in all three essential oils. It was determined that the oxygenated form of the molecule creates stable bonds with investigated enzyme FtsZ, and that this compound, through this mechanism of action participates in the antimicrobial activity.

  1. Cortical responses elicited by luminance and compound stimuli modulated by pseudo-random sequences: comparison between normal trichromats and congenital red-green color blinds.

    PubMed

    Risuenho, Bárbara B O; Miquilini, Letícia; Lacerda, Eliza Maria C B; Silveira, Luiz Carlos L; Souza, Givago S

    2015-01-01

    Conventional pattern-reversal visual evoked cortical potential (VECP) shows positivity for luminance and chromatic equiluminant stimuli while conventional pattern-onset VECP shows positivity for luminance pattern-onset and negativity for chromatic pattern-onset. We evaluated how the presentation mode affects VECPs elicited by luminance and compound (luminance plus chromatic) pseudo-random stimulation. Eleven normal trichromats and 17 red-green color-blinds were studied. Pattern-reversal and pattern-onset luminance and compound (luminance plus red-green) gratings were temporally modulated by m-sequence. We used a cross-correlation routine to extract the first order kernel (K1) and the first and second slices of the second order kernel (K2.1 and K2.2, respectively) from the VECP response. We integrated the amplitude of VECP components as a function of time in order to estimate its magnitude for each stimulus condition. We also used a normalized cross-correlation method in order to test the similarity of the VECP components. The VECP components varied with the presentation mode and the presence of red-green contrast in the stimuli. In trichromats, for compound conditions, pattern-onset K1, K2.1, and K2.2, and pattern-reversal K2.1 and K2.2 had negative-dominated waveforms at 100 ms. Small negativity or small positivity were observed in dichromats. Trichromats had larger VECP magnitude than color-blinds for compound pattern-onset K1 (with large variability across subjects), compound pattern-onset and pattern-reversal K2.1, and compound pattern-reversal K2.2. Trichromats and color-blinds had similar VECP amplitude for compound pattern-reversal K1 and compound pattern-onset K2.2, as well as for all luminance conditions. The cross-correlation analysis showed high similarity between waveforms of compound pattern-onset K2.1 and pattern-reversal K2.2 as well as pattern-reversal K2.1 and K2.2. We suggest that compound pattern-reversal K2.1 is an appropriate response to study

  2. 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+).

  3. Medicago truncatula increases its iron-uptake mechanisms in response to volatile organic compounds produced by Sinorhizobium meliloti.

    PubMed

    Orozco-Mosqueda, Maria del Carmen; Macías-Rodríguez, Lourdes I; Santoyo, Gustavo; Farías-Rodríguez, Rodolfo; Valencia-Cantero, Eduardo

    2013-11-01

    Medicago truncatula represents a model plant species for understanding legume-bacteria interactions. M. truncatula roots form a specific root-nodule symbiosis with the nitrogen-fixing bacterium Sinorhizobium meliloti. Symbiotic nitrogen fixation generates high iron (Fe) demands for bacterial nitrogenase holoenzyme and plant leghemoglobin proteins. Leguminous plants acquire Fe via "Strategy I," which includes mechanisms such as rhizosphere acidification and enhanced ferric reductase activity. In the present work, we analyzed the effect of S. meliloti volatile organic compounds (VOCs) on the Fe-uptake mechanisms of M. truncatula seedlings under Fe-deficient and Fe-rich conditions. Axenic cultures showed that both plant and bacterium modified VOC synthesis in the presence of the respective symbiotic partner. Importantly, in both Fe-rich and -deficient experiments, bacterial VOCs increased the generation of plant biomass, rhizosphere acidification, ferric reductase activity, and chlorophyll content in plants. On the basis of our results, we propose that M. truncatula perceives its symbiont through VOC emissions, and in response, increases Fe-uptake mechanisms to facilitate symbiosis.

  4. Screening for lead compounds and herbal extracts with potential anti-influenza viral activity.

    PubMed

    Klaywong, Konrapob; Khutrakul, Gachagorn; Choowongkomon, Kiattawee; Lekcharoensuk, Chalermpol; Petcharat, Nantawan; Leckcharoensuk, Porntippa; Ramasoota, Pongrama

    2014-01-01

    Nonstructural protein 1 (NS1) of the highly pathogenic avian influenza virus (H5N1) contains a conserved RNA binding domain (RBD) that inhibits antiviral functions of host-innate immune response. Dimerization of NS1 forms a central groove and binds to double stranded (ds) RNA. This region might serve as a potential drug target. In this study, three dimensional structure model of NS1 RBD protein was constructed and virtual screening was performed to identify lead compounds that bound within and around the central groove. The virtual screening showed that 5 compounds bound within the central groove with binding energy ranging between -16.05 and -17.36 Kcal/mol. Two commercially available compounds, estradiol and veratridine, were selected for using in an in vitro screening assay. The results showed that neither of the compounds could inhibit the association between dsRNA and NS1 RBD protein. In addition, 34 herbal extracts were examined for their inhibitory effects. Five of them were able to inhibit association between NS1 RBD and dsRNA in electrophoresis mobility shift assay. Four herbs, Terminalia belirica, Salacia chinensis, Zingiber montanum and Peltophorum pterocarpum, could reduce > 50% of infectivity of H5N1 in a cell-based assay, and it is worth further studying their potential use as source of antiviral drugs.

  5. 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.

  6. Base-modified thymidines capable of terminating DNA synthesis are novel bioactive compounds with activity in cancer cells

    PubMed Central

    Borland, Kayla M.; AbdulSalam, Safnas F.; Solivio, Morwena J.; Burke, Matthew P.; Wolfkiel, Patrick R.; Lawson, Sean M.; Stockman, Courtney A.; Andersen, Joel M.; Smith, Skyler; Tolstolutskaya, Julia N.; Gurjar, Purujit N.; Bercz, Aron P.; Merino, Edward J.; Litosh, Vladislav A.

    2015-01-01

    Current FDA-approved chemotherapeutic antimetabolites elicit severe side effects that warrant their improvement; therefore, we designed compounds with mechanisms of action focusing on inhibiting DNA replication rather than targeting multiple pathways. We previously discovered that 5-(α-substituted-2-nitrobenzyloxy)methyluridine-5′-triphosphates were exquisite DNA synthesis terminators; therefore, we synthesized a library of 35 thymidine analogs and evaluated their activity using an MTT cell viability assay of MCF7 breast cancer cells chosen for their vulnerability to these nucleoside derivatives. Compound 3a, having an α-tert-butyl-2-nitro-4-(phenyl)alkynylbenzyloxy group, showed an IC50 of 9 ± 1 μM. The compound is more selective for cancer cells than for fibroblast cells compared with 5-fluorouracil. Treatment of MCF7 cells with 3a elicits the DNA damage response as indicated by phosphorylation of γ-H2A. A primer extension assay of the 5′-triphosphate of 3a revealed that 3aTP is more likely to inhibit DNA polymerase than to lead to termination events upon incorporation into the DNA replication fork. PMID:25778768

  7. Bioassay-guided isolation and identification of antitermitic active compound from the leaf of Chinese cedar (Cryptomeria fortunei Hooibrenk).

    PubMed

    Xie, Yongjian; Huang, Qiuying; Lei, Chaoliang

    2013-01-01

    The persistent use of synthetic termiticides is at present of environmental concern and has resulted in the need to search for plant-derived compounds as an alternative for termite control. Antitermitic activity of Chinese cedar (Cryptomeria fortunei Hooibrenk) against Reticulitermes chinensis was demonstrated in laboratory tests. Bioactivity tests against the termite R. chinensis demonstrate that the lethal concentration (LC50) value of leaf essential oil is 2.80 mg/mL. Furthermore, α-terpineol, which was responsible for the antitermitic property and isolated from Chinese cedar that exhibited very strong antitermitic activity, was found to be significantly effective against R. chinensis with median LC50 values of 0.86 mg/mL. The findings suggested that the essential oil from Chinese cedar leaf and α-terpineol might be considered as a potent source for the production of effective, environmentally friendly and safe termiticides.

  8. Physcomitrella patens Activates Defense Responses against the Pathogen Colletotrichum gloeosporioides

    PubMed Central

    Reboledo, Guillermo; del Campo, Raquel; Alvarez, Alfonso; Montesano, Marcos; Mara, Héctor; Ponce de León, Inés

    2015-01-01

    The moss Physcomitrella patens is a suitable model plant to analyze the activation of defense mechanisms after pathogen assault. In this study, we show that Colletotrichum gloeosporioides isolated from symptomatic citrus fruit infects P. patens and cause disease symptoms evidenced by browning and maceration of tissues. After C. gloeosporioides infection, P. patens reinforces the cell wall by the incorporation of phenolic compounds and induces the expression of a Dirigent-protein-like encoding gene that could lead to the formation of lignin-like polymers. C. gloeosporioides-inoculated protonemal cells show cytoplasmic collapse, browning of chloroplasts and modifications of the cell wall. Chloroplasts relocate in cells of infected tissues toward the initially infected C. gloeosporioides cells. P. patens also induces the expression of the defense genes PAL and CHS after fungal colonization. P. patens reporter lines harboring the auxin-inducible promoter from soybean (GmGH3) fused to β-glucuronidase revealed an auxin response in protonemal tissues, cauloids and leaves of C. gloeosporioides-infected moss tissues, indicating the activation of auxin signaling. Thus, P. patens is an interesting plant to gain insight into defense mechanisms that have evolved in primitive land plants to cope with microbial pathogens. PMID:26389888

  9. Natural hydrazine-containing compounds: Biosynthesis, isolation, biological activities and synthesis.

    PubMed

    Le Goff, Géraldine; Ouazzani, Jamal

    2014-12-01

    Hydrazine, hydrazone and hydrazide derivatives are nitrogen-nitrogen bond containing compounds. Such molecules are relatively scarce in nature and have been isolated from plants, marine organisms and microorganisms. These compounds exhibit remarkable structural diversity and relevant biological activities. The enzymes involved in the formation of the N-N bond are still unknown, but many lines of evidence support the involvement of N-nitrosation and N-hydroxylation activating steps. Beside the challenging N-N bond, N-acylases catalyzing the C-N bond formation contribute to the chemical diversity of N-N-containing natural products (N2NP). This review examines the state of knowledge regarding the biosynthesis of N2NP, for which only two biosynthetic gene clusters have been investigated. Biological properties and chemical synthesis of hydrazines, hydrazones and hydrazides are also reported.

  10. Structure-activity relationships of tulipalines, tuliposides, and related compounds as inhibitors of MurA.

    PubMed

    Mendgen, Thomas; Scholz, Therese; Klein, Christian D

    2010-10-01

    The enzyme MurA performs an essential step in peptidoglycan biosynthesis and is therefore a target for the discovery of novel antibacterial compounds. We report here the inhibition of MurA by natural products from tulips (tulipalines and tuliposides), and the structure-activity relationships of various derivatives. The inhibition of MurA can be related to antibacterial activity, and MurA is probably one of the relevant molecular targets of the tulipaline derivatives. MurA inhibition by this class of compounds depends on the presence of the substrate UNAG, which indicates non-covalent suicide inhibition as observed previously for cnicin. With respect to selectivity, however, the reactivity against arbitrary sulfhydryl groups, such as in glutathione, could not yet be sufficiently separated from MurA inhibition in the present dataset.

  11. Development of UV-B screening compounds in response to variation in ambient levels of UV-B radiation

    NASA Astrophysics Data System (ADS)

    Sullivan, Joe H.; Xu, Chenping; Gao, Wei; Slusser, James R.

    2005-08-01

    The induction of UV-B screening compounds in response to exposure to UV-B radiation is a commonly reported response and is generally considered to be an adaptive response of plants for protection from UVinduced damage. However, a number of questions remain to be answered including the importance of qualitative and localization differences among species in providing protection, indirect consequences of changes in leaf secondary chemistry on ecological processes and the dose response of metabolite accumulation. In this study we utilized UV monitoring data provided on site by the USDA UV-B Monitoring and Research Program to monitor the changes in UV-screening compounds in soybeans under a range of UV-B levels due to natural variation in ambient UV-B radiation. Soybean cultivars Essex, Clark and Clark-magenta, an isoline of Clark that produces minimal levels of flavonols, were grown beneath shelters covered either with polyester to block most UV-B radiation or teflon which is nearly transparent in the UV range and harvested at regular intervals for pigment and protein analysis. Daily levels of weighted UV-B varied from <1 to >7 kJ m-2. Increases in UV-screening compounds showed a positive dose response to UV-B radiation in all cultivars with Essex showing the steepest dose response. UV-A also induced screening compounds in all species The hydroxycinnimates of the magenta isoline showed a steep dose response to UV-A and a rather constant (non dose specific) but small additional increment in response to UV-B. The Clark isoline, which produced primarily the flavonol quercetin, showed a dose response to UV-B intermediate between that of Clark-magenta and Essex. All three cultivars show similar tolerance to UV-B in field conditions indicating that UV-induced pigment production is adequate to protect them from excessive UV-B damage.

  12. Optimisation of ultrasound assisted extraction of phenolic compounds from Sparganii rhizoma with response surface methodology.

    PubMed

    Wang, Xinsheng; Wu, Yanfang; Chen, Guangyun; Yue, Wei; Liang, Qiaoli; Wu, Qinan

    2013-05-01

    The present study reports on the extraction of phenolic compounds from sparganii rhizome. Box-Behnken Design (BBD), a widely used form of response surface methodology (RSM), was used to investigate the effect of process variables on the ultrasound-assisted extraction (UAE). Three independent variables including ethanol concentration (%), extraction time (min) and solvent-to-material ratio (mL/g) were studied. The results showed that the optimal UAE condition was obtained with an ethanol concentration of 75.3%, an extraction time of 40min and a solvent-to-material ratio of 19.21mL/g for total phenols, and an ethanol concentration of 80%, an extraction time of 33.54min and solvent-to-material ratio of 22.72mL/g for combination of ρ-hydroxybenzaldehyde, ρ-coumaric acid, vanillic acid, ferulic acid, rutin and kaempferol. The experimental values under optimal conditions were in good consistent with the predicted values, which suggested UAE is more efficient process as compared to solvent extraction.

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  14. Synthesis and Anti-influenza A Virus Activity of 2,2-Dialkylamantadines and Related Compounds

    PubMed Central

    2012-01-01

    The synthesis of several 2,2-dialkyladamantyl-1-amines through the combination of a Ritter reaction with a Wagner–Meerwein rearrangement from noradamantane alcohols is reported. Several of the novel amines displayed low micromolar activities against several H1N1 influenza virus strains, including the amantadine-resistant A/PuertoRico/8/34 strain. Most of the compounds did not show cytotoxicity for MDCK cells. PMID:24900429

  15. Synthesis and Anti-influenza A Virus Activity of 2,2-Dialkylamantadines and Related Compounds.

    PubMed

    Torres, Eva; Fernández, Roser; Miquet, Stéphanie; Font-Bardia, Mercè; Vanderlinden, Evelien; Naesens, Lieve; Vázquez, Santiago

    2012-12-13

    The synthesis of several 2,2-dialkyladamantyl-1-amines through the combination of a Ritter reaction with a Wagner-Meerwein rearrangement from noradamantane alcohols is reported. Several of the novel amines displayed low micromolar activities against several H1N1 influenza virus strains, including the amantadine-resistant A/PuertoRico/8/34 strain. Most of the compounds did not show cytotoxicity for MDCK cells.

  16. Vitamin D modulation of the activity of estrogenic compounds in bone cells in vitro and in vivo.

    PubMed

    Somjen, Dalia

    2007-01-01

    Vitamin D analogs modulate different organs, including modulation of energy metabolism, through the induction of creatine kinase (CK) activity. Skeletal organs from vitamin D-depleted rats showed lower constituent CK than those from vitamin D-replete rats. Moreover, estradiol-17beta (E2) or dihydrotestosterone (DHT), which increased CK in organs from intact female or male rats, respectively, stimulated much less CK in vitamin D-depleted rats. Treatment of intact female rats with noncalcemic vitamin D analogs significantly upregulated E2- and DHT-induced CKresponse. These analogs upregulated the CK response to selective estrogen receptor modulators (SERMs) in organs from intact or ovariectomized (Ovx) female rats but abolished SERMs' inhibitory effect on E2-induced CK. These analogs significantly increased estradiol receptor alpha (ERalpha) protein in skeletal organs as well as histomorphological and biochemical changes due to this treatment followed by E2 or DHT. The analogs alone markedly altered the growth plate and the trabeculae and increased trabecular bone volume (%TB V) and trabecular width. The addition of E2 or DHT to this treatment restored all parameters as well as increased %TBV and cell proliferation. Treatment of Ovx female rats with JK 1624 F2-2 (JKF) decreased growth-plate width and increased %TB V, whereas QW1624 F2-2 (QW) restored growth-plate width and %TB V. Treatment of E2 with JKF restored %TBV and growth-plate width, whereas E2 with QW restored all parameters, including cortical width. There was also upregulation of the response of CK to E2 in both combined treatments. Our human-derived osteoblast (hObs)-like cell cultures respond to estrogenic compounds, and pretreating them with JKF upregulated the CK response to E2, raloxifene (Ral), and some phytoestrogens. ERalpha and ERbeta proteins, as well as mRNA, were modulated by CB 1093 (CB) and JKF. JKF increased specific nuclear E2 binding in female hObs but inhibited specific membranal E2

  17. Occurrence and removal of pharmaceutically active compounds in sewage treatment plants with different technologies

    USGS Publications Warehouse

    Ying, Guang-Guo; Kookana, Rai S.; Kolpin, Dana W.

    2009-01-01

    Occurrence of eight selected pharmaceutically active compounds (PhACs; caffeine, carbamazepine, triclosan, gemfibrozil, diclofenac, ibuprofen, ketoprofen and naproxen) were investigated in effluents from fifteen sewage treatment plants (STPs) across South Australia. In addition, a detailed investigation into the removal of these compounds was also carried out in four STPs with different technologies (Plant A: conventional activated sludge; plant B: two oxidation ditches; plant C: three bioreactors; and plant D: ten lagoons in series). The concentrations of these compounds in the effluents from the fifteen STPs showed substantial variations among the STPs, with their median concentrations ranging from 26 ng/L for caffeine to 710 ng/L for carbamazepine. Risk assessment based on the "worst case scenario" of the monitoring data from the present study suggested potential toxic risks to aquatic organisms posed by carbamazepine, triclosan and diclofenac associated with such effluent discharge. With the exception of carbamazepine and gemfibrozil, significant concentration decreases between influent and effluent were observed in the four STPs studied in more detail. Biodegradation was found to be the main mechanism for removing concentrations from the liquid waste stream for the PhACs within the four STPs, while adsorption onto sludge appeared to be a minor process for all target PhACs except for triclosan. Some compounds (e.g. gemfibrozil) exhibited variable removal efficiencies within the four STPs. Plant D (10 lagoons in series) was least efficient in the removal of the target PhACs; significant biodegradation of these compounds only occurred from the sixth or seventh lagoon.

  18. Active Hexose Correlated Compound Activates Immune Function to Decrease Chlamydia trachomatis Shedding in a Murine Stress Model

    PubMed Central

    Belay, Tesfaye; Fu, Chih-lung; Woart, Anthony

    2016-01-01

    A cold-induced stress mouse model for investigating chlamydia genital infection and immune response analysis was established in our laboratory. Previous results showed that cold-induced stress results in suppression of the immune response and increased intensity of chlamydia genital infection in the mouse model. The purpose of the present study was to evaluate the potential therapeutic value of active hexose correlated compound (AHCC) against chlamydia genital infection in mice. AHCC is an extract of mushroom commonly used as a dietary supplement is known to boost the immune system. Mice were infected intravaginally with Chlamydia trachomatis after a 24-day cold-stress application. Oral administration of AHCC to stressed or non-stressed mice was carried out seven days before infection and during the course of infection along with cervicovaginal swabbing. Cytokine production by peritoneal and splenic T cells isolated from AHCC-fed stressed mice and non-stressed mice was measured ELISA. Splenic T cells from both animal groups were co-cultured with mouse monocyte J774.2 cell line or cultured by addition of supernatants of AHCC-treated J774.2 cell line for 24 hours. Infection studies showed that AHCC-feeding compared to phosphate buffered saline (PBS)-feeding to stressed mice resulted in reduced Chlamydia trachomatis shedding from the genital tract. Levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) were significantly increased in stressed mice receiving AHCC compared to stressed mice receiving PBS. Production of interferon gamma (IFN-γ) and interleukin 2 (IL-2) in the AHCC group was significantly high compared to production in PBS-fed group. Splenic T cells from stressed and non-stressed cultured with supernatants of AHCC-treated J774.2 cell line resulted in significantly increased TNF-α or IFN-γ production. Results obtained in this study show that AHCC improves the function of immune cells as indicated by the restoration of levels of cytokines

  19. In silico inhibition of GABARAP activity using antiepileptic medicinal derived compounds

    PubMed Central

    Mathew, Shilu; Faheem, Muhammad; Al-Malki, Abdulrahman L; Kumosani, Taha A; Qadri, Ishtiaq

    2015-01-01

    Epilepsy is a neurological disorder affecting more than 50 million people worldwide. It can be controlled by antiepileptic drugs (AEDs) but more than 30% patients are still resistant to AEDs. To overcome this problem, researchers are trying to develop novel approaches to treat epilepsy including the use of herbal medicines. The γ-amino butyric acid type-A receptor associated protein (GABARAP) is ubiquitin-like modifier implicated in the intracellular trafficking of GABAAR. An in silico mutation was created at 116 amino acid position G116A, and an in silico study was carried out to identify the potential binding inhibitors (with antiepileptic properties) against the active sites of GABARAP. Five different plant derived compounds namely (a) Aconitine (b) Berberine (c) Montanine (d) Raubasine (e) Safranal were selected, and their quantitative structure-activity relationships (QSAR) have been conducted to search the inhibitory activity of the selected compounds. The results have shown maximum number of hydrogen bond (H-bond) interactions of Raubasine with highest interaction energy among all of the five compounds. So, Raubasine could be the best fit ligand of GABARAP but in vitro, and in vivo studies are necessary for further confirmation. PMID:26124559

  20. Bioactive compounds, antioxidant and binding activities and spear yield of Asparagus officinalis L.

    PubMed

    Lee, Jong Won; Lee, Jeong Hyun; Yu, In Ho; Gorinstein, Shela; Bae, Jong Hyang; Ku, Yang Gyu

    2014-06-01

    The aim of this investigation was to find a proper harvesting period and establishing fern number, which effects the spear yield, bioactive compounds and antioxidant activities of Asparagus officinalis L. Spears were harvested at 2, 4, and 6 weeks after sprouting. Control for comparison was used without harvest. Spears and total yield increased with prolonged spear harvest period. In harvest of 6 weeks long optimum spear yield was the highest and fern numbers were 5 ~ 8. Bioactive compounds (polyphenols, flavonoids, flavanols, tannins and ascorbic acid) and the levels of antioxidant activities by ferric-reducing/antioxidant power (FRAP) and cupric reducing antioxidant capacity (CUPRAC) assays in asparagus ethanol extracts significantly differed in the investigated samples and were the highest at 6 weeks harvest period (P < 0.05). The first and the second segments from the tip significantly increased with the increase of catalase (CAT). It was interesting to investigate in vitro how human serum albumin (HSA) interacts with polyphenols extracted from investigated vegetables. Therefore the functional properties of asparagus were studied by the interaction of polyphenol ethanol extracts with HSA, using 3D- FL. In conclusion, antioxidant status (bioactive compounds, binding and antioxidant activities) improved with the harvesting period and the first segment from spear tip. Appropriate harvesting is effective for higher asparagus yield and its bioactivity.

  1. 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.

  2. [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.

  3. Discovery and Preliminary Structure–Activity Relationship of Arylpiperazines as Novel, Brain-Penetrant Antiprion Compounds

    PubMed Central

    2013-01-01

    Creutzfeldt-Jakob disease and kuru in humans, BSE in cattle, and scrapie in sheep are fatal neurodegenerative disorders. Such illnesses are caused by the conversion and accumulation of a misfolded pathogenic isoform (termed PrPSc) of a normally benign, host cellular protein, denoted PrPC. We employed high-throughput screening enzyme-linked immunosorbent assays to evaluate compounds for their ability to reduce the level of PrPSc in Rocky Mountain Laboratory prion-infected mouse neuroblastoma cells (ScN2a-cl3). Arylpiperazines were among the active compounds identified, but the initial hits suffered from low potency and poor drug-likeness. The best of those hits, such as 1, 7, 13, and 19, displayed moderate antiprion activity with EC50 values in the micromolar range. Key analogues were designed and synthesized on the basis of the structure–activity relationship, with analogues 41, 44, 46, and 47 found to have submicromolar potency. Analogues 41 and 44 were able to penetrate the blood–brain barrier and achieved excellent drug concentrations in the brains of mice after oral dosing. These compounds represent good starting points for further lead optimization in our pursuit of potential drug candidates for the treatment of prion diseases. PMID:23847718

  4. 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

  5. Three data mining techniques to improve lazy structure-activity relationships for noncongeneric compounds.

    PubMed

    Sommer, Selina; Kramer, Stefan

    2007-01-01

    We present three simple, yet effective data mining techniques for lazy structure-activity relationships (SARs) of noncongeneric compounds. In lazy SARs, classifications are particularly tailored for each test compound. Therefore, it is possible to make the most of the structure of a test compound. In our case, we derive its substructures and use them to determine similar structures. To obtain a well-balanced and representative set of structural descriptors, we enrich this set by strongly activating or deactivating fragments from the training set and subsequently remove redundant fragments. Finally, we perform k-Nearest Neighbor classification for several values of k and take a vote among the resulting predictions. These techniques (enrichment, removing redundancy, and voting) are integrated into the system iSAR (instance-based structure-activity relationships) and tested individually to show the relative contribution to the system's performance. Experiments on three data sets indicate that this simple and lightweight approach performs at least on the same level as other, more complex approaches.

  6. Antioxidant activities and skin hydration effects of rice bran bioactive compounds entrapped in niosomes.

    PubMed

    Manosroi, Aranya; Chutoprapat, Romchat; Sato, Yuji; Miyamoto, Kukizo; Hsueh, Kesyin; Abe, Masahiko; Manosroi, Worapaka; Manosroi, Jiradej

    2011-03-01

    Bioactive compounds [ferulic acid (F), gamma-oryzanol (O) and phytic acid (P)] in rice bran have been widely used as antioxidants in skin care products. However, one of the major problems of antioxidants is the deterioration of their activities during long exposure to air and light. Niosomes have been used to entrap many degradable active agents not only for stability improvement, but also for increasing skin hydration. The objective of this study was to determine antioxidant activities [by in vitro ORAC (oxygen radical absorbance capacity) and ex vivo lipid peroxidation inhibition assay] and in vivo human skin hydration effects of gel and cream containing the rice bran extracts entrapped in niosomes. Gel and cream containing the rice bran extracts entrapped in niosomes showed higher antioxidant activity (ORAC value) at 20-28 micromol of Trolox equivalents (TE) per gram of the sample than the placebo gel and cream which gave 16-18 micromolTE/g. Human sebum treated with these formulations showed more lipid peroxidation inhibition activity than with no treatment of about 1.5 times. The three different independent techniques including corneometer, vapometer and confocal Raman microspectroscopy (CRM) indicated the same trend in human skin hydration enhancement of the gel or cream formulations containing the rice bran extracts entrapped in niosomes of about 20, 3 and 30%, respectively. This study has demonstrated the antioxidant activities and skin hydration enhancement of the rice bran bioactive compounds when entrapped in niosomes and incorporated in cream formulations.

  7. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin.

    PubMed

    Bandell, Michael; Story, Gina M; Hwang, Sun Wook; Viswanath, Veena; Eid, Samer R; Petrus, Matt J; Earley, Taryn J; Patapoutian, Ardem

    2004-03-25

    Six members of the mammalian transient receptor potential (TRP) ion channels respond to varied temperature thresholds. The natural compounds capsaicin and menthol activate noxious heat-sensitive TRPV1 and cold-sensitive TRPM8, respectively. The burning and cooling perception of capsaicin and menthol demonstrate that these ion channels mediate thermosensation. We show that, in addition to noxious cold, pungent natural compounds present in cinnamon oil, wintergreen oil, clove oil, mustard oil, and ginger all activate TRPA1 (ANKTM1). Bradykinin, an inflammatory peptide acting through its G protein-coupled receptor, also activates TRPA1. We further show that phospholipase C is an important signaling component for TRPA1 activation. Cinnamaldehyde, the most specific TRPA1 activator, excites a subset of sensory neurons highly enriched in cold-sensitive neurons and elicits nociceptive behavior in mice. Collectively, these data demonstrate that TRPA1 activation elicits a painful sensation and provide a potential molecular model for why noxious cold can paradoxically be perceived as burning pain.

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

    SciTech Connect

    Aziz, Gulzeb; Akselsen, Oyvind W.; Hansen, Trond V.; Paulsen, Ragnhild E.

    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 inhibited 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.

  9. 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.

  10. Optimization of ultrasound-assisted hydroalcoholic extraction of phenolic compounds from walnut leaves using response surface methodology.

    PubMed

    Nour, Violeta; Trandafir, Ion; Cosmulescu, Sina

    2016-10-01

    Context Walnut leaves are highly appreciated for their pharmacological effects and therapeutic properties which are mainly attributed to their high content of phenolic compounds. Objective This study optimizes ultrasound assisted hydroalcoholic extraction (UAE) of phenolic compounds from dried walnut leaves by the maximization of total phenolics content (TPC) and total flavanoids content (TFC) of the extracts. Materials and methods Optimal conditions with regard to ethanol concentration (X1: 12.17-95.83% v/v), extraction time (X2: 8.17-91.83 min) and liquid-to-solid ratio (X3: 4.96-25.04 v/w) were identified using central composite design combined with response surface methodology. A high-performance liquid chromatography method with diode-array detection was used to quantify phenolic acids (gallic, vanillic, chlorogenic, caffeic, syringic, p-coumaric, ferulic, sinapic, salicylic, ellagic and trans-cinnamic), flavonoids (catechin, epicatechin, rutin, myricetin and quercetin) and juglone in the extracts. Results Liquid-to-solid ratio and ethanol concentration proved to be the primary factors affecting the extraction efficiency. The maximum predicted TPC, under the optimized conditions (61% ethanol concentration, 51.28 min extraction time and 4.96 v/w liquid-to-solid ratio) was 10125.4 mg gallic acid equivalents per liter while maximum TFC (2925 mg quercetin equivalents per liter) occurred at 67.83% ethanol concentration, 4.96 v/w liquid-to-solid ratio and 49.37 min extraction time. High significant correlations were found between antioxidant activity and both TPC (R(2 )=( )0.81) and TFC (R(2 )=( )0.78). Discussion and conclusion Extracts very rich in polyphenols could be obtained from walnut leaves by using UAE, aimed at preparing dietary supplements, nutraceuticals or functional food ingredients.

  11. Novel phenotype in beagle dogs characterized by skin response to compound 48/80 focusing on skin mast cell degranulation.

    PubMed

    Uchida, Mitsuhiro; Ito, Fumi; Tsuchiya, Toshiyuki; Shoji, Yoko; Kurosawa, Toru

    2015-01-01

    Beagle dogs have long been employed in toxicology studies and as skin disease models. Compared with other experimental animal species, they are known to be susceptible to skin responses, such as rashes, from exposure to various chemical compounds. Here, a unique dog phenotype was identified that showed no skin response to compound 48/80, a mast cell degranulating agent. Although the skin responses to intradermal injection of polyoxyethylene castor oil derivative (HCO-60, a nonionic detergent), histamine dihydrochloride, concanavalin A (IgE receptor-mediated stimuli), or calcium ionophore A23187 were comparable in wild-type (WT) dogs and these nonresponder (NR) dogs, only the response to compound 48/80 was entirely absent from NR dogs. The skin mast cell density and histamine content per mast cell were histologically comparable between WT and NR dogs. By checking for skin responses to compound 48/80, NR dogs were found to exist at the proportion of 17-20% among four animal breeders. From retrospective analysis of in-house breeding histories, the NR phenotype appears to conform to the Mendelian pattern of recessive inheritance. The standard skin response in WT dogs developed at 2-4 months of age. In conclusion, this unique phenotype, typified by insensitivity in the compound 48/80-induced degranulation pathway in mast cells, has been widely retained by recessive inheritance in beagle dogs among general experimental animal breeders. The knowledge concerning this phenotype could lead to better utilization of dogs in studies and aid in model development.

  12. Detection of estrogenic activity in sediment-associated compounds using in vitro reporter gene assays.

    PubMed

    Legler, Juliette; Dennekamp, Martine; Vethaak, A Dick; Brouwer, Abraham; Koeman, Jan H; van der Burg, Bart; Murk, Albertinka J

    2002-07-03

    Sediments may be the ultimate sink for persistent (xeno-)estrogenic compounds released into the aquatic environment. Sediment-associated estrogenic potency was measured with an estrogen receptor-mediated luciferase reporter gene (ER-CALUX) assay and compared with a recombinant yeast screen. The ER-CALUX assay was more sensitive to 17beta-estradiol (E2) than the recombinant yeast screen, with an EC50 of 6 pM E2 compared to 100 pM in the yeast screen. Yeast cells were unable to distinguish the anti-estrogens ICI 182,780 and (4-hydroxy)tamoxifen, which were agonistic in the yeast. Acetone-soluble fractions of hexane/acetone extracts of sediments showed higher estrogenic potency than hexane-soluble extracts in the ER-CALUX assay. Sediments obtained from industrialized areas such as the Port of Rotterdam showed the highest estrogenic potency of the 12 marine sediments tested (up to 40 pmol estradiol equivalents per gram sediment). The estrogenic activity of individual chemicals that can be found in sediments including: alkylphenol ethoxylates and carboxylates; phthalates; and pesticides, was tested. Increasing sidechain length of various nonylphenol ethoxylates resulted in decreased estrogenic activity. Of the phthalates tested, butylbenzylphthalate was the most estrogenic, though with a potency approximately 100,000 times less than E2. The organochlorine herbicides atrazine and simazine failed to induce reporter gene activity. As metabolic activation may be required to induce estrogenic activity, a metabolic transformation step was added to the ER-CALUX assay using incubation of compounds with liver microsomes obtained from PCB-treated rats. Results indicate that metabolites of E2, NP and bisphenol A were less active than the parent compounds, while metabolites of methoxychlor were more estrogenic following microsomal incubations.

  13. Towards tailoring the magnetocaloric response in FeRh-based ternary compounds

    SciTech Connect

    Barua, Radhika Jiménez-Villacorta, Félix; Lewis, L. H.

    2014-05-07

    In this work, we demonstrate that the magnetocaloric response of FeRh-based compounds may be tailored for potential magnetic refrigeration applications by chemical modification of the FeRh lattice. Alloys of composition Fe(Rh{sub 1−x}A{sub x}) or (Fe{sub 1−x}B{sub x})Rh (A = Cu, Pd; B = Ni; 0 < x < 0.06) were synthesized via arc-melting and subsequent annealing in vacuum at 1000 °C for 48 h. The magnetocaloric properties of the FeRh-based systems were determined using isothermal M(H) curves measured in the vicinity of the magnetostructural temperature (T{sub t}). It is found that the FeRh working temperature range (δT{sub FWHM}) may be chemically tuned over a wide temperature range, 100 K ≤ T ≤ 400 K. While elemental substitution consistently decreases the magnetic entropy change (ΔS{sub mag}) of the FeRh-based ternary alloys from that of the parent FeRh compound (ΔS{sub mag},{sub FeRh} ∼ 17 J/kg K; ΔS{sub mag,FeRh-ternary =} 7–14 J/kg K at H{sub app} = 2 T), the net refrigeration capacity (RC