Sample records for identify active compounds

  1. Identifying non-point sources of endocrine active compounds and their biological impacts in freshwater lakes.

    PubMed

    Baker, Beth H; Martinovic-Weigelt, Dalma; Ferrey, Mark; Barber, Larry B; Writer, Jeffery H; Rosenberry, Donald O; Kiesling, Richard L; Lundy, James R; Schoenfuss, Heiko L

    2014-10-01

    Contaminants of emerging concern, particularly endocrine active compounds (EACs), have been identified as a threat to aquatic wildlife. However, little is known about the impact of EACs on lakes through groundwater from onsite wastewater treatment systems (OWTS). This study aims to identify specific contributions of OWTS to Sullivan Lake, Minnesota, USA. Lake hydrology, water chemistry, caged bluegill sunfish (Lepomis macrochirus), and larval fathead minnow (Pimephales promelas) exposures were used to assess whether EACs entered the lake through OWTS inflow and the resultant biological impact on fish. Study areas included two OWTS-influenced near-shore sites with native bluegill spawning habitats and two in-lake control sites without nearby EAC sources. Caged bluegill sunfish were analyzed for plasma vitellogenin concentrations, organosomatic indices, and histological pathologies. Surface and porewater was collected from each site and analyzed for EACs. Porewater was also collected for laboratory exposure of larval fathead minnow, before analysis of predator escape performance and gene expression profiles. Chemical analysis showed EACs present at low concentrations at each study site, whereas discrete variations were reported between sites and between summer and fall samplings. Body condition index and liver vacuolization of sunfish were found to differ among study sites as did gene expression in exposed larval fathead minnows. Interestingly, biological exposure data and water chemistry did not match. Therefore, although results highlight the potential impacts of seepage from OWTS, further investigation of mixture effects and life history factor as well as chemical fate is warranted. PMID:24974177

  2. Rules for identifying potentially reactive or promiscuous compounds.

    PubMed

    Bruns, Robert F; Watson, Ian A

    2012-11-26

    This article describes a set of 275 rules, developed over an 18-year period, used to identify compounds that may interfere with biological assays, allowing their removal from screening sets. Reasons for rejection include reactivity (e.g., acyl halides), interference with assay measurements (fluorescence, absorbance, quenching), activities that damage proteins (oxidizers, detergents), instability (e.g., latent aldehydes), and lack of druggability (e.g., compounds lacking both oxygen and nitrogen). The structural queries were profiled for frequency of occurrence in druglike and nondruglike compound sets and were extensively reviewed by a panel of experienced medicinal chemists. As a means of profiling the rules and as a filter in its own right, an index of biological promiscuity was developed. The 584 gene targets with screening data at Lilly were assigned to 17 subfamilies, and the number of subfamilies at which a compound was active was used as a promiscuity index. For certain compounds, promiscuous activity disappeared after sample repurification, indicating interference from occult contaminants. Because this type of interference is not amenable to substructure search, a "nuisance list" was developed to flag interfering compounds that passed the substructure rules. PMID:23061697

  3. FREQUENCY OF ORGANIC COMPOUNDS IDENTIFIED IN WATER

    EPA Science Inventory

    This study was initiated for the purpose of compiling a list of all organic compounds that have been found in water. This report contains the names of compounds found, their location or a reference to a published study, the type of water in which they are found, and the date of s...

  4. Screen of FDA-approved drug library identifies maprotiline, an antibiofilm and antivirulence compound with QseC sensor-kinase dependent activity in Francisella novicida.

    PubMed

    Dean, Scott N; van Hoek, Monique L

    2015-07-01

    Development of new therapeutics against Select Agents such as Francisella is critical preparation in the event of bioterrorism. Testing FDA-approved drugs for this purpose may yield new activities unrelated to their intended purpose and may hasten the discovery of new therapeutics. A library of 420 FDA-approved drugs was screened for antibiofilm activity against a model organism for human tularemia, Francisella (F.) novicida, excluding drugs that significantly inhibited growth. The initial screen was based on the 2-component system (TCS) dependent biofilm effect, thus, the QseC dependence of maprotiline anti-biofilm action was demonstrated. By comparing their FDA-approved uses, chemical structures, and other properties of active drugs, toremifene and polycyclic antidepressants maprotiline and chlorpromazine were identified as being highly active against F. novicida biofilm formation. Further down-selection excluded toremifene for its membrane active activity and chlorpromazine for its high antimicrobial activity. The mode of action of maprotiline against F. novicida was sought. It was demonstrated that maprotiline was able to significantly down-regulate the expression of the virulence factor IglC, encoded on the Francisella Pathogenicity Island (FPI), suggesting that maprotiline is exerting an effect on bacterial virulence. Further studies showed that maprotiline significantly rescued F. novicida infected wax worm larvae. In vivo studies demonstrated that maprotiline treatment could prolong time to disease onset and survival in F. novicida infected mice. These results suggest that an FDA-approved drug such as maprotiline has the potential to combat Francisella infection as an antivirulence agent, and may have utility in combination with antibiotics. PMID:26155740

  5. Microfluidic in vivo screen identifies compounds enhancing neuronal

    E-print Network

    Haggarty, Stephen

    Compound screening is a powerful tool to identify new therapeutic targets, drug leads, and elucidate the fundamental mechanisms of biological processes. We report here the results of the first in vivo small-molecule screens ...

  6. A Novel Way To Identify Precursors That Degrade To Perfluorinated Compounds In Activated Sludge Using Ion-Trap Time-Of-Flight Mass Spectrometry

    EPA Science Inventory

    An increasing number of studies have been conducted to investigate the environmental distribution of perfluorinated alkyl compounds (PFCs), many of which are known to be toxic in laboratory animals. Despite growing public concerns, fate and transport of PFCs are little known. M...

  7. PHEROMONAL ACTIVITY OF COMPOUNDS IDENTIFIED FROM MALE PHYLLOTRETA CRUCIFERAE: FIELD TESTS OF RACEMIC MIXTURES, PURE ENANTIOMERS, AND COMBINATIONS WITH ALLYL ISOTHIOCYANATE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Four himachalene sesquiterpenes and (+)-'-cadinene, previously identified as possible pheromone components from males of a North American population of Phyllotreta cruciferae Goeze (Coleoptera, Chrysomelidae), were tested for attractiveness in field traps in Hungary. A mixture of the four synthetic...

  8. A staining protocol for identifying secondary compounds in Myrtaceae1

    PubMed Central

    Retamales, Hernan A.; Scharaschkin, Tanya

    2014-01-01

    • Premise of the study: Here we propose a staining protocol using toluidine blue (TBO) and ruthenium red to reliably identify secondary compounds in the leaves of some species of Myrtaceae. • Methods and Results: Leaves of 10 species representing 10 different genera of Myrtaceae were processed and stained using five different combinations of ruthenium red and TBO. Optimal staining conditions were determined as 1 min of ruthenium red (0.05% aqueous) and 45 s of TBO (0.1% aqueous). Secondary compounds clearly identified under this treatment include mucilage in the mesophyll, polyphenols in the cuticle, lignin in fibers and xylem, tannins and carboxylated polysaccharides in the epidermis, and pectic substances in the primary cell walls. • Conclusions: Potential applications of this protocol include systematic, phytochemical, and ecological investigations in Myrtaceae. It might be applicable to other plant families rich in secondary compounds and could be used as a preliminary screening method for extraction of these elements. PMID:25309840

  9. Biological activity of vanadium compounds

    Microsoft Academic Search

    Anna Goc

    2006-01-01

    Vanadium compounds are characterised by a broad spectrum of action in vivo and in vitro. Their insulin-mimetic activity is manifested in their ability to normalize changes observed in both clinical and experimental\\u000a diabetes (i.e. hyperglycaemia, hyperlipidaemia, lowered cell sensitivity to insulin) through the regulation of carbohydrate\\u000a and lipid metabolism and the removal of secondary symptoms of this disease (as e.g.

  10. Zebrafish screen identifies novel compound with selective toxicity against leukemia.

    PubMed

    Ridges, Suzanne; Heaton, Will L; Joshi, Deepa; Choi, Henry; Eiring, Anna; Batchelor, Lance; Choudhry, Priya; Manos, Elizabeth J; Sofla, Hossein; Sanati, Ali; Welborn, Seth; Agarwal, Archana; Spangrude, Gerald J; Miles, Rodney R; Cox, James E; Frazer, J Kimble; Deininger, Michael; Balan, Kaveri; Sigman, Matthew; Müschen, Markus; Perova, Tatiana; Johnson, Radia; Montpellier, Bertrand; Guidos, Cynthia J; Jones, David A; Trede, Nikolaus S

    2012-06-14

    To detect targeted antileukemia agents we have designed a novel, high-content in vivo screen using genetically engineered, T-cell reporting zebrafish. We exploited the developmental similarities between normal and malignant T lymphoblasts to screen a small molecule library for activity against immature T cells with a simple visual readout in zebrafish larvae. After screening 26 400 molecules, we identified Lenaldekar (LDK), a compound that eliminates immature T cells in developing zebrafish without affecting the cell cycle in other cell types. LDK is well tolerated in vertebrates and induces long-term remission in adult zebrafish with cMYC-induced T-cell acute lymphoblastic leukemia (T-ALL). LDK causes dephosphorylation of members of the PI3 kinase/AKT/mTOR pathway and delays sensitive cells in late mitosis. Among human cancers, LDK selectively affects survival of hematopoietic malignancy lines and primary leukemias, including therapy-refractory B-ALL and chronic myelogenous leukemia samples, and inhibits growth of human T-ALL xenografts. This work demonstrates the utility of our method using zebrafish for antineoplastic candidate drug identification and suggests a new approach for targeted leukemia therapy. Although our efforts focused on leukemia therapy, this screening approach has broad implications as it can be translated to other cancer types involving malignant degeneration of developmentally arrested cells. PMID:22490804

  11. Zebrafish screen identifies novel compound with selective toxicity against leukemia

    PubMed Central

    Ridges, Suzanne; Heaton, Will L.; Joshi, Deepa; Choi, Henry; Eiring, Anna; Batchelor, Lance; Choudhry, Priya; Manos, Elizabeth J.; Sofla, Hossein; Sanati, Ali; Welborn, Seth; Agarwal, Archana; Spangrude, Gerald J.; Miles, Rodney R.; Cox, James E.; Frazer, J. Kimble; Deininger, Michael; Balan, Kaveri; Sigman, Matthew; Müschen, Markus; Perova, Tatiana; Johnson, Radia; Montpellier, Bertrand; Guidos, Cynthia J.; Jones, David A.

    2012-01-01

    To detect targeted antileukemia agents we have designed a novel, high-content in vivo screen using genetically engineered, T-cell reporting zebrafish. We exploited the developmental similarities between normal and malignant T lymphoblasts to screen a small molecule library for activity against immature T cells with a simple visual readout in zebrafish larvae. After screening 26 400 molecules, we identified Lenaldekar (LDK), a compound that eliminates immature T cells in developing zebrafish without affecting the cell cycle in other cell types. LDK is well tolerated in vertebrates and induces long-term remission in adult zebrafish with cMYC-induced T-cell acute lymphoblastic leukemia (T-ALL). LDK causes dephosphorylation of members of the PI3 kinase/AKT/mTOR pathway and delays sensitive cells in late mitosis. Among human cancers, LDK selectively affects survival of hematopoietic malignancy lines and primary leukemias, including therapy-refractory B-ALL and chronic myelogenous leukemia samples, and inhibits growth of human T-ALL xenografts. This work demonstrates the utility of our method using zebrafish for antineoplastic candidate drug identification and suggests a new approach for targeted leukemia therapy. Although our efforts focused on leukemia therapy, this screening approach has broad implications as it can be translated to other cancer types involving malignant degeneration of developmentally arrested cells. PMID:22490804

  12. Antiapicoplast and Gametocytocidal Screening To Identify the Mechanisms of Action of Compounds within the Malaria Box

    PubMed Central

    Bowman, Jessica D.; Merino, Emilio F.; Brooks, Carrie F.; Striepen, Boris; Carlier, Paul R.

    2014-01-01

    Malaria remains a significant infectious disease that causes millions of clinical cases and >800,000 deaths per year. The Malaria Box is a collection of 400 commercially available chemical entities that have antimalarial activity. The collection contains 200 drug-like compounds, based on their oral absorption and the presence of known toxicophores, and 200 probe-like compounds, which are intended to represent a broad structural diversity. These compounds have confirmed activities against the asexual intraerythrocytic stages of Plasmodium falciparum and low cytotoxicities, but their mechanisms of action and their activities in other stages of the parasite's life cycle remain to be determined. The apicoplast is considered to be a promising source of malaria-specific targets, and its main function during intraerythrocytic stages is to provide the isoprenoid precursor isopentenyl diphosphate, which can be used for phenotype-based screens to identify compounds targeting this organelle. We screened 400 compounds from the Malaria Box using apicoplast-targeting phenotypic assays to identify their potential mechanisms of action. We identified one compound that specifically targeted the apicoplast. Further analyses indicated that the molecular target of this compound may differ from those of the current antiapicoplast drugs, such as fosmidomycin. Moreover, in our efforts to elucidate the mechanisms of action of compounds from the Malaria Box, we evaluated their activities against other stages of the life cycle of the parasite. Gametocytes are the transmission stage of the malaria parasite and are recognized as a priority target in efforts to eradicate malaria. We identified 12 compounds that were active against gametocytes with 50% inhibitory concentration values of <1 ?M. PMID:24247137

  13. Gintonin, newly identified compounds from ginseng, is novel lysophosphatidic acids-protein complexes and activates G protein-coupled lysophosphatidic acid receptors with high affinity.

    PubMed

    Hwang, Sung Hee; Shin, Tae-Joon; Choi, Sun-Hye; Cho, Hee-Jung; Lee, Byung-Hwan; Pyo, Mi Kyung; Lee, Jun-Ho; Kang, Jiyeon; Kim, Hyeon-Joong; Park, Chan-Woo; Shin, Ho-Chul; Nah, Seung-Yeol

    2012-02-01

    Recently, we isolated a subset of glycolipoproteins from Panax ginseng, that we designated gintonin, and demonstrated that it induced [Ca2+]i transients in cells via G protein-coupled receptor (GPCR) signaling pathway(s). However, active components responsible for Ca2+ mobilization and the corresponding receptor(s) were unknown. Active component(s) for [Ca2+]i transients of gintonin were analyzed by liquid chromatography-electrospray ionization-tandem mass spectrometry and ion-mobility mass spectrometry, respectively. The corresponding receptor(s)were investigated through gene expression assays. We found that gintonin contains LPA C18:2 and other LPAs. Proteomic analysis showed that ginseng major latex-like protein and ribonuclease-like storage proteins are protein components of gintonin. Gintonin induced [Ca2+]i transients in B103 rat neuroblastoma cells transfected with human LPA receptors with high affinity in order of LPA2 >LPA5 > LPA1 > LPA3 > LPA4. The LPA1/LPA3 receptor antagonist Ki16425 blocked gintonin action in cells expressing LPA1 or LPA3. Mutations of binding sites in the LPA3 receptor attenuated gintonin action. Gintonin acted via pertussis toxin (PTX)-sensitive and -insensitive G protein-phospholipase C (PLC)-inositol 1,4,5-trisphosphate (IP3)-Ca2+ pathways. However, gintonin had no effects on other receptors examined. In human umbilical vein endothelial cells (HUVECs) gintonin stimulated cell proliferation and migration. Gintonin stimulated ERK1/2 phosphorylation. PTX blocked gintonin-mediated migration and ERK1/2 phosphorylation. In PC12 cells gintonin induced morphological changes, which were blocked by Rho kinase inhibitorY-27632. Gintonin contains GPCR ligand LPAs in complexes with ginseng proteins and could be useful in the development of drugs targeting LPA receptors. PMID:22286231

  14. [Anticancer activity of oxovanadium compounds].

    PubMed

    Abakumova, O Iu; Podobed, O V; Beliaeva, N F; Tochilkin, A I

    2013-01-01

    Cytotoxic and antitumor activity of the biligand vanadyl derivative of L-malic acid (bis(L-malato)oxovanadium(IV) (VO(mal)2) was investigated in comparison with inorganic vanadium(IV) compound--vanadyl sulfate (VOSO4) and also with oxovanadium monocomplex with L-malic acid (VO(mal)) and vanadyl biscomplex with acetylacetonate. In this purpose the effect of vanadyl compounds on growth of normal human skin fibroblasts and tumor cells of different lines: mouse fibrosarcoma (L929), rat pheochromocytome (PC12), human liver carcinoma (HepG2), virus transformated mouse fibroblast (NIN 3T3), virus transformated cells of human kidney (293) were investigated. The results showed that VO(mal)2 was not toxic for normal human skin fibroblasts but considerably inhibited growth of cancer cells in culture. Cytotoxic antitumor effect of vanadium complexes was found to be dependent on incubation time and concentration and on type of cells and nature of ligands of the central group of the complex (VO2+). These studies provide evidence that VO(mal)2 may be considered as a potential antitumor agent due to its low toxicity in non-tumor cells and significant anticancer activity. PMID:23987068

  15. High Content Screening of Diverse Compound Libraries Identifies Potent Modulators of Tubulin Dynamics

    PubMed Central

    2014-01-01

    Tubulin modulating agents such as the taxanes are among the most effective antimitotic cancer drugs, although resistance and toxicity present significant problems in their clinical use. However, most tubulin modulators are derived from complex natural products, which can make modification of their structure to address these problems difficult. Here, we report the discovery of new antimitotic compounds with simple structures that can be rapidly synthesized, through the phenotypic screening of a diverse compound library for the induction of mitotic arrest. We first identified a compound, which induced mitotic arrest in human cells at submicromolar concentrations. Its simple structure enabled rapid exploration of activity, defining a biphenylacetamide moiety required for activity, A family of analogues was synthesized, yielding optimized compounds that caused mitotic arrest and cell death in the low nanomolar range, comparable to clinically used antimitotic agents. These compounds can be synthesized in 1–3 steps and good yields. We show that one such compound targets tubulin, partially inhibiting colchicine but not vinblastine binding, suggesting that it acts allosterically to the known colchicine-binding site. Thus, our results exemplify the use of phenotypic screening to identify novel antimitotic compounds from diverse chemical libraries and characterize a family of biphenylacetamides (biphenabulins) that show promise for further development. PMID:24900887

  16. High Throughput Screening Identifies a Novel Compound Protecting Cardiomyocytes from Doxorubicin-Induced Damage

    PubMed Central

    Gergely, Szabolcs; Heged?s, Csaba; Lakatos, Petra; Kovács, Katalin; Gáspár, Renáta; Csont, Tamás; Virág, László

    2015-01-01

    Antracyclines are effective antitumor agents. One of the most commonly used antracyclines is doxorubicin, which can be successfully used to treat a diverse spectrum of tumors. Application of these drugs is limited by their cardiotoxic effect, which is determined by a lifetime cumulative dose. We set out to identify by high throughput screening cardioprotective compounds protecting cardiomyocytes from doxorubicin-induced injury. Ten thousand compounds of ChemBridge's DIVERSet compound library were screened to identify compounds that can protect H9C2 rat cardiomyocytes against doxorubicin-induced cell death. The most effective compound proved protective in doxorubicin-treated primary rat cardiomyocytes and was further characterized to demonstrate that it significantly decreased doxorubicin-induced apoptotic and necrotic cell death and inhibited doxorubicin-induced activation of JNK MAP kinase without having considerable radical scavenging effect or interfering with the antitumor effect of doxorubicin. In fact the compound identified as 3-[2-(4-ethylphenyl)-2-oxoethyl]-1,2-dimethyl-1H-3,1-benzimidazol-3-ium bromide was toxic to all tumor cell lines tested even without doxorubicine treatment. This benzimidazole compound may lead, through further optimalization, to the development of a drug candidate protecting the heart from doxorubicin-induced injury. PMID:26137186

  17. APPLICATION OF AN ANALYSIS PROTOCOL TO IDENTIFY ORGANIC COMPOUNDS NOT IDENTIFIED BY SPECTRUM MATCHING. PART 2: APPENDICES

    EPA Science Inventory

    Industrial wastewater survey samples were analyzed for organic compounds not identified by spectrum matching. Analysis of the samples proceeded from an initial packed column GC/MS analysis for Priority Pollutants, through computerized spectrum matching for other compounds, to the...

  18. APPLICATION OF AN ANALYSIS PROTOCOL TO IDENTIFY ORGANIC COMPOUNDS NOT IDENTIFIED BY SPECTRUM MATCHING. PART 1: TEXT

    EPA Science Inventory

    Industrial wastewater survey samples were analyzed for organic compounds not identified by spectrum matching. Analysis of the samples proceeded from an initial packed column GC/MS analysis for Priority Pollutants, through computerized spectrum matching for other compounds, to the...

  19. Chemical Transformations That Yield Compounds with Distinct Activity Profiles

    PubMed Central

    2011-01-01

    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. PMID:24900343

  20. Use of cell-based screening to identify small-molecule compounds that modulate claudin-4 expression.

    PubMed

    Watari, Akihiro; Hashegawa, Maki; Muangman, Thanchanok; Yagi, Kiyohito; Kondoh, Masuo

    2015-06-01

    Claudins constitute a family of at least 27 proteins with four transmembrane domains, and play a pivotal role in maintaining tight-junctions seals in diverse epithelial tissues. The expression of claudin-4 often changes in intestinal tissues of inflammatory bowel disease and various human cancers. Therefore, claudin-4 is a promising target for treatment of these diseases. In our previous study, we established a reporter cell line to monitor claudin-4 expression on the basis of a functional claudin-4 promoter. Using this cell line, we have performed a cell-based screen of a library containing 2642 biologically active small-molecule compounds to identify modulators of claudin-4 expression. The screen identified 24 potential modulators of the claudin-4 promoter activity. Fourteen of these compounds (12 of them novel) induced endogenous claudin-4 expression. The identified compounds might serve as lead compounds targeting aberrant gene expression in inflammatory bowel disease. PMID:25700824

  1. Antiosteoporotic activity of phenolic compounds from Curculigo orchioides.

    PubMed

    Jiao, Lei; Cao, Da-Peng; Qin, Lu-Ping; Han, Ting; Zhang, Qiao-Yan; Zhu, Zheng; Yan, Fei

    2009-09-01

    Six phenolic compounds isolated from Curculigo orchioides, including 2,6-dimethoxy benzoic acid (1), curculigoside A (2), curculigoside B (3), curculigine A (4), curculigine D (5) and 3,3',5,5'-tetramethoxy-7,9':7',9-diepoxylignan-4,4'-di-O-beta-D-glucopyranoside (6), together with the ethanol extract of Curculigo orchioides were evaluated for their activity on osteoblasts in neonatal rat calvaria cultures and multinucleated osteoclasts derived from rat marrow cells so as to characterize the antiosteoporotic components of this plant and explore the relationship of chemical structure with antiosteoporotic activity. The proliferation of osteoblast was assayed by MTT methods. The activity of ALP (alkaline phosphatase) and TRAP (tartrate-resistant acid phosphatase) was measured by p-nitrophenyl sodium phosphate assay. The TRAP stain was used to identify osteoclast in morphology. The resorption pit area on the bone slices formed by osteoclast was measured by computer image processing. The ethanol extract exhibited stimulatory effect on both the osteoblast proliferation and the ALP activity. Six compounds all increased the osteoblast proliferation, and compounds (1), (2) and (4) also slightly increased the osteoblastic ALP activity. Compounds (1), (2), (3), (6) and the ethanol extract decreased area of bone resorption pit, osteoclastic formation and TRAP activity. These results indicated that phenolic compounds are antiosteoporotic chemical constituents from Curculigo orchioides, and their activities are related with chemical structures. PMID:19328665

  2. Biologically active compounds from Aphyllophorales (polypore) fungi.

    PubMed

    Zjawiony, Jordan K

    2004-02-01

    This review describes biologically active natural products isolated from Aphyllophorales, many of which are known as polypores. Polypores are a large group of terrestrial fungi of the phylum Basdiomycota (basidiomycetes), and they along with certain Ascomycota are a major source of pharmacologically active substances. There are about 25 000 species of basidiomycetes, of which about 500 are members of the Aphyllophorales, a polyphyletic group that contains the polypores. Many of these fungi have circumboreal distributions in North America, Europe, and Asia and broad distributions on all inhabited continents and Africa; only a small number of the most common species with the most obvious fruiting bodies (basidiocarps) have been evaluated for biological activity. An estimated 75% of polypore fungi that have been tested show strong antimicrobial activity, and these may constitute a good source for developing new antibiotics. Numerous compounds from these fungi also display antiviral, cytotoxic, and/or antineoplastic activities. Additional important components of this vast arsenal of compounds are polysaccharides derived from the fungal cell walls. These compounds have attracted significant attention in recent years because of their immunomodulatory activities, resulting in antitumor effects. These high molecular weight compounds, often called biological response modifiers (BRM), or immunopotentiators, prevent carcinogenesis, show direct anticancer effects, and prevent tumor metastasis. Some of the protein-bound polysaccharides from polypores and other basidiomycetes have found their way to the market in Japan as anticancer drugs. Finally, numerous compounds with cardiovascular, phytotoxic, immunomodulatory, analgesic, antidiabetic, antioxidant, insecticidal, and nematocidal activities, isolated from polypores, are also presented. In fact many of the fungi mentioned in this paper have long been used in herbal medicine, including polypores such as Ganoderma lucidum (Reishi or Ling Zhi), Laetiporus sulphureus (Chicken-of-the-Woods), Trametes versicolor (Yun Zhi), Grifola umbellata (Zhu Lin), Inonotus obliquus (Chaga), and Wolfiporia cocos (Hoelen). PMID:14987072

  3. 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 ?-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 ?-glucosidase inhibitory activities were determined using the chromogenic method with p-nitrophenyl-?-D-glucopyranoside as substrate. Antioxidant activities were assessed through three kinds of radical scavenging assays (DPPH radical, ABTS radical and hydroxyl radical) & ?-carotene-linoleic acid assay. Results The results indicate FC is abundant of quercitrin, and hyperoside, and TC is abundant of 1?, 2?, 3?, 19?-tetrahydroxy-12-en-28-oic acid (265.2 mg/g) and corosolic acid (100.9 mg/g). The FC & the TC have strong ?-glucosidase inhibitory activities with IC50 of 8.72 ?g/mL and 3.67 ?g/mL, respectively. We find that FC show competitive inhibition against ?-glucosidase, while the TC exhibits noncompetitive inhibition. Furthermore, The FC exhibits significant radical scavenging activity with the EC50 values of 7.73 ?g/mL, 3.64 ?g/mL and 5.90 ?g/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 ?g/mL on inhibiting ?-carotene bleaching. Conclusion These results imply that the FC and the TC could be responsible for the good clinical effects of APL on T2MD through targeting oxidative stress and postprandial hyperglycaemia. So APL may be good sources of natural antioxidants and ?-glucosidase inhibitors exhibiting remarkable potential value for the therapy of T2DM. PMID:24410924

  4. Characterization of odor-active compounds in guava wine.

    PubMed

    Pino, Jorge A; Queris, Oscar

    2011-05-11

    The volatile compounds of guava wine were isolated by continuous solvent extraction and analyzed by GC-FID and GC-MS. A total of 124 volatile constituents were detected, and 102 of them were positively identified. The composition of guava wine included 52 esters, 24 alcohols, 11 ketones, 7 acids, 6 aldehydes, 6 terpenes, 4 phenols and derivatives, 4 lactones, 4 sulfur-compounds, and 5 miscellaneous compounds. The aroma-active areas in the gas chromatogram were screened by application of the aroma extract dilution analysis and by odor activity values. Twelve odorants were considered as odor-active volatiles: (E)-?-damascenone, ethyl octanoate, ethyl 3-phenylpropanoate, ethyl hexanoate, 3-methylbutyl acetate, 2-methyltetrahydrothiophen-3-one, 2,5-dimethyl-4-methoxy-3(2H)-furanone, ethyl (E)-cinnamate, ethyl butanoate, (E)-cinnamyl acetate, 3-phenylpropyl acetate, and ethyl 2-methylpropanoate. PMID:21417409

  5. DEVELOPMENT OF MICROPARTICLES CONTAINING ACTIVE COMPOUNDS

    Microsoft Academic Search

    J. Branquinho; M. Figueiredo; M. H. Gil

    The development of new methods of preparation and characterisation of microparticles (microcapsules and microspheres) with active compounds inside (liquid droplets or solid particles), has been intensively pursued. In fact, microencapsulation has many industrial applications, such us pharmaceutical, food, agro-chemistry and, recently, also in coating industry. Nowadays, there are new technologies that enable a more sophisticated control of certain properties concerning

  6. 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. PMID:17929093

  7. 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

  8. Identifying Bioaccumulative Halogenated Organic Compounds Using a Nontargeted Analytical Approach: Seabirds as Sentinels

    PubMed Central

    Millow, Christopher J.; Mackintosh, Susan A.; Lewison, Rebecca L.; Dodder, Nathan G.; Hoh, Eunha

    2015-01-01

    Persistent organic pollutants (POPs) are typically monitored via targeted mass spectrometry, which potentially identifies only a fraction of the contaminants actually present in environmental samples. With new anthropogenic compounds continuously introduced to the environment, novel and proactive approaches that provide a comprehensive alternative to targeted methods are needed in order to more completely characterize the diversity of known and unknown compounds likely to cause adverse effects. Nontargeted mass spectrometry attempts to extensively screen for compounds, providing a feasible approach for identifying contaminants that warrant future monitoring. We employed a nontargeted analytical method using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC/TOF-MS) to characterize halogenated organic compounds (HOCs) in California Black skimmer (Rynchops niger) eggs. Our study identified 111 HOCs; 84 of these compounds were regularly detected via targeted approaches, while 27 were classified as typically unmonitored or unknown. Typically unmonitored compounds of note in bird eggs included tris(4-chlorophenyl)methane (TCPM), tris(4-chlorophenyl)methanol (TCPMOH), triclosan, permethrin, heptachloro-1'-methyl-1,2'-bipyrrole (MBP), as well as four halogenated unknown compounds that could not be identified through database searching or the literature. The presence of these compounds in Black skimmer eggs suggests they are persistent, bioaccumulative, potentially biomagnifying, and maternally transferring. Our results highlight the utility and importance of employing nontargeted analytical tools to assess true contaminant burdens in organisms, as well as to demonstrate the value in using environmental sentinels to proactively identify novel contaminants. PMID:26020245

  9. USING AN ACCURATE MASS, TRIPLE QUADRUPOLE MASS SPECTROMETER AND AN ION CORRELATION PROGRAM TO IDENTIFY COMPOUNDS

    EPA Science Inventory

    Most compounds are not found in mass spectral libraries and must be identified by other means. Often, compound identities can be deduced from the compositions of the ions in their mass spectra and review of the chemical literature. Confirmation is provided by mass spectra and r...

  10. Identifying developmental vascular disruptor compounds using a predictive signature and alternative toxicity models

    EPA Science Inventory

    Identifying Developmental Vascular Disruptor Compounds Using a Predictive Signature and Alternative Toxicity Models Presenting Author: Tamara Tal Affiliation: U.S. EPA/ORD/ISTD, RTP, NC, USA Chemically induced vascular toxicity during embryonic development can result in a wide...

  11. Structure–radical scavenging activity relationships of phenolic compounds from traditional Chinese medicinal plants

    Microsoft Academic Search

    Yi-Zhong Cai; Mei Sun; Jie Xing; Qiong Luo; Harold Corke

    2006-01-01

    Traditional Chinese medicinal plants associated with anticancer contain a wide variety of natural phenolic compounds with various structural features and possessing widely differing antioxidant activity. The structure–radical scavenging activity relationships of a large number of representative phenolic compounds (e.g., flavanols, flavonols, chalcones, flavones, flavanones, isoflavones, tannins, stilbenes, curcuminoids, phenolic acids, coumarins, lignans, and quinones) identified in the traditional Chinese medicinal

  12. Identifying an active case of tuberculosis.

    PubMed

    Williams, G; Alarcon, E; Jittimanee, S; Walusimbi, M; Sebek, M; Berga, E; Villa, T S

    2008-04-01

    The best practice standards set out in chapter 2 of the Best Practice guide focus on the various aspects of identifying an active case of TB and aim to address some of the challenges associated with case detection. The importance of developing a good relationship with the patient from the start, when he or she is often most vulnerable, is emphasised. The first standard focuses on the assessment of someone who might have TB and the second gives detailed guidance about the collection of sputum for diagnosis. The standards are aimed at the health care worker, who assesses the patient when he or she presents at a health care facility and therefore needs to be familiar with the signs, symptoms and risk factors associated with TB. Having suspected TB, the health care worker then needs to ensure that the correct tests are ordered and procedures are followed so that the best quality samples possible are sent to the laboratory and all documentation is filled out clearly and correctly. The successful implementation of these standards can be measured by the accurate and prompt reporting of results, the registration of every case detected and the continued attendance of every patient who needs treatment. PMID:18371262

  13. Identifying inhibitory compounds in lignocellulosic biomass hydrolysates using an exometabolomics approach

    PubMed Central

    2014-01-01

    Background Inhibitors are formed that reduce the fermentation performance of fermenting yeast during the pretreatment process of lignocellulosic biomass. An exometabolomics approach was applied to systematically identify inhibitors in lignocellulosic biomass hydrolysates. Results We studied the composition and fermentability of 24 different biomass hydrolysates. To create diversity, the 24 hydrolysates were prepared from six different biomass types, namely sugar cane bagasse, corn stover, wheat straw, barley straw, willow wood chips and oak sawdust, and with four different pretreatment methods, i.e. dilute acid, mild alkaline, alkaline/peracetic acid and concentrated acid. Their composition and that of fermentation samples generated with these hydrolysates were analyzed with two GC-MS methods. Either ethyl acetate extraction or ethyl chloroformate derivatization was used before conducting GC-MS to prevent sugars are overloaded in the chromatograms, which obscure the detection of less abundant compounds. Using multivariate PLS-2CV and nPLS-2CV data analysis models, potential inhibitors were identified through establishing relationship between fermentability and composition of the hydrolysates. These identified compounds were tested for their effects on the growth of the model yeast, Saccharomyces. cerevisiae CEN.PK 113-7D, confirming that the majority of the identified compounds were indeed inhibitors. Conclusion Inhibitory compounds in lignocellulosic biomass hydrolysates were successfully identified using a non-targeted systematic approach: metabolomics. The identified inhibitors include both known ones, such as furfural, HMF and vanillin, and novel inhibitors, namely sorbic acid and phenylacetaldehyde. PMID:24655423

  14. Compounds from Gum Ammoniacum with Acetylcholinesterase Inhibitory Activity

    PubMed Central

    Adhami, Hamid-Reza; Lutz, Johannes; Kählig, Hanspeter; Zehl, Martin; Krenn, Liselotte

    2013-01-01

    The use of herbal medicinal preparations in dementia therapy has been studied based on experience from traditional medicine. A dichloromethane extract of gum ammoniacum, the gum-resin from Dorema ammoniacum D. Don had shown acetylcholinesterase (AChE) inhibitory activity in a previous study. The aim of this study was the isolation and characterization of the active compounds from this resin. The extract was investigated by a respective colorimetric microplate assay and the active zones were identified via TLC bioautography and isolated using several chromatographic techniques. The structures of the active components were characterized by one- and two-dimensional 1H and 13C NMR spectroscopy and mass spectrometry as (2?S,5?S)-2?-ethenyl-5?-(3-hy-droxy-6-methyl-4-oxohept-5-en-2-yl)-7-methoxy-2?-methyl-4H-spiro[chromene-3,1?-cyclopentane]-2,4-dione (1), which is an analogue of doremone A and a new natural compound, and as (2?S,5?R)-2?-ethenyl-5?-[(2R,4R)-4-hydroxy-6-methyl-3-oxohept-5-en-2-yl]-7-methoxy-2?-methyl-4H-spiro[chromene-3,1?-cyclo-pentane]-2,4-dione (2 = doremone A), (4E,8E)-1-(2,4-dihydroxyphenyl)-5,9,13-trimethyltetradeca-4,8,12-trien-1-one (3 = dshamirone), and 4,7-dihydroxy-3-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl]-2H-chromen-2-one (4 = am-moresinol). Dshamirone turned out to be the most active compound with an IC50 value for AChE inhibitory activity of 23.5 ?M, whereas the other substances showed weak activity. The concentrations of the analytes in the resin were determined by HPLC as 3.1%, 4.6%, 1.9%, and 9.9%, respectively. PMID:24106674

  15. 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. PMID:24437577

  16. Increasing analytical capacity in the search to identify compounds that kill young wheat stem sawfly larvae

    E-print Network

    Maxwell, Bruce D.

    Increasing analytical capacity in the search to identify compounds that kill young wheat stem insect pest species in wheat. Two examples that have some relevance to Montana are antibiosis to Hessian fly (HF) and to orange wheat blossom midge (OWBM), both occasional pests of wheat. In the case of both

  17. IDENTIFYING COMPOUNDS USING SOURCE CID ON AN ORTHOGONAL ACCELERATION TIME-OF-FLIGHT MASS SPECTROMETER

    EPA Science Inventory

    Exact mass libraries of ESI and APCI mass spectra are not commercially available In-house libraries are dependent on CID parameters and are instrument specific. The ability to identify compounds without reliance on mass spectral libraries is therefore more crucial for liquid sam...

  18. A NEW MASS SPECTROMETRIC TECHNIQUE FOR IDENTIFYING TRACE-LEVEL ORGANIC COMPOUNDS IN COMPLEX MIXTURES

    EPA Science Inventory

    Most organic compounds are not found in mass spectral libraries and cannot be easily identified from low resolution mass spectra. Ion Composition Elucidation (ICE) utilizes selected ion recording with a double focusing mass spectrometer in a new way to determine exact mas...

  19. Antioxidant activity of Magnolol, honokiol, and related phenolic compounds

    Microsoft Academic Search

    Masahiro Ogata; Midori Hoshi; Kumiko Shimotohno; Shiro Urano; Toyoshige Endo

    1997-01-01

    The antioxidant activity of 10 Japanese and Chinese crude drugs (Kampo drugs) was determined in vitro. Extract of Magnolia cortex, which had the highest antioxidant activity, contained phenolic compounds magnolol and honokiol. However, inhibitory effects\\u000a of these compounds on lipid oxidation were weaker than that of ?-tocopherol as measured by thiobarbituric acid assay. The\\u000a structure-activity relationship of phenolic compounds showed

  20. A rapid and sensitive high-throughput screening method to identify compounds targeting protein-nucleic acids interactions.

    PubMed

    Alonso, Nicole; Guillen, Roboan; Chambers, Jeremy W; Leng, Fenfei

    2015-04-30

    DNA-binding and RNA-binding proteins are usually considered 'undruggable' partly due to the lack of an efficient method to identify inhibitors from existing small molecule repositories. Here we report a rapid and sensitive high-throughput screening approach to identify compounds targeting protein-nucleic acids interactions based on protein-DNA or protein-RNA interaction enzyme-linked immunosorbent assays (PDI-ELISA or PRI-ELISA). We validated the PDI-ELISA method using the mammalian high-mobility-group protein AT-hook 2 (HMGA2) as the protein of interest and netropsin as the inhibitor of HMGA2-DNA interactions. With this method we successfully identified several inhibitors and an activator for HMGA2-DNA interactions from a collection of 29 DNA-binding compounds. Guided by this screening excise, we showed that netropsin, the specific inhibitor of HMGA2-DNA interactions, strongly inhibited the differentiation of the mouse pre-adipocyte 3T3-L1 cells into adipocytes, most likely through a mechanism by which the inhibition is through preventing the binding of HMGA2 to the target DNA sequences. This method should be broadly applicable to identify compounds or proteins modulating many DNA-binding or RNA-binding proteins. PMID:25653160

  1. Algicidal activity of marine Alteromonas sp. KNS-16 and isolation of active compounds.

    PubMed

    Cho, Ji Young

    2012-01-01

    The KNS-16 algicidal strain was isolated from a harmful alga bloom (HAB) area and identified as Alteromonas sp. based on 16S rDNA sequencing. The KNS-16 strain was found to control HABs by producing algicidal compounds in an indirect interaction. Four active compounds were isolated from KNS-16 culture, and their structures were analyzed by interpreting nuclear magnetic resonance and mass spectroscopy data. The structures were identified as 2-undecen-1'-yl-4-quinolone (1), 2-undecyl-4-quinolone (2), 3-hexyl-6-pentyl-4-hydroxyl-2H-pyran-2-one (3), and 6-heptyl-3-hexyl-4-hydroxyl-2H-pyran-2-one (4). Compound 1 was most active against HABs such as Heterosigma akashiwo, Cochlodinium polykrikoides, and Alexandrium tamarense with LC(50) values of 0.5-1.1 µg/mL. The four compounds exhibited high LC(50) values against aquaculture algae such as Tetaselmis suecica, Isochrysis galbana, and Pavlova lutheri at 39-66 µg/mL. Based on toxicity tests on the brine shrimp Artemia salina and the rotifer Brachionus rotundiformis, the four compounds showed ranges of 409-608 and 189-224 µg/mL of LC(50) for the two organisms, respectively. The LC(50) values for juvenile fish of Sebastes schlegelii were 284-304 µg/mL. PMID:22878186

  2. Activity: Identifying a solid using density

    NSDL National Science Digital Library

    Greg Schmidt, Henry Sibley High School Many versions of density labs exist. This version employs the use of uncertainty principles described in this module.

    Effective measurement techniques include the concept of measurement uncertainty. Students may make erroneous conclusions analyzing data using measurements that do not include the uncertainty of the measurement. In this lab, students determine a density range for a metal and identify the material based on this range.

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

    PubMed Central

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

    2015-01-01

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

  4. Compounds from Vitex polygama active against kidney diseases.

    PubMed

    Gallo, Margareth B C; Vieira, Paulo C; Fernandes, João B; da Silva, Maria Fátima das G F; Salimena-Pires, Fátima R

    2008-01-17

    Vitex polygama Cham. (Lamiaceae, formerly Verbenaceae) is a familiar Brazilian species popularly known as Tarumã whose leaf tea has been used by population to treat kidney diseases. The aim of this research was to investigate the hydroalcoholic extract of leaves in order to isolate the active compounds. Hydroalcoholic extract of leaves was obtained by stirring the previous hexane and methanol extracted leaves residue with 50% aqueous MeOH solution by ultra-sonic mixing. The obtained extract was partitioned with n-butanol. The yielded fraction was subsequently submitted to several chromatographic procedures to lead to the isolation of O-glycosidicflavones orientin and isoorientin as well as C-glycosylflavones schaftoside and carlinoside along with their isomers, known as potent anti-inflammatory, antinociceptive and antioxidant agents, then identified as the active constituents, justifying the folk use of the plant to combat and prevent kidney stone and inflammation. PMID:17981413

  5. A cell-based fascin bioassay identifies compounds with potential anti-metastasis or cognition-enhancing functions

    PubMed Central

    Kraft, Robert; Kahn, Allon; Medina-Franco, José L.; Orlowski, Mikayla L.; Baynes, Cayla; López-Vallejo, Fabian; Barnard, Kobus; Maggiora, Gerald M.; Restifo, Linda L.

    2013-01-01

    SUMMARY The actin-bundling protein fascin is a key mediator of tumor invasion and metastasis and its activity drives filopodia formation, cell-shape changes and cell migration. Small-molecule inhibitors of fascin block tumor metastasis in animal models. Conversely, fascin deficiency might underlie the pathogenesis of some developmental brain disorders. To identify fascin-pathway modulators we devised a cell-based assay for fascin function and used it in a bidirectional drug screen. The screen utilized cultured fascin-deficient mutant Drosophila neurons, whose neurite arbors manifest the ‘filagree’ phenotype. Taking a repurposing approach, we screened a library of 1040 known compounds, many of them FDA-approved drugs, for filagree modifiers. Based on scaffold distribution, molecular-fingerprint similarities, and chemical-space distribution, this library has high structural diversity, supporting its utility as a screening tool. We identified 34 fascin-pathway blockers (with potential anti-metastasis activity) and 48 fascin-pathway enhancers (with potential cognitive-enhancer activity). The structural diversity of the active compounds suggests multiple molecular targets. Comparisons of active and inactive compounds provided preliminary structure-activity relationship information. The screen also revealed diverse neurotoxic effects of other drugs, notably the ‘beads-on-a-string’ defect, which is induced solely by statins. Statin-induced neurotoxicity is enhanced by fascin deficiency. In summary, we provide evidence that primary neuron culture using a genetic model organism can be valuable for early-stage drug discovery and developmental neurotoxicity testing. Furthermore, we propose that, given an appropriate assay for target-pathway function, bidirectional screening for brain-development disorders and invasive cancers represents an efficient, multipurpose strategy for drug discovery. PMID:22917928

  6. Identifying Diverse Means for Assessing Physical Activity

    ERIC Educational Resources Information Center

    Perlman, Dana J.; Pearson, Phil

    2012-01-01

    Physical inactivity is of concern for the majority of age groups within the United States. Limited engagement in physical activity (PA) has been linked with an increased risk for a host of health problems, including but not limited to heart disease, diabetes and cancer. Benefits of PA are widely documented and accepted yet many people, especially…

  7. Anti-allergic activity of compounds from Kaempferia parviflora.

    PubMed

    Tewtrakul, Supinya; Subhadhirasakul, Sanan; Kummee, Sopa

    2008-02-28

    Kaempferia parviflora is one of the plants in the Zingiberaceae family, locally known in Thai as kra-chai-dam. In Thai traditional medicine, the decoction of Kaempferia parviflora powder with alcohol has been reported to cure allergy, asthma, impotence, gout, diarrhea, dysentery, peptic ulcer and diabetes. Therefore, the present study aimed to investigate anti-allergic substances from this plant. Bioassay-guided fractionation led to the isolation of seven methoxyflavone derivatives (1-7) from Kaempferia parviflora extract and they were identified on the basis of spectroscopic methods. Among the compounds tested, 5-hydroxy-3,7,3',4'-tetramethoxyflavone (5) possessed the highest anti-allergic activity against antigen-induced beta-hexosaminidase release as a marker of degranulation in RBL-2H3 cells with an IC(50) value of 8.0 microM, followed by 5-hydroxy-7-methoxyflavone (2, IC(50)=20.6 microM) and 5-hydroxy-7,4'-dimethoxyflavone (4, IC(50)=26.0 microM), whereas others showed moderate activities (IC(50)=37.5-66.5 microM). Structure-activity trends of 7-methoxyflavone derivatives on anti-allergic activity can be summarized as follows: (1) substitution with vicinal methoxyl groups at positions 3' and 4' conferred higher activity than only one methoxylation, (2) methoxylation at position 3 reduced activity and (3) methoxylation at position 5 showed higher activity than hydroxylation. Compounds 2, 4 and 5 were also determined for their mechanisms on ionomycin-induced beta-hexosaminidase release. The results indicated that the mechanism on inhibition of cell degranulation of compounds 2 and 5 mainly involve the inhibition of Ca(2+) influx to the cells, whereas that of 4 may be partly due to this inhibition. In regards to the active constituents for anti-allergic activity of Kaempferia parviflora, 5-hydroxy-3,7,3',4'-tetramethoxyflavone (5), 5-hydroxy-7-methoxyflavone (2) and 5-hydroxy-7,4'-dimethoxyflavone (4) are responsible for anti-allergic effect of this plant. The findings support the traditional use of Kaempferia parviflora rhizomes for treatment of allergy and allergy-related diseases. PMID:18077118

  8. Microalgae as sources of pharmaceuticals and other biologically active compounds

    Microsoft Academic Search

    Michael A. Borowitzka

    1995-01-01

    In the last decade the screening of microalgae, especially the cyanobacteria (blue-green algae), for antibiotics and pharmacologically\\u000a active compounds has received ever increasing interest. A large number of antibiotic compounds, many with novel structures,\\u000a have been isolated and characterised. Similarly many cyanobacteria have been shown to produce antiviral and antineoplastic\\u000a compounds. A range of pharmacological activities have also been observed

  9. Bacterial biofilm formation inhibitory activity revealed for plant derived natural compounds.

    PubMed

    Artini, M; Papa, R; Barbato, G; Scoarughi, G L; Cellini, A; Morazzoni, P; Bombardelli, E; Selan, L

    2012-01-15

    Use of herbal plant remedies to treat infectious diseases is a common practice in many countries in traditional and alternative medicine. However to date there are only few antimicrobial agents derived from botanics. Based on microbiological screening tests of crude plant extracts we identified four compounds derived from Krameria, Aesculus hippocastanum and Chelidonium majus that showed a potentially interesting antimicrobial activity. In this work we present an in depth characterization of the inhibition activity of these pure compounds on the formation of biofilm of Staphylococcus aureus as well as of Staphylococcus epidermidis strains. We show that two of these compounds possess interesting potential to become active principles of new drugs. PMID:22182580

  10. A Focused Small-Molecule Screen Identifies 14 Compounds with Distinct Effects on Toxoplasma gondii

    PubMed Central

    Kamau, Edwin T.; Srinivasan, Ananth R.; Brown, Mark J.; Fair, Matthew G.; Caraher, Erin J.

    2012-01-01

    Toxoplasma gondii is a globally ubiquitous pathogen that can cause severe disease in immunocompromised humans and the developing fetus. Given the proven role of Toxoplasma-secreted kinases in the interaction of Toxoplasma with its host cell, identification of novel kinase inhibitors could precipitate the development of new anti-Toxoplasma drugs and define new pathways important for parasite survival. We selected a small (n = 527) but diverse set of putative kinase inhibitors and screened them for effects on the growth of Toxoplasma in vitro. We identified and validated 14 noncytotoxic compounds, all of which had 50% effective concentrations in the nanomolar to micromolar range. We further characterized eight of these compounds, four inhibitors and four enhancers, by determining their effects on parasite motility, invasion, and the likely cellular target (parasite or host cell). Only two compounds had an effect on parasite motility and invasion. All the inhibitors appeared to target the parasite, and interestingly, two of the enhancers appeared to rather target the host cell, suggesting modulation of host cell pathways beneficial for parasite growth. For the four inhibitors, we also tested their efficacy in a mouse model, where one compound proved potent. Overall, these 14 compounds represent a new and diverse set of small molecules that are likely targeting distinct parasite and host cell pathways. Future work will aim to characterize their molecular targets in both the host and parasite. PMID:22908155

  11. Phenotype-driven chemical screening in zebrafish for compounds that inhibit collective cell migration identifies multiple pathways potentially involved in metastatic invasion

    PubMed Central

    Gallardo, Viviana E.; Varshney, Gaurav K.; Lee, Minnkyong; Bupp, Sujata; Xu, Lisha; Shinn, Paul; Crawford, Nigel P.; Inglese, James; Burgess, Shawn M.

    2015-01-01

    ABSTRACT In the last decade, high-throughput chemical screening has become the dominant approach for discovering novel compounds with therapeutic properties. Automated screening using in vitro or cultured cell assays have yielded thousands of candidate drugs for a variety of biological targets, but these approaches have not resulted in an increase in drug discovery despite major increases in expenditures. In contrast, phenotype-driven screens have shown a much stronger success rate, which is why we developed an in vivo assay using transgenic zebrafish with a GFP-marked migrating posterior lateral line primordium (PLLp) to identify compounds that influence collective cell migration. We then conducted a high-throughput screen using a compound library of 2160 annotated bioactive synthetic compounds and 800 natural products to identify molecules that block normal PLLp migration. We identified 165 compounds that interfere with primordium migration without overt toxicity in vivo. Selected compounds were confirmed in their migration-blocking activity by using additional assays for cell migration. We then proved the screen to be successful in identifying anti-metastatic compounds active in vivo by performing orthotopic tumor implantation assays in mice. We demonstrated that the Src inhibitor SU6656, identified in our screen, can be used to suppress the metastatic capacity of a highly aggressive mammary tumor cell line. Finally, we used CRISPR/Cas9-targeted mutagenesis in zebrafish to genetically validate predicted targets of compounds. This approach demonstrates that the migrating PLLp in zebrafish can be used for large-scale, high-throughput screening for compounds that inhibit collective cell migration and, potentially, anti-metastatic compounds. PMID:25810455

  12. Phenotype-driven chemical screening in zebrafish for compounds that inhibit collective cell migration identifies multiple pathways potentially involved in metastatic invasion.

    PubMed

    Gallardo, Viviana E; Varshney, Gaurav K; Lee, Minnkyong; Bupp, Sujata; Xu, Lisha; Shinn, Paul; Crawford, Nigel P; Inglese, James; Burgess, Shawn M

    2015-06-01

    In the last decade, high-throughput chemical screening has become the dominant approach for discovering novel compounds with therapeutic properties. Automated screening using in vitro or cultured cell assays have yielded thousands of candidate drugs for a variety of biological targets, but these approaches have not resulted in an increase in drug discovery despite major increases in expenditures. In contrast, phenotype-driven screens have shown a much stronger success rate, which is why we developed an in vivo assay using transgenic zebrafish with a GFP-marked migrating posterior lateral line primordium (PLLp) to identify compounds that influence collective cell migration. We then conducted a high-throughput screen using a compound library of 2160 annotated bioactive synthetic compounds and 800 natural products to identify molecules that block normal PLLp migration. We identified 165 compounds that interfere with primordium migration without overt toxicity in vivo. Selected compounds were confirmed in their migration-blocking activity by using additional assays for cell migration. We then proved the screen to be successful in identifying anti-metastatic compounds active in vivo by performing orthotopic tumor implantation assays in mice. We demonstrated that the Src inhibitor SU6656, identified in our screen, can be used to suppress the metastatic capacity of a highly aggressive mammary tumor cell line. Finally, we used CRISPR/Cas9-targeted mutagenesis in zebrafish to genetically validate predicted targets of compounds. This approach demonstrates that the migrating PLLp in zebrafish can be used for large-scale, high-throughput screening for compounds that inhibit collective cell migration and, potentially, anti-metastatic compounds. PMID:25810455

  13. 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

  14. Fractionation of phenolic compounds extracted from propolis and their activity in the yeast Saccharomyces cerevisiae.

    PubMed

    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

  15. Large-scale neurochemical metabolomics analysis identifies multiple compounds associated with methamphetamine exposure.

    PubMed

    McClay, Joseph L; Adkins, Daniel E; Vunck, Sarah A; Batman, Angela M; Vann, Robert E; Clark, Shaunna L; Beardsley, Patrick M; van den Oord, Edwin J C G

    2013-04-01

    Methamphetamine (MA) is an illegal stimulant drug of abuse with serious negative health consequences. The neurochemical effects of MA have been partially characterized, with a traditional focus on classical neurotransmitter systems. However, these directions have not yet led to novel drug treatments for MA abuse or toxicity. As an alternative approach, we describe here the first application of metabolomics to investigate the neurochemical consequences of MA exposure in the rodent brain. We examined single exposures at 3 mg/kg and repeated exposures at 3 mg/kg over 5 days in eight common inbred mouse strains. Brain tissue samples were assayed using high-throughput gas and liquid chromatography mass spectrometry, yielding quantitative data on >300 unique metabolites. Association testing and false discovery rate control yielded several metabolome-wide significant associations with acute MA exposure, including compounds such as lactate (p = 4.4 × 10(-5), q = 0.013), tryptophan (p = 7.0 × 10(-4), q = 0.035) and 2-hydroxyglutarate (p = 1.1 × 10(-4), q = 0.022). Secondary analyses of MA-induced increase in locomotor activity showed associations with energy metabolites such as succinate (p = 3.8 × 10(-7)). Associations specific to repeated (5 day) MA exposure included phosphocholine (p = 4.0 × 10(-4), q = 0.087) and ergothioneine (p = 3.0 × 10(-4), q = 0.087). Our data appear to confirm and extend existing models of MA action in the brain, whereby an initial increase in energy metabolism, coupled with an increase in behavioral locomotion, gives way to disruption of mitochondria and phospholipid pathways and increased endogenous antioxidant response. Our study demonstrates the power of comprehensive MS-based metabolomics to identify drug-induced changes to brain metabolism and to develop neurochemical models of drug effects. PMID:23554582

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

    PubMed

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

    2004-03-01

    Extracts of volatiles from foliage of three plants in the Apiaceae, Conium maculatum L. (hemlock), Coriandrum sativum L. (coriander), and Petroselinum crispum Mill. (Nym.) (parsley), previously shown to exhibit antifeedant activity in assays with the field slug, Deroceras reticulatum (Muller) (Limacidae: Pulmonata), were studied further to identify the active components. Coupled gas chromatography-mass spectrometry (GC-MS) and neurophysiological assays using tentacle nerve preparations resulted in the identification of 11 active compounds from the three extracts. Wheat flour feeding bioassays were used to determine which of these compounds had the highest antifeedant activity. One of the most active compounds was the alkaloid gamma-coniceine, from C. maculatum. The role of potentially toxic alkaloids as semiochemicals and the potential for using such compounds as crop protection agents to prevent slug feeding damage is discussed. PMID:15139308

  17. Biologically active compounds of semi-metals.

    PubMed

    Rezanka, Tomás; Sigler, Karel

    2008-02-01

    Semi-metals (boron, silicon, arsenic and selenium) form organo-metal compounds, some of which are found in nature and affect the physiology of living organisms. They include, e.g., the boron-containing antibiotics aplasmomycin, borophycin, boromycin, and tartrolon or the silicon compounds present in "silicate" bacteria, relatives of the genus Bacillus, which release silicon from aluminosilicates through the secretion of organic acids. Arsenic is incorporated into arsenosugars and arsenobetaines by marine algae and invertebrates, and fungi and bacteria can produce volatile methylated arsenic compounds. Some prokaryotes can use arsenate as a terminal electron acceptor while others can utilize arsenite as an electron donor to generate energy. Selenium is incorporated into selenocysteine that is found in some proteins. Biomethylation of selenide produces methylselenide and dimethylselenide. Selenium analogues of amino acids, antitumor, antibacterial, antifungal, antiviral, anti-infective drugs are often used as analogues of important pharmacological sulfur compounds. Other metalloids, i.e. the rare and toxic tellurium and the radioactive short-lived astatine, have no biological significance. PMID:17991498

  18. Biological activity of organometallic bismuth compounds

    Microsoft Academic Search

    Thomas Klapötke

    1988-01-01

    Summary The chemical aspects of organometallic bismuth(Ill) compounds are discussed with respect to the stability of the metal-carbon s bond, their low dipole moments, and the limited solubility of these complexes in hydrophilic solvents. A new Bi heterocycle, which is of potential interest in terms of stability and solution behaviour, was shown to exist as an intermediate under the conditions

  19. From Leaf Metabolome to In Vivo Testing: Identifying Antifeedant Compounds for Ecological Studies of Marsupial Diets.

    PubMed

    Marsh, Karen J; Yin, Baofa; Singh, Inder Pal; Saraf, Isha; Choudhary, Alka; Au, Jessie; Tucker, David J; Foley, William J

    2015-06-01

    Identifying specific plant secondary metabolites that influence feeding behavior can be challenging, but a solid understanding of animal preferences can guide efforts. Common brushtail possums (Trichosurus vulpecula) predominantly eat Eucalyptus species belonging to the subgenus Symphyomyrtus, and avoid eating those belonging to the Monocalyptus subgenus (also called subgenus Eucalyptus). Using an unbiased (1)H NMR metabolomics approach, a previous study identified unsubstituted B ring flavanones in most species of monocalypts examined, whereas these compounds were absent from symphyomyrtles. We hypothesised that unsubstituted B ring flavanones act as feeding deterrents for common brushtail possums. In the current study, we tested this hypothesis by comparing how much possums ate of a basal diet, with diets containing one of four structurally related compounds; pinocembrin, flavanone (unsubstituted B ring flavanones), chrysin (the flavone analogue of pinocembrin), and naringenin (a flavanone with B ring substitution). We found that pinocembrin and flavanone deterred feeding relative to the basal diet, but that chrysin and naringenin did not at equivalent concentrations. Thus, unsubstituted B-ring flavanones may explain why brushtail possums avoid eating monocalypt species. Furthermore, small differences in the structure of secondary compounds can have a large impact on antifeedant properties. These results demonstrate that metabolomics can be a valuable tool for ecologists seeking to understand herbivore feeding preferences. PMID:25994224

  20. Advanced steady-state model for the fate of hydrophobic and volatile compounds in activated sludge

    SciTech Connect

    Lee, K.C.; Rittmann, B.E.; Shi, J.; McAvoy, D.

    1998-09-01

    A steady-state, advanced, general fate model developed to study the fate of organic compounds in primary and activated-sludge systems. This model considers adsorption, biodegradation from the dissolved and adsorbed phases, bubble volatilization, and surface volatilization as removal mechanisms. A series of modeling experiments was performed to identify the key trends of these removal mechanisms for compounds with a range of molecular properties. With typical municipal wastewater treatment conditions, the results from the modeling experiments show that co-metabolic and primary utilization mechanisms give very different trends in biodegradation for the compounds tested. For co-metabolism, the effluent concentration increases when the influent concentration increases, while the effluent concentration remains unchanged when primary utilization occurs. For a highly hydrophobic compound, the fraction of compound removed from adsorption onto primary sludge can be very important, and the direct biodegradation of compound sorbed to the activated sludge greatly increases its biodegradation and reduces its discharge with the waste activated sludge. Volatilization from the surface of the primary and secondary systems is important for compounds with moderate to high volatilities, especially when these compounds are not biodegradable. Finally, bubble volatilization can be a major removal mechanism for highly volatile compounds even when they are highly biodegradable.

  1. 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 3295?gL(-)(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. PMID:24997902

  2. 6-Methylsulfinylhexyl isothiocyanate and its homologues as food-originated compounds with antibacterial activity against Escherichia coli and Staphylococcus aureus.

    PubMed

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

    1998-02-01

    Cruciferae plants, banana and coriander each showed antibacterial activity. The highest activity among the food-stuffs tested was found in the stems of wasabi. An ethereal extract from wasabi stems had potent antibacterial activity and we isolated the active compound from the extract. Instrumental analysis identified the compound as 6-methylsulfinylhexyl isothiocyanate. Some homologues of 6-methylsulfinylhexyl isothiocyanate were also active against Escherichia coli and Staphylococcus aureus. PMID:9532796

  3. Gametocytocidal Screen Identifies Novel Chemical Classes with Plasmodium falciparum Transmission Blocking Activity

    PubMed Central

    Sanders, Natalie G.; Sullivan, David J.; Mlambo, Godfree; Dimopoulos, George; Tripathi, Abhai K.

    2014-01-01

    Discovery of transmission blocking compounds is an important intervention strategy necessary to eliminate and eradicate malaria. To date only a small number of drugs that inhibit gametocyte development and thereby transmission from the mosquito to the human host exist. This limitation is largely due to a lack of screening assays easily adaptable to high throughput because of multiple incubation steps or the requirement for high gametocytemia. Here we report the discovery of new compounds with gametocytocidal activity using a simple and robust SYBR Green I- based DNA assay. Our assay utilizes the exflagellation step in male gametocytes and a background suppressor, which masks the staining of dead cells to achieve healthy signal to noise ratio by increasing signal of viable parasites and subtracting signal from dead parasites. By determining the contribution of exflagellation to fluorescent signal and using appropriate cutoff values, we were able to screen for gametocytocidal compounds. After assay validation and optimization, we screened an FDA approved drug library of approximately 1500 compounds, as well as the 400 compound MMV malaria box and identified 44 gametocytocidal compounds with sub to low micromolar IC50s. Major classes of compounds with gametocytocidal activity included quaternary ammonium compounds with structural similarity to choline, acridine-like compounds similar to quinacrine and pyronaridine, as well as antidepressant, antineoplastic, and anthelminthic compounds. Top drug candidates showed near complete transmission blocking in membrane feeding assays. This assay is simple, reproducible and demonstrated robust Z-factor values at low gametocytemia levels, making it amenable to HTS for identification of novel and potent gametocytocidal compounds. PMID:25157792

  4. A high-content screening assay in transgenic zebrafish identifies two novel activators of FGF signaling

    PubMed Central

    Saydmohammed, Manush; Vollmer, Laura L.; Onuoha, Ezenwa Obi; Vogt, Andreas; Tsang, Michael

    2015-01-01

    Zebrafish have become an invaluable vertebrate animal model to interrogate small molecule libraries for modulators of complex biological pathways and phenotypes. We have recently described the implementation of a quantitative, high-content imaging assay in multi-well plates to analyze the effects of small molecules on Fibroblast Growth Factor (FGF) signaling in vivo. Here we have evaluated the ability of the assay to identify compounds that hyperactivate FGF signaling from a test cassette of agents with known biological activities. Using a transgenic zebrafish reporter line for FGF activity, we screened 1040 compounds from an annotated library of known bioactive agents including FDA approved drugs. The assay identified two molecules, 8-hydroxyquinoline sulfate and pyrithione zinc that enhanced FGF signaling in specific areas of the brain. Subsequent studies revealed that both compounds specifically expanded FGF target gene expression. Furthermore, treatment of early stage embryos with either compound resulted in dorsalized phenotypes characteristic of hyperactivation of FGF signaling in early development. Documented activities for both agents included activation of extracellular signal-related kinase (ERK), consistent with FGF hyperactivation. To conclude, we demonstrate the power of automated quantitative high-content imaging to identify small molecule modulators of FGF. PMID:21932436

  5. Biological activities of phenolic compounds isolated from galls of Terminalia chebula Retz. (Combretaceae)

    Microsoft Academic Search

    Aranya Manosroi; Pensak Jantrawut; Hiroyuki Akazawa; Toshihiro Akihisa; Jiradej Manosroi

    2010-01-01

    The aqueous extract of galls from Terminalia chebula Retz. (Combretaceae) was fractionated on Diaion and refractionated on octadecyl silica column. Six phenolic compounds were isolated and identified as gallic acid (1), punicalagin (2), isoterchebulin (3), 1,3,6-tri-O-galloyl-?-D-glucopyranose (4), chebulagic acid (5) and chebulinic acid (6). All of the compounds showed stronger 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and melanin inhibitory activities than ascorbic

  6. Activation of shallow dopants in II-VI compounds

    SciTech Connect

    Walukiewicz, W.

    1995-08-01

    The amphoteric native defect model is applied to the understanding of the variations in the dopant activation efficiency in II-VI compounds. It is shown that the location of the common energy reference, the Fermi level stabilization energy, relative to the band edges can be used to determine the doping induced reduction of the formation energy and the enhancement of the concentration of compensating native defects. The model is applied to the most extensively studied compound semiconductors as well as to ternary and quaternary alloys. The effects of the compound ionicity on the dopant activation are briefly discussed.

  7. An Integrated Approach for Identification and Target Validation of Antifungal Compounds Active against Erg11p

    PubMed Central

    Helliwell, Stephen B.; Pfeifer, Martin; Trunzer, Markus; De Bonnechose, Sophie; Zimmerlin, Alfred; Tao, Jianshi; Richie, Daryl; Hofmann, Andreas; Reinker, Stefan; Frederiksen, Mathias; Movva, N. Rao; Porter, Jeffrey A.; Ryder, Neil S.; Parker, Christian N.

    2012-01-01

    Systemic life-threatening fungal infections represent a significant unmet medical need. Cell-based, phenotypic screening can be an effective means of discovering potential novel antifungal compounds, but it does not address target identification, normally required for compound optimization by medicinal chemistry. Here, we demonstrate a combination of screening, genetic, and biochemical approaches to identify and characterize novel antifungal compounds. We isolated a set of novel non-azole antifungal compounds for which no target or mechanism of action is known, using a screen for inhibition of Saccharomyces cerevisiae proliferation. Haploinsufficiency profiling of these compounds in S. cerevisiae suggests that they target Erg11p, a cytochrome P450 family member, which is the target of azoles. Consistent with this, metabolic profiling in S. cerevisiae revealed a buildup of the metabolic intermediates prior to Erg11p activity, following compound treatment. Further, human cytochrome P450 is also inhibited in in vitro assays by these compounds. We modeled the Erg11p protein based on the human CYP51 crystal structure, and in silico docking of these compounds suggests that they interact with the heme center in a manner similar to that of azoles. Consistent with these docking observations, Candida strains carrying azole-resistant alleles of ERG11 are also resistant to the compounds in this study. Thus, we have identified non-azole Erg11p inhibitors, using a systematic approach for ligand and target characterization. PMID:22615293

  8. Lipoxygenase inhibitory activity of Cuspidaria pulchra and isolated compounds.

    PubMed

    Alvarenga, Tavane A; Bertanha, Camila S; de Oliveira, Pollyanna F; Tavares, Denise C; Gimenez, Valéria M M; Silva, Márcio L A; Cunha, Wilson R; Januário, Ana H; Pauletti, Patrícia M

    2015-06-01

    This work evaluated the in vitro inhibitory activity of the crude ethanolic extract from the aerial parts of Cuspidaria pulchra (Cham.) L.G. Lohmann against 15-lipoxygenase (15-LOX). The bioassay-guided fractionation of the n-butanol fraction, which displayed the highest activity, led to the isolation of three compounds: caffeoylcalleryanin (1), verbascoside (2) and 6-hydroxyluteolin-7-O-?-glucoside (3). Assessment of the ability of the isolated compounds to inhibit 15-LOX revealed that compounds 1, 2 and 3 exerted strong 15-LOX inhibitory activity; IC50 values were 1.59, 1.76 and 2.35 ?M respectively. The XTT assay showed that none of the isolated compounds seemed to be significantly toxic. PMID:25428032

  9. Inhibitory compound of tyrosinase activity from the sprout of Polygonum hydropiper L. (Benitade).

    PubMed

    Miyazawa, Mitsuo; Tamura, Naotaka

    2007-03-01

    A tyrosinase inhibitor was isolated from the sprout of Polygonum hydropiper L. (Benitade) by activity-guided fractionation and identified as (2R,3R)-+-taxifolin (1) by spectroscopic means. Compound 1 inhibited 70% of tyrosinase activity at a concentration of 0.50 mM. ID50 (50% inhibition dose) value of compound 1 was 0.24 mM. As compared with tyrosinase inhibitor known cosmetic agent such as arbutin and kojic acid, compound 1 was more inhibited than the former and showed inhibitory effect equal to that of the latter. To study the inhibitory effect of (2R,3R)-+-taxifolin derivatives against tyrosinase activity, 3,7,3',4'-taxifolin tetraacetate (2) and 5,7,3',4'-taxifolin teramethyl ether (3) were also assayed together with compound 1. PMID:17329865

  10. ACTIVATED CARBON ADSORPTION OF TRACE ORGANIC COMPOUNDS

    EPA Science Inventory

    Research was conducted to determine how effectively humic substances and the trace contaminants 2-methylisoborneol (MIB), geosmin, the chlorophenols and polynuclear aromatic hydrocarbons were adsorbed by activated carbon under the competitive adsorption conditions encountered in ...

  11. Vanadium compounds. Their action on alkaline phosphatase activity.

    PubMed

    Cortizo, A M; Salice, V C; Etcheverry, S B

    1994-06-01

    The direct effect of different vanadium compounds upon alkaline phosphatase (ALP) activity was investigated. Vanadate and vanadyl inhibited both the soluble and particulate ALP activity from UMR.106 cells and from bovine intestinal ALP. We have also shown the inhibition of ALP activity in the soluble fraction of osteoblasts by peroxo and hydroperoxo vanadium compounds. ALP activity in the particulate fraction was not inhibited by these species; nor was the bovine intestinal ALP. Using inhibitors of Tyr-phosphatase (PTPases), the soluble ALP was partially characterized as a PTPase. The major activity in the particulate fraction represents the bone-specific ALP-activity. This study demonstrates that different forms of vanadium are direct inhibitors of ALP activity. This effect is dependent on the enzymatic activity investigated and on the origin of the ALP. PMID:7946923

  12. Antifungal activity of fractions and two pure compounds of flowers from Wedelia paludosa (Acmela brasiliensis) (Asteraceae).

    PubMed

    Sartori, M R K; Pretto, J B; Cruz, A B; Bresciani, L F V; Yunes, R A; Sortino, M; Zacchino, S A; Cechinel, V Filho

    2003-08-01

    Wedelia paludosa (Acmela brasiliensis) (Asteraceae), a traditionally used native Brazilian medicinal plant, showed antifungal activity against dermatophytes in dilution tests. The hexane, dichloromethane and butanol fractions displayed activity against Epidermophyton floccosum, Trichophyton rubrum and Trichophyton mentagrophytes, with minimal inhibitory concentrations between 250 and 1000 microg/mL. Two pure compounds, identified as kaurenoic acid (1) and luteolin (2), also showed activity against these dermatophytes. PMID:12967035

  13. Selenium compounds activate early barriers of tumorigenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Selenium chemoprevention by apoptosis has been well studied, but it is not clear whether selenium can activate early barriers of tumorigenesis, namely senescence and DNA damage response. To address this issue, we treated normal and cancerous cells with a gradient concentration of sodium selenite, me...

  14. Identification of the phenolic compounds contributing to antibacterial activity in ethanol extracts of Brazilian red propolis.

    PubMed

    Inui, Saori; Hatano, Ai; Yoshino, Megumi; Hosoya, Takahiro; Shimamura, Yuko; Masuda, Shuichi; Ahn, Mok-Ryeon; Tazawa, Shigemi; Araki, Yoko; Kumazawa, Shigenori

    2014-01-01

    The purpose of this study is to identify the quantity and antibacterial activity of the individual phenolic compounds in Brazilian red propolis. Quantitative analysis of the 12 phenolic compounds in Brazilian red propolis was carried out using reversed-phase high-performance liquid chromatography. The main phenolic compounds in Brazilian red propolis were found to be (3S)-vestitol (1), (3S)-neovestitol (2) and (6aS,11aS)-medicarpin (4) with quantities of 72.9, 66.9 and 30.8 mg g of ethanol extracts(- 1), respectively. Moreover, the antibacterial activities of each compound against Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa were evaluated by measuring the minimum inhibitory concentrations. In particular, compound 4 exhibited the most potent antibacterial activity among all the assayed compounds against selected bacteria, indicating that 4 is the most active compound in Brazilian red propolis extracts. Thus, Brazilian red propolis may be used as food additives and pharmaceuticals to protect against bacteria. PMID:24666260

  15. Use of reference compounds in antioxidant activity assessment.

    PubMed

    Nenadis, Nikolaos; Lazaridou, Olga; Tsimidou, Maria Z

    2007-07-11

    The choice of reference compounds is examined as a "critical control point" of antioxidant activity assessment. Gallic, caffeic, sinapic, uric, and ascorbic acids, isoeugenol, and Trolox were tested using different redox (FRAP, Folin-Ciocalteu) and radical scavenging (DPPH*, ABTS*+, CBA, ORAC) assays. The ability to chelate transition metals was assessed to support some of the findings. Analytes were also tested in liposomes. On the basis of the findings, we do not recommend uric acid (due to solubility constrains) and ascorbic acid (due to fast degradation kinetics) as references. The behavior of the rest of the compounds could not always be attributed to typical structural characteristics. Selection of suitable reference compounds for in vitro antioxidant activity assays is not an easy task to achieve. The choice of reference compounds has to remain at the convenience of the researchers, with regard to the aim of the study. PMID:17579432

  16. TESTS ON LUMINOUS COMPOUNDS ACTIVATED WITH PROMETHIUM 147

    Microsoft Academic Search

    Veit

    1963-01-01

    Luminous compounds activated with Pm¹⁴⁷ are commercially available. ; The reasons why Pm¹⁴⁷ was given preference are outlined. The activity, ; the natural decrease in luminosity, the luminous capacity in powder form and ; applied to surfaces (coated objects), and the dependence on the crystal size of ; the phosphor are described. Radiation intensity and absence of radioactive ; contamination

  17. Antifungal Activity of Extractable Conifer Heartwood Compounds Toward Phytophthora ramorum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Individual compounds and ethyl acetate extracts from heartwood of seven conifer species were tested for fungicidal activity against Phytophthora ramorum. Extracts from incense and western redcedar exhibited the strongest activity (EC50 589 and 646 ppm, respectively), yellow-cedar, western juniper, ...

  18. Ganoderma lucidum and its pharmaceutically active compounds.

    PubMed

    Boh, Bojana; Berovic, Marin; Zhang, Jingsong; Zhi-Bin, Lin

    2007-01-01

    Ganoderma lucidum is a wood-degrading basidiomycete with numerous pharmacological effects. Since the mushroom is very rare in nature, artificial cultivation of fruiting bodies has been known on wood logs and on sawdust in plastic bags or bottles. Biotechnological cultivation of G. lucidum mycelia in bioreactors has also been established, both on solid substrates and in liquid media by submerged cultivation of fungal biomass. The most important pharmacologically active constituents of G. lucidum are triterpenoids and polysaccharides. Triterpenoids have been reported to possess hepatoprotective, anti-hypertensive, hypocholesterolemic and anti-histaminic effects, anti-tumor and anti-engiogenic activity, effects on platelet aggregation and complement inhibition. Polysaccharides, especially beta-d-glucans, have been known to possess anti-tumor effects through immunomodulation and anti-angiogenesis. In addition, polysaccharides have a protective effect against free radicals and reduce cell damage caused by mutagens. PMID:17875480

  19. EXAMINATION OF RHIZOSPHERE-ASSOCIATED MICROBES FOR PRODUCTION OF COMPOUNDS ACTIVE AGAINST PLANT-PARASITIC NEMATODES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In vitro studies identified fungi and bacteria that produce compounds active against plant-parasitic nematodes. Assays of fungus culture filtrates were conducted with Heterodera glycines (soybean cyst nematode: SCN) and Meloidogyne incognita (root-knot nematode: RKN). The tested filtrates exhibite...

  20. Anti-Inflammatory Activity of Sulfur-Containing Compounds from Garlic

    PubMed Central

    Lee, Da Yeon; Li, Hua; Lim, Hyo Jin; Lee, Hwa Jin; Jeon, Raok

    2012-01-01

    Abstract We identified four anti-inflammatory sulfur-containing compounds from garlic, and their chemical structures were identified as Z- and E-ajoene and oxidized sulfonyl derivatives of ajoene. The sulfur compounds inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) and the expression of the pro-inflammatory cytokines tumor necrosis factor-?, interleukin-1?, and interleukin-6 in lipopolysaccharide (LPS)-activated macrophages. Western blotting and reverse transcription–polymerase chain reaction analysis demonstrated that these sulfur compounds attenuated the LPS-induced expression of the inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins and mRNA. Moreover, these sulfur-containing compounds suppressed the nuclear factor-?B (NF-?B) transcriptional activity and the degradation of inhibitory-?B? in LPS-activated macrophages. Furthermore, we observed that they markedly inhibited the LPS-induced phosphorylations of p38 mitogen-activated protein kinases and extracellular signal-regulated kinases (ERK) at 20??M. These data demonstrate that the sulfur compounds from garlic, (Z, E)-ajoene and their sulfonyl analogs, can suppress the LPS-induced production of NO/PGE2 and the expression of iNOS/COX-2 genes by inhibiting the NF-?B activation and the phosphorylations of p38 and ERK. Taken together, these data show that Z- and E-ajoene and their sulfonyl analogs from garlic might have anti-inflammatory therapeutic potential. PMID:23057778

  1. Biological Activities of Phenolic Compounds Present in Virgin Olive Oil

    PubMed Central

    Cicerale, Sara; Lucas, Lisa; Keast, Russell

    2010-01-01

    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. PMID:20386648

  2. Synthesis and Biological Activity on Some Organoantimony (III) Compounds

    Microsoft Academic Search

    Ravi Kant; Amresh K. Chandrashekar; Anil K. S. Kumar

    2008-01-01

    Organoantimony (III) amides of the type Ar2SbL; (Ar = C6H5, C6F5, C6H4F; L = succinimide and phthallimide) were synthesized and assayed for their biological activities. These compounds exhibited significant in-vitro antitumor activity against human breast adenocarcinoma cell line (MCF-7), mammary cancer cell line (EVSA-7), and antibacterial activity against human pathogenic bacteria viz. Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiela pneumoniae. These

  3. Emodin is identified as the active component of ether extracts from Rhizoma Polygoni Cuspidati, for anti-MRSA activity.

    PubMed

    Cao, Feng; Peng, Wei; Li, Xiaoli; Liu, Ming; Li, Bin; Qin, Rongxin; Jiang, Weiwei; Cen, Yanyan; Pan, Xichun; Yan, Zifei; Xiao, Kangkang; Zhou, Hong

    2015-06-01

    This study investigated the anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity and chemical compositions of ether extracts from Rhizoma Polygoni Cuspidati (ET-RPC). Significant anti-MRSA activities of ET-RPC against MRSA252 and MRSA clinical strains were tested in in vitro antibacterial experiments, such as inhibition zone diameter test, minimal inhibitory concentration test, and dynamic bacterial growth assay. Subsequently, 7 major compounds of ET-RPC were purified and identified as polydatin, resveratrol-4-O-d-(6'-galloyl)-glucopyranoside, resveratrol, torachryson-8-O-glucoside, emodin-8-O-glucoside, 6-hydroxy-emodin, and emodin using liquid chromatography - electrospray ionization - tandem mass spectrometry. After investigation of anti-MRSA activities of the 7 major compounds, only emodin had significant anti-MRSA activity. Further, transmission electron microscopy was used to observe morphological changes in the cell wall of MRSA252, and the result revealed that emodin could damage the integrity of cell wall, leading to loss of intracellular components. In summary, our results showed ET-RPC could significantly inhibit bacterial growth of MRSA strains. Emodin was identified as the major compound with anti-MRSA activity; this activity was related to destruction of the integrity of the cell wall and cell membrane. PMID:25966789

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

    PubMed

    Stumpfe, Dagmar; Dimova, Dilyana; Bajorath, Jürgen

    2015-07-01

    Scaffold hopping and activity cliff formation define opposite ends of the activity landscape feature spectrum. To rationalize these events at the level of scaffolds, active compounds involved in scaffold hopping were required to contain topologically distinct scaffolds but have only limited differences in potency, whereas compounds involved in activity cliffs were required to share the same scaffold but have large differences in potency. A systematic search was carried out for compounds involved in scaffold hopping and/or activity cliff formation. Results obtained for compound data sets covering more than 300 human targets revealed clear trends. If scaffolds represented multiple but fewer than 10 active compounds, nearly 90% of all scaffolds were exclusively involved in hopping events. With increasing compound coverage, the fraction of scaffolds involved in both scaffold hopping and activity cliff formation significantly increased to more than 50%. However, ?40% of the scaffolds representing large numbers of active compounds continued to be exclusively involved in scaffold hopping. More than 200 scaffolds with broad target coverage were identified that consistently represented potent compounds and yielded an abundance of scaffold hops in the low-nanomolar range. These and other subsets of scaffolds we characterized are of prime interest for structure-activity relationship (SAR) exploration and compound design. Therefore, the complete scaffold classification generated in the course of our analysis is made freely available. PMID:25982076

  5. Prediction of antifungal activity of gemini imidazolium compounds.

    PubMed

    Pa?kowski, ?ukasz; B?aszczy?ski, Jerzy; Skrzypczak, Andrzej; B?aszczak, Jan; Nowaczyk, Alicja; Wróblewska, Joanna; Ko?uszko, Sylwia; Gospodarek, Eugenia; S?owi?ski, Roman; Krysi?ski, Jerzy

    2015-01-01

    The progress of antimicrobial therapy contributes to the development of strains of fungi resistant to antimicrobial drugs. Since cationic surfactants have been described as good antifungals, we present a SAR study of a novel homologous series of 140 bis-quaternary imidazolium chlorides and analyze them with respect to their biological activity against Candida albicans as one of the major opportunistic pathogens causing a wide spectrum of diseases in human beings. We characterize a set of features of these compounds, concerning their structure, molecular descriptors, and surface active properties. SAR study was conducted with the help of the Dominance-Based Rough Set Approach (DRSA), which involves identification of relevant features and relevant combinations of features being in strong relationship with a high antifungal activity of the compounds. The SAR study shows, moreover, that the antifungal activity is dependent on the type of substituents and their position at the chloride moiety, as well as on the surface active properties of the compounds. We also show that molecular descriptors MlogP, HOMO-LUMO gap, total structure connectivity index, and Wiener index may be useful in prediction of antifungal activity of new chemical compounds. PMID:25961015

  6. Characterization of pharmacologically active compounds that inhibit poliovirus and enterovirus 71 infectivity.

    PubMed

    Arita, Minetaro; Wakita, Takaji; Shimizu, Hiroyuki

    2008-10-01

    Poliovirus (PV) and enterovirus 71 (EV71) cause severe neurological symptoms in their infections of the central nervous system. To identify compounds with anti-PV and anti-EV71 activities that would not allow the emergence of resistant mutants, we performed drug screening by utilizing a pharmacologically active compound library targeting cellular factors with PV and EV71 pseudoviruses that encapsidated luciferase-encoding replicons. We have found that metrifudil (N-[2-methylphenyl]methyl)-adenosine) (an A2 adenosine receptor agonist), N(6)-benzyladenosine (an A1 adenosine receptor agonist) and NF449 (4,4',4'',4'''-[carbonylbis[imino-5,1,3-benzenetriyl bis(carbonyl-imino)

  7. Two new compounds from Crataegus pinnatifida and their antithrombotic activities.

    PubMed

    Zhou, Chen-Chen; Huang, Xiao-Xiao; Gao, Pin-Yi; Li, Fei-Fei; Li, Dian-Ming; Li, Ling-Zhi; Song, Shao-Jiang

    2014-01-01

    One new sesquiterpene, (1?,4a?,8a?)-1-isopropanol-4a-methyl-8-methylenedecahydronaphthalene (1), with one new phenylpropanoid, threo-2-(4-hydroxy-3,5-dimethoxyphenyl)-3-(4-hydroxy-3-methoxyphenyl)-3-ethoxypropan-1-ol (2), along with four known phenylpropanoids were isolated from Crataegus pinnatifida. The structures of compounds 1 and 2 were elucidated on the basis of 1D, 2D NMR analyses, and HR-ESI-MS. The antithrombotic activity in vitro of all isolates was assayed, and only compound 1 exhibited potent antithrombotic activity by inhibiting platelet aggregation in rat plasma by 81.4% at 1 mg/ml. PMID:24161196

  8. Dietary fibre content and antioxidant activity of phenolic compounds present in Mexican chia ( Salvia hispanica L.) seeds

    Microsoft Academic Search

    E. Reyes-Caudillo; A. Tecante; M. A. Valdivia-López

    2008-01-01

    Chia seeds from two different regions in the states of Jalisco and Sinaloa were analyzed for soluble and insoluble fibre and antioxidant activity of phenolic compounds. The soluble and insoluble fibre content of the Sinaloa and Jalisco seeds was similar. The major compounds identified in hydrolyzed and crude extracts were quercetin and kaempferol, while caffeic and chlorogenic acids were present

  9. Quantitative high-throughput screening: A titration-based approach that efficiently identifies biological activities in large chemical libraries

    Microsoft Academic Search

    James Inglese; Douglas S. Auld; Ajit Jadhav; Ronald L. Johnson; Anton Simeonov; Adam Yasgar; Wei Zheng; Christopher P. Austin

    2006-01-01

    High-throughput screening (HTS) of chemical compounds to identify modulators of molecular targets is a mainstay of pharmaceutical development. Increasingly, HTS is being used to identify chemical probes of gene, pathway, and cell functions, with the ultimate goal of comprehensively delineating relationships between chemical structures and biological activities. Achieving this goal will require methodologies that efficiently generate pharmacological data from the

  10. Prioritizing testing of organic compounds detected as gas phase air pollutants: structure-activity study for human contact allergens.

    PubMed Central

    Johnson, R; Macina, O T; Graham, C; Rosenkranz, H S; Cass, G R; Karol, M H

    1997-01-01

    Organic compounds that are used or generated anthropogenically in large quantities in cities can be identified through their presence in the urban atmosphere and in air pollutant source emissions. Compounds identified by this method were screened to evaluate their potential to act as contact allergens. The CASE and MULTICASE computer programs, which are based on the detection of structure-activity relationships (SAR), were used to evaluate this potential. These relationships first are determined by comparing chemical structures to biological activity within a learning set comprised of 458 compounds, each of which had been tested experimentally in human trials for its sensitization potential. Using the information contained in this learning set, CASE and MULTICASE predicted the activity of 238 compounds found in the atmosphere for their ability to act as contact allergens. The analysis finds that 21 of 238 compounds are predicted to be active contact allergens (probability >0.5), with potencies ranging from mild to very strong. The compounds come from chemical classes that include chlorinated aromatics and chlorinated hydrocarbons, N-containing compounds, phenols, alkenes, and an S-containing compound. Using the measured airborne concentrations or emission rates of these compounds as an indication of the extent of their use, together with their predicted potencies, provides an efficient method to prioritize the experimental assessment of contact sensitization of untested organic compounds that can be detected as air pollutants. Images Figure 1. PMID:9300925

  11. Identifying Emotions on the Basis of Neural Activation

    PubMed Central

    Kassam, Karim S.; Markey, Amanda R.; Cherkassky, Vladimir L.; Loewenstein, George; Just, Marcel Adam

    2013-01-01

    We attempt to determine the discriminability and organization of neural activation corresponding to the experience of specific emotions. Method actors were asked to self-induce nine emotional states (anger, disgust, envy, fear, happiness, lust, pride, sadness, and shame) while in an fMRI scanner. Using a Gaussian Naïve Bayes pooled variance classifier, we demonstrate the ability to identify specific emotions experienced by an individual at well over chance accuracy on the basis of: 1) neural activation of the same individual in other trials, 2) neural activation of other individuals who experienced similar trials, and 3) neural activation of the same individual to a qualitatively different type of emotion induction. Factor analysis identified valence, arousal, sociality, and lust as dimensions underlying the activation patterns. These results suggest a structure for neural representations of emotion and inform theories of emotional processing. PMID:23840392

  12. Merging bioactivity with liquid chromatography-mass spectrometry-based chemometrics to identify minor immunomodulatory compounds from a Micronesian adaptogen, Phaleria nisidai.

    PubMed

    Kulakowski, Daniel M; Wu, Shi-Biao; Balick, Michael J; Kennelly, Edward J

    2014-10-17

    This study presents a strategy based on repeatable reversed-phase LC-TOF-MS methods and chemometric statistical tools, including untargeted PCA and supervised OPLS-DA models, to identify low-yielding compounds with potent immunostimulant activity in Phaleria nisidai (Thymelaeaceae), a plant with a history of use as an adaptogen on the islands of Palau in Micronesia. IFN? ELISA assays were used to classify chromatographic fractions according to imunomodulatory activity prior to LC-TOF-MS chemometric analysis to target and identify compounds likely to contribute to observed activity. Simplexin, a daphnane diterpene ester, was identified for the first time from this genus and caused an increase in the production of cytokines (IFN?, IL1?, IL6, and IL13) by peripheral blood mononuclear cells. Five other daphnane diterpene esters were tentatively identified for the first time from this plant based on mass spectral data and are marker metabolites distinguishing active from inactive fractions. This analytical approach increased the efficiency of bioactivity-guided fractionation and has the potential to minimize redundant isolation and identify minor constituents with potent activity from a complex matrix. PMID:25218635

  13. Uptake, metabolism and mutagenic activity of aromatic glycidyl compounds.

    PubMed

    Seiler, J P

    1984-10-01

    Aromatic diglycidyl compounds are very active mutagens when assayed in in vitro tests. In vivo, however, resorcinol diglycidyl ether provided no evidence for the clastogenic activity, while diglycidylaniline exhibited definite mutagenic activity in the micronucleus test. Since the only difference between these two compounds lies in the binding mode of the glycidyl groups to the aromatic nucleus (i.e. ether oxygen vs. aminic nitrogen), this apparent discrepancy in mutagenic activity led to the question of the mechanisms involved in such an activity difference. Although no clear signs of differential uptake or excretion could be detected in mice, differences could be seen in the spectrum of urinary metabolites; while resorcinol diglycidyl ether seemed to become fully converted to the genetically inactive bis-diol compound, a sizeable proportion of diglycidylaniline was converted only to the diol-epoxide. In vitro investigations and enzyme kinetic measurements with postmitochondrial supernatant of rat or mouse liver homogenate (S-9) finally yielded the biochemical explanation for this behaviour, as they showed a very low affinity of the diol-epoxide metabolite of diglycidylaniline for the epoxide hydrolase, normally involved in the degradation of such compounds. The diol-epoxide obtained from resorcinol diglycidyl ether, on the other hand, has an affinity to the degradation enzyme similar to, or even higher than, the one measured with the parent substance. PMID:6386198

  14. Removal of pharmaceutically active compounds in nitrifying-denitrifying plants.

    PubMed

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

    2005-01-01

    The behaviour of nine pharmaceutically active compounds (PhACs) of different diagnostic groups is studied during a nitrifying-denitrifying process in an activated sludge system. The compounds selected cover a wide range of frequently used substances such as anti-epileptics (carbamazepine), tranquillisers (diazepam), anti-depressants (fluoxetine and citalopram), anti-inflammatories (ibuprofen, naproxen and diclofenac) and estrogens (estradiol and ethinylestradiol). The main objective of this research is to investigate the effect of acclimation of biomass on the removal rates of these compounds, either by maintaining a high sludge retention time or at long-term operation. The removal rates achieved for nitrogen and carbon in the experimental unit exceed 90% and were not affected by the addition of PhACs. Carbamazepine, diazepam and diclofenac were only removed to a small extent. On the other hand, higher removal rates have been observed for naproxen and ibuprofen (68% and 82%), respectively. PMID:16312946

  15. ORIGINAL PAPER Nitrate reductase activity and nitrogen compounds in xylem

    E-print Network

    ORIGINAL PAPER Nitrate reductase activity and nitrogen compounds in xylem exudate of Juglans nigra is limited. We fertilized 1-year-old, half-sib black walnut (Juglans nigra L.) seedlings with ammonium (NH4 Nitrate Á Nitrate reductase Á Ammonium Á Xylem exudate Introduction Black walnut (Juglans nigra L.) is one

  16. Nanoparticle Formation of Organic Compounds With Retained Biological Activity

    E-print Network

    Zare, Richard N.

    : Many pharmaceuticals are formulated as powders to aid drug delivery. A major problem is how to produce powders having high purity, controlled morphology, and retained bioactivity. We demonstrate the use active compounds many of these processing steps can cause loss of bioactivity caused by shock and heat

  17. Biologically active compounds from European mistletoe (Viscum album L.)

    Microsoft Academic Search

    J. Renata Ochocka; Arkadiusz Piotrowski

    2002-01-01

    European mistletoe (Viscum album L.) is a commonly occurring semiparasite of trees. The extracts from European mistletoe have been shown to possess immunostimulatory and cytotoxic activity on tumor cells, and are used in Europe in adjuvant cancer therapy. Recently, a number of studies performed have been leading to the identification and characterization of bioactive compounds. Apoptosis-inducing and ribosome-inactivating lectins as

  18. Effects of polyhydroxy compounds on beetle antifreeze protein activity.

    PubMed

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

    2009-02-01

    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

  19. The synthesis and surface active properties of certain amphoteric compounds

    Microsoft Academic Search

    W. M. Linfield; P. G. Abend; G. A. Davis

    1963-01-01

    In order to gain some insight into the correlation between chemical structure and surface active properties, a number of amphoteric\\u000a surface active agents were synthesized. All of these compounds possessed both a quaternary ammonium group and an anionic functional\\u000a group. The anionic functional group was either a carboxylate, sulfonate, or a sulfate group. The molecules possessed either\\u000a one or two

  20. 2-Phenylaminonaphthoquinones and related compounds: synthesis, trypanocidal and cytotoxic activities.

    PubMed

    Sieveking, Ivan; Thomas, Pablo; Estévez, Juan C; Quiñones, Natalia; Cuéllar, Mauricio A; Villena, Juan; Espinosa-Bustos, Christian; Fierro, Angélica; Tapia, Ricardo A; Maya, Juan D; López-Muñoz, Rodrigo; Cassels, Bruce K; Estévez, Ramon J; Salas, Cristian O

    2014-09-01

    A series of new 2-aminonaphthoquinones and related compounds were synthesized and evaluated in vitro as trypanocidal and cytotoxic agents. Some tested compounds inhibited epimastigote growth and trypomastigote viability. Several compounds showed similar or higher activity and selectivity as compared with current trypanocidal drug, nifurtimox. Compound 4l exhibit higher selectivity than nifurtimox against Trypanosoma cruzi in comparison with Vero cells. Some of the synthesized quinones were tested against cancer cells and normal fibroblasts, showing that certain chemical modifications on the naphthoquinone moiety induce and excellent increase the selectivity index of the cytotoxicity (4g and 10). The results presented here show that the anti-T. cruzi activity of 2-aminonaphthoquinones derivatives can be improved by the replacement of the benzene ring by a pyridine moiety. Interestingly, the presence of a chlorine atom at C-3 and a highly lipophilic alkyl group or aromatic ring are newly observed elements that should lead to the discovery of more selective cytotoxic and trypanocidal compounds. PMID:25127463

  1. 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

  2. Identifying Associations between Student Achievement and Parental Involvement Activities

    ERIC Educational Resources Information Center

    Waddle, Ann R.

    2011-01-01

    The revision and renewal of the Elementary and Secondary Education Act of 1965 will likely expand its parental involvement component to engage educators, parents, and community partners in supporting public education for children. This revisions call for best practices, but current literature fails to identify specific activities associated…

  3. Cytotoxic and Antimigratory Activities of Phenolic Compounds from Dendrobium brymerianum.

    PubMed

    Klongkumnuankarn, Pornprom; Busaranon, Kesarin; Chanvorachote, Pithi; Sritularak, Boonchoo; Jongbunprasert, Vichien; Likhitwitayawuid, Kittisak

    2015-01-01

    Chromatographic separation of a methanol extract prepared from the whole plant of Dendrobium brymerianum led to the isolation of eight phenolic compounds. Among the isolated compounds (1-8), moscatilin (1), gigantol (3), lusianthridin (4), and dendroflorin (6) showed appreciable cytotoxicity against human lung cancer cell lines with IC50 values of 196.7, 23.4, 65.0, and 125.8??g/mL, respectively, and exhibited antimigratory property at nontoxic concentrations. This study is the first report on the biological activities of this plant. PMID:25685168

  4. 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, ?-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.

  5. Antitumor activity of compounds isolated from leaves of Eriobotrya japonica.

    PubMed

    Ito, Hideyuki; Kobayashi, Eri; Li, Shu-Hua; Hatano, Tsutomu; Sugita, Daigo; Kubo, Naoki; Shimura, Susumu; Itoh, Yoshio; Tokuda, Harukuni; Nishino, Hoyoku; Yoshida, Takashi

    2002-04-10

    In a search for possible antitumor agents from natural sources, megastigmane glycosides and polyphenolic constituents isolated from the leaves of Eriobotrya japonica (Rosaceae) were found to inhibit the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced activation of Epstein-Barr virus early antigen in Raji cells. Roseoside and procyanidin B-2 were among the active compounds found in an in vitro assay; these compounds were further assessed for antitumor activity in vivo in a two-stage carcinogenesis assay on mouse skin. Roseoside significantly delayed carcinogenesis induced by peroxynitrite (initiator) and TPA (promoter), and its potency was comparable to that of a green tea polyphenol, (-)-epigallocatechin 3-O-gallate, in the same assay. PMID:11929303

  6. 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 ?g/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

  7. 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 ?g/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

  8. A covalent peptide inhibitor of RGS4 identified in a focused one-bead, one compound library screen

    PubMed Central

    Roof, Rebecca A; Roman, David L; Clements, Samuel T; Sobczyk-Kojiro, Katarzyna; Blazer, Levi L; Ota, Shodai; Mosberg, Henry I; Neubig, Richard R

    2009-01-01

    Background Regulators of G protein signaling (RGSs) accelerate GTP hydrolysis by G? subunits and profoundly inhibit signaling by G protein-coupled receptors (GPCRs). The distinct expression patterns and pathophysiologic regulation of RGS proteins suggest that inhibitors may have therapeutic potential. We recently described a focused one-bead, one-compound (OBOC) library screen to identify peptide inhibitors of RGS4. Here we extend our observations to include another peptide with a different mechanism of action. Results Peptide 5nd (Tyr-Trp-c [Cys-Lys-Gly-Leu-Cys]-Lys-NH2, S-S) blocks the RGS4-G?o interaction with an IC50 of 28 ?M. It forms a covalent, dithiothreitol (DTT) sensitive adduct with a mass consistent with the incorporation of one peptide per RGS. Peptide 5nd activity is abolished by either changing its disulfide bridge to a methylene dithioether bridge, which cannot form disulfide bridges to the RGS, or by removing all cysteines from the RGS protein. However, no single cysteine in RGS4 is completely necessary or sufficient for 5nd activity. Conclusion Though it has some RGS selectivity, 5nd appears to be a partially random cysteine modifier. These data suggest that it inhibits RGS4 by forming disulfide bridges with the protein. PMID:19463173

  9. 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 ?-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.

  10. Antimicrobial activity of an endophytic Xylaria sp.YX-28 and identification of its antimicrobial compound 7-amino-4-methylcoumarin

    Microsoft Academic Search

    Xiaoli Liu; Mingsheng Dong; Xiaohong Chen; Mei Jiang; Xin Lv; Jianzhong Zhou

    2008-01-01

    An endophytic Xylaria sp., having broad antimicrobial activity, was isolated and characterized from Ginkgo biloba L. From the culture extracts of this fungus, a bioactive compound P3 was isolated by bioactivity-guided fractionation and\\u000a identified as 7-amino-4-methylcoumarin by nuclear magnetic resonance, infrared, and mass spectrometry spectral data. The compound\\u000a showed strong antibacterial and antifungal activities in vitro against Staphylococcus aureus [minimal

  11. FP Tethering: a screening technique to rapidly identify compounds that disrupt protein-protein interactions.

    PubMed

    Lodge, Jean M; Rettenmaier, T Justin; Wells, James A; Pomerantz, William C; Mapp, Anna K

    2014-03-01

    Tethering is a screening technique for discovering small-molecule fragments that bind to pre-determined sites via formation of a disulphide bond. Tethering screens traditionally rely upon mass spectrometry to detect disulphide bind formation, which requires a time-consuming liquid chromatography step. Here we show that Tethering can be performed rapidly and inexpensively using a homogenous fluorescence polarization (FP) assay that detects displacement of a peptide ligand from the protein target as an indirect readout of disulphide formation. We apply this method, termed FP Tethering, to identify fragments that disrupt the protein-protein interaction between the KIX domain of the transcriptional coactivator CBP and the transcriptional activator peptide pKID. PMID:24795804

  12. Phosphatidylinositol 4-Kinase III Beta Is a Target of Enviroxime-Like Compounds for Antipoliovirus Activity? †

    PubMed Central

    Arita, Minetaro; Kojima, Hirotatsu; Nagano, Tetsuo; Okabe, Takayoshi; Wakita, Takaji; Shimizu, Hiroyuki

    2011-01-01

    Enviroxime is an antienterovirus compound that targets viral protein 3A and/or 3AB and suppresses a step in enterovirus replication by unknown mechanism. To date, four antienterovirus compounds, i.e., GW5074, Flt3 inhibitor II, TTP-8307, and AN-12-H5, are known to have similar mutations in the 3A protein-encoding region causing resistance to enviroxime (a G5318A [3A-Ala70Thr] mutation in poliovirus [PV]) and are considered enviroxime-like compounds. Recently, antienterovirus activity of a phosphatidylinositol 4-kinase III beta (PI4KB) inhibitor, PIK93, was reported, suggesting that PI4KB is an important host factor targetable by antienterovirus compounds (N. Y. Hsu et al., Cell 141:799-811, 2010). In this study, we analyzed the inhibitory effects of previously identified enviroxime-like compounds (GW5074 and AN-12-H5) and a newly identified antienterovirus compound, T-00127-HEV1, on phosphoinositide (PI) kinases. We found that T-00127-HEV1 inhibited PI4KB activity with a higher specificity for than other PI kinases, in contrast to GW5074, which had a broad specificity for PI kinases. In contrast, AN-12-H5 showed no inhibitory effect on PI4KB activity and only moderate inhibitory effects on PI 3-kinase activity. Small interfering RNA (siRNA) screening targeting PI kinases identified PI4KB is a target of GW5074 and T-00127-HEV1, but not of AN-12-H5, for anti-PV activity. Interestingly, T-00127-HEV1 and GW5074 did not inhibit hepatitis C virus (HCV) replication, in contrast to a strong inhibitory effect of AN-12-H5. These results suggested that PI4KB is an enterovirus-specific host factor required for the replication process and targeted by some enviroxime-like compounds (T-00127-HEV1 and GW5074) and that enviroxime-like compounds may have targets other than PI kinases for their antiviral effect. PMID:21177810

  13. Synthesis and Structure activity relationships of EGCG Analogues, A Recently Identified Hsp90 Inhibitor

    PubMed Central

    Khandelwal, Anuj; Hall, Jessica

    2014-01-01

    Epigallocatechin-3-gallate (EGCG), the principal polyphenol isolated from green tea, was recently shown to inhibit Hsp90, however structure-activity relationships for this natural product have not yet been produced. Herein, we report the synthesis and biological evaluation of EGCG analogues to establish structure-activity relationships between EGCG and Hsp90. All four rings as well as the linker connecting the C- and the D-rings were systematically investigated, which led to the discovery of compounds that inhibit Hs90 and display improvement in efficacy over EGCG. Anti-proliferative activity of all the analogues was determined against MCF-7 and SKBr3 cell lines and Hsp90 inhibitory activity of four most potent analogues was further evaluated by western blot analyses and degradation of Hsp90-dependent client proteins. Prenyl substituted aryl ester of 3,5-dihydroxychroman-3-ol ring system was identified as novel scaffold that exhibit Hsp90 inhibitory activity. PMID:23834230

  14. Antiplasmodial activities of 4-aminoquinoline-statine compounds.

    PubMed

    Vaiana, Nadia; Marzahn, Melissa; Parapini, Silvia; Liu, Peng; Dell'Agli, Mario; Pancotti, Andrea; Sangiovanni, Enrico; Basilico, Nicoletta; Bosisio, Enrica; Dunn, Ben M; Taramelli, Donatella; Romeo, Sergio

    2012-09-15

    We report the discovery of new potent inhibitors of the growth of Plasmodium falciparum chloroquine (CQ)-resistant W2 strain. These compounds were designed using the double drug approach by introducing a residue able to enhance the accumulation of plasmepsins inhibitors into the food vacuole. Some of the molecules were more active than CQ against CQ-resistant strain and showed good selectivity against cathepsin D. PMID:22884991

  15. Degradation of volatile organic compounds with thermally activated persulfate oxidation

    Microsoft Academic Search

    Kun-Chang Huang; Zhiqiang Zhao; George E. Hoag; Amine Dahmani; Philip A. Block

    2005-01-01

    This study investigated the extent and treatability of the degradation of 59 volatile organic compounds (VOCs) listed in the EPA SW-846 Method 8260B with thermally activated persulfate oxidation. Data on the degradation of the 59 VOCs (in mixture) reacted with sodium persulfate in concentrations of 1gl?1 and 5gl?1 and at temperatures of 20°C, 30°C, and 40°C were obtained. The results

  16. Identification of thyroid hormone receptor active compounds using a quantitative high-throughput screening platform.

    PubMed

    Freitas, Jaime; Miller, Nicole; Mengeling, Brenda J; Xia, Menghang; Huang, Ruili; Houck, Keith; Rietjens, Ivonne M C M; Furlow, J David; Murk, Albertinka J

    2014-01-01

    To adapt the use of GH3.TRE-Luc reporter gene cell line for a quantitative high-throughput screening (qHTS) platform, we miniaturized the reporter gene assay to a 1536-well plate format. 1280 chemicals from the Library of Pharmacologically Active Compounds (LOPAC) and the National Toxicology Program (NTP) 1408 compound collection were analyzed to identify potential thyroid hormone receptor (TR) agonists and antagonists. Of the 2688 compounds tested, eight scored as potential TR agonists when the positive hit cut-off was defined at ?10% efficacy, relative to maximal triiodothyronine (T3) induction, and with only one of those compounds reaching ?20% efficacy. One common class of compounds positive in the agonist assays were retinoids such as all-trans retinoic acid, which are likely acting via the retinoid-X receptor, the heterodimer partner with the TR. Five potential TR antagonists were identified, including the antiallergy drug tranilast and the anxiolytic drug SB 205384 but also some cytotoxic compounds like 5-fluorouracil. None of the inactive compounds were structurally related to T3, nor had been reported elsewhere to be thyroid hormone disruptors, so false negatives were not detected. None of the low potency (>100µM) TR agonists resembled T3 or T4, thus these may not bind directly in the ligand-binding pocket of the receptor. For TR agonists, in the qHTS, a hit cut-off of ?20% efficacy at 100 µM may avoid identification of positives with low or no physiological relevance. The miniaturized GH3.TRE-Luc assay offers a promising addition to the in vitro test battery for endocrine disruption, and given the low percentage of compounds testing positive, its high-throughput nature is an important advantage for future toxicological screening. PMID:24772387

  17. Identification of Thyroid Hormone Receptor Active Compounds Using a Quantitative High-Throughput Screening Platform

    PubMed Central

    Freitas, Jaime; Miller, Nicole; Mengeling, Brenda J.; Xia, Menghang; Huang, Ruili; Houck, Keith; Rietjens, Ivonne M.C.M.; Furlow, J. David; Murk, Albertinka J.

    2014-01-01

    To adapt the use of GH3.TRE-Luc reporter gene cell line for a quantitative high-throughput screening (qHTS) platform, we miniaturized the reporter gene assay to a 1536-well plate format. 1280 chemicals from the Library of Pharmacologically Active Compounds (LOPAC) and the National Toxicology Program (NTP) 1408 compound collection were analyzed to identify potential thyroid hormone receptor (TR) agonists and antagonists. Of the 2688 compounds tested, eight scored as potential TR agonists when the positive hit cut-off was defined at ?10% efficacy, relative to maximal triiodothyronine (T3) induction, and with only one of those compounds reaching ?20% efficacy. One common class of compounds positive in the agonist assays were retinoids such as all-trans retinoic acid, which are likely acting via the retinoid-X receptor, the heterodimer partner with the TR. Five potential TR antagonists were identified, including the antiallergy drug tranilast and the anxiolytic drug SB 205384 but also some cytotoxic compounds like 5-fluorouracil. None of the inactive compounds were structurally related to T3, nor had been reported elsewhere to be thyroid hormone disruptors, so false negatives were not detected. None of the low potency (>100µM) TR agonists resembled T3 or T4, thus these may not bind directly in the ligand-binding pocket of the receptor. For TR agonists, in the qHTS, a hit cut-off of ?20% efficacy at 100 µM may avoid identification of positives with low or no physiological relevance. The miniaturized GH3.TRE-Luc assay offers a promising addition to the in vitro test battery for endocrine disruption, and given the low percentage of compounds testing positive, its high-throughput nature is an important advantage for future toxicological screening. PMID:24772387

  18. New compound sets identified from high throughput phenotypic screening against three kinetoplastid parasites: an open resource.

    PubMed

    Peña, Imanol; Pilar Manzano, M; Cantizani, Juan; Kessler, Albane; Alonso-Padilla, Julio; Bardera, Ana I; Alvarez, Emilio; Colmenarejo, Gonzalo; Cotillo, Ignacio; Roquero, Irene; de Dios-Anton, Francisco; Barroso, Vanessa; Rodriguez, Ana; Gray, David W; Navarro, Miguel; Kumar, Vinod; Sherstnev, Alexander; Drewry, David H; Brown, James R; Fiandor, Jose M; Julio Martin, J

    2015-01-01

    Using whole-cell phenotypic assays, the GlaxoSmithKline high-throughput screening (HTS) diversity set of 1.8 million compounds was screened against the three kinetoplastids most relevant to human disease, i.e. Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei. Secondary confirmatory and orthogonal intracellular anti-parasiticidal assays were conducted, and the potential for non-specific cytotoxicity determined. Hit compounds were chemically clustered and triaged for desirable physicochemical properties. The hypothetical biological target space covered by these diversity sets was investigated through bioinformatics methodologies. Consequently, three anti-kinetoplastid chemical boxes of ~200 compounds each were assembled. Functional analyses of these compounds suggest a wide array of potential modes of action against kinetoplastid kinases, proteases and cytochromes as well as potential host-pathogen targets. This is the first published parallel high throughput screening of a pharma compound collection against kinetoplastids. The compound sets are provided as an open resource for future lead discovery programs, and to address important research questions. PMID:25740547

  19. Isolation, identification, and antioxidant activity of anthocyanin compounds in Camarosa strawberry

    Microsoft Academic Search

    Ana B. Cerezo; Elyana Cuevas; P. Winterhalter; M. C. Garcia-Parrilla; A. M. Troncoso

    2010-01-01

    This paper explores the bioactive composition of strawberry (Camarosa variety) [Fragaria ×ananassa (Rosaceae Family)] describing its anthocyanin composition and measuring the antioxidant activity (AA) of isolated pigments.Pelargonidin-3-glucoside was the major compound followed by pelargonidin-3-rutinoside and 11 pelargonidin and cyanidin derivatives, determined by LC–DAD–MS. Additionally, delphinidin-3-glucoside, peonidin-3-glucoside, and cyanidin-3-galactoside were tentatively identified for the first time in strawberry. Another original contribution

  20. Antioxidant and Antiproliferative Activity of Diospyros lotus L. Extract and Isolated Compounds

    Microsoft Academic Search

    Monica Rosa Loizzo; Ataa Said; Rosa Tundis; Usama W. Hawas; Khaled Rashed; Federica Menichini; Natale Giuseppe Frega; Francesco Menichini

    2009-01-01

    The object of the study was to determine the chemical composition of Diospyros lotus L. extract and their antioxidant and antiproliferative properties. Eight compounds were isolated from D. lotus and identified as gallic acid, methylgallate, ellagic acid, kaempferol, quercetin, myricetin, myricetin 3-O-?-glucuronide, and myricetin-3-O-?-rhamnoside. D. lotus extract tested in different in vitro systems (DPPH, ABTS, FRAP, and Fe2+ chelating activity

  1. USE OF BIOASSAY-DIRECTED CHEMICAL ANALYSIS FOR IDENTIFYING MUTAGENIC COMPOUNDS IN URBAN AIR AND COMBUSTION EMISSIONS

    EPA Science Inventory

    Bioassay-directed chemical analysis fractionation has been used for 30 years to identify mutagenic classes of compounds in complex mixtures. Most studies have used the Salmonella (Ames) mutagenicity assay, and we have recently applied this methodology to two standard reference sa...

  2. Repurposing of the Open Access Malaria Box for Kinetoplastid Diseases Identifies Novel Active Scaffolds against Trypanosomatids.

    PubMed

    Kaiser, Marcel; Maes, Louis; Tadoori, Leela Pavan; Spangenberg, Thomas; Ioset, Jean-Robert

    2015-06-01

    Phenotypic screening had successfully been used for hit generation, especially in the field of neglected diseases, in which feeding the drug pipeline with new chemotypes remains a constant challenge. Here, we catalyze drug discovery research using a publicly available screening tool to boost drug discovery. The Malaria Box, assembled by the Medicines for Malaria Venture, is a structurally diverse set of 200 druglike and 200 probelike compounds distilled from more than 20,000 antimalarial hits from corporate and academic libraries. Repurposing such compounds has already identified new scaffolds against cryptosporidiosis and schistosomiasis. In addition to initiating new hit-to-lead activities, screening the Malaria Box against a plethora of other parasites would enable the community to better understand the similarities and differences between them. We describe the screening of the Malaria Box and triaging of the identified hits against kinetoplastids responsible for human African trypanosomiasis (Trypanosoma brucei), Chagas disease (Trypanosoma cruzi), and visceral leishmaniasis (Leishmania donovani and Leishmania infantum). The in vitro and in vivo profiling of the most promising active compounds with respect to efficacy, toxicity, pharmacokinetics, and complementary druggable properties are presented and a collaborative model used as a way to accelerate the discovery process discussed. PMID:25690568

  3. Identifying Sources of Volatile Organic Compounds and Aldehydes in a High Performance Building

    SciTech Connect

    Ortiz, Anna C.; Russell, Marion; Lee, Wen-Yee; Apte, Michael; Maddalena, Randy

    2010-09-20

    The developers of the Paharpur Business Center (PBC) and Software Technology Incubator Park in New Delhi, India offer an environmentally sustainable building with a strong emphasis on energy conservation, waste minimization and superior indoor air quality (IAQ). To achieve the IAQ goal, the building utilizes a series of air cleaning technologies for treating the air entering the building. These technologies include an initial water wash followed by ultraviolet light treatment and biolfiltration using a greenhouse located on the roof and numerous plants distributed throughout the building. Even with the extensive treatment of makeup air and room air in the PBC, a recent study found that the concentrations of common volatile organic compounds and aldehydes appear to rise incrementally as the air passes through the building from the supply to the exhaust. This finding highlights the need to consider the minimization of chemical sources in buildings in combination with the use of advanced air cleaning technologies when seeking to achieve superior IAQ. The goal of this project was to identify potential source materials for indoor chemicals in the PBC. Samples of building materials, including wood paneling (polished and unpolished), drywall, and plastic from a hydroponic drum that was part of the air cleaning system, were collected from the building for testing. All materials were collected from the PBC building and shipped to the Lawrence Berkeley National Laboratory (LBNL) for testing. The materials were pre-conditioned for two different time periods before measuring material and chemical specific emission factors for a range of VOCs and Aldehydes. Of the six materials tested, we found that the highest emitter of formaldehyde was new plywood paneling. Although polish and paint contribute to some VOC emissions, the main influence of the polish was in altering the capacity of the surface to accumulate formaldehyde. Neither the new nor aged polish contributed significantly to formaldehyde emissions. The VOC emission stream (excluding formaldehyde) was composed of up to 18 different chemicals and the total VOC emissions ranged in magnitude from 7 mu g/m2/h (old wood with old polish) to>500 mu g/m2/h (painted drywall). The formaldehyde emissions from drywall and old wood with either new or old polish were ~;;15 mu g/m2/h while the new wood material emitted>100 mu g/m2/h. However, when the projected surface area of each material in the building was considered, the new wood, old wood and painted drywall material all contributed substantially to the indoor formaldehyde loading while the coatings contributed primarily to the VOCs.

  4. Antioxidant activity and phenolic compounds in selected herbs.

    PubMed

    Zheng, W; Wang, S Y

    2001-11-01

    The antioxidant capacities (oxygen radical absorbance capacity, ORAC) and total phenolic contents in extracts of 27 culinary herbs and 12 medicinal herbs were determined. The ORAC values and total phenolic contents for the medicinal herbs ranged from 1.88 to 22.30 micromol of Trolox equivalents (TE)/g of fresh weight and 0.23 to 2.85 mg of gallic acid equivalents (GAE)/g of fresh weight, respectively. Origanum x majoricum, O. vulgare ssp. hirtum, and Poliomintha longiflora have higher ORAC and phenolic contents as compared to other culinary herbs. The ORAC values and total phenolic content for the culinary herbs ranged from 2.35 to 92.18 micromol of TE/g of fresh weight and 0.26 to 17.51 mg of GAE/g of fresh weight, respectively. These also were much higher than values found in the medicinal herbs. The medicinal herbs with the highest ORAC values were Catharanthus roseus, Thymus vulgaris, Hypericum perforatum, and Artemisia annua. A linear relationship existed between ORAC values and total phenolic contents of the medicinal herbs (R = 0.919) and culinary herbs (R = 0.986). High-performance liquid chromatography (HPLC) coupled with diode-array detection was used to identify and quantify the phenolic compounds in selected herbs. Among the identified phenolic compounds, rosmarinic acid was the predominant phenolic compound in Salvia officinalis, Thymus vulgaris, Origanum x majoricum, and P. longiflora, whereas quercetin-3-O-rhamnosyl-(1 --> 2)-rhamnosyl-(1 --> 6)-glucoside and kaempferol-3-O-rhamnosyl-(1 --> 2)-rhamnosyl-(1 --> 6)-glucoside were predominant phenolic compounds in Ginkgo biloba leaves. PMID:11714298

  5. Geometric complexity identifies platelet activation in familial hypercholesterolemic patients.

    PubMed

    Bianciardi, Giorgio; Aglianò, Margherita; Volpi, Nila; Stefanutti, Claudia

    2015-06-01

    Familial hypercholesterolemia (FH), a genetic disease, is associated with a severe incidence of athero-thrombotic events, related, also, to platelet hyperreactivity. A plethora of methods have been proposed to identify those activated circulating platelets, none of these has proved really effective. We need efficient methods to identify the circulating platelet status in order to follow the patients after therapeutic procedures. We propose the use of computerized fractal analysis for an objective characterization of the complexity of circulating platelet shapes observed by means of transmission electron microscopy in order to characterize the in vivo hyperactivated platelets of familial hypercholesterolemic patients, distinguishing them from the in vivo resting platelets of healthy individuals. Platelet boundaries were extracted by means of automatically image analysis. Geometric complexity (fractal dimension, D) by box counting was automatically calculated. The platelet boundary observed by electron microscopy is fractal, the shape of the circulating platelets is more complex in FH (n?=?6) than healthy subjects (n?=?5, P?activated platelets from healthy subjects show an analogous increase of D. The observed high D in the platelet boundary in FH originates from the in vivo platelet activation. Computerized fractal analysis of platelet shape observed by transmission electron microscopy can provide accurate, quantitative data to study platelet activation in familial hypercholesterolemia and after administration of drugs or other therapeutic procedures. Microsc. Res. Tech. 78:519-522, 2015. © 2015 Wiley Periodicals, Inc. PMID:25877374

  6. Orally active opioid compounds from a non-poppy source.

    PubMed

    Raffa, Robert B; Beckett, Jaclyn R; Brahmbhatt, Vivek N; Ebinger, Theresa M; Fabian, Chrisjon A; Nixon, Justin R; Orlando, Steven T; Rana, Chintan A; Tejani, Ali H; Tomazic, Robert J

    2013-06-27

    The basic science and clinical use of morphine and other "opioid" drugs are based almost exclusively on the extracts or analogues of compounds isolated from a single source, the opium poppy (Papaver somniferum). However, it now appears that biological diversity has evolved an alternative source. Specifically, at least two alkaloids isolated from the plant Mitragyna speciosa, mitragynine ((E)-2-[(2S,3S)-3-ethyl-8-methoxy-1,2,3,4,6,7,12,12b-octahydroindolo[3,2-h]quinolizin-2-yl]-3-methoxyprop-2-enoic acid methyl ester; 9-methoxy coryantheidine; MG) and 7-hydroxymitragynine (7-OH-MG), and several synthetic analogues of these natural products display centrally mediated (supraspinal and spinal) antinociceptive (analgesic) activity in various pain models. Several characteristics of these compounds suggest a classic "opioid" mechanism of action: nanomolar affinity for opioid receptors, competitive interaction with the opioid receptor antagonist naloxone, and two-way analgesic cross-tolerance with morphine. However, other characteristics of the compounds suggest novelty, particularly chemical structure and possible greater separation from side effects. We review the chemical and pharmacological properties of these compounds. PMID:23517479

  7. Supplementation with Active Hexose Correlated Compound Increases the Innate Immune Response of Young Mice to Primary Influenza Infection 1

    Microsoft Academic Search

    Barry W. Ritz; Shoko Nogusa; Elizabeth A. Ackerman; Elizabeth M. Gardner

    2006-01-01

    The emergence of H5N1 avian influenza and the threat of new or adapted viruses in bioterrorism have created an urgent interest in identifying agents to enhance the immune response to primary virus infection. Active hexose correlated compound (AHCC) is a natural mushroom extract reported to increase natural killer (NK) cell activity, survival, and bacterial clearance in young mice. However, the

  8. Supplementation with Active Hexose Correlated Compound Increases the Innate Immune Response of Young Mice to Primary Influenza Infection1

    Microsoft Academic Search

    Barry W. Ritz; Shoko Nogusa; Elizabeth A. Ackerman; Elizabeth M. Gardner

    The emergence of H5N1 avian influenza and the threat of new or adapted viruses in bioterrorism have created an urgent interest in identifying agents to enhance the immune response to primary virus infection. Active hexose correlated compound (AHCC) is a natural mushroom extract reported to increase natural killer (NK) cell activity, survival, and bacterial clearance in young mice. However, the

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

    PubMed

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

    2003-09-01

    Two dihydrochalcones (1 and 2) were isolated from Piper elongatum Vahl by activity-guided fractionation against extracellular promastigotes of Leishmania braziliensis in vitro. Their structures were elucidated by spectral analysis, including homonuclear and heteronuclear correlation NMR experiments. Derivatives 3-7 and 20 synthetic related compounds (8-27) were also assayed to establish the structural requirements for antileishmanial activity. Compounds 1-11 that proved to be more active that ketoconazol, used as positive control, were further assayed against promastigotes of Leishmania tropica and Leishmania infantum. Compounds 7 and 11, with a C(6)-C(3)-C(6) system, proved to be the most promising compounds, with IC(50) values of 2.98 and 3.65 microg/mL, respectively, and exhibited no toxic effect on macrophages (around 90% viability). Correlation between the molecular structures and antileishmanial activity is discussed in detail. PMID:12927858

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

    Microsoft Academic Search

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

    2003-01-01

    Two dihydrochalcones (1 and 2) were isolated from Piper elongatum Vahl by activity-guided fractionation against extracellular promastigotes of Leishmania braziliensis in vitro. Their structures were elucidated by spectral analysis, including homonuclear and heteronuclear correlation NMR experiments. Derivatives 3–7 and 20 synthetic related compounds (8–27) were also assayed to establish the structural requirements for antileishmanial activity. Compounds 1–11 that proved to

  11. Compounds from Wedelia chinensis synergistically suppress androgen activity and growth in prostate cancer cells.

    PubMed

    Lin, Feng-Min; Chen, Li-Ru; Lin, En-Hau; Ke, Ferng-Chun; Chen, Hsin-Yi; Tsai, Meng-Jen; Hsiao, Pei-Wen

    2007-12-01

    Chronic inflammation can augment tumor development in various types of cancers, including prostate cancer (PCa). Reduction of inflammation is therefore an important anticancer therapeutic opportunity. Here, we report four anti-proliferative phytocompounds in Wedelia chinensis, an oriental herbal medicine, identified through their ability to modulate the androgen receptor (AR) activation of transcription from prostate-specific antigen promoter in PCa cells. The 50% inhibition concentration values of indole-3-carboxylaldehyde, wedelolactone, luteolin and apigenin, were 34.9, 0.2, 2.4 and 9.8 muM, respectively. A formula that combined the phytocompounds in the same proportions as in the herbal extract decreased the dosage of each compound required to achieve maximal AR inhibition. In correlation with the AR suppression effect, these active compounds specifically inhibited the growth of AR-dependent PCa cells and as a combination formula they also synergistically suppressed growth in AR-dependent PCa cells. Our study has identified synergistic effects of active compounds in W. chinensis and demonstrated their potential in PCa prevention and therapy. The paradigm of multiple activities and synergism is a useful framework to investigate the therapeutic effects of whole extracts from assorted medicinal plant species. PMID:17942463

  12. 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

    2013-01-01

    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)-5?-spirostan-3?,6?,23?-triol-3,6-di-O-?-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. PMID:23846754

  13. Hexyl decanoate, the first trail pheromone compound identified in a stingless bee, Trigona recursa.

    PubMed

    Jarau, Stefan; Schulz, Claudia M; Hrncir, Michael; Francke, Wittko; Zucchi, Ronaldo; Barth, Friedrich G; Ayasse, Manfred

    2006-07-01

    Foragers of many species of stingless bees guide their nestmates to food sources by means of scent trails deposited on solid substrates between the food and the nest. The corresponding trail pheromones are generally believed to be produced in the mandibular glands, although definitive experimental proof has never been provided. We tested the trail following behavior of recruits of Trigona recursa in field experiments with artificial scent trails branching off from natural scent trails of this stingless bee. First-time recruits (newcomers) did not follow these trails when they were laid with pure solvent or mandibular gland extract. However, they did follow trails made with labial gland extract. Chemical analyses of labial gland secretions revealed that hexyl decanoate was the dominant component (72.4 +/- 1.9% of all volatiles). Newcomers were significantly attracted to artificial trails made with synthetic hexyl decanoate, demonstrating its key function in eliciting scent-following behavior. According to our experiments with T. recursa, the trail pheromone is produced in the labial glands and not in the mandibular glands. Hexyl decanoate is the first component of a trail pheromone identified and proved to be behaviorally active in stingless bees. PMID:16718558

  14. A Fluorescence-Based Thermal Shift Assay Identifies Inhibitors of Mitogen Activated Protein Kinase Kinase 4

    PubMed Central

    Krishna, Sankar N.; Luan, Chi-Hao; Mishra, Rama K.; Xu, Li; Scheidt, Karl A.; Anderson, Wayne F.; Bergan, Raymond C.

    2013-01-01

    Prostate cancer (PCa) is the second highest cause of cancer death in United States males. If the metastatic movement of PCa cells could be inhibited, then mortality from PCa could be greatly reduced. Mitogen-activated protein kinase kinase 4 (MAP2K4) has previously been shown to activate pro-invasion signaling pathways in human PCa. Recognizing that MAP2K4 represents a novel and validated therapeutic target, we sought to develop and characterize an efficient process for the identification of small molecules that target MAP2K4. Using a fluorescence-based thermal shift assay (FTS) assay, we first evaluated an 80 compound library of known kinase inhibitors, thereby identifying 8 hits that thermally stabilized MAP2K4 in a concentration dependent manner. We then developed an in vitro MAP2K4 kinase assay employing the biologically relevant downstream substrates, JNK1 and p38 MAPK, to evaluate kinase inhibitory function. In this manner, we validated the performance of our initial FTS screen. We next applied this approach to a 2000 compound chemically diverse library, identified 7 hits, and confirmed them in the in vitro kinase assay. Finally, by coupling our structure-activity relationship data to MAP2K4's crystal structure, we constructed a model for ligand binding. It predicts binding of our identified inhibitory compounds to the ATP binding pocket. Herein we report the creation of a robust inhibitor-screening platform with the ability to inform the discovery and design of new and potent MAP2K4 inhibitors. PMID:24339940

  15. Studies on the antioxidant activities of some new chromone compounds.

    PubMed

    K?adna, Aleksandra; Berczy?ski, Pawe?; Piechowska, Teresa; Kruk, Irena; Aboul-Enein, Hassan Y; Ceylan-Unlusoy, Meltem; Verspohl, Eugen J; Ertan, Rahmiye

    2014-11-01

    Recent reviews evidence that the naturally occurring compounds containing the chromone skeleton exhibit antiradical activities, providing protection against oxidative stress. The antioxidant activities of 13 new synthesized chromonyl-2,4-thiazolidinediones, chromonyl-2,4-imidazolidinediones and chromonyl-2-thioxoimidzolidine-4-ones were evaluated using in vitro antioxidant assays, including superoxide anion radical (O2(-•)), hydroxyl radical (HO(•)), 2,2-diphenyl-1-picryl-hydrazyl free radical (DPPH(•)) scavenging capacity and total antioxidant capacity ferric ion reducing activity. Superoxide anion radical was produced using potassium superoxide/18-crown-6-ether dissolved in dimethylsulfoxide, and the Fenton-like reaction (Fe(II)?+ H2O2) was a generator of hydroxyl radicals. Chemiluminescence, spectrophotometry, electron paramagnetic resonance (EPR) and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as the spin trap were the measurement techniques. The results showed that the majority of the chromone derivatives tested showed a strong scavenging effect towards free radicals, similar to the chemiluminescence reaction with superoxide anion radical with a high activity, inhibition of the DMPO-OOH radical EPR signal (24-58%), the DMPO-OH radical EPR signal (4-75%) and DPPH radical EPR signal (6-100%) at 1 mmol/L. Several of the examined compounds exhibited the high reduction potentials. The results obtained show that the new synthesized chromone derivatives may directly scavenger reactive oxygen species and thus may play a protective role against oxidative damage. PMID:24482260

  16. Screening for Antiviral Activities of Isolated Compounds from Essential Oils

    PubMed Central

    Astani, Akram; Reichling, Jürgen; Schnitzler, Paul

    2011-01-01

    Essential oil of star anise as well as phenylpropanoids and sesquiterpenes, for example, trans-anethole, eugenol, ?-eudesmol, farnesol, ?-caryophyllene and ?-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 ?-caryophyllene displayed a high selectivity index of 140. The presence of ?-caryophyllene in many essential oils might contribute strongly to their antiviral ability. These results indicate that phenylpropanoids and sesquiterpenes present in essential oils contribute to their antiviral activity against HSV. PMID:20008902

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

    PubMed Central

    Antholine, William E.

    2013-01-01

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

  18. UTSW Investigators Develop Functional Signature Ontology (FUSION), a Method for Identifying Compounds That Target Cancer Pathways

    Cancer.gov

    In a new study published in Science Signaling, CTD2 investigators from University of Texas (UTSW) Southwestern Medical Center devised a novel bioinformatics approach that, when coupled with high-throughput screening, helps reveal compounds that may target potential cancer-related pathways.

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

    PubMed

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

    2014-04-01

    In our previous study, we reported the interesting in vitro antiplasmodial activity of some Rwandan plant extracts. This gave rise to the need for these extracts to also be evaluated in vivo and to identify the compounds responsible for their antiplasmodial activity. The aim of our study was, on the one hand, to evaluate the antiplasmodial activity in vivo and the safety of the selected Rwandan medicinal plants used in the treatment of malaria, with the objective of promoting the development of improved traditional medicines and, on the other hand, to identify the active ingredients in the plants. Plant extracts were selected according to their selectivity index. The in vivo antiplasmodial activity of aqueous, methanolic, and dichloromethane extracts was then evaluated using the classical 4-day suppressive test on Plasmodium berghei infected mice. The activity of the plant extracts was estimated by measuring the percentage of parasitemia reduction, and the survival of the experimental animals was recorded. A bioguided fractionation was performed for the most promising plants, in terms of antiplasmodial activity, in order to isolate active compounds identified by means of spectroscopic and spectrometric methods. The highest level of antiplasmodial activity was observed with the methanolic extract of Fuerstia africana (>?70?%) on days 4 and 7 post-treatment after intraperitoneal injection and on day 7 using oral administration. After oral administration, the level of parasitemia reduction observed on day 4 post-infection was 44?% and 37?% with the aqueous extract of Terminalia mollis and Zanthoxylum chalybeum, respectively. However, the Z. chalybeum extract presented a high level of toxicity after intraperitoneal injection, with no animals surviving on day 1 post-treatment. F. africana, on the other hand, was safer with 40?% mouse survival on day 20 post-treatment. Ferruginol is already known as the active ingredient in F. Africana, and ellagic acid (IC50?=?175?ng/mL) and nitidine (IC50?=?77.5?ng/mL) were identified as the main active constituents of T. mollis and Z. chalybeum, respectively. F. africana presented very promising antiplasmodial activity in vivo. Although most of the plants tested showed some level of antiplasmodial activity, some of these plants may be toxic. This study revealed for the first time the role of ellagic acid and nitidine as the main antimalarial compounds in T. mollis and Z. chalybeum, respectively. PMID:24710900

  20. Phenolic Compounds from Halimodendron halodendron (Pall.) Voss and Their Antimicrobial and Antioxidant Activities.

    PubMed

    Wang, Jihua; Lou, Jingfeng; Luo, Chao; Zhou, Ligang; Wang, Mingan; Wang, Lan

    2012-01-01

    Halimodendron halodendron has been used as forage in northwestern China for a long time. Its young leaves and flowers are edible and favored by indigenous people. In this study, eleven phenolic compounds were bioassay-guided and isolated from the aerial parts of H. halodendron for the first time. They were identified by means of physicochemical and spectrometric analysis as quercetin (1), 3,5,7,8,4'-pentahydroxy-3'-methoxy flavone (2), 3-O-methylquercetin (3), 3,3'-di-O-methylquercetin (4), 3,3'-di-O-methylquercetin-7-O-?-d-glucopyranoside (5), isorhamentin-3-O-?-d-rutinoside (6), 8-O-methylretusin (7), 8-O-methylretusin-7-O-?-d-glucopyranoside (8), salicylic acid (9), p-hydroxybenzoic acid (ferulic acid) (10), and 4-hydroxy-3-methoxy cinnamic acid (11). They were sorted as flavonols (1-6), soflavones (7 and 8), and phenolic acids (9-11). Among the compounds, flanools 1-4 revealed a strong antibacterial activity with minimum inhibitory concentration (MIC) values of 50-150 ?g/mL, and median inhibitory concentration (IC(50)) values of 26.8-125.1 ?g/mL. The two isoflavones (7 and 8) showed moderate inhibitory activity on the test bacteria. Three phenolic acids (9, 10 and 11) showed strong antibacterial activity with IC(50) values of 28.1-149.7 ?g/mL. Antifungal activities of the compounds were similar to their antibacterial activities. All these phenolic compounds showed significant antimicrobial activity with a broad spectrum as well as antioxidant activity based on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and ?-carotene-linoleic acid bleaching assays. In general, the flavonol aglycones with relatively low polarity exhibited stronger activities than the glycosides. The results suggest the potential of this plant as a source of functional food ingredients and provide support data for its utilization as forage as well. PMID:23109858

  1. Phenolic Compounds from Halimodendron halodendron (Pall.) Voss and Their Antimicrobial and Antioxidant Activities

    PubMed Central

    Wang, Jihua; Lou, Jingfeng; Luo, Chao; Zhou, Ligang; Wang, Mingan; Wang, Lan

    2012-01-01

    Halimodendron halodendron has been used as forage in northwestern China for a long time. Its young leaves and flowers are edible and favored by indigenous people. In this study, eleven phenolic compounds were bioassay-guided and isolated from the aerial parts of H. halodendron for the first time. They were identified by means of physicochemical and spectrometric analysis as quercetin (1), 3,5,7,8,4?-pentahydroxy-3?-methoxy flavone (2), 3-O-methylquercetin (3), 3,3?-di-O-methylquercetin (4), 3,3?-di-O-methylquercetin-7-O-?-d-glucopyranoside (5), isorhamentin-3-O-?-d-rutinoside (6), 8-O-methylretusin (7), 8-O-methylretusin-7-O-?-d-glucopyranoside (8), salicylic acid (9), p-hydroxybenzoic acid (ferulic acid) (10), and 4-hydroxy-3-methoxy cinnamic acid (11). They were sorted as flavonols (1–6), soflavones (7 and 8), and phenolic acids (9–11). Among the compounds, flanools 1–4 revealed a strong antibacterial activity with minimum inhibitory concentration (MIC) values of 50–150 ?g/mL, and median inhibitory concentration (IC50) values of 26.8–125.1 ?g/mL. The two isoflavones (7 and 8) showed moderate inhibitory activity on the test bacteria. Three phenolic acids (9, 10 and 11) showed strong antibacterial activity with IC50 values of 28.1–149.7 ?g/mL. Antifungal activities of the compounds were similar to their antibacterial activities. All these phenolic compounds showed significant antimicrobial activity with a broad spectrum as well as antioxidant activity based on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and ?-carotene-linoleic acid bleaching assays. In general, the flavonol aglycones with relatively low polarity exhibited stronger activities than the glycosides. The results suggest the potential of this plant as a source of functional food ingredients and provide support data for its utilization as forage as well. PMID:23109858

  2. Global proteome analysis identifies active immunoproteasome subunits in human platelets.

    PubMed

    Klockenbusch, Cordula; Walsh, Geraldine M; Brown, Lyda M; Hoffman, Michael D; Ignatchenko, Vladimir; Kislinger, Thomas; Kast, Juergen

    2014-12-01

    The discovery of new functions for platelets, particularly in inflammation and immunity, has expanded the role of these anucleate cell fragments beyond their primary hemostatic function. Here, four in-depth human platelet proteomic data sets were generated to explore potential new functions for platelets based on their protein content and this led to the identification of 2559 high confidence proteins. During a more detailed analysis, consistently high expression of the proteasome was discovered, and the composition and function of this complex, whose role in platelets has not been thoroughly investigated, was examined. Data set mining resulted in identification of nearly all members of the 26S proteasome in one or more data sets, except the ?5 subunit. However, ?5i, a component of the immunoproteasome, was identified. Biochemical analyses confirmed the presence of all catalytically active subunits of the standard 20S proteasome and immunoproteasome in human platelets, including ?5, which was predominantly found in its precursor form. It was demonstrated that these components were assembled into the proteasome complex and that standard proteasome as well as immunoproteasome subunits were constitutively active in platelets. These findings suggest potential new roles for platelets in the immune system. For example, the immunoproteasome may be involved in major histocompatibility complex I (MHC I) peptide generation, as the MHC I machinery was also identified in our data sets. PMID:25146974

  3. Cloxacepride and related compounds: a new series of orally active antiallergic compounds.

    PubMed

    Metz, G; Pindell, M H; Chen, H L

    1983-07-01

    4-[[(p-Chlorophenoxy)acetyl]amino]-5-chloro-2-methoxy-N-[2-(diethylamino)ethyl]benzamide (cloxacepride, 1), exhibited substantial oral antiallergic potential in a reaginic PCA test in rats over a wide range of antigenic challenge times. Available reference compounds with oral activity, such as doxantrazole and 7-(2-hydroxyethoxy)-9-oxoxanthene-2-carboxylic acid (AH 7725, 4), were active only when administered 15 min before challenge: 4, in particular, was not consistent in effect. Oral ED50 values for cloxacepride of 46-49 mg/kg were comparable to that of theophylline and to an intravenous injection of 2 mg/kg of disodium chromoglycate (DSCG) followed by immediate challenge. Following oral ED50 doses, 1 showed slower onset and longer duration of action than theophylline. The absence of inhibition of systemic anaphylaxis and of antihistaminic activity suggests specific effect or reaginic antigen antibody reactions. Structure-activity relationships of various chemical modifications were investigated and discussed in terms of essential substituents. PMID:6134832

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

    Microsoft Academic Search

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

    2005-01-01

    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

  5. 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 ?g/g dry sample. Myricetin is the dominant flavonoid in all extracts. Its level varied from 2.75 ?g/g dry sample in acetone extract to 5.28 ?g/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. PMID:24803703

  6. 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

  7. Laccase catalyzed synthesis of iodinated phenolic compounds with antifungal activity.

    PubMed

    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

  8. Identifying key non-volatile compounds in ready-to-drink green tea and their impact on taste profile.

    PubMed

    Yu, Peigen; Yeo, Angelin Soo-Lee; Low, Mei-Yin; Zhou, Weibiao

    2014-07-15

    Thirty-nine non-volatile compounds in seven ready-to-drink (RTD) green tea samples were analysed and quantified using liquid chromatography. Taste reconstruction experiments using thirteen selected compounds were conducted to identify the key non-volatile tastants. Taste profiles of the reconstructed samples did not differ significantly from the RTD tea samples. To investigate the taste contribution and significance of individual compounds, omission experiments were carried out by removing individual or a group of compounds. Sensory evaluation revealed that the astringent- and bitter-tasting (-)-epigallocatechin gallate, bitter-tasting caffeine, and the umami-tasting l-glutamic acid were the main contributors to the taste of RTD green tea. Subsequently, the taste profile of the reduced recombinant, comprising of a combination of these three compounds and l-theanine, was found to not differ significantly from the sample recombinant and RTD tea sample. Lastly, regression models were developed to objectively predict and assess the intensities of bitterness and astringency in RTD green teas. PMID:24594147

  9. Aminobenzoic Acid Compounds as HOCl Traps for Activated Neutrophils

    Microsoft Academic Search

    Zhi-Wu She; Dennis C. Mays; W. Bruce Davis

    1997-01-01

    This study was designed to develop traps for hypochlorous acid (HOCl) which could be used to detect HOCl in the microenvironment of activated neutrophils. Reagent HOCl was found to react with para-aminobenzoic acid (PABA) in aqueous solution to produce a predominant metabolite detectable by high performance liquid chromatography (HPLC). Mass spectroscopy and nuclear magnetic resonance identified this metabolite as the

  10. Structure-activity relationships of 44 halogenated compounds for iodotyrosine deiodinase-inhibitory activity.

    PubMed

    Shimizu, Ryo; Yamaguchi, Masafumi; Uramaru, Naoto; Kuroki, Hiroaki; Ohta, Shigeru; Kitamura, Shigeyuki; Sugihara, Kazumi

    2013-12-01

    The aim of this study was to investigate the possible influence of halogenated compounds on thyroid hormone metabolism via inhibition of iodotyrosine deiodinase (IYD) activity. The structure-activity relationships of 44 halogenated compounds for IYD-inhibitory activity were examined in vitro using microsomes of HEK-293 T cells expressing recombinant human IYD. The compounds examined were 17 polychlorinated biphenyls (PCBs), 15 polybrominated diphenyl ethers (PBDEs), two agrichemicals, five antiparasitics, two pharmaceuticals and three food colorants. Among them, 25 halogenated phenolic compounds inhibited IYD activity at the concentration of 1×10(-4)M or 6×10(-4)M. Rose bengal was the most potent inhibitor, followed by erythrosine B, phloxine B, benzbromarone, 4'-hydroxy-2,2',4-tribromodiphenyl ether, 4-hydroxy-2,3',3,4'-tetrabromodiphenyl ether, 4-hydroxy-2',3,4',5,6'-pentachlorobiphenyl, 4'-hydroxy-2,2',4,5'-tetrabromodiphenyl ether, triclosan, and 4-hydroxy-2,2',3,4',5-pentabromodiphenyl ether. However, among PCBs and PBDEs without a hydroxyl group, including their methoxylated metabolites, none inhibited IYD activity. These results suggest that halogenated compounds may disturb thyroid hormone homeostasis via inhibition of IYD, and that the structural requirements for IYD-inhibitory activity include halogen atom and hydroxyl group substitution on a phenyl ring. PMID:24012475

  11. THE OPTX PROJECT. V. IDENTIFYING DISTANT ACTIVE GALACTIC NUCLEI

    SciTech Connect

    Trouille, L. [Center for Interdisciplinary Exploration and Research in Astrophysics (CIERA) and Department of Physics and Astronomy, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208 (United States); Barger, A. J.; Tremonti, C. [Department of Astronomy, University of Wisconsin-Madison, 475 N. Charter Street, Madison, WI 53706 (United States)

    2011-11-20

    The Baldwin, Phillips, and Terlevich emission-line ratio diagnostic ([O III]/H{beta} versus [N II]/H{alpha}, hereafter BPT diagram) efficiently separates galaxies whose signal is dominated by star formation (BPT-SF) from those dominated by active galactic nucleus (AGN) activity (BPT-AGN). Yet this BPT diagram is limited to z < 0.5, the redshift at which [N II]{lambda}6584 leaves the optical spectral window. Using the Sloan Digital Sky Survey (SDSS), we construct a new diagnostic, or TBT diagram, that is based on rest-frame g - z color, [Ne III]{lambda}3869, and [O II]{lambda}{lambda}3726 + 3729 and can be used for galaxies out to z < 1.4. The TBT diagram identifies 98.7% of the SDSS BPT-AGN as TBT-AGN and 97% of the SDSS BPT-SF as TBT-SF. Furthermore, it identifies 97% of the OPTX Chandra X-ray-selected AGNs as TBT-AGN. This is in contrast to the BPT diagram, which misidentifies 20% of X-ray-selected AGNs as BPT-SF. We use the Great Observatories Origins Deep Survey North and Lockman Hole galaxy samples, with their accompanying deep Chandra imaging, to perform X-ray and infrared stacking analyses to further validate our TBT-AGN and TBT-SF selections; that is, we verify the dominance of AGN activity in the former and star formation activity in the latter. Finally, we address the inclusion of the majority of the BPT-comp (sources lying between the BPT-SF and BPT-AGN regimes) in our TBT-AGN regime. We find that the stacked BPT-comp source is X-ray hard (({Gamma}{sub eff}) = 1.0{sup +0.4}{sub -0.4}) and has a high X-ray luminosity to total infrared luminosity ratio. This suggests that, on average, the X-ray signal in BPT-comp is dominated by obscured or low accretion rate AGN activity rather than by star formation, supporting their inclusion in the TBT-AGN regime.

  12. Combined Rational Design and a High Throughput Screening Platform for Identifying Chemical Inhibitors of a Ras-activating Enzyme.

    PubMed

    Evelyn, Chris R; Biesiada, Jacek; Duan, Xin; Tang, Hong; Shang, Xun; Papoian, Ruben; Seibel, William L; Nelson, Sandra; Meller, Jaroslaw; Zheng, Yi

    2015-05-15

    The Ras family small GTPases regulate multiple cellular processes, including cell growth, survival, movement, and gene expression, and are intimately involved in cancer pathogenesis. Activation of these small GTPases is catalyzed by a special class of enzymes, termed guanine nucleotide exchange factors (GEFs). Herein, we developed a small molecule screening platform for identifying lead hits targeting a Ras GEF enzyme, SOS1. We employed an ensemble structure-based virtual screening approach in combination with a multiple tier high throughput experimental screen utilizing two complementary fluorescent guanine nucleotide exchange assays to identify small molecule inhibitors of GEF catalytic activity toward Ras. From a library of 350,000 compounds, we selected a set of 418 candidate compounds predicted to disrupt the GEF-Ras interaction, of which dual wavelength GDP dissociation and GTP-loading experimental screening identified two chemically distinct small molecule inhibitors. Subsequent biochemical validations indicate that they are capable of dose-dependently inhibiting GEF catalytic activity, binding to SOS1 with micromolar affinity, and disrupting GEF-Ras interaction. Mutagenesis studies in conjunction with structure-activity relationship studies mapped both compounds to different sites in the catalytic pocket, and both inhibited Ras signaling in cells. The unique screening platform established here for targeting Ras GEF enzymes could be broadly useful for identifying lead inhibitors for a variety of small GTPase-activating GEF reactions. PMID:25825487

  13. Apatite Formation: Why It May Not Work as Planned, and How to Conclusively Identify Apatite Compounds

    PubMed Central

    2013-01-01

    Calcium phosphate apatites are inorganic compounds encountered in many different mineralized tissues. Bone mineral, for example, is constituted of nanocrystalline nonstoichiometric apatite, and the production of “analogs” through a variety of methods is frequently reported. In another context, the ability of solid surfaces to favor the nucleation and growth of “bone-like” apatite upon immersion in supersaturated fluids such as SFB is commonly used as one evaluation index of the “bioactivity” of such surfaces. Yet, the compounds or deposits obtained are not always thoroughly characterized, and their apatitic nature is sometimes not firmly assessed by appropriate physicochemical analyses. Of particular importance are the “actual” conditions in which the precipitation takes place. The precipitation of a white solid does not automatically indicate the formation of a “bone-like carbonate apatite layer” as is sometimes too hastily concluded: “all that glitters is not gold.” The identification of an apatite phase should be carefully demonstrated by appropriate characterization, preferably using complementary techniques. This review considers the fundamentals of calcium phosphate apatite characterization discussing several techniques: electron microscopy/EDX, XRD, FTIR/Raman spectroscopies, chemical analyses, and solid state NMR. It also underlines frequent problems that should be kept in mind when making “bone-like apatites.” PMID:23984373

  14. Apatite formation: why it may not work as planned, and how to conclusively identify apatite compounds.

    PubMed

    Drouet, Christophe

    2013-01-01

    Calcium phosphate apatites are inorganic compounds encountered in many different mineralized tissues. Bone mineral, for example, is constituted of nanocrystalline nonstoichiometric apatite, and the production of "analogs" through a variety of methods is frequently reported. In another context, the ability of solid surfaces to favor the nucleation and growth of "bone-like" apatite upon immersion in supersaturated fluids such as SFB is commonly used as one evaluation index of the "bioactivity" of such surfaces. Yet, the compounds or deposits obtained are not always thoroughly characterized, and their apatitic nature is sometimes not firmly assessed by appropriate physicochemical analyses. Of particular importance are the "actual" conditions in which the precipitation takes place. The precipitation of a white solid does not automatically indicate the formation of a "bone-like carbonate apatite layer" as is sometimes too hastily concluded: "all that glitters is not gold." The identification of an apatite phase should be carefully demonstrated by appropriate characterization, preferably using complementary techniques. This review considers the fundamentals of calcium phosphate apatite characterization discussing several techniques: electron microscopy/EDX, XRD, FTIR/Raman spectroscopies, chemical analyses, and solid state NMR. It also underlines frequent problems that should be kept in mind when making "bone-like apatites." PMID:23984373

  15. Identification of electrophysiologically-active compounds for New World screwworm, Cochliomyia hominivorax, in larval wound fluid.

    PubMed

    Cork, A

    1994-04-01

    Acidic and non-acidic fractions from extracts of fluid from sheep wounds infested with larvae of Cochliomyia hominivorax (Coquerel) were analysed by linked gas chromatography and electroantennography in order to detect electrophysiologically-active compounds that could be potential attractants. Responses to twenty-six electrophysiologically-active compounds were observed and, on the basis of electron impact and chemical ionization mass spectrometry and co-chromatography with authentic compounds, twenty-five of these compounds were characterized. The most abundant compounds identified in the larval wound fluid were straight and methyl-branched aliphatic carboxylic acids, ranging from C2- to C5-carbon chain length. Butanoic acid, for example, was found to be present at approximately 0.45 mg/ml. Aliphatic carboxylic acids with longer chain lengths were also observed but in trace amounts. Three aromatic carboxylic acids, benzoic, phenylethanoic and 3-phenylpropanoic acids were also present but only phenylethanoic and 3-phenylpropanoic acids elicited electroantennographic responses. Phenol and indole were by far the most abundant components of the non-acid fraction of the larval wound fluid with all other components, except delta-valerolactam, present at levels of less than 5% that of phenol which was present at a concentration of 0.05 mg/ml. Electroantennographic studies of straight-chain aliphatic carboxylic acids showed that pentanoic acid elicited the strongest response from C. hominivorax. Similar studies showed that 1-octen-3-ol elicited stronger responses than 3-methylphenol, indole, phenol or dimethyldisulphide. 3-Methylindole, which was not found in the wound fluid, also elicited a strong response. The potential behavioural significance of these compounds is discussed in relation to that of known attractants of C. hominivorax and other dipteran pests of mammals. PMID:8025323

  16. Characterization of the most aroma-active compounds in cherry tomato by application of the aroma extract dilution analysis.

    PubMed

    Selli, Serkan; Kelebek, Hasim; Ayseli, Mehmet Turan; Tokbas, Habip

    2014-12-15

    Aroma and aroma-active compounds of cherry tomato (Lycopersicum esculentum) was analyzed by gas chromatography-mass spectrometry-olfactometry (GC-MS-O). According to sensory analysis, the aromatic extract obtained by liquid-liquid extraction was representative of tomato odour. A total of 49 aroma compounds were identified and quantified in fresh cherry tomato. Aldehydes were qualitatively and quantitatively the most dominant volatiles in cherry tomato, followed by alcohols. Aroma extract dilution analysis (AEDA) was used for the determination of aroma-active compounds of tomato sample. A total of 21 aroma-active compounds were detected in aromatic extract of fresh tomato, of which 18 were identified. On the basis of the flavour dilution (FD) factor, the most powerful aroma-active compounds identified in the extract were (Z)-3-hexenal (FD=1024) and (E)-2-hexenal (FD=256), which were described as the strong green-grassy and green-leafy odour, respectively. The major organic acid and sugar found were citric acid and fructose, respectively. PMID:25038709

  17. Screening potato genotypes for antioxidant activity, identification of the responsible compounds, and differentiating Russet Norkotah strains using AFLP and microsatellite marker analysis 

    E-print Network

    Hale, Anna Louise

    2005-02-17

    as having high antioxidant activity and high total carotenoid levels, were fine screened via HPLC to determine specific phenolic and carotenoid compounds present in potato. The objective of the study was to identify parents for use in the Texas breeding...

  18. Inhibition of Peroxidase Activity of Cytochrome c: De Novo Compound Discovery and Validation.

    PubMed

    Bakan, Ahmet; Kapralov, Alexandr A; Bayir, Hulya; Hu, Feizhou; Kagan, Valerian E; Bahar, Ivet

    2015-09-01

    Cytochrome c (cyt c) release from mitochondria is accepted to be the point of no return for eliciting a cascade of interactions that lead to apoptosis. A strategy for containing sustained apoptosis is to reduce the mitochondrial permeability pore opening. Pore opening is enhanced by peroxidase activity of cyt c gained upon its complexation with cardiolipin in the presence of reactive oxygen species. Blocking access to the heme group has been proposed as an effective intervention method for reducing, if not eliminating, the peroxidase activity of cyt c. In the present study, using a combination of druggability simulations, pharmacophore modeling, virtual screening, and in vitro fluorescence measurements to probe peroxidase activity, we identified three repurposable drugs and seven compounds that are validated to effectively inhibit the peroxidase activity of cyt c. PMID:26078313

  19. 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.

  20. Screening of compounds for antimicrosporidial activity in vitro.

    PubMed

    Didier, E S; Maddry, J A; Kwong, C D; Green, L C; Snowden, K F; Shadduck, J A

    1998-01-01

    Relatively few effective compounds are available for treating microsporidiosis in humans. In this study, several compounds were assayed for activity against Encephalitozoon intestinalis (Cali, Kotler et Orenstein, 1993) and Vittaforma corneae Shadduck, Meccoli, Davis et Font, 1990 in vitro. Of the benzimidazoles tested, albendazole was most effective and the MIC50 values were 8.0 ng/ml and 55.0 ng/ml for E. intestinalis and V. corneae, respectively. Fumagillin and its analogue, TNP-470 were nearly equally effective against both E. intestinalis and V. corneae. The MIC50 values of fumagillin were 0.52 ng/ml and 0.81 ng/ml, and the MIC50 values of TNP-470 were 0.35 ng/ml and 0.38 ng/ml for E. intestinalis and V. corneae, respectively. In addition, 12 of 44 purines and pteridines with putative tubulin binding activity that were synthesized at Southern Research Institute (SRI), inhibited microsporidial replication by more than 50% at concentrations that were not toxic to the host cells. Several chitin synthesis/assembly inhibitors inhibited growth of the microsporidia in vitro but were toxic for the host cells making it difficult to interpret the results. One exception was lufenuron, which caused no significant toxicity to the host cells and expressed approximate MIC50 values of 2.95 micrograms/ml and 6.3 micrograms/ml against E. intestinalis and V. corneae, respectively. These results warrant further studies on albendazole, fumagillin, TNP-470, lufenuron, and the selected SRI purines and pteridines for developing therapeutic strategies for microsporidiosis. PMID:9684323

  1. 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

  2. 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 ?-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

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

    SciTech Connect

    Hagvall, Lina [Department of Chemistry, Dermatochemistry and Skin Allergy, University of Gothenburg, SE-412 96 Gothenburg (Sweden); Baron, Jens Malte [Department of Dermatology and Allergology, University Hospital RWTH Aachen, Aachen (Germany); Boerje, Anna [Department of Chemistry, Dermatochemistry and Skin Allergy, University of Gothenburg, SE-412 96 Gothenburg (Sweden); Weidolf, Lars [Discovery DMPK and Bioanalytical Chemistry, AstraZeneca R and D Moelndal, SE-421 83 Moelndal (Sweden); Merk, Hans [Department of Dermatology and Allergology, University Hospital RWTH Aachen, Aachen (Germany); Karlberg, Ann-Therese [Department of Chemistry, Dermatochemistry and Skin Allergy, University of Gothenburg, SE-412 96 Gothenburg (Sweden)], E-mail: karlberg@chem.gu.se

    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.

  4. Comparison of antioxidant activities of different colored wheat grains and analysis of phenolic compounds.

    PubMed

    Liu, Qin; Qiu, Yang; Beta, Trust

    2010-08-25

    Extracts from six wheat varieties (three purple, one yellow, two red, and one white) were evaluated and compared for their antioxidant capacities against oxygen radical and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. Phenolic composition in the extracts was examined by high-performance liquid chromatography and mass spectrometry. The results showed that Charcoal purple wheat had remarkable antioxidant activity (up to 6899 ?mol/100 g) followed by Red Fife wheat and yellow Luteus wheat. White AC Vista wheat, due to its lowest phenolic content, exhibited the weakest antioxidant property. The major phenolic composition identified in wheat grains consisted of phenolic acids, flavones, flavonols, and anthocyanins. The former three components were detected in all of the wheat varieties, whereas anthocyanins were identified only in purple wheat. Therefore, anthocyanins could be the major compounds distinguishing purple wheats from other colored wheats with high antioxidant activity. PMID:20669971

  5. A Substrate Pharmacophore for the Human Organic Cation/Carnitine Transporter Identifies Compounds Associated with Rhabdomyolysis

    PubMed Central

    Ekins, Sean; Diao, Lei; Polli, James E.

    2012-01-01

    The human Organic Cation/Carnitine Transporter (hOCTN2), is a high affinity cation/carnitine transporter expressed widely in human tissues and is physiologically important for the homeostasis of L-carnitine. The objective of this study was to elucidate the substrate requirements of this transporter via computational modelling based on published in vitro data. Nine published substrates of hOCTN2 were used to create a common features pharmacophore that was validated by mapping other known OCTN2 substrates. The pharmacophore was used to search a drug database and retrieved molecules that were then used as search queries in PubMed for instances of a side effect (rhabdomyolysis) associated with interference with L-carnitine transport. The substrate pharmacophore was comprised of two hydrogen bond acceptors, a positive ionizable feature and ten excluded volumes. The substrate pharmacophore also mapped 6 out of 7 known substrate molecules used as a test set. After searching a database of ~800 known drugs, thirty drugs were predicted to map to the substrate pharmacophore with L-carnitine shape restriction. At least 16 of these molecules had case reports documenting an association with rhabdomyolysis and represent a set for prioritizing for future testing as OCTN2 substrates or inhibitors. This computational OCTN2 substrate pharmacophore derived from published data partially overlaps a previous OCTN2 inhibitor pharmacophore and is also able to select compounds that demonstrate rhabdomyolysis, further confirming the possible linkage between this side effect and hOCTN2. PMID:22339151

  6. Catalytic ozonation of sulfonated aromatic compounds in the presence of activated carbon

    Microsoft Academic Search

    P. C. C. Faria; J. J. M. Órfão; M. F. R. Pereira

    2008-01-01

    The ozonation of two model compounds (benzenesulfonic acid and sulfanilic acid) was carried out in the presence of activated carbon. With the aim of evaluating the role of the activated carbon surface chemistry during the ozonation, two activated carbon samples were assessed. Activated carbon promoted ozonation increased the rate of removal of the selected aromatic compounds and, most of all,

  7. Selective targeting of neuroblastoma tumour-initiating cells by compounds identified in stem cell-based small molecule screens

    PubMed Central

    Smith, Kristen M; Datti, Alessandro; Fujitani, Mayumi; Grinshtein, Natalie; Zhang, Libo; Morozova, Olena; Blakely, Kim M; Rotenberg, Susan A; Hansford, Loen M; Miller, Freda D; Yeger, Herman; Irwin, Meredith S; Moffat, Jason; Marra, Marco A; Baruchel, Sylvain; Wrana, Jeffrey L; Kaplan, David R

    2010-01-01

    Neuroblastoma (NB) is the most deadly extra-cranial solid tumour in children necessitating an urgent need for effective and less toxic treatments. One reason for the lack of efficacious treatments may be the inability of existing drugs to target the tumour-initiating or cancer stem cell population responsible for sustaining tumour growth, metastases and relapse. Here, we describe a strategy to identify compounds that selectively target patient-derived cancer stem cell-like tumour-initiating cells (TICs) while sparing normal paediatric stem cells (skin-derived precursors, SKPs) and characterize two therapeutic candidates. DECA-14 and rapamycin were identified as NB TIC-selective agents. Both compounds induced TIC death at nanomolar concentrations in vitro, significantly reduced NB xenograft tumour weight in vivo, and dramatically decreased self-renewal or tumour-initiation capacity in treated tumours. These results demonstrate that differential drug sensitivities between TICs and normal paediatric stem cells can be exploited to identify novel, patient-specific and potentially less toxic therapies. PMID:20721990

  8. Pharmacologically active compounds in the Anoectochilus and Goodyera species.

    PubMed

    Du, Xiao-Ming; Irino, Nobuto; Furusho, Norihiro; Hayashi, Jun; Shoyama, Yukihiro

    2008-04-01

    The extract of Anoectochilus formosanus showed significant activity in decreasing the levels of the cytosolic enzymes LDH, GOT, and GPT, and the result demonstrated that A. formosanus possessed prominent hepatoprotective activity against CCl(4)-induced hepatotoxicity. Moreover, in the results of the test using aurothioglucose-induced obese mice, the extract showed a significant antihyperliposis effect. A. formosanus grown in the wild and propagated by tissue culture contain ten compounds, including a major known component, (3R)-3-(beta-D-glucopyranosyloxy)butanolide (kinsenoside; 1), and two new components, (3R)-3-(beta-D-glucopyranosyloxy)-4-hydroxybutanoic acid (2) and 2-[(beta-D-glucopyranosyloxy)methyl]-5-hydroxymethylfuran (3), along with the known compounds, isopropyl-beta-D-glucopyranoside (4), (R)-3,4-dihydroxybutanoic acid gamma-lactone (5), 4-(beta-D-glucopyranosyloxy) benzyl alcohol (6), (6R,9S)-9-(beta-D-glucopyranosyloxy)megastigma-4,7-dien-3-one (7), and (3R)-3-(beta-D-glucopyranosyloxy)-4-hydroxybutanolide (8). Since a higher concentration of kinsenoside (1) was detected in the crude drugs A. formosanus and A. koshunensis by high-performance liquid chromatography (HPLC) analysis, we proved a simple purification system for kinsenoside (1), giving 180 mg of kinsenoside (1) from 1 g of dried samples for further pharmacological experiments. In an anti-hyperliposis assay using high-fat-diet rats, 1 significantly reduced the weights of the body and the liver, and also decreased the triglyceride level in the liver compared to those of control rats. On the other hand, the epimer of 1, (3S)-3-(beta-D-glucopyranosyloxy)butanolide, goodyeroside A (9), which was isolated from the Goodyera species, had no effect for anti-hyperliposis. In aurothioglucose-induced obese mice, 1 suppressed the body and liver weight increase, significantly ameliorated the triglyceride level in the liver, and also reduced the deposition of uterine fat pads. The anti-hepatoxic activities of 9 and goodyerosides B (10) were studied on injury induced by CCl(4) in primary cultured rat hepatocytes by measuring the levels of LDH, GOT, and GPT. In the CCl(4)-treated control group, there were marked increases in LDH, GOT, and GPT activities compared with the normal group. In contrast, these levels were suppressed in 9- and 10-treated groups. Goodyerin (11), a new typical flavone glycoside, exhibited a significant and dose-dependent sedative and anticonvulsant effect. PMID:18404313

  9. Targeted analysis of bioactive phenolic compounds and antioxidant activity of Macedonian red wines.

    PubMed

    Ivanova-Petropulos, Violeta; Ricci, Arianna; Nedelkovski, Dusko; Dimovska, Violeta; Parpinello, Giuseppina P; Versari, Andrea

    2015-03-15

    Phenolic composition of twenty-two Macedonian red wines, including ten autochthonous monovarietal Vranec wines produced with different yeasts for fermentation, and twelve wines from international varieties (Syrah, Merlot and Cabernet Sauvignon) from different wine regions was studied. All wines presented relatively high value of total phenols and antioxidant activity. A total of 19 phenolic compounds were identified and quantified using HPLC-DAD and among them, malvidin-3-glucoside and its derivatives were the major compounds, followed by the petunidin derivatives, while caftaric acid was the predominant cinnamic acid derivative in all wines. The anthocyanin content was mainly affected by the grape variety and to a less extent by the yeast used in fermentation. In particular, the use of locally isolated yeasts affected higher amount of anthocyanins and phenolic acids compared to the wines fermented with commercial yeasts. Principal Component Analysis showed a satisfactory grouping of red wines according to the grape variety. PMID:25308688

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

    PubMed Central

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

    2011-01-01

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

  11. Volatile compounds of Lamiaceae exhibit a synergistic antibacterial activity with streptomycin

    PubMed Central

    Araújo, Sthéfane G.; Alves, Lucas F.; Pinto, Maria Eduarda A.; Oliveira, Graziela T.; Siqueira, Ezequias P.; Ribeiro, Rosy I. M. A.; Ferreira, Jaqueline M. S.; Lima, Luciana A. R. S.

    2014-01-01

    Bacterial infections cause thousands of deaths in the world every year. In most cases, infections are more serious because the patient is already weakened, and often, the bacteria are already resistant to the antibiotics used. Counterparting this negative scenario, the interest in medicinal plants as an alternative to the synthetic antimicrobial drugs is blossoming worldwide. In the present work, we identified the volatile compounds of ethanol extracts of Melissa officinalis, Mentha sp., Ocimum basilicum, Plectranthus barbatus, and Rosmarinus officinalis by gas chromatography/mass spectrometry (GC/MS). Also was evaluated antimicrobial activity of ethanol extracts against 6 bacteria of clinical interest, and was tested the interaction of these extracts with a commercial antibiotic streptomycin. Phytol was a compound identified in all extracts by GC/MS, being majoritary component in Plectranthus barbatus and Rosmarinus officinalis. The Gram-positive bacteria were more sensitive to ethanol extracts, and Plectranthus barbatus and Rosmarinus officinalis were the most active extracts. Ethanol extracts exhibited a synergetic effect with streptomycin. These results encourage additional studies, in order to evaluate the possibilities of using ethanol extracts of Lamiaceae family as natural source for antibacterial activity. PMID:25763039

  12. Rejection of organic micropollutants (disinfection by-products, endocrine disrupting compounds, and pharmaceutically active compounds) by NF\\/RO membranes

    Microsoft Academic Search

    Katsuki Kimura; Gary Amy; Jörg E. Drewes; Thomas Heberer; Tae-Uk Kim; Yoshimasa Watanabe

    2003-01-01

    The growing demand on water resources has increased interest in wastewater reclamation for potable reuse, in which rejection of organic micropollutants such as disinfection by-products (DBPs), endocrine disrupting compounds (EDCs), and pharmaceutically active compounds (PhACs) is of great concern. The objective of this study was to investigate the rejection of DBPs, EDCs, and PhACs by nanofiltration (NF) and reverse osmosis

  13. 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. PMID:15209943

  14. Occurrence, fate, and ecosystem implications of endocrine active compounds in select rivers of Minnesota

    NASA Astrophysics Data System (ADS)

    Writer, J.; Keefe, S.; Barber, L. B.; Brown, G.; Schoenfuss, H.; Kiesling, R.; Gray, J. L.

    2009-12-01

    Select endocrine active compounds (EACs) were measured in four rivers in southern Minnesota. Additionally, caged and wild fish were assessed for indication of endocrine disruption using plasma vitellogenin and histopathology. Low concentrations of EACs were identified in all rivers, as was elevated plasma vitellogenin in caged and wild fish, indicating potential endocrine disruption. To evaluate the persistence of these compounds in small rivers, a tracer study was performed on one of the rivers (Redwood River) using Lagrangian sampling coupled with hydrologic modeling incorporating transient storage. Mass exchange (transient storage, sorption) and degradation were approximated as pseudo first order processes, and in-stream removal rates were then computed by comparing conservative tracer concentrations to organic compound concentrations. Production of estrone and 4-nonylphenol in the studied reach as a result of biochemical transformation from their parent compounds (17?-estradiol and alkylphenolpolyethoxylates, respectively) was quantified. The distance required for 17?-estradiol and nonylphenol to undergo a 50% reduction in concentration was >2 km and >10 km, respectively. These results indicate that EACs are transported several kilometers downstream from discharge sources and therefore have the potential of adversely impacting the lotic ecosystem over these distances.

  15. Antioxidant compounds, antioxidant activity and phenolic content in peel from three tropical fruits from Yucatan, Mexico.

    PubMed

    Moo-Huchin, Víctor M; Moo-Huchin, Mariela I; Estrada-León, Raciel J; Cuevas-Glory, Luis; Estrada-Mota, Iván A; Ortiz-Vázquez, Elizabeth; Betancur-Ancona, David; Sauri-Duch, Enrique

    2015-01-01

    The aim of this study was to determine the antioxidant compounds, antioxidant activity and content of individual phenolic compounds of freeze-dried peel from three tropical fruits grown in Yucatan, México: purple star apple (Chrysophyllum cainito L.), yellow cashew and red cashew (Anacardium occidentale). The freeze-dried peels were good source of antioxidant compounds. ABTS and DPPH values in the peel from each fruit were 3050.95-3322.31 ?M Trolox/100g dry weight (DW) or 890.19-970.01 mg of vitamin C/100 g DW, and 1579.04-1680.90 ?M Trolox/100 g DW or 340.18-362.18 mg of vitamin C/100 g DW, respectively. Six phenolic compounds were identified in the peel from the tropical fruits studied: ferulic, caffeic, sinapic, gallic, ellagic and myricetin. This study demonstrated that freeze-dried peels from purple star apple, yellow cashew and red cashew, could serve as potential sources of antioxidants for use in food and pharmaceutical industries. PMID:25053022

  16. Virtual Screening of compounds from Tabernaemontana divaricata for potential anti-bacterial activity

    PubMed Central

    Gogoi, Rashmi Rekha; Gogoi, Dhrubajyoti; Bezbaruah, Rajib Lochan

    2014-01-01

    Virtual Screening and Molecular Docking analysis for Tabernaemontana divaricata derived 66 Law Molecular Weight Compounds (LMW) was conducted and to identified and predicted novel molecules as a inhibitor of Streptococcus pneumonia. The investigation has revealed several compounds with optimum binding towards Penicillin-binding proteins, Sialidases, Aspartate betasemialdehide dehydrogenase cell membrane protein of Streptococcus pneumonia. Docking results were computed in term of binding energy, ligand efficiency and number of hydrogen bonding. Apparicine (-5.14), 5-Hydroxyvoaphylline (-4.78), Voacangine (-4.7), 19-Hydroxycoronaridine (-4.44) and Coronaridine (-4.72) are identified as most suitable to bind with N-acetylglucosamine-1- phosphate uridyltransferase receptor. Ervaticine (-6.33), Ibogamine (-6.15), Methylvoaphylline (-5.74) and Coronaridine hydroxyindolenine (-5.32) has showed novel binding against the penicillin-binding proteins. Ervaticine (-6.42), 5-oxo-11-hydroxy voaphylline (-6.18), Conolobine B (-6.02) has found optimum binding against the active site of NanB sialidase of Streptococcus pneumonia. The compounds 3S-Cyanocoronaridine (-6.71), 19-Epivoacristine (-5.48) and Ervaticine(-5.45) interacting with aspartate beta-semialdehide and found suitable with least docking score. PMID:24748755

  17. Virtual Screening of compounds from Tabernaemontana divaricata for potential anti-bacterial activity.

    PubMed

    Gogoi, Rashmi Rekha; Gogoi, Dhrubajyoti; Bezbaruah, Rajib Lochan

    2014-01-01

    Virtual Screening and Molecular Docking analysis for Tabernaemontana divaricata derived 66 Law Molecular Weight Compounds (LMW) was conducted and to identified and predicted novel molecules as a inhibitor of Streptococcus pneumonia. The investigation has revealed several compounds with optimum binding towards Penicillin-binding proteins, Sialidases, Aspartate betasemialdehide dehydrogenase cell membrane protein of Streptococcus pneumonia. Docking results were computed in term of binding energy, ligand efficiency and number of hydrogen bonding. Apparicine (-5.14), 5-Hydroxyvoaphylline (-4.78), Voacangine (-4.7), 19-Hydroxycoronaridine (-4.44) and Coronaridine (-4.72) are identified as most suitable to bind with N-acetylglucosamine-1- phosphate uridyltransferase receptor. Ervaticine (-6.33), Ibogamine (-6.15), Methylvoaphylline (-5.74) and Coronaridine hydroxyindolenine (-5.32) has showed novel binding against the penicillin-binding proteins. Ervaticine (-6.42), 5-oxo-11-hydroxy voaphylline (-6.18), Conolobine B (-6.02) has found optimum binding against the active site of NanB sialidase of Streptococcus pneumonia. The compounds 3S-Cyanocoronaridine (-6.71), 19-Epivoacristine (-5.48) and Ervaticine(-5.45) interacting with aspartate beta-semialdehide and found suitable with least docking score. PMID:24748755

  18. VeloceGenomics: An Accelerated in Vivo Drug Discovery Approach to Rapidly Predict the Biologic, Drug-Like Activity of Compounds, Proteins, or Genes

    Microsoft Academic Search

    Ruben Papoian; Andreas Scherer; Muriel Saulnier; Frank Staedtler; André Cordier; Francois Legay; Gerard Maurer; Joerg Staeheli; Jacky Vonderscher; Salah-Dine Chibout

    2005-01-01

    :Purpose. The aim of this study is to test the predictive power of in vivo multiorgan RNA expression profiling in identifying the biologic activity of molecules. Methods. Animals were treated with compound A or B. At the end of the treatment period, in vivo multiorgan microarray-based gene expression data were collected. Investigators masked to the identity of the compounds analyzed

  19. Antimicrobial activity of a compound isolated from an oil-macerated garlic extract.

    PubMed

    Yoshida, H; Iwata, N; Katsuzaki, H; Naganawa, R; Ishikawa, K; Fukuda, H; Fujino, T; Suzuki, A

    1998-05-01

    A compound showing antimicrobial activity was isolated from an oil-macerated garlic extract by silica gel column chromatography and preparative TLC. On basis of the results of NMR and MS analyses, it was identified as Z-4,5,9-trithiadeca-1,6-diene-9-oxide (Z-10-devinylajoene; Z-10-DA). Z-10-DA exhibited a broad spectrum of antimicrobial activity against such microorganisms as gram-positive and gram-negative bacteria and yeasts. The antimicrobial activity of Z-10-DA was comparable to that of Z-ajoene, but was superior to that of E-ajoene. Z-10-DA and Z-ajoene are different in respect of substitution of the allyl group by the methyl group flanking a sulfinyl group. This result suggests that substitution by the methyl group would also be effective for the inhibition of microbial growth. PMID:9648236

  20. EVALUATION OF THE REMOVAL OF POTENTIALLY HORMONALLY ACTIVE COMPOUNDS (ENDOCRINE DISRUPTING COMPOUNDS) BY DRINKING WATER TREATMENT PROCESSES.

    EPA Science Inventory

    A number of the chemicals identified as potential EDCs may be present in surface or ground waters used as drinking water sources due to their introduction from domestic and industrial sewage treatment systems and wet-weather runoff. Many of these compounds have already been show...

  1. Inhibition of tyrosinase activity by polyphenol compounds from Flemingia philippinensis roots.

    PubMed

    Wang, Yan; Curtis-Long, Marcus J; Lee, Byong Won; Yuk, Heung Joo; Kim, Dae Wook; Tan, Xue Fei; Park, Ki Hun

    2014-02-01

    Flemingia philippinensis is used as a foodstuff or medicinal plant in the tropical regions of China. The methanol (95%) extract of the roots of this plant showed potent tyrosinase inhibition (80% inhibition at 30?g/ml). Activity-guided isolation yielded six polyphenols that inhibited both the monophenolase (IC50=1.01-18.4?M) and diphenolase (IC50=5.22-84.1?M) actions of tyrosinase. Compounds 1-6 emerged to be three new polyphenols and three known flavanones, flemichin D, lupinifolin and khonklonginol H. The new compounds (1-3) were identified as dihydrochalcones which we named fleminchalcones (A-C), respectively. The most potent inhibitor, dihydrochalcone (3) showed significant inhibitions against both the monophenolase (IC50=1.28?M) and diphenolase (IC50=5.22?M) activities of tyrosinase. Flavanone (4) possessing a resorcinol group also inhibited monophenolase (IC50=1.79?M) and diphenolase (IC50=7.48?M) significantly. In kinetic studies, all isolated compounds behaved as competitive inhibitors. Fleminchalcone A was found to have simple reversible slow-binding inhibition against monophenolase. PMID:24412339

  2. Comparative study of SoxR activation by redox-active compounds

    PubMed Central

    Singh, Atul K.; Shin, Jung-Ho; Lee, Kang-Lok; Imlay, James A.; Roe, Jung-Hye

    2013-01-01

    Summary SoxR from E. coli and related enterobacteria is activated by a broad range of redox-active compounds through oxidation or nitrosylation of its [2Fe-2S] cluster. Activated SoxR then induces SoxS, which subsequently activates more than 100 genes in response. In contrast, non-enteric SoxRs directly activate their target genes in response to redox-active compounds that include endogenously produced metabolites. We compared the responsiveness of SoxRs from Streptomyces coelicolor (ScSoxR), Pseudomonas aeruginosa (PaSoxR) and E. coli (EcSoxR), all expressed in S. coelicolor, toward natural or synthetic redox-active compounds. EcSoxR responded to all compounds examined, whereas ScSoxR was insensitive to oxidants such as paraquat (Eh ?440 mV) and menadione sodium bisulfite (Eh ?45 mV) and to NO generators. PaSoxR was insensitive only to some NO generators. Whole cell EPR analysis of SoxRs expressed in E. coli revealed that the [2Fe-2S]1+ of ScSoxR was not oxidizable by paraquat, differing from EcSoxR and PaSoxR. The mid-point redox potential of purified ScSoxR was determined to be ?185 ± 10 mV, higher by ~100 mV than those of EcSoxR and PaSoxR, supporting its limited response to paraquat. The overall sensitivity profile indicates that both redox potential and kinetic reactivity determine the differential responses of SoxRs toward various oxidants. PMID:24112649

  3. Tracking heavy water (D2O) incorporation for identifying and sorting active microbial cells.

    PubMed

    Berry, David; Mader, Esther; Lee, Tae Kwon; Woebken, Dagmar; Wang, Yun; Zhu, Di; Palatinszky, Marton; Schintlmeister, Arno; Schmid, Markus C; Hanson, Buck T; Shterzer, Naama; Mizrahi, Itzhak; Rauch, Isabella; Decker, Thomas; Bocklitz, Thomas; Popp, Jürgen; Gibson, Christopher M; Fowler, Patrick W; Huang, Wei E; Wagner, Michael

    2015-01-13

    Microbial communities are essential to the function of virtually all ecosystems and eukaryotes, including humans. However, it is still a major challenge to identify microbial cells active under natural conditions in complex systems. In this study, we developed a new method to identify and sort active microbes on the single-cell level in complex samples using stable isotope probing with heavy water (D2O) combined with Raman microspectroscopy. Incorporation of D2O-derived D into the biomass of autotrophic and heterotrophic bacteria and archaea could be unambiguously detected via C-D signature peaks in single-cell Raman spectra, and the obtained labeling pattern was confirmed by nanoscale-resolution secondary ion MS. In fast-growing Escherichia coli cells, label detection was already possible after 20 min. For functional analyses of microbial communities, the detection of D incorporation from D2O in individual microbial cells via Raman microspectroscopy can be directly combined with FISH for the identification of active microbes. Applying this approach to mouse cecal microbiota revealed that the host-compound foragers Akkermansia muciniphila and Bacteroides acidifaciens exhibited distinctive response patterns to amendments of mucin and sugars. By Raman-based cell sorting of active (deuterated) cells with optical tweezers and subsequent multiple displacement amplification and DNA sequencing, novel cecal microbes stimulated by mucin and/or glucosamine were identified, demonstrating the potential of the nondestructive D2O-Raman approach for targeted sorting of microbial cells with defined functional properties for single-cell genomics. PMID:25550518

  4. Tracking heavy water (D2O) incorporation for identifying and sorting active microbial cells

    PubMed Central

    Berry, David; Mader, Esther; Lee, Tae Kwon; Woebken, Dagmar; Wang, Yun; Zhu, Di; Palatinszky, Marton; Schintlmeister, Arno; Schmid, Markus C.; Hanson, Buck T.; Shterzer, Naama; Mizrahi, Itzhak; Rauch, Isabella; Decker, Thomas; Bocklitz, Thomas; Popp, Jürgen; Gibson, Christopher M.; Fowler, Patrick W.; Huang, Wei E.; Wagner, Michael

    2015-01-01

    Microbial communities are essential to the function of virtually all ecosystems and eukaryotes, including humans. However, it is still a major challenge to identify microbial cells active under natural conditions in complex systems. In this study, we developed a new method to identify and sort active microbes on the single-cell level in complex samples using stable isotope probing with heavy water (D2O) combined with Raman microspectroscopy. Incorporation of D2O-derived D into the biomass of autotrophic and heterotrophic bacteria and archaea could be unambiguously detected via C-D signature peaks in single-cell Raman spectra, and the obtained labeling pattern was confirmed by nanoscale-resolution secondary ion MS. In fast-growing Escherichia coli cells, label detection was already possible after 20 min. For functional analyses of microbial communities, the detection of D incorporation from D2O in individual microbial cells via Raman microspectroscopy can be directly combined with FISH for the identification of active microbes. Applying this approach to mouse cecal microbiota revealed that the host-compound foragers Akkermansia muciniphila and Bacteroides acidifaciens exhibited distinctive response patterns to amendments of mucin and sugars. By Raman-based cell sorting of active (deuterated) cells with optical tweezers and subsequent multiple displacement amplification and DNA sequencing, novel cecal microbes stimulated by mucin and/or glucosamine were identified, demonstrating the potential of the nondestructive D2O-Raman approach for targeted sorting of microbial cells with defined functional properties for single-cell genomics. PMID:25550518

  5. Characterization, chemical optimization and anti-tumour activity of a tubulin poison identified by a p53-based phenotypic screen

    PubMed Central

    Staples, Oliver D.; Hollick, Jonathan J.; Campbell, Johanna; Higgins, Maureen; McCarthy, Anna R.; Appleyard, Virginia; Murray, Karen E.; Baker, Lee; Thompson, Alastair; Ronseaux, Sebastien; Slawin, Alexandra M.Z.; Lane, David P.; Westwood, Nicholas J.; Lain, Sonia

    2009-01-01

    A robust p53 cell-based assay that exploits p53’s function as a transcription factor was used to screen a small molecule library and identify bioactive small molecules with potential antitumor activity. Unexpectedly, the majority of the highest ranking hit compounds from this screen arrest cells in mitosis and most of them impair polymerization of tubulin in cells and in vitro. One of these novel compounds, JJ78:1, was subjected to structure-activity relationship studies and optimized leading to the identification of JJ78:12. This molecule is significantly more potent than the original hit JJ78:1, as it is active in cells at two-digit nanomolar concentrations and shows clear antitumor activity in a mouse xenograft model as a single agent. The effects of nocodazole, a well established tubulin poison, and JJ78:12 on p53 levels are remarkably similar, supporting that tubulin depolymerization is the main mechanism by which JJ78:12 treatment leads to p53 activation in cells. In summary, these results identify JJ78:12 as a potential cancer therapeutic, demonstrate that screening for activators of p53 in a cell-based assay is an effective way to identify inhibitors of mitosis progression and highlights p53’s sensitivity to alterations during mitosis. PMID:18971638

  6. Reliability of facial muscle activity to identify vowel utterance

    Microsoft Academic Search

    Ganesh R Naik; Dinesh K Kumar; Sridhar P Arjunan

    2008-01-01

    This paper evaluates the reliability of the use of muscle activation during unuttered (silent) vowel by an individual and reports the study of repeating of the experiments over several days. Surface electromyogram has been used as an indicator of muscle activity and independent component analysis (ICA) has been used to separate the electrical activity from different muscles. The results demonstrate

  7. Production of antioomycete compounds active against the phytopathogens Phytophthora sojae and Aphanomyces cochlioides by clavicipitoid entomopathogenic fungi.

    PubMed

    Putri, Sastia Prama; Ishido, Kei-Ichi; Kinoshita, Hiroshi; Kitani, Shigeru; Ihara, Fumio; Sakihama, Yasuko; Igarashi, Yasuhiro; Nihira, Takuya

    2014-05-01

    A total of 412 strains belonging to 14 genera of clavicipitoid entomopathogenic fungi (EPF) were screened for activities against two economically important plant pathogenic oomycetes, Phytophthora sojae and Aphanomyces cochlioides. To identify the antioomycete compounds produced by EPF, the extracts of 13 highly active EPF strains were characterized in detail by high performance liquid chromatography with diode array detection and high-resolution mass spectrometric detection and antioomycete assay. The antioomycete activity of several Metarhizium extracts was associated with previously isolated aurovertins, fungerin, N-(methyl-3-oxodec-6-enoyl)-2-pyrroline, and N-(methyl-3-oxodecanoyl)-2-pyrroline. The depsipeptide beauvericin was confirmed to be one of the active principles of three strains of Isaria tenuipes, which strongly inhibited mycelial growth of both P. sojae and A. cochlioides. Two known bioactive metabolites, paecilosetin and aranorosinol A, together with a novel and potent antioomycete compound, farinomalein, were isolated from the extracts of Isaria farinosa and all compounds were confirmed to have antioomycete activity. Identification of 8 antioomycete compounds from 13 clavicipitioid EPF demonstrated a new potential use of EPF as a source of compounds for the control of soil-borne plant pathogenic oomycetes. PMID:24268864

  8. Zebrafish promoter microarrays identify actively transcribed embryonic genes

    E-print Network

    Wardle, Fiona C

    We have designed a zebrafish genomic microarray to identify DNA-protein interactions in the proximal promoter regions of over 11,000 zebrafish genes. Using these microarrays, together with chromatin immunoprecipitation ...

  9. Characterization of aroma-active compounds, sensory properties, and proteolysis in Ezine cheese.

    PubMed

    Yuceer, Y Karagul; Tuncel, B; Guneser, O; Engin, B; Isleten, M; Yasar, K; Mendes, M

    2009-09-01

    Ezine cheese is a white pickled cheese ripened in tinplate containers for at least 8 mo. A mixture of milk from goat, sheep, and cow is used to make Ezine cheese. Ezine cheese has geographical indication status. The purposes of this study were to determine and compare the changes in basic composition, aroma, and sensory characteristics, and proteolytic activity of Ezine cheese stored in tinplate containers and plastic vacuum packages during storage. Aroma-active compounds were determined by thermal desorption gas chromatography olfactometry. To evaluate the proteolytic activity, casein and nitrogen fractions were determined. The results indicated that compounds identified at high intensities were dimethyl sulfide, ethyl butyrate, hexanal, ethyl pentanoate, (Z)-4-heptenal, 1-octen-3-one, acetic acid, butyric acid, and p-cresol. Characteristic descriptive terms were cooked, whey, creamy, animal-like, sour, and salty. The level of proteolysis increased in Ezine cheese during storage. Ezine cheese can be ripened in small-size packaging after 3 mo of storage. Approximately 6 mo is sufficient to produce the characteristic properties of Ezine cheese. PMID:19700675

  10. Identifying active methane-oxidizers in thawed Arctic permafrost by proteomics

    NASA Astrophysics Data System (ADS)

    Lau, C. M.; Stackhouse, B. T.; Chourey, K.; Hettich, R. L.; Vishnivetskaya, T. A.; Pfiffner, S. M.; Layton, A. C.; Mykytczuk, N. C.; Whyte, L.; Onstott, T. C.

    2012-12-01

    The rate of CH4 release from thawing permafrost in the Arctic has been regarded as one of the determining factors on future global climate. It is uncertain how indigenous microorganisms would interact with such changing environmental conditions and hence their impact on the fate of carbon compounds that are sequestered in the cryosol. Multitudinous studies of pristine surface cryosol (top 5 cm) and microcosm experiments have provided growing evidence of effective methanotrophy. Cryosol samples corresponding to active layer were sampled from a sparsely vegetated, ice-wedge polygon at the McGill Arctic Research Station at Axel Heiberg Island, Nunavut, Canada (N79°24, W90°45) before the onset of annual thaw. Pyrosequencing of 16S rRNA gene indicated the occurrence of methanotroph-containing bacterial families as minor components (~5%) in pristine cryosol including Bradyrhizobiaceae, Methylobacteriaceae and Methylocystaceae within alpha-Proteobacteria, and Methylacidiphilaceae within Verrucomicrobia. The potential of methanotrophy is supported by preliminary analysis of metagenome data, which indicated putative methane monooxygenase gene sequences relating to Bradyrhizobium sp. and Pseudonocardia sp. are present. Proteome profiling in general yielded minute traces of proteins, which likely hints at dormant nature of the soil microbial consortia. The lack of specific protein database for permafrost posted additional challenge to protein identification. Only 35 proteins could be identified in the pristine cryosol and of which 60% belonged to Shewanella sp. Most of the identified proteins are known to be involved in energy metabolism or post-translational modification of proteins. Microcosms amended with sodium acetate exhibited a net methane consumption of ~65 ngC-CH4 per gram (fresh weight) of soil over 16 days of aerobic incubation at room temperature. The pH in microcosm materials remained acidic (decreased from initial 4.7 to 4.5). Protein extraction and characterization identified ~350 proteins, confirmed enhanced microbial activities and significant shift in community structure within the microcosms. Although the activity of Shewanella sp. was suppressed by the incubation conditions, other bacteria were activated. This was shown by at least 3-fold increase in the number of identified proteins, which were primarily players in cellular energy metabolism. Among them, Geobacter sp. and methane-oxidizers, Bradyrhizobium sp., Methylosinus sp. and Methylocystis sp. appear dominant. In order to advance the protein database for better biodiversity and functional identification, we are currently using duo extraction protocols and consolidating metagenome data obtained from the same soil samples. A depth profile (from active to permafrost layer) for methanotrophs is being determined by examining pristine cores, thawed cryosols as well as enrichment cultures. The proteome information from these samples will be presented, which will be complemented by molecular studies.

  11. Synthesis and anticancer activity of focused compound libraries from the natural product lead, oroidin.

    PubMed

    Dyson, Lauren; Wright, Anthony D; Young, Kelly A; Sakoff, Jennette A; McCluskey, Adam

    2014-03-01

    Oroidin (1), (E)-N-(3-(2-amino-1H-imidazol-4-yl)allyl)-4,5-dibromo-1H-pyrrole-2-carboxamide, is a pyrrole alkaloid isolated from the marine sponge Agelas oroides. Routine screening in a panel of twelve cancer cell lines revealed 1 to be poorly cytotoxic with the 50% growth inhibition concentration (GI50) of 42 ?M in MCF-7 (breast) cells and 24 ?M in A2780 (ovarian) cells and >50 ?M in all other cell lines tested. The development of eight focused libraries comprising thirty compounds total identified N-(biphenyl-4-ylmethyl)-1H-pyrrole-2-carboxamide (4l), N-benzyl-4,5-dibromo-1H-pyrrole-2-carboxamide (5a) and N-(biphenyl-4-ylmethyl)-4,5-dibromo-1H-pyrrole-2-carboxamide (5l) as potent inhibitors of cell growth in our panel of cell lines. Of these compounds GI50 values of <5 ?M were observed with 4l against HT29 (colon) and SW480 (colon); 5a against HT29; and 5l against HT29, SW480, MCF-7, A431 (skin), Du145 (prostate), BE2-C (neuroblastoma) and MIA (pancreas) cell lines. As a cancer class, colon cancer appears to be more sensitive to the oroidin series of compounds, with analogue 5l being the most active. PMID:24508308

  12. Synthesis and biological activity of urea and thiourea derivatives from 2-aminoheterocyclic compounds

    Microsoft Academic Search

    P. A. Yonova; G. M. Stoilkova

    2004-01-01

    Thirty-eight N-substituted-N?-(2-thiozolyl and furfuryl)ureas and thioureas were prepared by reaction of 2-aminothiazole and\\u000a 2-furfurylamine with the appropriate iso(thio)cyanate. All compounds were tested for herbicidal activity and selectivity on\\u000a seedlings of wheat (a monocotyledonous plant) and cucumber (a dicotyledonous plant). Only one compound (1) out of 14 ureas was characterized by considerable herbicidal activity against the wheat seedlings and two compounds

  13. Synthesis and Biological Activity of Urea and Thiourea Derivatives from 2-Aminoheterocyclic Compounds

    Microsoft Academic Search

    P. A. Yonova; G. M. Stoilkova

    2004-01-01

    Thirty-eight N-substituted-N'-(2-thiazolyl and furfuryl)ureas and thioureas were prepared by reaction of 2-aminothiazole and 2-furfurylamine with the appropriate iso(thio)cyanate. All compounds were tested for herbicidal activity and selectivity on seedlings of wheat (a monocotyledonous plant) and cucumber (a dicotyledonous plant). Only one compound (1) out of 14 ureas was characterized by considerable herbicidal activity against the wheat seedlings and two compounds

  14. Mosquito repelling activity of compounds occurring in Achillea millefolium L. (asteraceae)

    Microsoft Academic Search

    H. Tunón; W. Thorsell; L. Bohlin

    1994-01-01

    An ethanol extract ofAchillea millefolium L. showed repelling properties against the mosquito,Aedes aegypti L. Prepared fractions from the extract contained several active compounds which were characterized by thin layer chromatography,\\u000a high performance liquid chromatography, gas chromatography and mass spectroscopy. Of 35 compounds tested, the most active\\u000a were the nitrogen containing compound stachydrine, the carboxylic acids, caffeic, chlorogenic, and salicylic acids,

  15. Identifying healthcare activities using a real-time location system.

    PubMed

    Cagle, Rick; Darling, Erika; Kim, Bo

    2014-01-01

    This article discusses human resource allocation in a Veterans Health Administration audiology clinic as a model for clinics facing similar challenges in maximizing quality, safety, and effectiveness of care. A framework is proposed combining automatic identification technology with simulation and visualization software, asserting a relationship between location of staff within the facility and clinical activity, focusing healthcare staff on high-value activities to deliver safe, quality care. This enables "what-if" analyses of potential resource allocation scenarios, correlating location information from radiofrequency identification tags worn by clinicians and technicians in the clinic as part of a real-time location system, then inferring probable activity from the data. Once the baseline "as-is" can be established, the model will be refined to supply predictive analyses of resource allocation and management. Simulations of activities in specialized spaces saves time managing resources, which means more time can be spent on patient safety and increased satisfaction. PMID:25807605

  16. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture.

    PubMed

    de Wilde, Adriaan H; Jochmans, Dirk; Posthuma, Clara C; Zevenhoven-Dobbe, Jessika C; van Nieuwkoop, Stefan; Bestebroer, Theo M; van den Hoogen, Bernadette G; Neyts, Johan; Snijder, Eric J

    2014-08-01

    Coronaviruses can cause respiratory and enteric disease in a wide variety of human and animal hosts. The 2003 outbreak of severe acute respiratory syndrome (SARS) first demonstrated the potentially lethal consequences of zoonotic coronavirus infections in humans. In 2012, a similar previously unknown coronavirus emerged, Middle East respiratory syndrome coronavirus (MERS-CoV), thus far causing over 650 laboratory-confirmed infections, with an unexplained steep rise in the number of cases being recorded over recent months. The human MERS fatality rate of ? 30% is alarmingly high, even though many deaths were associated with underlying medical conditions. Registered therapeutics for the treatment of coronavirus infections are not available. Moreover, the pace of drug development and registration for human use is generally incompatible with strategies to combat emerging infectious diseases. Therefore, we have screened a library of 348 FDA-approved drugs for anti-MERS-CoV activity in cell culture. If such compounds proved sufficiently potent, their efficacy might be directly assessed in MERS patients. We identified four compounds (chloroquine, chlorpromazine, loperamide, and lopinavir) inhibiting MERS-CoV replication in the low-micromolar range (50% effective concentrations [EC(50)s], 3 to 8 ?M). Moreover, these compounds also inhibit the replication of SARS coronavirus and human coronavirus 229E. Although their protective activity (alone or in combination) remains to be assessed in animal models, our findings may offer a starting point for treatment of patients infected with zoonotic coronaviruses like MERS-CoV. Although they may not necessarily reduce viral replication to very low levels, a moderate viral load reduction may create a window during which to mount a protective immune response. PMID:24841269

  17. Structural characterisation and antioxidant activity evaluation of phenolic compounds from cold-pressed Perilla frutescens var. arguta seed flour.

    PubMed

    Zhou, Xiao-Jing; Yan, Lin-Lin; Yin, Pei-Pei; Shi, Ling-Ling; Zhang, Jing-Hua; Liu, Yu-Jun; Ma, Chao

    2014-12-01

    A total of 11 phenolic compounds, as well as sucrose (12) and tryptophan (13), were isolated from cold-pressed Perilla frutescens var. arguta seed flour using column chromatography, and their chemical structures were identified as 3'-dehydroxyl-rosmarinic acid-3-o-glucoside (1), rosmarinic acid-3-o-glucoside (2), rosmarinic acid (3), rosmarinic acid methyl ester (4), luteolin (5), luteolin-5-o-glucoside (6), apigenin (7), caffeic acid (8), caffeic acid-3-o-glucoside (9), vanillic acid (10) and cimidahurinine (11) using NMR and time-of-flight mass spectrometry. Of these components, compound 1 is novel, and this is the first report of compounds 10 and 11 in perilla seeds. HPLC quantification combined with antioxidant activity evaluation revealed that rosmarinic acid and rosmarinic acid-3-o-glucoside were the dominant phenolic antioxidants with strong antioxidant activities. PMID:24996318

  18. Sorption of boric acid and borax by activated carbon impregnated with various compounds

    Microsoft Academic Search

    Lj. V. Rajakovi?; M. Dj. Risti?

    1996-01-01

    The separation of boron compounds, boric acid and borax from aqueous solution by activated carbon before and after impregnation with various compounds was studied. A series of activated carbons was prepared from coconut shell impregnated with calcium and barium chlorides, citric and tartaric acids. The examined processes were performed in batch and continuous systems under equilibrium and dynamic conditions. Impregnation

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

    DOEpatents

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

    2007-04-03

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

  20. Discovery of a Novel Compound with Anti-Venezuelan Equine Encephalitis Virus Activity That Targets the Nonstructural Protein 2

    PubMed Central

    Chung, Dong-Hoon; Jonsson, Colleen B.; Tower, Nichole A.; Chu, Yong-Kyu; Sahin, Ergin; Golden, Jennifer E.; Noah, James W.; Schroeder, Chad E.; Sotsky, Julie B.; Sosa, Melinda I.; Cramer, Daniel E.; McKellip, Sara N.; Rasmussen, Lynn; White, E. Lucile; Schmaljohn, Connie S.; Julander, Justin G.; Smith, Jeffrey M.; Filone, Claire Marie; Connor, John H.; Sakurai, Yasuteru; Davey, Robert A.

    2014-01-01

    Alphaviruses present serious health threats as emerging and re-emerging viruses. Venezuelan equine encephalitis virus (VEEV), a New World alphavirus, can cause encephalitis in humans and horses, but there are no therapeutics for treatment. To date, compounds reported as anti-VEEV or anti-alphavirus inhibitors have shown moderate activity. To discover new classes of anti-VEEV inhibitors with novel viral targets, we used a high-throughput screen based on the measurement of cell protection from live VEEV TC-83-induced cytopathic effect to screen a 340,000 compound library. Of those, we identified five novel anti-VEEV compounds and chose a quinazolinone compound, CID15997213 (IC50?=?0.84 µM), for further characterization. The antiviral effect of CID15997213 was alphavirus-specific, inhibiting VEEV and Western equine encephalitis virus, but not Eastern equine encephalitis virus. In vitro assays confirmed inhibition of viral RNA, protein, and progeny synthesis. No antiviral activity was detected against a select group of RNA viruses. We found mutations conferring the resistance to the compound in the N-terminal domain of nsP2 and confirmed the target residues using a reverse genetic approach. Time of addition studies showed that the compound inhibits the middle stage of replication when viral genome replication is most active. In mice, the compound showed complete protection from lethal VEEV disease at 50 mg/kg/day. Collectively, these results reveal a potent anti-VEEV compound that uniquely targets the viral nsP2 N-terminal domain. While the function of nsP2 has yet to be characterized, our studies suggest that the protein might play a critical role in viral replication, and further, may represent an innovative opportunity to develop therapeutic interventions for alphavirus infection. PMID:24967809

  1. Discovery of a novel compound with anti-venezuelan equine encephalitis virus activity that targets the nonstructural protein 2.

    PubMed

    Chung, Dong-Hoon; Jonsson, Colleen B; Tower, Nichole A; Chu, Yong-Kyu; Sahin, Ergin; Golden, Jennifer E; Noah, James W; Schroeder, Chad E; Sotsky, Julie B; Sosa, Melinda I; Cramer, Daniel E; McKellip, Sara N; Rasmussen, Lynn; White, E Lucile; Schmaljohn, Connie S; Julander, Justin G; Smith, Jeffrey M; Filone, Claire Marie; Connor, John H; Sakurai, Yasuteru; Davey, Robert A

    2014-06-01

    Alphaviruses present serious health threats as emerging and re-emerging viruses. Venezuelan equine encephalitis virus (VEEV), a New World alphavirus, can cause encephalitis in humans and horses, but there are no therapeutics for treatment. To date, compounds reported as anti-VEEV or anti-alphavirus inhibitors have shown moderate activity. To discover new classes of anti-VEEV inhibitors with novel viral targets, we used a high-throughput screen based on the measurement of cell protection from live VEEV TC-83-induced cytopathic effect to screen a 340,000 compound library. Of those, we identified five novel anti-VEEV compounds and chose a quinazolinone compound, CID15997213 (IC50?=?0.84 µM), for further characterization. The antiviral effect of CID15997213 was alphavirus-specific, inhibiting VEEV and Western equine encephalitis virus, but not Eastern equine encephalitis virus. In vitro assays confirmed inhibition of viral RNA, protein, and progeny synthesis. No antiviral activity was detected against a select group of RNA viruses. We found mutations conferring the resistance to the compound in the N-terminal domain of nsP2 and confirmed the target residues using a reverse genetic approach. Time of addition studies showed that the compound inhibits the middle stage of replication when viral genome replication is most active. In mice, the compound showed complete protection from lethal VEEV disease at 50 mg/kg/day. Collectively, these results reveal a potent anti-VEEV compound that uniquely targets the viral nsP2 N-terminal domain. While the function of nsP2 has yet to be characterized, our studies suggest that the protein might play a critical role in viral replication, and further, may represent an innovative opportunity to develop therapeutic interventions for alphavirus infection. PMID:24967809

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

    PubMed

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

    2015-03-15

    The bound phenolic compounds in rice bran were released and extracted with ethyl acetate based on alkaline digestion. An investigation of the chemical constituents of EtOAc extract has led to the isolation of a new compound, para-hydroxy methyl benzoate glucoside (8), together with nine known compounds, cycloeucalenol cis-ferulate (1), cycloeucalenol trans-ferulate (2), trans-ferulic acid (3), trans-ferulic acid methyl ester (4), cis-ferulic acid (5), cis-ferulic acid methyl ester (6), methyl caffeate (7), vanillic aldehyde (9) and para-hydroxy benzaldehyde (10). The structures of these compounds were determined using a combination of spectroscopic methods and chemical analysis. Among the compounds isolated, compound 3, 5 and 7 exhibited strong DPPH and ABTS(+) radical scavenging activities, followed by compounds 4 and 6. Compound 1 and 2 showed potent DPPH and ABTS(+) radical scavenging activities, compound 8 displayed moderate antioxidant activity against ABTS(+) radical, whereas compound 9 and 10 showed weak antioxidant activity. PMID:25308640

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

    PubMed Central

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

    2012-01-01

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

  4. Two compounds from allelopathic rice accession and their inhibitory activity on weeds and fungal pathogens.

    PubMed

    Kong, Chuihua; Xu, Xiaohua; Zhou, Bin; Hu, Fei; Zhang, Chaoxian; Zhang, Maoxin

    2004-04-01

    A flavone (5,7,4'-trihydroxy-3',5'-dimethoxyflavone), a cyclohexenone (3-isopropyl-5-acetoxycyclohexene-2-one-1) and a liquid mixture of low polarity, containing long-chain and cyclic hydrocarbons, were isolated from leaves of allelopathic rice accession PI 312777 using column chromatography. Their structures and constituents were identified by means of HR-MS, NMR and GC/MS analyses, respectively. Bioassays showed that both the flavone and cyclohexenone significantly inhibited the growth of weeds Echinochloa crus-galli, Cyperus difformis and Cyperus iris, and the spore germination of fungal pathogens Pyricularia oryzae and Rhizoctonia solani at all tested concentrations. Moreover, the combination of the inactive mixture of low polarity and the active flavone or cyclohexenone significantly enhanced the inhibitory activities on weed growth. In addition, the two compounds and the mixture of low polarity from the leaves of PI312777 did not inhibit the rice growth at the same concentrations. It was also established that both compounds could be released into the soil, and was especially induced by E. crus-galli. The results suggest that 5,7,4'-trihydroxy-3',5'-dimethoxyflavone and 3-isopropyl- 5-acetoxycyclohexene-2-one-1 may act as allelochemicals participating in the defense of rice against weeds and pathogens. PMID:15110693

  5. Biologically active vitamin B12 compounds in foods for preventing deficiency among vegetarians and elderly subjects.

    PubMed

    Watanabe, Fumio; Yabuta, Yukinori; Tanioka, Yuri; Bito, Tomohiro

    2013-07-17

    The usual dietary sources of vitamin B12 are animal-source based foods, including meat, milk, eggs, fish, and shellfish, although a few plant-based foods such as certain types of dried lavers (nori) and mushrooms contain substantial and considerable amounts of vitamin B12, respectively. Unexpectedly, detailed characterization of vitamin B12 compounds in foods reveals the presence of various corrinoids that are inactive in humans. The majority of edible blue-green algae (cyanobacteria) and certain edible shellfish predominately contain an inactive corrinoid known as pseudovitamin B12. Various factors affect the bioactivity of vitamin B12 in foods. For example, vitamin B12 is partially degraded and loses its biological activity during cooking and storage of foods. The intrinsic factor-mediated gastrointestinal absorption system in humans has evolved to selectively absorb active vitamin B12 from naturally occurring vitamin B12 compounds, including its degradation products and inactive corrinoids that are present in daily meal foods. The objective of this review is to present up-to-date information on various factors that can affect the bioactivity of vitamin B12 in foods. To prevent vitamin B12 deficiency in high-risk populations such as vegetarians and elderly subjects, it is necessary to identify plant-source foods that contain high levels of bioactive vitamin B12 and, in conjunction, to prepare the use of crystalline vitamin B12-fortified foods. PMID:23782218

  6. Ellagic Acid, the Active Compound of Phyllanthus urinaria, Exerts In Vivo Anti-Angiogenic Effect and Inhibits MMP-2 Activity

    PubMed Central

    Huang, Sheng-Teng; Wang, Chen-Yu; Yang, Rong-Chi; Wu, Hsiao-Ting; Yang, Su-Hui; Cheng, Yung-Chi; Pang, Jong-Hwei S.

    2011-01-01

    This study aimed to assess the potential anti-angiogenic mechanism of Phyllanthus urinaria (P. urinaria) and characterize the major compound in P. urinaria that exerts anti-angiogenic effect. The water extract of P. urinaria and Ellagic Acid were used to evaluate the anti-angiogenic effect in chorioallantoic membrane (CAM) in chicken embryo and human vascular endothelial cells (HUVECs). The matrix metalloproteinase-2 (MMP-2) activity was determined by gelatin zymography. The mRNA expressions of MMP-2, MMP-14 and tissue inhibitor of metalloproteinase-2 (TIMP-2) were analyzed by reverse transcription polymerase chain reaction (RT-PCR). Level of MMP-2 proteins in conditioned medium or cytosol was determined by western blot analysis. We confirmed that P. urinaria's in vivo anti-angiogenic effect was associated with a reduction in MMP-2 activity. Ellagic acid, one of the major polyphenolic components as identified in P. urinaria by high performance liquid chromatography mass spectrometry (HPLC/MS), exhibited the same anti-angiogenic effect in vivo. Both P. urinaria and Ellagic Acid inhibited MMP-2 activity in HUVECs with unchanged mRNA level. The mRNA expression levels of MMP-14 and TIMP-2 were not altered either. Results from comparing the change of MMP-2 protein levels in conditioned medium and cytosol of HUVECs after the P. urinaria or Ellagic Acid treatment revealed an inhibitory effect on the secretion of MMP-2 protein. This study concluded that Ellagic Acid is the active compound in P. urinaria to exhibit anti-angiogenic activity and to inhibit the secretion of MMP-2 protein from HUVECs. PMID:20007260

  7. 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. PMID:16188263

  8. Bioassay-guided isolation and identification of active compounds from Fructus Arctii against Dactylogyrus intermedius (Monogenea) in goldfish ( Carassius auratus )

    Microsoft Academic Search

    Gao-xue Wang; Jing Han; Ting-ting Feng; Fu-yuan Li; Bin Zhu

    2009-01-01

    Dactylogyrus intermedius is a significant monogenean parasite on the gills of cyprinid fishes and can cause serious problem in fish aquaculture. In\\u000a the present study, bioassay-guided fractionation was employed to identify the active compounds from Fructus Arctii against\\u000a D. intermedius. Five solvents (petroleum ether, chloroform, ethyl acetate, ethanol, and water) were applied for the extraction of Fructus\\u000a Arctii. Among them,

  9. Identification of Aroma-Active Compounds in Malaysian Pomelo (Citrus grandis (L.) Osbeck) Peel by Gas Chromatography-Olfactometry

    Microsoft Academic Search

    M-W Cheong; S-Q Liu; J. Yeo; H-K Chionh; K. Pramudya; P. Curran; B. Yu

    2011-01-01

    Malaysian pink and white pomelo (Citrusgrandis (L.) Osbeck) peels were extracted with dichloromethane (DCM). Using GC-FID\\/MS and gas chromatography-olfactometry (GC-O), 50 and 47 aroma-active compounds were identified in pink and white pomelo peel extracts, respectively. The potency of each odorant in both pomelo peel extracts was determined by aroma extraction dilution analysis (AEDA). On the basis of flavor dilution (FD)

  10. A thioredoxin with antioxidant activity identified from Eriocheir sinensis.

    PubMed

    Mu, Changkao; Zhao, Jianmin; Wang, Lingling; Song, Linsheng; Song, Xiaoyan; Zhang, Huan; Qiu, Limei; Gai, Yunchao; Cui, Zhaoxia

    2009-05-01

    Thioredoxin, with a redox-active disulfide/dithiol in the active site, is the major ubiquitous disulfide reductase responsible for maintaining proteins in their reduced state. In the present study, the cDNA encoding thioredoxin-1 (designated EsTrx1) was cloned from Chinese mitten crab Eriocheir sinensis by using rapid amplification of cDNA ends (RACE) approaches. The full-length cDNA of EsTrx1 was of 641 bp, containing a 5' untranslated region (UTR) of 17 bp, a 3' UTR of 306 bp with a poly (A) tail, and an open reading frame (ORF) of 318 bp encoding a polypeptide of 105 amino acids. The high similarity of EsTrx1 with Trx1s from other animals indicated that EsTrx1 should be a new member of the Trx1 sub-family. Quantitative real-time PCR analysis revealed the presence of EsTrx1 transcripts in gill, gonad, hepatopancreas, muscle, heart and haemocytes. The expression of EsTrx1 mRNA in haemocytes was up-regulated after Listonella anguillarum challenge, reached the maximum level at 6h post-stimulation, and then dropped back to the original level gradually. In order to elucidate its biological functions, EsTrx1 was recombined and expressed in E. coli BL21 (DE3). The rEsTrx1 was demonstrated to possess the expected redox activity in enzymatic analysis, and to be more potent than GSH in antioxidant capacity. These results together indicated that EsTrx1 could function as an important antioxidant in a physiological context, and perhaps is involved in the responses to bacterial challenge. PMID:19269333

  11. Analysis of aroma-active compounds in three sweet osmanthus (Osmanthus fragrans) cultivars by GC-olfactometry and GC-MS*

    PubMed Central

    Cai, Xuan; Mai, Rong-zhang; Zou, Jing-jing; Zhang, Hong-yan; Zeng, Xiang-ling; Zheng, Ri-ru; Wang, Cai-yun

    2014-01-01

    Objective: Aroma is the core factor in aromatherapy. Sensory evaluation of aromas differed among three sweet osmanthus (Osmanthus fragrans) cultivar groups. The purpose of this study was to investigate the aroma-active compounds responsible for these differences. Methods: Gas chromatography-olfactometry (GC-O) and GC-mass spectrometry (GC-MS) were used to analyze the aroma-active compounds and volatiles of creamy-white (‘Houban Yingui’, HBYG), yellow (‘Liuye Jingui’, LYJG), and orange (‘Gecheng Dangui’, GCDG) cultivars. Results: Seventeen aroma-active compounds were detected among 54 volatiles. trans-?-Ocimene, trans-?-ionone, and linalool, which were major volatiles, were identified as aroma-active, while cis-3-hexenyl butanoate, ?-terpinene, and hexyl butanoate were also aroma-active compounds, although their contents were low. Analysis of the odors was based on the sum of the modified frequency (MF) values of aroma-active compounds in different odor groups. HBYG contained more herb odors, contributed by cis-?-ocimene and trans-?-ocimene, while LYJG had more woody/violet/fruity odors released by trans-?-ionone, ?-ionone, and hexyl butanoate. In GCDG, the more floral odors were the result of cis-linalool oxide, trans-linalool oxide, and linalool. Conclusions: Aroma-active compounds were not necessarily only the major volatiles: some volatiles with low content also contributed to aroma. The aroma differences among the three cultivars resulted from variation in the content of different odor groups and in the intensities of aroma-active compounds. PMID:25001223

  12. Antimicrobial activity and cytotoxicity of the ethanol extract, fractions and eight compounds isolated from Eriosema robustum (Fabaceae)

    PubMed Central

    2013-01-01

    Background The aim of this study was to evaluate the antimicrobial activity and the cytotoxicity of the ethanol crude extract, fractions and isolated compounds from the twigs of Eriosema robustum, a plant used for the treatment of coughs and skin diseases. Methods Column chromatographic and spectroscopic techniques were used to isolate and identify eight compounds, robusflavones A (1) and B (2), orostachyscerebroside A (3), stigmasterol (4), 1-O-heptatriacontanoyl glycerol (5), eicosanoic acid (6), 3-O-?-D-glucopyranoside of sitosterol (7) and 6-prenylpinocembrin (8), from E. robustum. A two-fold serial microdilution method was used to determine the minimum inhibitory concentration (MIC) against fungi and bacteria, and the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide reduction assay was used to evaluate the cytotoxicity. Results Fraction B had significant antimicrobial activity against Aspergillus fumigatus and Cryptoccocus neoformans (MIC 0.08 mg/ml), whilst the crude extract and fraction A had moderate activity against A. fumigatus and Candida albicans (MIC 0.16 mg/ml). Fraction A however had excellent activity against Staphylococcus aureus (MIC 0.02 mg/ml), Enterococcus faecalis and Escherichia coli (MIC 0.04 mg/ml). The crude extract had significant activity against S. aureus, E. faecalis and E. coli. Fraction B had good activity against E. faecalis and E. coli (MIC 0.08 mg/ml). All the isolated compounds had a relatively weak antimicrobial activity. An MIC of 65 ?g/ml was obtained with robusflavones A (1) and B (2) against C. albicans and A. fumigatus, orostachyscerebroside A (3) against A. fumigatus, and robusflavone B (2) against C. neoformans. Compound 8 had the best activity against bacteria (average MIC 55 ?g/ml). The 3 fractions and isolated compounds had LC50 values between 13.20 to?>?100 ?g/ml against Vero cells yielding selectivity indices between 0.01 and 1.58. Conclusion The isolated compounds generally had a much lower activity than expected based on the activity of the fractions from which they were isolated. This may be the result of synergism between different compounds in the complex extracts or fractions. The results support the traditional use of E. robustum to treat infections. The crude extract had a good activity and low preparation cost, and may be useful in topical applications to combat microbial infections. PMID:24165199

  13. Production of anthraquinones, phenolic compounds and biological activities from hairy root cultures of Polygonum multiflorum Thunb.

    PubMed

    Thiruvengadam, Muthu; Praveen, Nagella; Kim, Eun-Hye; Kim, Seung-Hyun; Chung, Ill-Min

    2014-05-01

    Polygonum multiflorum Thunb. is a highly important medicinal plant producing anthraquinones (emodin and physcion) and phenolic compounds which has pharmaceutical use. In vitro seedling explants such as roots, internodals, nodals and leaves were inoculated with A. rhizogenes strain KCTC 2703. Transformed roots were induced from internodals and leaf explants. Six transgenic clones of hairy roots were established and confirmed by polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR) using rolC specific primers. Hairy roots cultured using MS liquid medium supplemented with 30 g/l sucrose showed highest accumulation of biomass (99.05 g/l FW [fresh weight] and 10.95 g/l DW [dry weight]) and highest production of anthraquinones content (emodin 211.32 ?g/g DW and physcion 353.23 ?g/g DW) were observed at 20 days. Nearly 9.5-fold increment of biomass was evident in suspension cultures at 20 days of culture and hairy root biomass produced in suspension cultures possessed 3.7- and 3.5-fold higher content of emodin and physcion, respectively, when compared with the untransformed control roots. MS basal liquid medium was superior for the growth of hairy roots and production of anthraquinones compared with other culture media evaluated (SH, B5 and N6), with MS-basal liquid medium supplemented with 30 g/l sucrose was optimal for secondary metabolite production. A total of 23 polyphenolic compounds were identified and quantified from P. multiflorum untransformed and hairy roots, which includes hydroxybenzoic acids, hydroxycinnamic acids, flavonols and other groups of phenolic compounds. The ultra-performance liquid chromatography (UPLC) analysis of the phenolic compounds profile revealed that pyrogallol, hesperidin, naringenin and formononetin were higher in hairy roots compared to untransformed roots. The total phenolics, flavonoids content, antioxidant and antimicrobial activity was high in hairy roots compared to untransformed roots. This is the first report for the production of anthraquinones (emodin and physcion), phenolic compounds and biological activities from hairy root cultures of P. multiflorum. PMID:24091894

  14. Supercritical CO2 extraction of functional compounds from Spirulina and their biological activity.

    PubMed

    K G, Mallikarjun Gouda; K, Udaya Sankar; R, Sarada; G A, Ravishankar

    2015-06-01

    Supercritical carbon dioxide (SCCO2) extraction and fractionation of Spirulina platensis was carried out to obtain functional compounds with antioxidant, antimicrobial and enzyme inhibitory activities. Extraction of SCCO2 was carried out using 200 g of Spirulina powder at 40?ºC under 120 bar pressure with CO2 flow rate of 1.2 kg h(-1). SCCO2 fraction obtained was further treated with hexane and ethyl acetate to identify its components. Individual components were identified by comparing mass spectra of samples with standard data and retention indices (RI) of C5-C20 n-alkanes mixture using the kovat index formula. The phenolic and flavonoid content of the SCCO2 extract was found to be 0.34?±?0.01 g/100 g and 0.12?±?0.01 g/100 g respectively. The SCCO2 extract had antioxidant activity with IC50 value of 109.6?±?3.0 ?g mL(-1) for DPPH (2,2-Diphenyl-1-picryl hydrazyl radical), IC50 value of 81.66?±?2.5 ?g mL(-1) for reducing power and IC50 value of 112.70?±?0.8 ?g mL(-1) for hydroxyl radical scavenging activity. Further, antioxidant activity study on oxidative induced DNA damage was analysed to elucidate the positive role of SCCO2 extract. SCCO2 extracts showed high antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus FRI 722 and Bacillus cereus F 4810) compared to that of Gram negative bacteria (Escherichia coli MTCC 108 and Yersinia enterocolitica MTCC 859). The SCCO2 extract exhibited inhibitory activity on both Angiotensin-1 converting enzyme and ?-glucosidase with IC50 values of 274?±?1.0 ?g mL(-1) and 307?±?2.0 ?g mL(-1) respectively. PMID:26028745

  15. Reactivity studies of antitumor active dirhodium compounds with DNA oligonucleotides 

    E-print Network

    Kang, Mijeong

    2007-04-25

    oligonucleotides were investigated by the techniques of mass spectrometry, HPLC, and NMR spectroscopic analytical methods. The relative reactivities of three dirhodium compounds, namely Rh2(O2CCH3)4, Rh2(O2CCF3)4, and [Rh2(O2CCH3)2(CH3CN)6](BF4)2, with DNA...

  16. The dietary compounds resveratrol and genistein induce activating transcription factor 3 while suppressing inhibitor of DNA binding/differentiation-1.

    PubMed

    Bottone, Frank G; Alston-Mills, Brenda

    2011-06-01

    Various chemopreventive compounds alter gene expression, possibly explaining their biological activity. One gene induced by a variety of chemopreventive compounds is the one coding for the transcription factor activating transcription factor 3 (ATF3). In this study, we performed microarray analysis on mRNA isolated from human colorectal cancer cells overexpressing ATF3 to ascertain the biological activity of this gene in cancer. As a result, 64 genes were induced or repressed. One gene identified by microarray analysis as repressed by overexpression of ATF3 was inhibitor of DNA binding/differentiation-1 (Id1). Id1 is important to cell growth and proliferation and therefore may represent an important downstream target of ATF3 responsible for the biological activity of ATF3. Id1 interacts with ATF3, thereby sequestering its activity, making it an ideal candidate for further study. The induction of ATF3 and repression of Id1 in these cells were confirmed at the mRNA and protein levels by semiquantitative real-time reverse transcription-polymerase chain reaction and western blot analysis, respectively. To determine if the repression of Id1 seen following microarray analysis of these cells occurred following treatment with dietary compounds with known chemotherapeutic activity, human colorectal cancer cells were treated with resveratrol and genistein, and their expression was determined. As a result, ATF3 was induced, and Id1 was repressed, by these compounds and by sulindac sulfide, a positive control, at the mRNA and protein level. Further work is needed to determine the molecular mechanism(s) responsible for the regulation of Id1 and to determine if biological activity of ATF3 overexpression is mediated by repression of Id1 by these compounds. PMID:21554132

  17. Identifying criminal activities at the operating system level

    NASA Astrophysics Data System (ADS)

    Hussain, Khaled; Sapre, Sampada; Hajgude, Poonam

    2005-05-01

    This paper presents a scheme to support curtailing illegal activities that are carried out with the help of computers. The paper focuses on determining criminal character of a user by analyzing user"s interactions with the computer at the operating system level. Doing this at the operating system level gives an advantage of catching all interactions of the user with the computer. User interaction information is obtained during the system use and this information is classified using neural network. Neural network does the processing to obtain the criminal character of the user. A sample test was conducted on 200 different users (50 criminal users and 150 normal users). The results reported show that the proposed system is practical and accurate.

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

    PubMed

    Oszmia?ski, Jan; Wojdy?o, Aneta; Nowicka, Paulina; Teleszko, Miros?awa; Cebulak, Tomasz; Wolanin, Mateusz

    2015-01-01

    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. PMID:25793543

  19. 5-Hydroxytryptamine2A receptor binding activity of compounds from Litsea sessilis.

    PubMed

    Chung, Lip Yong; Lo, Mee Wah; Mustafa, Muhammad Rais; Goh, Swee Hock; Imiyabir, Zamrie

    2009-03-01

    A 96-well microplate filtration based 5-HT(2A) receptor-radioligand binding assay was optimized and adopted to carry out a bioassay-guided fractionation of the methanol extract of the leaves of Litsea sessilis. This purification led to the isolation of two compounds identified as (+)-boldine (1) and (+)-dehydrovomifoliol (2). (+)-Boldine binds to 5-HT(2A) receptors at high concentrations with a K(i) value of 2.16 microm. However, (+)-dehydrovomifoliol showed minimal competitive inhibition on the binding of [(3)H]ketanserin to the same receptor with a K(i) value of 2.06 mm. These results suggest that (+)-boldine influences the activity of 5-HT(2A) receptors through competitive binding as an agonist or antagonist. PMID:18844258

  20. Reductive alkylation of active methylene compounds with carbonyl derivatives, calcium hydride and a heterogeneous catalyst.

    PubMed

    Guyon, Carole; Duclos, Marie-Christine; Sutter, Marc; Métay, Estelle; Lemaire, Marc

    2015-07-01

    A one-pot two-step reaction (Knoevenagel condensation - reduction of the double bond) has been developed using calcium hydride as a reductant in the presence of a supported noble metal catalyst. The reaction between carbonyl compounds and active methylene compounds such as methylcyanoacetate, 1,3-dimethylbarbituric acid, dimedone and the more challenging dimethylmalonate, affords the corresponding monoalkylated products in moderate to good yields (up to 83%) with minimal reduction of the starting carbonyl compounds. PMID:26053131

  1. Antifungal activity of a new phenolic compound from capitulum of a head rot-resistant sunflower genotype.

    PubMed

    Prats, Elena; Galindo, Juan C; Bazzalo, Maria E; León, Alberto; Macías, Francisco A; Rubiales, Diego; Jorrín, Jesús V

    2007-12-01

    In a previous study, we observed that bract and corolla extracts from a Sclerotinia sclerotiorum-resistant sunflower contained high amounts of the known coumarins scopoletin, scopolin, and ayapin. There was a correlation between coumarin concentration and disease resistance. Thin layer chromatography showed higher concentrations of three other compounds in the resistant genotype when compared to the susceptible. A bioassay-directed purification that used column chromatography and HPLC allowed the isolation of a new compound, 3-acetyl-4-acetoxyacetophenone, and known compounds, demethoxyencecalin and 3-acetyl-4-hydroxyacetophenone. Structures were assigned from spectral data, and bioactivities were characterized by in vitro bioassays against S. sclerotiorum. The new compound, 3-acetyl-4-acetoxyacetophenone, had an antifungal activity similar to the coumarin ayapin, previously described as a potent Sclerotinia inhibitor. The speed and simplicity by which these compounds can be detected make them suitable for use in screening procedures that may identify genotypes with valuable levels of resistance. A screening of seven sunflower genotypes in a field experiment showed a correlation between these compounds and resistance to Sclerotinia. PMID:18034282

  2. Rapid evaluation of the antibacterial activity of arylene-ethynylene compounds.

    PubMed

    Corbitt, Thomas S; Zhou, Zhijun; Tang, Yanli; Graves, Steven W; Whitten, David G

    2011-08-01

    A series of oligo(arylene-ethynylene) (1-3 repeat units) compounds functionalized with quaternary ammonium groups was screened for their antibacterial activity in the dark and with activation by long-wavelength (365 nm) UV irradiation. Several of these compounds have effective bactericidal activity (>99.9% killing) at concentrations between 0.01 and 10 ?g/mL. Our approach uses flow cytometry to rapidly screen and evaluate the susceptibility of bacterial populations. The rapidity, high information content, and accuracy of this approach make it an extremely valuable method for the study of antibacterial compounds. PMID:21714540

  3. [Rough sets theory in structure-activity relationship analysis of quaternary pyridinium compounds].

    PubMed

    Krysi?ski, J

    1991-12-01

    Relationship between chemical structure and antimicrobial activity of 53 quaternary pyridinium compounds is analysed using the theory of rough sets. The compounds are described by 8 attributes concerning structure and are divided into 5 classes of activity. The description builds up an information system. Using the rough sets approach a smallest set of attributes significant for a high quality of classification has been found. A decision algorithm has been derived from the information system showing important relations between structure and activity. It may be helpful in supporting decisions concerning synthesis of new antimicrobial compounds. PMID:1818327

  4. [Importance of estrogens and estrogen-active compounds for udder health in cattle. A review].

    PubMed

    Zdunczyk, S; Zerbe, H; Hoedemaker, M

    2003-11-01

    High oestrogen concentrations in blood or high intake of oestrogen-active compounds with forage can be associated with an enhanced occurrence of udder diseases. Mean somatic cell count (MSCC) can increase and milk yield can decrease. Subclinically infected udder quarters can develop clinical mastitis and the rate of new infections can be high. This review describes concentrations of oestrogens in peripheral blood plasma in cattle and occurrence of oestrogen-active compounds in forage. Relationships between oestrogens or oestrogen-active compounds and udder health are presented. The possible mechanisms of enhanced susceptibility of the udder to infection under the influence of oestrogens are discussed. PMID:14679840

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

    PubMed

    Raki?, 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. PMID:24857621

  6. Isolation and Chemical Structural Characterisation of a Compound with Antioxidant Activity from the Roots of Senna italica

    PubMed Central

    Mokgotho, Matlou Phineas; Gololo, Stanley Sechene; Masoko, Peter; Shai, Leshwene Jeremiah; Bagla, Victor Patrick; Eloff, Jacobus Nicolaas

    2013-01-01

    Senna italica, a member of the Fabaceae family (subfamily Caesalpiniaceae), is widely used in South African traditional medicine to treat a number of disease conditions. Aqueous extracts of the plant are mainly used to treat sexually transmitted infections and intestinal complications. The roots of S. italica were ground to a fine powder and sequentially extracted with n-hexane, dichloromethane, acetone, and methanol using serial exhaustive extraction (SEE) method. Thin layer chromatography was used to analyse the phytochemical composition of the extracts and DPPH radical scavenging method to detect the presence of antioxidant compounds. The bioassay guided fractionation of the acetone fraction afforded an antioxidant compound with free radical scavenging activity. The isolated compound was subsequently identified as 3,4?,5-trihydroxystilbene (resveratrol). This study represents the first report of the stilbene resveratrol in S. italica. PMID:23843877

  7. [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. PMID:11530643

  8. Partition of Volatile Organic Compounds in Activated Sludge and Wastewater

    Microsoft Academic Search

    Jun-Hong Lin; Ming-Shean Chou

    2006-01-01

    The Henry’s law constant is important in the gas-liquid mass transfer process. Apparent dimensionless Henry’s law constant, or the gas-liquid partition coefficient (K’H), for both hydrophilic (methanol, isopropyl alcohol, and acetone) and hydrophobic (toluene and p-xylene) organic compounds in deionized (DI) water, a wastewater with a maximum total dissolved organic carbon (DOC) content of 700 mg\\/L, and DI water mixed

  9. Isolation and identification of active compounds from Drimys winteri barks.

    PubMed

    Cechinel Filho, V; Schlemper, V; Santos, A R; Pinheiro, T R; Yunes, R A; Mendes, G L; Calixto, J B; Delle Monache, F

    1998-10-01

    The barks of Drimys winteri are used in folk medicine as a remedy to treat several diseases, including dolorous processes. Previous pre-clinical experiments carried out in our laboratories revealed that the hydroalcoholic extract of this plant showed anti-allergenic, anti-inflammatory and antinociceptive properties. Such promising results led us to determine the analgesic compounds present in D. winteri. Through conventional chromatographic procedures with fractions of CH2Cl2 and EtOAc obtained from methanolic extract, it was found that polygodial (1), 1-beta-(p-methoxycynnamyl) polygodial (2), taxifolin (3) and astilbin (4), are the main components of these fractions. Compounds 1 and 2 exhibited marked antinociceptive action by intraperitoneal and oral routes against acetic acid-induced abdominal constrictions in mice, suggesting that they are responsible, at least partially, for the antinociceptive effects of this plant. In addition, both compounds were notably more potent than aspirin and acetaminophen, two well-known drugs used here as comparison. PMID:9849632

  10. Isolation and characterization of phenolic compounds and anthocyanins from Murta (Ugni molinae Turcz.) fruits. Assessment of antioxidant and antibacterial activity.

    PubMed

    Junqueira-Gonçalves, Maria Paula; Yáñez, Lina; Morales, Carolina; Navarro, Muriel; A Contreras, Rodrigo; Zúñiga, Gustavo E

    2015-01-01

    Berry fruit consumption has become important in the promotion of human health, mainly due to their phenolic compounds, which have been associated with protection against different pathologies, as well as antimicrobial and other biological activities. Consequently, there has been a growing interest in identifying natural antioxidants and antimicrobials from these plants. This study aimed to characterize the phenolic chemical composition and anthocyanin profile of murta (Ugni molinae Turcz.) fruit, and to evaluate the antioxidant and antimicrobial activity of its extracts (ethanolic and methanolic). LC/MS of the ethanolic extracts showed the presence of three major compounds: caffeic acid 3-glu, quercetin-3-glu and quercetin, while in the methanolic acid extract they were cyanidin-3-glucoside, pelargonidin-3-arabinose and delphinidin-3-glucoside. The antioxidant activity of ethanolic extracts (DPPH· and ORAC assays) was higher than that of methanol acid extracts or purified anthocynins. Furthermore, the methanol acid extract showed an inhibitory activity against the bacteria E. coli and S. typhi similar to that of standard antibiotics. The results suggest that the antioxidant activity of the ethanolic extract is regulated by the high content of phenolic compounds and the fruit's characteristic color is due to the content of pelargonidin-3-arabinose and delphinidin-3-glucoside. The obtained results demonstrated the appreciable antioxidant and antibacterial activities, providing opportunities to explore murta extracts as biopreservatives. PMID:25838172

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

    Microsoft Academic Search

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

    1986-01-01

    The identification of certain organic compounds in drinking water has led water treatment specialists to be increasingly concerned about the eventual risks of such pollutants to the health of consumers. Our experiments focused on the role of ozone and granular activated carbon in removing mutagenic compounds and precursors that become toxic after chlorination. We found that if a sufficient dose

  12. 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...

  13. Possible mode of action for insulinomimetic activity of vanadyl(IV) compounds in adipocytes

    Microsoft Academic Search

    Kenji Kawabe; Yutaka Yoshikawa; Yusuke Adachi; Hiromu Sakurai

    2006-01-01

    Vanadyl(IV) ions (+4 oxidation state of vanadium) and their complexes have been shown to have in vitro insulinomimetic activity and to be effective in treating animals with diabetes mellitus. Although, researchers have proposed many vanadyl compounds for the treatment of diabetes patients, the mode of action of vanadyl compounds remains controversial. In order to evaluate the mode of action of

  14. BPR0L075, a Novel Synthetic Indole Compound with Antimitotic Activity in Human Cancer Cells, Exerts Effective Antitumoral Activity in Vivo

    Microsoft Academic Search

    Ching-Chuan Kuo; Hsing-Pang Hsieh; Wen-Yu Pan; Ching-Ping Chen; Jing-Ping Liou; Shiow-Ju Lee; Yi-Ling Chang; Li-Tzong Chen; Chiung-Tong Chen; Jang-Yang Chang

    2004-01-01

    BPR0L075 is a novel synthetic compound discovered through research to identify new microtubule inhibitors. BPR0L075 inhibits tubulin polym- erization through binding to the colchicine-binding site of tubulin. Cyto- toxic activity of BPR0L075 in a variety of human tumor cell lines has been ascertained, with IC50 values in single-digit nanomolar ranges. As deter- mined by flow cytometry, human cervical carcinoma KB

  15. Using Cs-137, C-14 and biomarker compounds to identify reasons for C and N losses in resampled profiles

    NASA Astrophysics Data System (ADS)

    Baisden, W. T.; Parfitt, R. L.; Schipper, L. A.; Filley, T. R.; Ross, C.

    2008-12-01

    A New Zealand data set of archived and resampled pasture soil profiles has identified a systematic pattern large soil C and N losses and gains that appear to be related to land-use intensity. We use isotope and organic geochemistry techniques in selected archived and resampled soil horizons to identify reasons for the observed large soil C and N losses and gains in intensive flat non-allophanic pasture and hill country soil profiles, respectively. These techniques allow us to examine 3 of the ~10 hypotheses proposed to explain the large losses initially observed in intensive pasture soils. These three hypotheses are: (1) soil C and N changes may be due to erosion and deposition; (2) pre-European forest-derived organic matter is being lost; and (3) changes in litter quality are reducing the amount of plant C and N stabilized in soil. To test hypothesis (1), we use 137Cs, accumulated in the soil clay fraction from nuclear fallout between 1945 and 1965. Measurements comparing archived (post-1965) and resampled horizons show losses or gains of 137Cs, which we interpret as erosion and deposition, respectively. Apparent wind erosion of up to ~6 cm of surface soil explains large surface soil C losses in 2 flat profiles, while apparent deposition explains soil C gains in two hill country profiles. Measurements of 14C assist in the evaluation of hypothesis (2) by suggesting that, after accounting for 137Cs-estimated erosion or deposition, surface soils are mainly losing C fixed since bomb 14C was injected into the atmosphere (post-1950). In contrast, soil C losses below 40 cm depth are dominated by C derived from pre-European forests. Biomarker compounds, particularly lignin-derivatives, allow us to evaluate hypotheses (2) and (3). Results to date suggest that failure to stabilize grass-derived C is more important than losses of forest-derived C in explaining soil C losses in the upper 30 cm. More broadly, biomarker and 137Cs measurements suggest that steady-state assumptions must be carefully applied in models of C and N in New Zealand pasture soils, and will be inappropriate in some circumstances. Based on these studies of 3-5 selected profiles, we examine approaches to broaden the use of these techniques to identify reasons for C and N losses and gains as the resampling of archived New Zealand soil profiles continues.

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

    E-print Network

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

    2007-01-01

    , 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...

  17. 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

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

    PubMed

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

    2015-03-01

    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

  19. Compound A, a selective glucocorticoid receptor modulator, enhances heat shock protein Hsp70 gene promoter activation.

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  1. Identification of aroma active compounds of cereal coffee brew and its roasted ingredients.

    PubMed

    Majcher, Ma?gorzata A; Klensporf-Pawlik, Dorota; Dziadas, Mariusz; Jele?, Henryk H

    2013-03-20

    Cereal coffee is a coffee substitute made mainly from roasted cereals such as barley and rye (60-70%), chicory (15-20%), and sugar beets (6-10%). It is perceived by consumers as a healthy, caffeine free, non-irritating beverage suitable for those who cannot drink regular coffee made from coffee beans. In presented studies, typical Polish cereal coffee brew has been subjected to the key odorants analysis with the application of gas chromatography-olfactometry (GC-O) and aroma extract dilution analysis (AEDA). In the analyzed cereal coffee extract, 30 aroma-active volatiles have been identified with FD factors ranging from 16 to 4096. This approach was also used for characterization of key odorants in ingredients used for the cereal coffee production. Comparing the main odors detected in GC-O analysis of roasted cereals brew to the odor notes of cereal coffee brew, it was evident that the aroma of cereal coffee brew is mainly influenced by roasted barley. Flavor compound identification and quantitation has been performed with application of comprehensive multidimentional gas chromatography and time-of-flight mass spectrometry (GCxGC-ToFMS). The results of the quantitative measurements followed by calculation of the odor activity values (OAV) revealed 17 aroma active compounds of the cereal coffee brew with OAV ranging from 12.5 and 2000. The most potent odorant was 2-furfurylthiol followed by the 3-mercapto-3-methylbutyl formate, 3-isobutyl-2-methoxypyrazine and 2-ethyl-3,5-dimethylpyrazine, 2-thenylthiol, 2,3-butanedione, 2-methoxy phenol and 2-methoxy-4-vinyl phenol, 3(sec-butyl)-2-methoxypyrazine, 2-acetyl-1-pyrroline, 3-(methylthio)-propanal, 2,3-pentanedione, 4-hydroxy-2,5-dimethyl-3-(2H)-furanone, (E,E)-2,4-decadienal, (Z)-4-heptenal, phenylacetaldehyde, and 1-octen-3-one. PMID:23414530

  2. In vitro antimicrobial activity of GSQ1530, a new heteroaromatic polycyclic compound.

    PubMed

    Ge, Yigong; Difuntorum, Stacey; Touami, Sofia; Critchley, Ian; Bürli, Roland; Jiang, Vernon; Drazan, Ken; Moser, Heinz

    2002-10-01

    GSQ1530 is a compound derived from a newly identified class of antibiotics referred to as heteroaromatic polycyclic (HARP) antibiotics. The aim of this study was to assess the in vitro antimicrobial activity of GSQ1530. By using an NCCLS broth microdilution assay, the activities of GSQ1530 and other antibiotics were coevaluated against 215 clinical isolates. The MICs at which 90% of isolates are inhibited (MIC(90)s) of GSQ1530 for methicillin-susceptible Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) were 2 and 4 micro g/ml, respectively. The MIC(90)s of GSQ1530 for the streptococci tested were 2 micro g/ml or less, regardless of their susceptibilities to other antibiotics. The MIC(90) of GSQ1530 for the enterococci tested (including vancomycin-resistant enterococci) was 4 micro g/ml. No cross-resistance was found between GSQ1530 and other known antibiotics. In a separate assay, GSQ1530 demonstrated excellent activity against vancomycin-intermediate-susceptible staphylococci (MIC(90), 1 micro g/ml). The minimal bactericidal concentration test was conducted with 73 clinical isolates; GSQ1530 was cidal against streptococci and staphylococci but static against enterococci. An in vitro killing kinetic study revealed a time-dependent profile, with at least a 3-log reduction of bacterial growth within 6 h after exposure to four times the MICs of GSQ1530 for both S. aureus and Streptococcus pneumoniae. The checkerboard study showed that GSQ1530 had a synergistic interaction with rifampin against MRSA. The test medium was found to have little effect on in vitro antimicrobial potency. The MICs of GSQ1530 for gram-positive cocci were 4- to 32-fold higher in the presence of serum proteins. GSQ1530 has high levels of plasma protein binding (91 and 89% for rat and human plasma, respectively). These preliminary results demonstrate that GSQ1530, a representative compound of our novel HARP antibiotics, has broad-spectrum activity against gram-positive bacteria. This novel class of antibacterial compounds is profiled in vivo to assess the therapeutic potential in humans. Ongoing in vivo studies will assess whether this class of molecules has promising in vivo efficacy and safety profiles. PMID:12234840

  3. [Characterization of aroma active compounds in blood orange juice by solid phase microextraction and gas chromatography-mass spectrometry-olfactometry].

    PubMed

    Qiao, Yu; Xie, Bijun; Zhang, Yan; Zhang, Yun; Pan, Siyi

    2008-07-01

    Volatile compounds of fresh blood orange juice were analyzed by solid phase microextraction and gas chromatography-mass spectrometry (SPME-GC-MS) and the aroma active compounds were identified by olfactometry. The volatile compounds were extracted by headspace solid phase microextraction (HS-SPME) using a divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) fiber for 40 min at 40 degrees C. The analysis was carried out using an HP 6890N GC equipped with an HP-5 column (30 m x 0.25 mm x 0.25 microm ) directly connected to an HP 5975 series mass selective detector and a sniffing port (ODP2, Gerstel) using helium as carrier gas. Compound identifications were made by the comparison of the mass spectra, retention times, retention indices (I(R)) and odor of the volatile components in the extracts with those of the corresponding reference standards. Forty-six compounds were identified by GC-MS and I(R). The major components of the juice were limonene (86.36%), linalool (3.69%), beta-myrcene (1.79%), octanal (1.32%) and valencene (1.27%). GC-MS-olfactometry analysis was performed to determine 34 compounds with aroma activity, of which 23 compounds were identified. The major contributors to orange juice aroma activity are ethyl butanoate, octanal, gamma-terpinene, 4-acetyl-1-methyleyclohexene, decanal, (-)-carvone, geranyl acetate, valencene. These compounds of strong aroma intensity represent 7.22% of the total volatile compounds. Other four unknown compounds (I(R), <800; I(R) = 1020, 1143, 1169, separately) are also the major contributors to the overall aroma. PMID:18959252

  4. 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. PMID:25766797

  5. 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. PMID:23586066

  6. 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

  7. Optimal Design of Experiments for Identifying the Model Parameters of Gyroscope on a Centrifuge and Vibration Table Compound Test Syste

    Microsoft Academic Search

    Wang Yuegang

    2006-01-01

    Overloading and vibration compound test system which is combined by centrifuge and vibration table offers a new way for ground test to simulate flight. It is an important thing must be solved in the design of experiments for gyroscope under compound environment how to meet the requirement of linear acceleration and avoid influence of angle velocity of centrifuge. After analyzing

  8. [Application of chemiluminescent analysis for comparative assessment of antioxidant activity of some pharmacological compounds].

    PubMed

    Fedorova, T N

    2003-01-01

    A comparative analysis of the antioxidant activity of a series of pharmacological compounds was performed in vitro using Fe2+ induced chemiluminescence of lipoproteins. With respect to the protective action against lipoprotein oxidation, the compounds studied can be arranged in the following order: trolox > carnosine > emoxypine > L-carnitine = mildronate. The results show good prospects for using the proposed chemiluminescent technique for evaluating the antioxidant activity of pharmaceuticals. PMID:14650218

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

    Microsoft Academic Search

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

    2005-01-01

    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).

  10. Developmental toxicity and structure-activity relationships of ochratoxin A and related compounds in Hydra attenuata 

    E-print Network

    Taylor, Monica Ann

    1988-01-01

    DEVELOPMENTAL TOXICITY AND STRUCTURE-ACTIVITY RELATIONSHIPS OF OCHRATOXIN A AND RELATED COMPOUNDS IN HYDRA ATTENUATA A Thesis by MONICA ANN TAYLOR Submitted to the Office of Graduate Studies of Texas ARM University in Partial fulfillment... of the requirements for the degree of MASTER OF SCIENCE December 1988 Major Subject: Food Science and Technology DEVELOPMENTAL TOXICITY AND STRUCTURE-ACTIVITY RELATIONSHIPS OF OCHRATOXIN A AND RELATED COMPOUNDS IN ~HY R ATTENUATA A Thesis by MONICA ANN TAYLOR...

  11. 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 ?-pyrone influenced antitrypanosomal property. In particular, ?-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. PMID:22116743

  12. 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

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

    PubMed

    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

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

    PubMed

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

    2015-01-01

    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 [?-glutinol, ?-amyrin, kaempferol, luteolin, quercetin, kaempferol-3-O-glucoside, kaempferol-3-O-rutinoside, methyl chlorogenate, chlorogenic acid, hyuganin E, 5-(hydroxymethyl)-2-furaldehyde, ?-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 ? peptide (A?25-35)-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 A?25-35-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 A?25-35-induced neurotoxicity. PMID:25786165

  15. 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. PMID:24803014

  16. 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??g?mL?1; the pure compounds eupomatenoid-1, fargesin, and (8R,8?R,9R)-cubebin were active against M. tuberculosis H37Rv (MIC = 50??g?mL?1), while fargesin presented activity against three monoresistant strains of M. tuberculosis H37Rv and a MDR clinical isolate of M. tuberculosis (MIC < 50??g?mL?1). Both the extract and eupomatenoid-1 were very active against E. histolytica and G. lamblia (IC50 < 0.624??g?mL?1); in contrast, fargesin and (8R,8?R,9R)-cubebin were moderately active (IC50 < 275??g?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

  17. Antiproliferative activity of Saponaria vaccaria constituents and related compounds.

    PubMed

    Balsevich, J John; Ramirez-Erosa, Irving; Hickie, Robert A; Dunlop, Donna M; Bishop, Greg G; Deibert, Leah K

    2012-01-01

    Total methanolic extracts of Saponaria vaccaria seed derived from several varieties, as well as various purified components obtained through successive chromatographic separations of total extracts were evaluated for their growth inhibitory activity in WiDr (colon), MDA-MB-231 (breast), NCI-417 (lung) and PC-3 (prostate) human cancer cells as well as the non-tumorigenic fibroblast BJ (CRL-2522) cell line using MTT colorimetric assay. Purified bisdesmosidic saponins segetoside H and I were further examined using microscopy and apoptosis assays. Bisdesmosidic saponins exhibited dose-dependent growth inhibitory and selective apoptosis-inducing activity. Growth inhibitory effects were particularly strong in a breast (MDA-MB-231) and a prostate (PC-3) cancer cell line. Total extracts exhibited a different preference being most active against a colon cancer cell line (WiDr). In a comparison of varieties, all of the total seed extracts exhibited similar dose-dependent activities, but with some variation in potency. Monodesmosidic saponins vaccarosides A and B, phenolic vaccarin, and cyclopeptide segetalin A, co-occurring seed substituents, did not exhibit activity. The non-tumorigenic fibroblast cell line BJ (CRL 2522) was growth inhibited but did not undergo apoptosis when treated with bisdesmosidic saponins at low micromolar concentrations. Saponin-rich extracts from Kochia scoparia seed and Chenopodium quinoa were also evaluated alongside Saponaria saponins but did not exhibit activity. Closely related Quillaja saponins exhibited activity but were less potent. PMID:22056663

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

    PubMed

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

    2015-05-01

    A new alkenylphenol, bavinol A (1), together with six known compounds (2-7) were isolated from the aerial parts of Piper bavinum (Piperaceae). The chemical structures of these compounds were determined by spectroscopic analyses including 2D NMR spectroscopy. The anti-Alzheimer effects of compounds 1-7 were evaluated from acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity assays. Bavinol A (1), ampelopsin (3), and violanthin (4) exhibited AChE inhibitory activities with IC50 values of 29.80, 59.47 and 79.80 ?M. Compound 1 also showed the most potent BChE inhibitory activity with an IC50 value of 19.25 ?M. PMID:25005067

  19. Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds.

    PubMed Central

    Shibata, S

    2001-01-01

    More than 25 dammarane-type tetracyclic triterpenoid saponins have been isolated from ginseng, the root and rhizome of Panax ginseng C.A. Meyer (Araliaceae). The genuine sapogenins of those saponins, 20(S)-protopanaxa-diol and -triol, were identified as 20(S) 12beta-hydroxy-and 20(S) 6alpha,12beta-dihydroxy-dammarenediol-II, respectively. There are two types of preparations from ginseng: white ginseng prepared by drying after peelling off and red ginseng prepared by steaming and drying. Some partly deglycosylated saponins such as ginsenoside Rh-1, Rh-2, and Rg-3 are obtained from red ginseng as artifacts produced during steaming. Several workers studied the metabolic transformation by human intestinal bacteria after oral administration of ginsenoside Rb-1 and Rb-2 and found that the stepwise deglyco-sylation yielded compound K and finally 20(S)-protopanaxadiol. Ginsenoside Rg-1 was converted into 20(S)-protopanaxatriol via ginsenoside Rh-1. Yun et al. in Korea conducted the epidemiological case-control studies of ginseng and suggested its cancer preventing activities. Kitagawa et al. demonstrated in vitro that ginsenosides, especially 20(R)-ginsenoside Rg-3, specifically inhibited cancer cell invasion and metastasis. Azuma et al. found that ginsenoside Rb-2 inhibited tumor angiogenesis, and Kikuchi et al. reported that ginsenoside Rh-2 inhibited the human ovarian cancer growth in nude mice. Recently, ginsenoside Rg-3 was produced as an anti-angiogenic anti-cancer drug in China. The aforementioned reports suggest that less glycosylated protopanaxadiol derivatives are effective in cancer prevention. Apart from Ginseng tetracyclic triterpenoid saponins, some oleanane-type pentacyclic triterpenoid compounds showed the anti-carcinogenic activity in the two-stage anti-cancer-promotion experiments in vitro and in vivo. PMID:11748374

  20. Isolation and potential cancer chemopreventive activities of phenolic compounds of beer

    Microsoft Academic Search

    C. Gerhäuser; A. P. Alt; K. Klimo; J. Knauft; N. Frank; H. Becker

    2002-01-01

    Beer contains a variety of phenolic compounds. During the brewing process, some of these compounds are removed by polyvinylpolypyrrolidone\\u000a (PVPP) to prevent haze formation. We have analyzed the phytochemical composition of a PVPP residue as well as of unstabilized\\u000a beer and isolated a total of 51 compounds. Eight structures were identified as novel, i.e., 2-(4?-hydroxyphenyl)-3,5-dihydroxybenzoic\\u000a acid (6), 2?-(4?-hydroxyphenyl)isoferulic acid ester

  1. Pharmacologically active compounds in the Anoectochilus and Goodyera species

    Microsoft Academic Search

    Xiao-Ming Du; Nobuto Irino; Norihiro Furusho; Jun Hayashi; Yukihiro Shoyama

    2008-01-01

    The extract of Anoectochilus formosanus showed significant activity in decreasing the levels of the cytosolic enzymes LDH, GOT, and GPT, and the result demonstrated\\u000a that A. formosanus possessed prominent hepatoprotective activity against CCl4-induced hepatotoxicity. Moreover, in the results of the test using aurothioglucose-induced obese mice, the extract showed\\u000a a significant antihyperliposis effect. A. formosanus grown in the wild and propagated

  2. Identifying unknown minerals and compounds from X-ray diffraction patterns using the Johnson and Vand FORTRAN 4 computer program

    NASA Technical Reports Server (NTRS)

    Kyte, F. T.

    1976-01-01

    Automated computer identification of minerals and compounds from unknown samples is provided along with detailed instructions and worked examples for use in graduate level courses in mineralogy and X-ray analysis applications.

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

    PubMed

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

    2013-09-01

    The antioxidant activity of extracts obtained from different parts of Georgian flora species Hamamelis virginiana L., Astragalus caucasicus Pall., Astragalus microcephalus Willd., Vitis vinifera L., Rhododendron ponticum L., Rhododendron Ungernii Trautv., Ginkgo biloba L., Salvia officinalis L., Querqus iberica Stev., Maclura aurantiaca Nutt., Cotinus coggygria Ledeb., Fraxinus ornus L., Urtica dioica L., Rhododendron caucasicum Pall., Pueraria hirsuta Matsum., Geranium pusillum L., Astragalus Tanae Sosn., Pinus silvestris L. has been studied. Comparison with ethylentetraacetate and ?-tocopherole revealed high efficacy of all extracts studied. 45 individual phenolic compounds were isolated and described by chemical examination of biologically active objects. Common sage (Salvia officinalis) extract turned out as the most active (200 %). The chemical study revealed the dominant content of condensed tannins and low molecular phenolic compounds, which may be attributed to the high antioxidant activity. Biologically active antiatherosclerotic food additive "Salbin" was developed on the basis of Common sage - Salvia officinalis L. phenolic compounds. PMID:24099817

  4. Evaluation of Tier I screening approaches for detecting endocrine-active compounds (EACs).

    PubMed

    O'Connor, John C; Cook, Jon C; Marty, M Sue; Davis, Leonard G; Kaplan, A Michael; Carney, Edward W

    2002-01-01

    In 1996, Congress passed legislation requiring the U.S. Environmental Protection Agency (EPA) to implement screening/testing strategies for endocrine-active compounds (EACs). In response, EPA convened the Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) to advise the agency on a strategy to screen and test xenobiotics for endocrine disruption. EDSTAC completed their charter in 1998 by recommending a tiered screening and testing scheme to evaluate compounds for their potential to act as agonists or antagonists to the estrogen or androgen receptors, steroid biosynthesis inhibitors, or their ability to alter thyroid function. For Tier I, the EDSTAC-recommended screening battery comprised eight different assays, but EDSTAC also proposed two alternative batteries that were deemed worthy of further evaluation. The challenge currently confronting EPA is to choose among the Tier I screening options and then to standardize protocols, validate the assays, and determine the criteria for judging a compound as positive or negative in the battery. The purpose of the current review is to: (1) provide an overview of the three EDSTAC options, (2) evaluate the data currently available for the individual assays of the three EDSTAC options and discuss the strengths and limitations of each, and (3) provide a final recommendation for a Tier I screen based on the experiences of the authors who have used all of the individual assays under consideration by EDSTAC. The goal of this report is not to provide an exhaustive historical review of each assay, but rather to summarize some of the more relevant data from available published reports as it relates to current proposed study designs for those particular assays. Based on the current data, a Tier I screening battery consisting of in vitro receptor binding assays, a 3-day uterotrophic assay, and a 15-day intact male assay are recommended as the preferred approach on which future validation efforts should be focused. This screening approach is a mode-of-action screen that will identify specific types of endocrine activity. Because it utilizes many endpoints from the same test animals (i.e., it integrates), it is the most cost-effective and efficient option in terms of animal usage. The mode-of-action screening approach advances scientific understanding and is preferred over other options based on apical tests, as these essentially are reproductive effects screens that are not necessarily specific for endocrine activity. Because Tier II tests include the critical apical endpoints used in the pubertal models, a mode-of-action approach provides complementary rather than redundant data. By identifying the potential mode of action, critical endpoints can be included in Tier II studies that will be used to define dose-response curves and no observed adverse effect levels (NOAELs)/no observed effect levels (NOELs) for the compound. PMID:12487364

  5. Antimicrobial activity of sulfur compounds derived from cabbage.

    PubMed

    Kyung, K H; Fleming, H P

    1997-01-01

    Selected sulfur compounds found in cabbage and its fermentation product, sauerkraut, were tested for minimum inhibitory concentration (MIC) against growth of 15 species of bacteria and 4 species of yeasts. S-Methyl-L-cysteine sulfoxide, sinigrin, and dimethyl sulfide at 500 ppm were not inhibitory to any of the bacteria and yeasts tested. Dimethyl disulfide at 500 ppm retarded some, but did not prevent growth of any of the test microorganisms. Dimethyl trisulfide had an MIC to bacteria of 200 ppm and to yeast of 20 ppm. Methyl methanethiosulfinate had an MIC between 50 and 200 ppm for all bacteria, and between 6 and 10 ppm for all yeasts tested. Methyl methanethiosulfonate had an MIC between 20 and 100 ppm for bacteria and between 50 and 500 ppm for yeasts. Allyl isothiocyanate had an MIC between 50 and 500 ppm for bacteria and between 1 and 4 ppm for yeasts. Methyl methanethiosulfinate was 10 to 100 times more inhibitory against Listeria monocytogenes at pH values of 5, 6, and 7 and was much less influenced by pH than was sodium benzoate. PMID:10465044

  6. Microbial derived surface active compounds: properties and screening concept.

    PubMed

    Mnif, Inès; Ghribi, Dhouha

    2015-07-01

    Biosurfactants are surface-active biomolecules that are produced by a variety of microorganisms. They have gained biotechnologist interest for high diversity and their efficient action in comparison to synthetic emulsifiers. So, we discussed a wide array of screening method based on direct and indirect surface and interfacial tension measurements. Also, this review describes biosurfactant physicochemical properties and natural role in the environment. Also, it presents their tolerance to extreme conditions of temperature, pH and ionic strength, low toxicity and biodegradability. Functional properties like emulsification, foaming, solubilizing and membrane permeabilizing activities were also discussed along with their related application. PMID:25997688

  7. Pulmonary metabolism of foreign compounds: its role in metabolic activation.

    PubMed Central

    Cohen, G M

    1990-01-01

    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. PMID:2200668

  8. Investigating the Effect of Emetic Compounds on Chemotaxis in Dictyostelium Identifies a Non-Sentient Model for Bitter and Hot Tastant Research

    PubMed Central

    Robery, Steven; Mukanowa, Janina; Percie du Sert, Nathalie; Andrews, Paul L. R.; Williams, Robin S. B.

    2011-01-01

    Novel chemical entities (NCEs) may be investigated for emetic liability in a range of unpleasant experiments involving retching, vomiting or conditioned taste aversion/food avoidance in sentient animals. We have used a range of compounds with known emetic /aversive properties to examine the possibility of using the social amoeba, Dictyostelium discoideum, for research into identifying and understanding emetic liability, and hence reduce adverse animal experimentation in this area. Twenty eight emetic or taste aversive compounds were employed to investigate the acute (10 min) effect of compounds on Dictyostelium cell behaviour (shape, speed and direction of movement) in a shallow chemotaxic gradient (Dunn chamber). Compound concentrations were chosen based on those previously reported to be emetic or aversive in in vivo studies and results were recorded and quantified by automated image analysis. Dictyostelium cell motility was rapidly and strongly inhibited by four structurally distinct tastants (three bitter tasting compounds - denatonium benzoate, quinine hydrochloride, phenylthiourea, and the pungent constituent of chilli peppers - capsaicin). In addition, stomach irritants (copper chloride and copper sulphate), and a phosphodiesterase IV inhibitor also rapidly blocked movement. A concentration-dependant relationship was established for five of these compounds, showing potency of inhibition as capsaicin (IC50?=?11.9±4.0 µM) > quinine hydrochloride (IC50?=?44.3±6.8 µM) > denatonium benzoate (IC50?=?129±4 µM) > phenylthiourea (IC50?=?366±5 µM) > copper sulphate (IC50?=?1433±3 µM). In contrast, 21 compounds within the cytotoxic and receptor agonist/antagonist classes did not affect cell behaviour. Further analysis of bitter and pungent compounds showed that the effect on cell behaviour was reversible and not cytotoxic, suggesting an uncharacterised molecular mechanism of action for these compounds. These results therefore demonstrate that Dictyostelium has potential as a non-sentient model in the analysis of the molecular effects of tastants, although it has limited utility in identification of emetic agents in general. PMID:21931717

  9. Screening of natural compounds as activators of the keap1-nrf2 pathway.

    PubMed

    Wu, Kai C; McDonald, Peter R; Liu, Jie; Klaassen, Curtis D

    2014-01-01

    Nuclear factor erythroid 2-related factor 2 is a master regulator that promotes transcription of cytoprotective genes in response to oxidative/electrophilic stress. A large number of natural dietary compounds are thought to protect against oxidative stress, and a few have been reported to induce genes involved in antioxidant defense through activating nuclear factor erythroid 2-related factor 2. Therefore, a library of 54 natural compounds were collected to determine whether they are nuclear factor erythroid 2-related factor 2 activators and to compare their efficacy and potency to activate nuclear factor erythroid 2-related factor 2. The assay utilized AREc32 cells that contain a luciferase gene under the control of antioxidant response element promoters. Each natural compound was tested at 13 concentrations between 0.02 and 30?µM. Known nuclear factor erythroid 2-related factor 2 activators tert-butylhydroquinone and 2-cyano-3,12-dioxooleana-1,9-diene-28-imidazolide were used as positive controls in parallel with the natural compounds. Among the 54 tested natural compounds, andrographolide had the highest efficacy, followed by trans-chalcone, sulforaphane, curcumin, flavone, kahweol, and carnosol, all of which had better efficacy than tert-butylhydroquinone. Among the compounds tested, 2-cyano-3,12-dioxooleana-1,9-diene-28-imidazolide was the most potent, having an EC50 of 0.41?µM. Seven of the natural compounds, namely andrographolide, trans-chalcone, sulforaphane, curcumin, flavone, kahweol, and cafestol had lower EC50 values than tert-butylhydroquinone but higher than 2-cyano-3,12-dioxooleana-1,9-diene-28-imidazolide. The present study provides insights into which natural compounds activate the Keap1-nuclear factor erythroid 2-related factor 2 pathway and thus might be useful for detoxifying oxidative/electrophilic stress. PMID:24310212

  10. Granular activated carbons from nutshells for the uptake of metals and organic compounds

    Microsoft Academic Search

    C. A. Toles; W. E. Marshall; M. M. Johns

    1997-01-01

    Almond and pecan shells were chosen as hard, lignocellulosic precursors for the production of granular activated carbons (GACs) in order to create carbons for the adsorption of both organic compounds and metals. They were activated either chemically, with H3PO4, or physically, with CO2, under a variety of conditions. Following activation, a portion of the GACs were oxidized with air.The acid-activated

  11. Identifiers Identifiers

    E-print Network

    Brass, Stefan

    , July 1998. . Tim Berners­Lee: Cool URIs don't change. [http://www.w3.org/Provider/Style/URI] . Uniform://archive.ncsa.uiuc.edu/demoweb/url­primer.html] . T. Berners­Lee, R. Fielding, L. Masinter: Uniform Resource Identifiers (URI): Generic Syntax. RFC Names. RFC 1737, December 1994, 7 pages. . T. Berners­Lee, L. Masinter, M. McCahill: Uniform Resource

  12. Identifiers Identifiers

    E-print Network

    Brass, Stefan

    , July 1998. . Tim Berners­Lee: Cool URIs don't change. [http://www.w3.org/Provider/Style/URI] Stefan://archive.ncsa.uiuc.edu/demoweb/url­primer.html] . T. Berners­Lee, R. Fielding, L. Masinter: Uniform Resource Identifiers (URI): Generic Syntax. RFC Names. RFC 1737, December 1994, 7 pages. . T. Berners­Lee, L. Masinter, M. McCahill: Uniform Resource

  13. Redox-Active Selenium Compounds—From Toxicity and Cell Death to Cancer Treatment

    PubMed Central

    Misra, Sougat; Boylan, Mallory; Selvam, Arun; Spallholz, Julian E.; Björnstedt, Mikael

    2015-01-01

    Selenium is generally known as an antioxidant due to its presence in selenoproteins as selenocysteine, but it is also toxic. The toxic effects of selenium are, however, strictly concentration and chemical species dependent. One class of selenium compounds is a potent inhibitor of cell growth with remarkable tumor specificity. These redox active compounds are pro-oxidative and highly cytotoxic to tumor cells and are promising candidates to be used in chemotherapy against cancer. Herein we elaborate upon the major forms of dietary selenium compounds, their metabolic pathways, and their antioxidant and pro-oxidant potentials with emphasis on cytotoxic mechanisms. Relative cytotoxicity of inorganic selenite and organic selenocystine compounds to different cancer cells are presented as evidence to our perspective. Furthermore, new novel classes of selenium compounds specifically designed to target tumor cells are presented and the potential of selenium in modern oncology is extensively discussed. PMID:25984742

  14. Contribution of Identified Active Faults to Near Fault Seismic Hazard in the Flinders Ranges

    E-print Network

    Sandiford, Mike

    Contribution of Identified Active Faults to Near Fault Seismic Hazard in the Flinders Ranges Paul analysis at a site near an active fault in the Flinders Ranges. Two categories of earthquake sources were used to represent the seismic hazard at the site. The first consists of active faults, and used

  15. Effects of ammonium compounds on the foliar activity of acifluorfen

    E-print Network

    Schaffers, William Clemens

    1989-01-01

    and ammonium sulfate increased the activity of dichlorprop on Stellaria m dia (L. ) Vill. (53) Picloram (4-amino-3, 5, 6-trichloro-2-pyridinecarboxylic acid) has also shown a response to inorganic salts. The addition of ammonium sulfate to picloram spray...

  16. Antioxidant Activity of Plant Extracts Containing Phenolic Compounds

    Microsoft Academic Search

    Marja P. Kähkönen; Anu I. Hopia; Heikki J. Vuorela; Jussi-Pekka Rauha; Kalevi Pihlaja; Tytti S. Kujala; Marina Heinonen

    1999-01-01

    The antioxidative activity of a total of 92 phenolic extracts from edible and nonedible plant materials (berries, fruits, vegetables, herbs, cereals, tree materials, plant sprouts, and seeds) was examined by autoxidation of methyl linoleate. The content of total phenolics in the extracts was determined spectrometrically according to the Folin-Ciocalteu procedure and calculated as gallic acid equivalents (GAE). Among edible plant

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

    SciTech Connect

    Jacobs, Miriam N. [Molecular Toxicology Group, School of Biomedical and Molecular Sciences, University of Surrey Guildford GU2 7XH (United Kingdom)]. E-mail: miriam.jacobs@jrc.it; Nolan, Gail T. [Molecular MET, DMPK, GlaxoSmithKline, Park Road, Ware, Herts (United Kingdom); Hood, Steven R. [Molecular MET, DMPK, GlaxoSmithKline, Park Road, Ware, Herts (United Kingdom)

    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 hormone metabolism with potential adverse health effects in exposed individuals.

  18. Chelating compound, chrysoidine, is more effective in both antiprion activity and brain endothelial permeability than quinacrine.

    PubMed

    Doh-ura, Katsumi; Tamura, Kazuhiko; Karube, Yoshiharu; Naito, Mikihiko; Tsuruo, Takashi; Kataoka, Yasufumi

    2007-05-01

    1. As an extension of our previous study of quinacrine and its derivatives, chelating chemicals were screened to obtain more effective, better brain-permeable antiprion compounds using either prion-infected neuroblastoma cells or brain capillary endothelial cells.2. Eleven chemicals were found to have antiprion activity. Most of them shared a common structure consisting of benzene or naphthalene at either end of an azo bond. Structure-activity data suggest that chelating activity is not necessary but might contribute to the antiprion action.3. Chrysoidine, a representative compound found here, was about 27 times more effective in the antiprion activity and five times more efficiently permeable through the brain capillary endothelial cells than quinacrine was.4. These chemicals might be useful as compounds for development of therapeutics for prion diseases. PMID:17235694

  19. Evaluation of anxiolytic activity of compound Valeriana jatamansi Jones in mice

    PubMed Central

    2012-01-01

    Background Compound Valeriana jatamansi Jones is a formula for treating anxiety-related diseases in the clinic, which is composed of Valeriana jatamansi Rhizoma et Radix, Ziziphi Spinosae Semen, Albiziae Cortex and Junci Medulla. The purpose of this study was to explore the anxiolytic properties of this compound in mice. Methods Male ICR mice were treated with compound Valerianae Jatamansi Jones (1.2 g/kg, 2.4 g/kg, 4.8 g/kg), saline, diazepam (2 mg/kg) orally for 10 days and then exposed to elevated maze-plus (EPM) and light–dark box (LDB). The effects of the compound on spontaneous activity were evaluated by locomotor activity test. We further investigated the mechanism of action underlying the anxiolytic-like effect of compound by pre-treating animals with antagonists of benzodiazepine (flumazenil, 3mg/kg) prior to evaluation using EPM and LDB. Results Compound Valerianae Jatamansi Jones (2.4, 4.8 g/kg, p.o.) significantly increased entries (P<0.05) into and time spent (P<0.05) on the open arms of the EPM, and number of transitions (P<0.05) and time spent (P<0.05) in the light compartment of the LDB. However, the anxiolytic-like effects of compound were significantly reduced by pre-treatment with flumazenil (P>0.05). In addition, compound Valerianae Jatamansi Jones treatment didn’t affect the spontaneous activity in mice (P> 0.05). Conclusions The present study supports the hypothesis that compound Valeriana jatamansi Jones exert anxiolytic action but no sedative effects in mice and that this effect might be mediated by benzodiazepine receptors. PMID:23171285

  20. Bioactive compounds and antioxidant activity of Rosa canina L. biotypes from spontaneous flora of Transylvania

    PubMed Central

    2013-01-01

    Background The theoretical, but especially the practical values of identifying the biochemical compounds from the Rosa canina L. fruits are of present interest, this aspect being illustrated by the numerous researches. It was reported that the Rosa canina L. fruit, with its high ascorbic acid, phenolics and flavonoids contents, have antioxidant, antimutagenic and anticarcinogenic effects. This study was performed on order to evaluate the amount of the main phytochemicals (vitamin C, total polyphenols, and total flavonoids) content and their antioxidant activity. Results The results obtained revealed that the average amounts of vitamin C within the studied genotypes were: 360.22 mg/100 g frozen pulp (var. transitoria f. ramosissima, altitude 1250 m) and 112.20 mg/100 g frozen pulp (var. assiensis, altitude 440 m), giving a good correlation between the vitamin C content of the rosehip and the altitude. The total polyphenols content varied from 575 mg/100 g frozen pulp (var. transitoria f. ramosissima) to 326 mg/100 g frozen pulp (var. lutetiana f. fallens). The total flavonoids content showed the highest value for var. assiensis variant 163.3 mg/100 g frozen pulp and the lowest value attributed to var. transitoria f. montivaga 101.3 mg/100 g frozen pulp. The antioxidant activity of eight rose hip extracts from wild Transylvania populations was investigated through DPPH method. The antioxidant activity revealed a good correlation only with vitamin C content and total polyphenols. Conclusion Eight Rose hip fruit species were compared taking into consideration the ascorbic acid, total polyphenols, total flavonoids contents and their antioxidant activity. Based on these results, two of the rosehip genotypes that were analysed could be of perspective for these species’ amelioration, due to their content of phytochemicals mentioned above. These varieties are var. transitoria f. ramosissima (Bistrita-Nasaud, Agiesel) and var. transitoria f. montivaga (Bistrita-Nasaud, Salva) which can be used as a potential source of natural antioxidants. PMID:23618509

  1. 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.

  2. Antifungal activity of extracts and select compounds in heartwood of seven western conifers toward Phytophthora ramorum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Individual compounds and ethyl acetate extracts from heartwood of seven conifer species were tested for fungicidal activity against Phytophthora ramorum. Extracts from incense and western red cedar exhibited the strongest activity (EC50 589 and 646 ppm, respectively), yellow-cedar, western juniper,...

  3. Novel imidazole compounds as a new series of potent, orally active inhibitors of 5-lipoxygenase

    Microsoft Academic Search

    Takashi Mano; Rodney W Stevens; Kazuo Ando; Kazunari Nakao; Yoshiyuki Okumura; Minoru Sakakibara; Takako Okumura; Tetsuya Tamura; Kimitaka Miyamoto

    2003-01-01

    Replacement of the dihydroquinolinone pharmacophore of Zeneca's ZD2138 by ionizable imidazolylphenyl moiety has lead to the discovery of a novel series of potent and orally active 5-lipoxygenase (5-LO) inhibitors. The synthesis and structure–activity relationship (SAR) of this series of compounds are described herein.

  4. Synthesis of a Physiologically Active Compound of the Pellitorine Structure

    Microsoft Academic Search

    L. Crombie; S. H. Harper

    1949-01-01

    PELLITORINE, isolated from the roots of pellitory, Anacyclus pyrethrum, has aroused renewed interest since it has been shown to possess insecticidal activity. It has been stated by Jacobson1 to possess a `knockdown value' against house-flies equal to, and a toxicity somewhat more than half, that of the pyrethrins tested at the same concentration. Pellitorine (m.p. 72°) was shown by Gulland

  5. Larvicidal activity of isobutylamides identified in Piper nigrum fruits against three mosquito species.

    PubMed

    Park, Il-Kwon; Lee, Sang-Gil; Shin, Sang-Chul; Park, Ji-Doo; Ahn, Young-Joon

    2002-03-27

    The insecticidal activity of materials derived from the fruits of Piper nigrum against third instar larvae of Culex pipiens pallens, Aedes aegypti, and A. togoi was examined and compared with that of commercially available piperine, a known insecticidal compound from Piper species. The biologically active constituents of P. nigrum fruits were characterized as the isobutylamide alkaloids pellitorine, guineensine, pipercide, and retrofractamide A by spectroscopic analysis. Retrofractamide A was isolated from P. nigrum fruits as a new insecticidal principle. On the basis of 48-h LC(50) values, the compound most toxic to C. pipiens pallens larvae was pipercide (0.004 ppm) followed by retrofractamide A (0.028 ppm), guineensine (0.17 ppm), and pellitorine (0.86 ppm). Piperine (3.21 ppm) was least toxic. Against A. aegypti larvae, larvicidal activity was more pronounced in retrofractamide A (0.039 ppm) than in pipercide (0.1 ppm), guineensine (0.89 ppm), and pellitorine (0.92 ppm). Piperine (5.1 ppm) was relatively ineffective. Against A. togoi larvae, retrofractamide A (0.01 ppm) was much more effective, compared with pipercide (0.26 ppm), pellitorine (0.71 ppm), and guineensine (0.75 ppm). Again, very low activity was observed with piperine (4.6 ppm). Structure-activity relationships indicate that the N-isobutylamine moiety might play a crucial role in the larvicidal activity, but the methylenedioxyphenyl moiety does not appear essential for toxicity. Naturally occurring Piper fruit-derived compounds merit further study as potential mosquito larval control agents or as lead compounds. PMID:11902925

  6. 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.

  7. Noxious Cold Ion Channel TRPA1 Is Activated by Pungent Compounds and Bradykinin

    Microsoft Academic Search

    Michael Bandell; Gina M. Story; Sun Wook Hwang; Veena Viswanath; Samer R. Eid; Matt J. Petrus; Taryn J. Earley; Ardem Patapoutian

    2004-01-01

    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

  8. Biosynthesis of the active compounds of Isatis indigotica based on transcriptome sequencing and metabolites profiling

    PubMed Central

    2013-01-01

    Backgroud Isatis indigotica is a widely used herb for the clinical treatment of colds, fever, and influenza in Traditional Chinese Medicine (TCM). Various structural classes of compounds have been identified as effective ingredients. However, little is known at genetics level about these active metabolites. In the present study, we performed de novo transcriptome sequencing for the first time to produce a comprehensive dataset of I. indigotica. Results A database of 36,367 unigenes (average length?=?1,115.67 bases) was generated by performing transcriptome sequencing. Based on the gene annotation of the transcriptome, 104 unigenes were identified covering most of the catalytic steps in the general biosynthetic pathways of indole, terpenoid, and phenylpropanoid. Subsequently, the organ-specific expression patterns of the genes involved in these pathways, and their responses to methyl jasmonate (MeJA) induction, were investigated. Metabolites profile of effective phenylpropanoid showed accumulation pattern of secondary metabolites were mostly correlated with the transcription of their biosynthetic genes. According to the analysis of UDP-dependent glycosyltransferases (UGT) family, several flavonoids were indicated to exist in I. indigotica and further identified by metabolic profile using UPLC/Q-TOF. Moreover, applying transcriptome co-expression analysis, nine new, putative UGTs were suggested as flavonol glycosyltransferases and lignan glycosyltransferases. Conclusions This database provides a pool of candidate genes involved in biosynthesis of effective metabolites in I. indigotica. Furthermore, the comprehensive analysis and characterization of the significant pathways are expected to give a better insight regarding the diversity of chemical composition, synthetic characteristics, and the regulatory mechanism which operate in this medical herb. PMID:24308360

  9. Identifying essential proteins from active PPI networks constructed with dynamic gene expression

    PubMed Central

    2015-01-01

    Essential proteins are vitally important for cellular survival and development, and identifying essential proteins is very meaningful research work in the post-genome era. Rapid increase of available protein-protein interaction (PPI) data has made it possible to detect protein essentiality at the network level. A series of centrality measures have been proposed to discover essential proteins based on the PPI networks. However, the PPI data obtained from large scale, high-throughput experiments generally contain false positives. It is insufficient to use original PPI data to identify essential proteins. How to improve the accuracy, has become the focus of identifying essential proteins. In this paper, we proposed a framework for identifying essential proteins from active PPI networks constructed with dynamic gene expression. Firstly, we process the dynamic gene expression profiles by using time-dependent model and time-independent model. Secondly, we construct an active PPI network based on co-expressed genes. Lastly, we apply six classical centrality measures in the active PPI network. For the purpose of comparison, other prediction methods are also performed to identify essential proteins based on the active PPI network. The experimental results on yeast network show that identifying essential proteins based on the active PPI network can improve the performance of centrality measures considerably in terms of the number of identified essential proteins and identification accuracy. At the same time, the results also indicate that most of essential proteins are active. PMID:25707432

  10. New antiinflammatory compounds that inhibit tumor necrosis factor production: probable interaction with protein kinase C activation.

    PubMed

    Lang, F; Robert, J M; Boucrot, P; Welin, L; Petit, J Y

    1995-10-01

    We have previously described a family of benzamide derivatives that showed antiinflammatory activity in vivo on carragenin-induced paw edema and experimental cerebral edema. Those compounds inhibited eicosanoids production from activated macrophages (M phi) without inhibiting cyclooxygenase. To further investigate their antiinflammatory activity and compare it to that of classical cyclooxygenase inhibitors, we analyzed their effect on the production of a major proinflammatory cytokine, tumor necrosis factor (TNF-alpha), by in vitro-activated peritoneal macrophages. We show that, in marked contrast with ibuprofen, flurbiprofen and indomethacin which all significantly enhanced TNF production, the two benzamide derivatives tested, JM34 and JM42, significantly inhibited TNF-alpha production by zymosan or lipopolysaccharide-activated M phi. Those compounds did not interfere with the calcium-dependent pathway because they did not affect TNF production of either mice peritoneal M phi or human T cell clones induced by the calcium ionophore A23187 alone. More likely, these benzamide derivatives acted mainly at the level of the protein kinase C (PKC) pathway because: 1) After treatment of M phi with PKC inhibitors which significantly inhibited TNF production, our compounds showed no additional inhibition. 2) Our compounds significantly inhibited TNF production of M phi stimulated with the phorbol ester phorbol di-butyrate alone or in combination with A23187. 3) After depletion of PKC by prolonged phorbol di-butyrate treatment of M phi, inhibition of TNF production by our compounds was markedly decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7562546

  11. Bioactive compounds and prebiotic activity in Thailand-grown red and white guava fruit (Psidium guajava L.).

    PubMed

    Thuaytong, W; Anprung, P

    2011-06-01

    This research involves the comparison of bioactive compounds, volatile compounds and prebiotic activity of white guava (Psidium guajava L.) cv. Pansithong and red guava cv. Samsi. The antioxidant activity values determined by 2-diphenyl-1-picryhydrazyl (DPPH) free radical scavenging and ferric reducing antioxidant power (FRAP) assays were 10.28 µg fresh weight (fw)/µg DPPH and 78.56 µg Trolox equivalent (TE)/g fw for white guava and 7.82 µg/µg DPPH, fw and 111.06 µM TE/g fw for red guava. Ascorbic acid contents were 130 and 112mg/100g fw total phenolics contents 145.52 and 163.36 mg gallic acid equivalents (GAE)/100 g fw and total flavonoids contents 19.06 and 35.85 mg catechin equivalents (CE)/100 g fw, in white and red guava, respectively. Volatile compounds in guava were analyzed by the solid-phase microextraction (SPME)/gas chromatography (GC)/mass spectrometry (MS) method. The major constituents identified in white and red guavas were cinnamyl alcohol, ethyl benzoate, ß-caryophyllene, (E)-3-hexenyl acetate and ?-bisabolene. Prebiotic activity scores for Lactobacillus acidophilus LA-5 and Bifidobacterium lactis BB-12 were 0.12 and 0.28 in white guava, respectively, and 0.13 and 0.29 in red guava, respectively. PMID:21652766

  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. Effects of ammonium compounds on the foliar activity of acifluorfen 

    E-print Network

    Schaffers, William Clemens

    1989-01-01

    pH changes are the primary mechanism (18, 43) . Dinitrophenol was shown to have a greater effect in reducing Avena coleoptile growth at lower pHs (11). The activity of 2, 4-D has been shown to be greater in acid solutions (2, 9, 30, 32, 51, 58... on the translocation of 2, 4, 5-T in blackjack oak and winged elm. Proc. South. Weed Conf. 20:382-386. 6. Baur, J. R. and R. W. Bovey. 1970. The uptake of picloram by potato tuber tissue. Weed Sci. 18:22-24. 7. Baur, J. R. , R. W. Bovey, R. D. Baker and I. Riley...

  14. Pectins and xyloglucans exhibit antimutagenic activities against nitroaromatic compounds.

    PubMed

    Hensel, A; Meier, K

    1999-06-01

    Because a high daily consumption of polysaccharides-containing food is assessed to decrease the risk of cancer of the gastrointestinal system, different types of carbohydrates were investigated for their antimutagenic activity against different standard mutagens. Within the screening pronounced antimutagenic effects were found for xyloglucan and different pectins and pectin-like rhamnogalacturonans against 1-nitropyrene induced mutagenicity. Inhibition rates were dose-dependent and varied between 20 and 50%. Concerning the mode of action a direct interaction of the polymers with the cells is claimed, protecting the organisms from the mutagenic attack. PMID:10418322

  15. Sample Preparation Methods and Pre-harvest Factors Influencing the Contents of Bioactive Compounds and Antioxidant Activity in Peppers 

    E-print Network

    Bae, Hae Jin

    2012-02-14

    Peppers are a rich source of diverse bioactive compounds with potential health-promoting properties. The levels of bioactive compounds and antioxidant activity can be affected by analytical methods, pre-harvest factors, ...

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

    NASA Astrophysics Data System (ADS)

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

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

  17. Oxidation of pharmaceutically active compounds by a ligninolytic fungal peroxidase.

    PubMed

    Eibes, Gemma; Debernardi, Gianfranco; Feijoo, Gumersindo; Moreira, M Teresa; Lema, Juan M

    2011-06-01

    Pharmaceuticals are an important group of emerging pollutants with increasing interest due to their rising consumption and the evidence for ecotoxicological effects associated to trace amounts in aquatic environments. In this paper, we assessed the potential degradation of a series of pharmaceuticals: antibiotics (sulfamethoxazole), antidepressives (citalopram hydrobromide and fluoxetine hydrochloride), antiepileptics (carbamazepine), anti-inflammatory drugs (diclofenac and naproxen) and estrogen hormones (estrone, 17?-estradiol, 17?-ethinylestradiol) by means of a versatile peroxidase (VP) from the ligninolytic fungus Bjerkandera adusta. The effects of the reaction conditions: VP activity, organic acid concentration and H(2)O(2) addition rate, on the kinetics of the VP based oxidation system were evaluated. Diclofenac and estrogens were completely degraded after only 5-25 min even with a very low VP activity (10 U l(-1)). High degradation percentages (80%) were achieved for sulfamethoxazole and naproxen. Low or undetectable removal yields were observed for citalopram (up to 18%), fluoxetine (lower than 10%) and carbamazepine (not degraded). PMID:20972884

  18. Comparison of predicted and derived measures of volatile organic compounds inside four relocatable classrooms due to identified interior finish sources

    Microsoft Academic Search

    Alfred T. Hodgson; Derek G. Shendell; William J. Fisk; Michael G. Apte

    2003-01-01

    Indoor exposures to toxic and odorous volatile organic compounds (VOCs) are of general concern. Recently, VOCs in portable or relocatable classrooms (RCs) have received particular attention. However, very little was known about indoor environmental quality (IEQ) and the sources, composition, and indoor concentrations of VOCs in RCs. This project task focused on developing and demonstrating a process for selecting interior

  19. UTSW Investigators Develop Functional Signature Ontology (FUSION), a Method for Identifying Compounds That Target Cancer Pathways | Office of Cancer Genomics

    Cancer.gov

    In a new study published in Science Signaling, CTD2 investigators from University of Texas (UTSW) Southwestern Medical Center devised a novel bioinformatics approach that, when coupled with high-throughput screening, helps reveal compounds that may target potential cancer-related pathways.

  20. Characterization of aroma-active compounds in dry flower of Malva sylvestris L. by GC-MS-O analysis and OAV calculations.

    PubMed

    Usami, Atsushi; Kashima, Yusei; Marumoto, Shinsuke; Miyazawa, Mitsuo

    2013-01-01

    In this study, the aroma-active compounds in the dried flower of Malva sylvestris L. were extracted by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS), and gas chromatography-olfactometry (GC-O) and aroma extraction dilution analysis (AEDA). A light yellow oil with a sweet odor was obtained with a percentage yield of 0.039% (w/w), and 143 volatile compounds (89.86%) were identified by GC-MS. The main compounds were hexadecanoic acid (10.1%), pentacosane (4.8%) and 6,10,14-trimethyl-2-pentadecanone (4.1%). The essential oil consisted mainly of hydrocarbons (25.40%) followed by, alcohols (18.78%), acids (16.66%), ethers (5.01%) ketones (7.28%), esters(12.43%), aldehydes (2.30%) and others (2.00%). Of these compounds, 20 were determined by GC-O and AEDA, to be odor-active (FD (flavor dilution) factor ? 1). ?-Damascenone (FD = 9, sweet), phenylacetaldehyde (FD = 8, floral, honey-like) and (E)-?-ocimene (FD = 8, spicy) were the most intense aroma-active compounds in M. sylvestris. In order to determine the relative contribution of each of the compounds to the aroma of M. sylvestris, odor activity values (OAVs) were used. ?-Damascenone had the highest odor activity values (OAV) (50,700), followed by (E)-?-ionone (15,444) and decanal (3,510). In particular, ?-damascenone had a high FD factors, and therefore, this compound was considered to be the main aroma-active components of the essential oil. On the basis of AEDA, OAVs, and sensory evaluation results, ?-damascenone is estimated to be the main aroma-active compound of the essential oil. PMID:23985485

  1. Using Model-Eliciting Activities as a Tool to Identify and Develop Mathematically Creative Students

    ERIC Educational Resources Information Center

    Coxbill, Emmy; Chamberlin, Scott A.; Weatherford, Jennifer

    2013-01-01

    Traditional classroom methods for identifying mathematically creative students have been inadequate. Identifying students who could potentially be mathematically creative is instrumental in the development of students and in meeting their affective and educational needs. One prospective identification tool is the use of model-eliciting activities…

  2. 41 CFR 102-75.340 - Where hazardous substance activity has been identified on property proposed for disposal, what...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...false Where hazardous substance activity has been identified on property proposed for...340 Where hazardous substance activity has been identified on property proposed for...existence of hazardous substance activity has been brought to the attention of...

  3. 41 CFR 102-75.340 - Where hazardous substance activity has been identified on property proposed for disposal, what...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...false Where hazardous substance activity has been identified on property proposed for...340 Where hazardous substance activity has been identified on property proposed for...existence of hazardous substance activity has been brought to the attention of...

  4. Inverse Virtual Screening allows the discovery of the biological activity of natural compounds.

    PubMed

    Lauro, Gianluigi; Masullo, Milena; Piacente, Sonia; Riccio, Raffaele; Bifulco, Giuseppe

    2012-06-01

    A small library of phenolic natural compounds belonging to different chemical classes was screened on a panel of targets involved in the genesis and progression of cancer. The re-investigation of their potential activity was achieved through the Inverse Virtual Screening approach. The normalization of the predicted binding energies permitted the selection of promising compounds on definite targets, avoiding the selection of false positive results. In vitro biological tests revealed the inhibitory activity of xanthohumol and isoxanthohumol on PDK1 and PKC protein kinases. This study validates the robustness of the Inverse Virtual Screening in silico approach as a useful tool for the identification of the specific biological activity of a given set of compounds. PMID:22537682

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

    PubMed

    K?rm?z?bekmez, Hasan; Uysal, Görkem Berk; Masullo, Milena; Demirci, Fatih; Ba?c?, 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?g/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 0.18-0.56mg/mL, suggesting an activity comparable with that of ascorbic acid (IC50: 0.07mg/mL). To the best of our knowledge, the present study constitutes the first phytochemical and bioactivity investigation on G. iconica. PMID:25963162

  6. Using wearable cameras to categorise type and context of accelerometer-identified episodes of physical activity

    PubMed Central

    2013-01-01

    Background Accelerometers can identify certain physical activity behaviours, but not the context in which they take place. This study investigates the feasibility of wearable cameras to objectively categorise the behaviour type and context of participants’ accelerometer-identified episodes of activity. Methods Adults were given an Actical hip-mounted accelerometer and a SenseCam wearable camera (worn via lanyard). The onboard clocks on both devices were time-synchronised. Participants engaged in free-living activities for 3 days. Actical data were cleaned and episodes of sedentary, lifestyle-light, lifestyle-moderate, and moderate-to-vigorous physical activity (MVPA) were identified. Actical episodes were categorised according to their social and environmental context and Physical Activity (PA) compendium category as identified from time-matched SenseCam images. Results There were 212 days considered from 49 participants from whom SenseCam images and associated Actical data were captured. Using SenseCam images, behaviour type and context attributes were annotated for 386 (out of 3017) randomly selected episodes (such as walking/transportation, social/not-social, domestic/leisure). Across the episodes, 12 categories that aligned with the PA Compendium were identified, and 114 subcategory types were identified. Nineteen percent of episodes could not have their behaviour type and context categorized; 59% were outdoors versus 39% indoors; 33% of episodes were recorded as leisure time activities, with 33% transport, 18% domestic, and 15% occupational. 33% of the randomly selected episodes contained direct social interaction and 22% were in social situations where the participant wasn’t involved in direct engagement. Conclusion Wearable camera images offer an objective method to capture a spectrum of activity behaviour types and context across 81% of accelerometer-identified episodes of activity. Wearable cameras represent the best objective method currently available to categorise the social and environmental context of accelerometer-defined episodes of activity in free-living conditions. PMID:23406270

  7. 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. PMID:22902129

  8. Innovative cosmeceuticals: sirtuin activators and anti-glycation compounds.

    PubMed

    Farris, Patricia K

    2011-09-01

    Skin aging is a combination of natural aging with superimposed photoaging. Naturally aged skin is thin, fragile and finely wrinkled whereas photoaged skin is rough and thickened with deep coarse wrinkles. In addition photoaging is characterized by mottled pigmentation, solar lentigines, telangectasias and a loss of elasticity. The science behind skin aging has exploded in the past decade. Skin aging has now been defined on both a cellular and molecular level. The study of genomics in aging skin provides us with potential targets as points for intervention. In this regard, the science behind skin aging becomes a platform for the development of new anti-aging strategies and products. In this paper two new and emerging approaches to treat aging skin will be discussed. Sirtuin activating and anti-glycation products are already being marketed by cosmetic and pharmaceutical companies. These anti-aging approaches are backed by basic science research and the ingredients used are supported by proof of concept studies although clinical trials are often lacking. It is this bench to beauty counter approach to cosmeceuticals that remains an industry standard today. PMID:21925370

  9. Antibacterial Activities of Naturally Occurring Compounds against Mycobacterium avium subsp. paratuberculosis?

    PubMed Central

    Wong, Stella Y. Y.; Grant, Irene R.; Friedman, Mendel; Elliott, Christopher T.; Situ, Chen

    2008-01-01

    The antibacterial activities of 18 naturally occurring compounds (including essential oils and some of their isolated constituents, apple and green tea polyphenols, and other plant extracts) against three strains of Mycobacterium avium subsp. paratuberculosis (a bovine isolate [NCTC 8578], a raw-milk isolate [806R], and a human isolate [ATCC 43015]) were evaluated using a macrobroth susceptibility testing method. M. avium subsp. paratuberculosis was grown in 4 ml Middlebrook 7H9 broth containing 10% oleic acid-albumin-dextrose-catalase, 0.05% Tween 80 (or 0.2% glycerol), and 2 ?g/ml mycobactin J supplemented with five concentrations of each test compound. The changes in the optical densities of the cultures at 600 nm as a measure of CFU were recorded at intervals over an incubation period of 42 days at 37°C. Six of the compounds were found to inhibit the growth of M. avium subsp. paratuberculosis. The most effective compound was trans-cinnamaldehyde, with a MIC of 25.9 ?g/ml, followed by cinnamon oil (26.2 ?g/ml), oregano oil (68.2 ?g/ml), carvacrol (72.2 ?g/ml), 2,5-dihydroxybenzaldehyde (74 ?g/ml), and 2-hydroxy-5-methoxybenzaldehyde (90.4 ?g/ml). With the exception of carvacrol, a phenolic compound, three of the four most active compounds are aldehydes, suggesting that the structure of the phenolic group or the aldehyde group may be important to the antibacterial activity. No difference in compound activity was observed between the three M. avium subsp. paratuberculosis strains studied. Possible mechanisms of the antimicrobial effects are discussed. PMID:18676709

  10. A High-Content, Multiplexed Screen in Human Breast Cancer Cells Identifies Profilin-1 Inducers with Anti-Migratory Activities

    PubMed Central

    Hulkower, Keren; Stern, Andrew M.; Boltz, R. C. “Dutch”; Roy, Partha; Vogt, Andreas

    2014-01-01

    Profilin-1 (Pfn-1) is a ubiquitously expressed actin-binding protein that is essential for normal cell proliferation and migration. In breast cancer and several other adenocarcinomas, Pfn-1 expression is downregulated when compared to normal tissues. Previous studies from our laboratory have shown that genetically modulating Pfn-1 expression significantly impacts proliferation, migration, and invasion of breast cancer cells in vitro, and mammary tumor growth, dissemination, and metastatic colonization in vivo. Therefore, small molecules that can modulate Pfn-1 expression could have therapeutic potential in the treatment of metastatic breast cancer. The overall goal of this study was to perform a multiplexed phenotypic screen to identify compounds that inhibit cell motility through upregulation of Pfn-1. Screening of a test cassette of 1280 compounds with known biological activities on an Oris™ Pro 384 cell migration platform identified several agents that increased Pfn-1 expression greater than two-fold over vehicle controls and exerted anti-migratory effects in the absence of overt cytotoxicity in MDA-MB-231 human breast cancer cells. Concentration-response confirmation and orthogonal follow-up assays identified two bona fide inducers of Pfn-1, purvalanol and tyrphostin A9, that confirmed in single-cell motility assays and Western blot analyses. SiRNA-mediated knockdown of Pfn-1 abrogated the inhibitory effect of tyrphostin A9 on cell migration, suggesting Pfn-1 is mechanistically linked to tyrphostin A9?s anti-migratory activity. The data illustrate the utility of the high-content cell motility assay to discover novel targeted anti-migratory agents by integrating functional phenotypic analyses with target-specific readouts in a single assay platform. PMID:24520372

  11. 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. PMID:16395649

  12. Adsorption of phenolic compounds by activated carbon--a critical review.

    PubMed

    Dabrowski, A; Podko?cielny, P; Hubicki, Z; Barczak, M

    2005-02-01

    Adsorption of phenol and its derivatives on activated carbons is considered based on numerous papers related to this issue. Special attention is paid to the effects of carbon surface functionalities, pH of solution and heterogeneity effects that accompany adsorption of phenolic compounds. Moreover, in this paper the most important aspects are overviewed referring to irreversible adsorption of phenols and impact of different substituents of phenolic compounds on their uptake by activated carbons is considered. Finally, some remarks pertaining to applications of novel adsorbents for phenol adsorption are discussed and illustrated by means of a few examples. PMID:15664613

  13. Phenolic compounds with pancreatic lipase inhibitory activity from Korean yam (Dioscorea opposita).

    PubMed

    Yang, Min Hye; Chin, Young-Won; Yoon, Kee Dong; Kim, Jinwoong

    2014-02-01

    Abstract Twenty-three phenolic compounds were isolated from Dioscorea opposita by bioactivity-guided method and their inhibitory effect against pancreatic lipase was evaluated. A total of 15 isolates reduced lipase activity at IC50 values of less than 50 µM and 3,3',5-trihydroxy-2'-methoxybibenzyl showed the highest inhibition with an IC50 value of 8.8 µM. This study is a first to reveal the pancreatic lipase inhibitory activity by both D. opposita and its isolated compounds. PMID:23327640

  14. Efficient discovery of responses of proteins to compounds using active learning

    PubMed Central

    2014-01-01

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

  15. X-ray and DFT Study of Glaucocalyxin A Compound with Cytotoxic Activity

    NASA Astrophysics Data System (ADS)

    Wang, Fu-dong; Wang, Tao; Wu, An-an; Ding, Lan; Wang, Han-qing

    2009-06-01

    The title compound glaucocalyxin A (1) (7?, 14?-dihydroxy-ent-kaur-16-en-3,15-dione) isolated from the leaves of isodon excisoides was characterized by IR, 1H NMR, 13C NMR, 1H-1H COSY, HMQC, HMBC, and EIMS, and its crystal structure was determined by single-crystal X-ray diffraction. The X-ray crystal structure revealed that the molecular backbone of the chosen crystal is a tetracyclic system, including three six-membered rings and a five-membered ring, and the three six-membered rings are in a chair-like conformation. The five-membered ring adopts a twisted envelope-like conformation, and its geometrical parameters were compared with theoretical calculations at the B3LYP and HF level of theory. The molecules form extensive networks through the intra- and intermolecular hydrogen bonds. The experimental NMR data were interpreted with the aid of magnetic shielding constant calculations, by means of the GIAO (gauge-lncluding atomic orbitals) method. Calculated and experimental results were compared with a satisfactory level of agreement. Molecular electrostatic potential map was used in an attempt to identify key features of the diterpenoid glaucocalyxin A that is necessary for its activity. Calculations of molecular electrostatic potential and stabilization energies suggest that the protonation of glaucocalyxin A will be able to occur on carbonyl oxygen atoms.

  16. Activity put in context: Identifying implicit task context within the user's document interaction

    E-print Network

    North Carolina at Chapel Hill, University of

    Activity put in context: Identifying implicit task context within the user's document interaction with their documents within the file system, Confluence also traces user activity within the user interfaceRank Permission to make digital or hard copies of all or part of this work for personal or classroom use

  17. Identifying Facilitators and Barriers to Physical Activity for Adults with Down Syndrome

    ERIC Educational Resources Information Center

    Mahy, J.; Shields, N.; Taylor, N. F.; Dodd, K. J.

    2010-01-01

    Background: Adults with Down syndrome are typically sedentary, and many do not participate in the recommended levels of physical activity per week. The aim of this study was to identify the facilitators and barriers to physical activity for this group. Method: Semi-structured interviews were conducted to elicit the views of adults with Down…

  18. GWAS of butyrylcholinesterase activity identifies four novel loci, independent effects within BCHE

    E-print Network

    Nyholt, Dale R.

    GWAS of butyrylcholinesterase activity identifies four novel loci, independent effects within BCHE 63110, USA Received July 6, 2011; Revised and Accepted August 18, 2011 Serum butyrylcholinesterase (BCHE have conducted a genome-wide association scan to discover genetic variants affecting BCHE activity

  19. Effects of cyclodiene compounds on calcium pump activity in rat brain and heart.

    PubMed

    Mehrotra, B D; Moorthy, K S; Reddy, S R; Desaiah, D

    1989-01-01

    The in vitro and in vivo effects of aldrin, dieldrin, and endrin on calmodulin regulated Ca2+-pump activity in rat brain synaptosomes and heart sarcoplasmic reticulum were investigated. All the 3 cyclodiene compounds inhibited both brain synaptosomal and heart sarcoplasmic reticulum Ca2+-pump activity in vitro in a concentration dependent manner. Calmodulin depleted Ca2+-pump activity was insensitive to the action of toxic compounds. Oral administration of pesticides (0.5-10 mg/kg) to rats similarly decreased the Ca2+-pump activity, in addition to decreasing the levels of calmodulin of both brain and heart thus indicating disruption in membrane Ca2+ transport mechanisms. Exogenous addition of calmodulin (1-20 micrograms) could effectively reverse the pesticide induced inhibition. Ca2+-pump activity is more sensitive to the 3 cyclodiene compounds in brain than in heart. The results of the present study indicate that the cyclodiene compounds may produce neurotoxic effects by altering calmodulin regulated calcium dependent events in neurons. PMID:2536969

  20. New Classes of Alanine Racemase Inhibitors Identified by High-Throughput Screening Show Antimicrobial Activity against Mycobacterium tuberculosis

    PubMed Central

    Anthony, Karen G.; Strych, Ulrich; Yeung, Kacheong R.; Shoen, Carolyn S.; Perez, Oriana; Krause, Kurt L.; Cynamon, Michael H.; Aristoff, Paul A.; Koski, Raymond A.

    2011-01-01

    Background In an effort to discover new drugs to treat tuberculosis (TB) we chose alanine racemase as the target of our drug discovery efforts. In Mycobacterium tuberculosis, the causative agent of TB, alanine racemase plays an essential role in cell wall synthesis as it racemizes L-alanine into D-alanine, a key building block in the biosynthesis of peptidoglycan. Good antimicrobial effects have been achieved by inhibition of this enzyme with suicide substrates, but the clinical utility of this class of inhibitors is limited due to their lack of target specificity and toxicity. Therefore, inhibitors that are not substrate analogs and that act through different mechanisms of enzyme inhibition are necessary for therapeutic development for this drug target. Methodology/Principal Findings To obtain non-substrate alanine racemase inhibitors, we developed a high-throughput screening platform and screened 53,000 small molecule compounds for enzyme-specific inhibitors. We examined the ‘hits’ for structural novelty, antimicrobial activity against M. tuberculosis, general cellular cytotoxicity, and mechanism of enzyme inhibition. We identified seventeen novel non-substrate alanine racemase inhibitors that are structurally different than any currently known enzyme inhibitors. Seven of these are active against M. tuberculosis and minimally cytotoxic against mammalian cells. Conclusions/Significance This study highlights the feasibility of obtaining novel alanine racemase inhibitor lead compounds by high-throughput screening for development of new anti-TB agents. PMID:21637807

  1. Identification of a Series of Compounds with Potent Antiviral Activity for the Treatment of Enterovirus Infections

    PubMed Central

    2013-01-01

    Rhinovirus (genus enterovirus) infections are responsible for many of the severe exacerbations of asthma and chronic obstructive pulmonary disease. Other members of the genus can cause life-threatening acute neurological infections. There is currently no antiviral drug approved for the treatment of such infections. We have identified a series of potent, broad-spectrum antiviral compounds that inhibit the replication of the human rhinovirus, Coxsackie virus, poliovirus, and enterovirus-71. The mechanism of action of the compounds has been established as inhibition of a lipid kinase, PI4KIII?. Inhibition of hepatitis C replication in a replicon assay correlated with enterovirus inhibition. PMID:24900715

  2. Identification of a series of compounds with potent antiviral activity for the treatment of enterovirus infections.

    PubMed

    MacLeod, Angus M; Mitchell, Dale R; Palmer, Nicholas J; Van de Poël, Hervé; Conrath, Katja; Andrews, Martin; Leyssen, Pieter; Neyts, Johan

    2013-07-11

    Rhinovirus (genus enterovirus) infections are responsible for many of the severe exacerbations of asthma and chronic obstructive pulmonary disease. Other members of the genus can cause life-threatening acute neurological infections. There is currently no antiviral drug approved for the treatment of such infections. We have identified a series of potent, broad-spectrum antiviral compounds that inhibit the replication of the human rhinovirus, Coxsackie virus, poliovirus, and enterovirus-71. The mechanism of action of the compounds has been established as inhibition of a lipid kinase, PI4KIII?. Inhibition of hepatitis C replication in a replicon assay correlated with enterovirus inhibition. PMID:24900715

  3. High-Throughput Screening of a Collection of Known Pharmacologically Active Small Compounds for Identification of Candida albicans Biofilm Inhibitors

    PubMed Central

    Siles, Samuel A.; Srinivasan, Anand; Pierce, Christopher G.

    2013-01-01

    Candida albicans is the most common etiologic agent of systemic fungal infections with unacceptably high mortality rates. The existing arsenal of antifungal drugs is very limited and is particularly ineffective against C. albicans biofilms. To address the unmet need for novel antifungals, particularly those active against biofilms, we have screened a small molecule library consisting of 1,200 off-patent drugs already approved by the Food and Drug Administration (FDA), the Prestwick Chemical Library, to identify inhibitors of C. albicans biofilm formation. According to their pharmacological applications that are currently known, we classified these bioactive compounds as antifungal drugs, as antimicrobials/antiseptics, or as miscellaneous drugs, which we considered to be drugs with no previously characterized antifungal activity. Using a 96-well microtiter plate-based high-content screening assay, we identified 38 pharmacologically active agents that inhibit C. albicans biofilm formation. These drugs were subsequently tested for their potency and efficacy against preformed biofilms, and we identified three drugs with novel antifungal activity. Thus, repurposing FDA-approved drugs opens up a valuable new avenue for identification and potentially rapid development of antifungal agents, which are urgently needed. PMID:23689719

  4. Analysis of Phenolic Compounds and Antioxidant Activity in Wild Blackberry Fruits.

    PubMed

    Oszmia?ski, Jan; Nowicka, Paulina; Teleszko, Miros?awa; Wojdy?o, Aneta; Cebulak, Tomasz; Oklejewicz, Krzysztof

    2015-01-01

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

  5. Removal characteristics of trace compounds of landfill gas by activated carbon adsorption.

    PubMed

    Shin, Ho-Chul; Park, Jin-Won; Park, Kwinam; Song, Ho-Cheol

    2002-01-01

    The removal characteristics of trace compounds and moisture in raw landfill gas (LFG) were studied. The LFG from the extraction well was saturated with water and moisture was eliminated by physical methods including cyclone-type dehydrator and compressor. The moisture removal efficiency of dehydrator and compressor was above 80%. As the moisture contents of LFG decreased, the toxic compounds like aromatics and chlorinated compounds were effectively removed by using the granular activated carbon. The breakthrough time and adsorption capacity of benzene, toluene, and ethyl benzene decreased rapidly when the relative humidity is over 60%. The effect of moisture was more pronounced at lower adsorbate concentrations tested than at higher concentrations. The breakthrough curves for multi-component mixtures show displacement effects. In the course of competing adsorption, adsorbates with strong interaction force to displace weakly bounded substances. Adsorption by activated carbon is in descending order of xylene, ethylbenzene, toluene, tri or tetrachloroethylene, benzene, carbon tetrachloride and chloroform in LFG, respectively. PMID:12152829

  6. Overall migration and kinetics of release of antioxidant compounds from citrus extract-based active packaging.

    PubMed

    Contini, Claudia; Valzacchi, Sandro; O'Sullivan, Michael; Simoneau, Catherine; Dowling, Denis P; Monahan, Frank J

    2013-12-11

    Overall migration (OM) tests were conducted on an antioxidant active packaging prepared by coating plasma pretreated and untreated polyethylene terepthalate (PET) trays with a citrus extract. The release of antioxidant compounds into food simulants was measured to permit their subtraction from OM values in line with active packaging legislation. The results demonstrated the compliance of the packaging with the limit for OM for plastic material in contact with food. The validity of the procedure for OM in aqueous food simulants was questioned, with the loss of volatile compounds during evaporation of the simulant resulting in an underestimation of total compounds released. The study showed a total release of 75% of the citrus extract coating into water and 25% into oil, which decreased to 45 and 12.5%, respectively, following plasma pretreatment of the trays. PMID:24274366

  7. Synthesis and “in Vitro” Trypanocidal Activity Evaluation of Some Organo-iron Compounds.

    PubMed Central

    Neto, Alberto F.; Cardoso, Silvia A.; Albuquerque, Sérgio; Miller, Joseph

    2002-01-01

    Eight organo-iron ferrocene derivatives and arenocenium salts were prepared and evaluated by “in vitro” assay against one strain of Trypanosoma cruzi (Y). Six of the eight organo-iron compounds assayed, piperazinium diferrocenoate 1, ?6-(o-xylene)-?5-(cyclopentadienyl) Iron(II) hexafluorophosphate 3, ?6-(mesitylene)-?5-(cyclopentadienyl) iron(II) hexafluorphosphate 5, ?6-(durene)-?5-(cyclopentadienyl) iron(II) hexafluorphosphate 6, ?6-(?-chlorotoluene)-?5-(cyclopentadienyl) Iron(II) hexafluorphosphate 7 and ?6-(chlorobenzene)-?5-(cyclopentadienyl) iron(II) picrate 8 , were poorly active in the “in vitro” assays. Only two compounds 1,1'–(N-pyperidinocarbonyl) ferrocene 2(IC50=2.4 ?g/mL) and ?6-(o-xylene)-?5(cyclopentadienyl) iron(II) picrate 4 (IC50=12.08 ?g/mL), were more active. Thus, some of the compounds are promising to be used against Chagas' disease as a prophylactic agents. PMID:18476014

  8. Inhibitory effects of compounds from Zingiberaceae species on platelet activating factor receptor binding.

    PubMed

    Jantan, Ibrahim; Pisar, Mazura; Sirat, Hasnah Mohd; Basar, Norazah; Jamil, Shajarahtunnur; Ali, Rasadah Mat; Jalil, Juriyati

    2004-12-01

    Ten compounds isolated from Alpinia mutica Roxb., Curcuma xanthorrhiza Roxb. and Kaempferia rotunda Linn. (Family: Zingiberaceae) were investigated for their platelet-activating factor (PAF) antagonistic activities on rabbit platelets using 3H-PAF as a ligand. Among them, four compounds showed significant inhibitory effects. Alpinetin and 5,6-dehydrokawain isolated from A. mutica exhibited IC50 values of 41.6 and 59.3 microM, respectively. The IC50 values of 3-deacetylcrotepoxide and 2-hydroxy-4,4',6'-trimethoxychalcone from K. rotunda were 45.6 and 57.4 microM, respectively. 1-Methoxy-2-methyl-5-(1',5'-dimethylhex-4'-enyl)-benzene, synthesized by methylation of xanthorrhizol which was obtained from C. xanthorrhiza, showed an IC50 value of 40.9 microM. The results indicated that these compounds were relatively strong PAF receptor binding inhibitors. PMID:15742349

  9. Mechanistic computational model of ovarian steroidogenesis to predict biochemical responses to endocrine active compounds.

    PubMed

    Breen, Michael S; Villeneuve, Daniel L; Breen, Miyuki; Ankley, Gerald T; Conolly, Rory B

    2007-06-01

    Sex steroids, which have an important role in a wide range of physiological and pathological processes, are synthesized primarily in the gonads and adrenal glands through a series of enzyme-mediated reactions. The activity of steroidogenic enzymes can be altered by a variety of endocrine active compounds (EAC), some of which are therapeutics and others that are environmental contaminants. A steady-state computational model of the intraovarian metabolic network was developed to predict the synthesis and secretion of testosterone (T) and estradiol (E2), and their responses to EAC. Model predictions were compared to data from an in vitro steroidogenesis assay with ovary explants from a small fish model, the fathead minnow. Model parameters were estimated using an iterative optimization algorithm. Model-predicted concentrations of T and E2 closely correspond to the time-course data from baseline (control) experiments, and dose-response data from experiments with the EAC, fadrozole (FAD). A sensitivity analysis of the model parameters identified specific transport and metabolic processes that most influence the concentrations of T and E2, which included uptake of cholesterol into the ovary, secretion of androstenedione (AD) from the ovary, and conversions of AD to T, and AD to estrone (E1). The sensitivity analysis also indicated the E1 pathway as the preferred pathway for E2 synthesis, as compared to the T pathway. Our study demonstrates the feasibility of using the steroidogenesis model to predict T and E2 concentrations, in vitro, while reducing model complexity with a steady-state assumption. This capability could be useful for pharmaceutical development and environmental health assessments with EAC. PMID:17436109

  10. In silico approach to screen compounds active against parasitic nematodes of major socio-economic importance

    PubMed Central

    2011-01-01

    Background Infections due to parasitic nematodes are common causes of morbidity and fatality around the world especially in developing nations. At present however, there are only three major classes of drugs for treating human nematode infections. Additionally the scientific knowledge on the mechanism of action and the reason for the resistance to these drugs is poorly understood. Commercial incentives to design drugs that are endemic to developing countries are limited therefore, virtual screening in academic settings can play a vital role is discovering novel drugs useful against neglected diseases. In this study we propose to build robust machine learning model to classify and screen compounds active against parasitic nematodes. Results A set of compounds active against parasitic nematodes were collated from various literature sources including PubChem while the inactive set was derived from DrugBank database. The support vector machine (SVM) algorithm was used for model development, and stratified ten-fold cross validation was used to evaluate the performance of each classifier. The best results were obtained using the radial basis function kernel. The SVM method achieved an accuracy of 81.79% on an independent test set. Using the model developed above, we were able to indentify novel compounds with potential anthelmintic activity. Conclusion In this study, we successfully present the SVM approach for predicting compounds active against parasitic nematodes which suggests the effectiveness of computational approaches for antiparasitic drug discovery. Although, the accuracy obtained is lower than the previously reported in a similar study but we believe that our model is more robust because we intentionally employed stringent criteria to select inactive dataset thus making it difficult for the model to classify compounds. The method presents an alternative approach to the existing traditional methods and may be useful for predicting hitherto novel anthelmintic compounds. PMID:22373185

  11. Genotoxicity and subchronic toxicity evaluation of Active Hexose Correlated Compound (AHCC)

    Microsoft Academic Search

    H. Fujii; N. Nishioka; R. R. Simon; R. Kaur; B. Lynch; A. Roberts

    2011-01-01

    Active Hexose Correlated Compound (AHCC), a mushroom extract rich in ?-1,4 linked glucans, is associated with immunostimulatory effects. AHCC is used in Japan as a dietary supplement to boost immune function and it also is purported to improve the symptoms of cancer and liver disease patients. A series of toxicological studies were conducted on a freeze dried preparation of AHCC

  12. 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...

  13. Adsorption of phenolic compounds by activated carbon—a critical review

    Microsoft Academic Search

    A. D?browski; P. Podko?cielny; Z. Hubicki; M. Barczak

    2005-01-01

    Adsorption of phenol and its derivatives on activated carbons is considered based on numerous papers related to this issue. Special attention is paid to the effects of carbon surface functionalities, pH of solution and heterogeneity effects that accompany adsorption of phenolic compounds. Moreover, in this paper the most important aspects are overviewed referring to irreversible adsorption of phenols and impact

  14. Efficiency of sewage sludge treatment technologies to eliminating endocrine active compounds

    Microsoft Academic Search

    M. Gehring; D. Vogel; L. Tennhardt; D. Weltin; B. Bilitewski

    Hormonal disturbances caused by environmental pollutants have become one of the most important issues regarding environmental and human health. In order to investigate the efficiency of sewage sludge treatment technologies to eliminating endocrine active compounds (EACs) samplings have been carried out at 13 municipal sewage treatment plants (STPs) and one co-fermentation facility in Germany. Laboratory experiments have been conducted simulating

  15. DETECTION OF ROOT-ASSOCIATED MICROBES THAT PRODUCE COMPOUNDS ACTIVE AGAINST PLANT-PARASITIC NEMATODES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rhizosphere-inhabiting bacteria and fungi isolated from soil and plant roots, and known to be active against plant-pathogenic fungi, were assayed in vitro for production of compounds antagonistic to root-knot nematode (Meloidogyne incognita). In addition, culture filtrates of fungi isolated from eg...

  16. Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer

    Microsoft Academic Search

    Yizhong Cai; Qiong Luo; Mei Sun; Harold Corke

    2004-01-01

    Cancer prevention and treatment using traditional Chinese medicines have attracted increasing interest. This study characterizes antioxidant activity and phenolic compounds of traditional Chinese medicinal plants associated with anticancer, comprising 112 species from 50 plant families. The improved ABTS•+ method was used to systematically assess the total antioxidant capacity (Trolox equivalent antioxidant capacity, TEAC) of the medicinal extracts. The TEAC values

  17. Structure Property Relationships for Dirhodium Antitumor Active Compounds: Reactions with Biomolecules and In Cellulo Studies

    E-print Network

    Aguirre-Flores, Jessica Dafhne

    2011-02-22

    Schematic representation of inorganic complexes that exhibit anticancer activity ................................................. 16 I-10 Scheme that depicts the proposed mechanism of cisplatin action... .......................................................................................... 19 I-11 Adducts formed after binding of cisplatin to DNA ................... 20 I-12 Schematic representation of dirhodium tetracarboxylate (Top). Bridging ligands of compounds studied as anticancer agents (Bottom...

  18. 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...

  19. 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…

  20. The dynamic adsorption behaviour of volatile organic compounds on activated carbon honeycomb monoliths

    Microsoft Academic Search

    M. Yates; J. Blanco; M. A. Martín-Luengo

    2002-01-01

    Adsorption offers an efficient technology for removing volatile organic compounds (VOCs) from air pollution sources. Often activated carbons (ACs) are employed owing to their large specific surface areas, high micropore volumes, rapid adsorption capabilities and selectivity towards organic molecules compared to water vapour or air. However, when large volumes of gas have to be treated pressure drop limitations may arise

  1. Effect of harvesting time on phenolic compounds and antiradical scavenging activity of Borago officinalis seed extracts

    Microsoft Academic Search

    B. Mhamdi; W. Aidi Wannes; J. Sriti; I. Jellali; R. Ksouri; B. Marzouk

    2010-01-01

    Borage seeds (Borago officinalis L.) were sampled in Amdoun region (North of Tunisia) during their ripening stage in order to analyse their phenolic compounds and to ascertain their antiradical scavenging activity. The harvesting time effect on some physical properties of borage seed was significant. The increase of dry weight (from 10 to 90%) during ripeness was correlated negatively with that

  2. A Novel Method for the Determination of Gross Transuranic Activity in Uranium Compounds

    SciTech Connect

    Mann, D.K.; Tucker, M.C.

    1998-11-16

    A Method is described to determine gross transuranic activity present in Uranium compounds and HP smears. From one count and one spectrum, three or more isotopes can be quantified. The method involves a simple digestion prep, sample extraction and precipitation. Results are obtained quickly with a very small expenditure on the part of the analytical lab.

  3. Determining the chemical activity of hydrophobic organic compounds in soil using polymer coated vials

    Microsoft Academic Search

    Fredrik Reichenberg; Foppe Smedes; Jan-Åke Jönsson; Philipp Mayer

    2008-01-01

    BACKGROUND: In soils contaminated by hydrophobic organic compounds, the concentrations are less indicative of potential exposure and distribution than are the associated chemical activities, fugacities and freely dissolved concentrations. The latter can be measured by diffusive sampling into thin layers of polymer, as in, for example, solid phase micro-extraction. Such measurements require equilibrium partitioning of analytes into the polymer while

  4. 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...

  5. New Generation of Chromatographic Packings and Columns for Determination of Biologically Active Compounds

    Microsoft Academic Search

    Bogus?aw Buszewski; Sylwia Kowalska; Katarzyna Krupczy?ska

    2005-01-01

    Analysis of biologically active substances is particularly important in the pharmaceutical and biomedical area. For separation of polar compounds or complex mixtures by normal (NP) or reversed phase liquid chromatography (RP-HPLC) and\\/or electromigration techniques, it is necessary to apply a new generation of packings and columns with strictly defined properties. It is connected to the definition of chromatographic behavior and

  6. Active hexose correlated compound enhances tumor surveillance through regulating both innate and adaptive immune responses

    Microsoft Academic Search

    Yunfei Gao; Dongqing Zhang; Buxiang Sun; Hajime Fujii; Ken-Ichi Kosuna; Zhinan Yin

    2006-01-01

    Active hexose correlated compound (AHCC) is a mixture of polysaccharides, amino acids, lipids and minerals derived from cocultured mycelia of several species of Basidiomycete mushrooms. AHCC has been implicated to modulate immune functions and plays a protective role against infection. However, the potential role of AHCC in tumor immune surveillance is unknown. In this study, C57BL\\/6 mice were orally administered

  7. Differential Effects of Procaspase-3 Activating Compounds in the Induction of Cancer Cell Death

    E-print Network

    Hergenrother, Paul J.

    Differential Effects of Procaspase-3 Activating Compounds in the Induction of Cancer Cell Death ions in vitro, induce apoptotic death of cancer cells in culture, and reduce tumor burden in vivo. Ip with spontaneously occurring lymphoma. Here we show that PAC-1 and S-PAC-1 have similar mechanisms of cell death

  8. Pharmacology of nootropics and metabolically active compounds in relation to their use in dementia

    Microsoft Academic Search

    C. D. Nicholson

    1990-01-01

    The development of effective drugs for the treatment of dementia is an important therapeutic target. Drugs which stop the progression of dementia have not been developed; however, nootropics and metabolically active compounds such as the vinca alkaloids and the ergot alkaloids as well as alkylxanthines are widely used to alleviate the symptoms. This review summarises animal studies investigating the mechanism

  9. Efficiency of Biological Activator Formulated Material (BAFM) for volatile organic compounds removal – preliminary batch culture tests with activated sludge

    Microsoft Academic Search

    Charline Corre; Catherine Couriol; Abdeltif Amrane; Eric Dumont; Yves Andrès; Pierre Le Cloirec

    2012-01-01

    During biological degradation, such as biofiltration of air loaded with volatile organic compounds, the pollutant is passed through a bed packed with a solid medium acting as a biofilm support. To improve microorganism nutritional equilibrium and hence to enhance the purification capacities, a Biological Activator Formulated Material (BAFM) was developed, which is a mixture of solid nutrients dissolving slowly in

  10. Active hexose correlated compound activates immune function to decrease bacterial load in a murine model of intramuscular infection

    Microsoft Academic Search

    Hernan Aviles; Phyllis O’Donnell; Julia Orshal; Hajime Fujii; Buxiang Sun; Gerald Sonnenfeld

    2008-01-01

    BackgroundInfection is a serious, costly, and common complication of surgery and constitutes the principal cause of late death in patients undergoing surgery. The objective of this study was to clarify the mechanisms by which active hexose correlated compound (AHCC) increases survival in a murine model of intramuscular infection.

  11. 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. PMID:25393824

  12. Impact of surface properties of activated carbons on oxidative coupling of phenolic compounds

    Microsoft Academic Search

    R. D. Vidic; C. H. Tessmer; L. J. Uranowski

    1997-01-01

    Previous studies showed that activated carbons exhibit significantly different behavior for the removal of phenolic compounds in the presence and absence of molecular oxygen. Increase in capacity under oxic conditions (presence of oxygen) as high as 2.5 fold was observed for 2-methylphenol adsorption on a bituminous coal-based activated carbon. The present study was initiated to evaluate some of the possible

  13. Non-volatile taste active compounds in the meat of Chinese mitten crab ( Eriocheir sinensis)

    Microsoft Academic Search

    De-Wei Chen; Min Zhang

    2007-01-01

    The non-volatile taste active compounds, including soluble sugars, succinic acid, free amino acids and flavour 5?-nucleotides in the meat of Chinese mitten crab (Eriocheir sinensis) were analyzed, and their taste impacts were evaluated by taste active values (TAVs) and equivalent umami concentration (EUC) methods. The total free amino acid content of crab meat was 20.9mg\\/g. Arginine, glycine and alanine were

  14. Roseroot ( Rhodiola rosea L.): Effect of Internal and External Factors on Accumulation of Biologically Active Compounds

    Microsoft Academic Search

    Z. W?glarz; J. L. Przyby?; A. Geszprych

    Roseroot (Rhodiola rosea L.) is a perennial that grows wild in the mountains of Siberia, Central Europe and North America. Its underground organs\\u000a (rhizomes with roots) are used as a medicinal raw material; the plant is considered to be one of the most active adaptogens.\\u000a The most important biologically active constituents of the raw material are phenolic compounds, including tyrosol

  15. Antioxidant activity, browning and volatile Maillard compounds in Pedro Ximénez sweet wines under accelerated oxidative aging

    Microsoft Academic Search

    N. López de Lerma; J. Peinado; J. Moreno; R. A. Peinado

    2010-01-01

    Pedro Ximénez wine, aged by thermal treatment during 10, 20 and 30 days in the presence or absence of oak chips, was studied in terms of antioxidant activity, browning and volatile Maillard compounds. The phenolic fractions obtained by the SepPack tC-18 column revealed that the antioxidant activity after 10 days of thermal treatment was due to the presence of phenols

  16. Organocatalytic enantioselective tandem aldol-cyclization reaction of ?-isothiocyanato imides and activated carbonyl compounds

    PubMed Central

    Guang, Jie; Zhao, Cong-Gui

    2011-01-01

    The organocatalytic enantioselective tandem aldol-cyclization reactions of ?-isothiocyanato imides and activated carbonyl compounds, such as isatins, an ?-ketolactone and a 1,2-dione, have been studied with cinchona alkaloid-derived thiourea-catalysts. This methodology provided an easy way to access enantiomerically enriched spirobicyclic thiocarbamates with high yields and good to excellent stereoselectivity, which have been demonstrated to be useful precursors for the synthesis of biologically active molecules. PMID:21921975

  17. Importance of a pyrogallol-type structure in catechin compounds for apoptosis-inducing activity

    Microsoft Academic Search

    Kouichi Saeki; Sumio Hayakawa; Mamoru Isemura; Toshio Miyase

    2000-01-01

    Several catechin compounds were examined for their ability to induce apoptosis in human hystiocytic lymphoma U937 cells. Catechins with a pyrogallol-type structure in a B-ring induced apoptosis and a 3-O-gallate group in cis-relationship to the B ring enhanced the activity. Catechins without a pyrogallol-type structure in a molecule lacked activity. These data suggest the important role of the 5?(3?)-hydroxyl group

  18. Human myeloperoxidase activity is inhibited in vitro by quercetin. Comparison with three related compounds

    Microsoft Academic Search

    J. Pincemail; C. Deby; A. Thirion; M. de Bruyn-Dister; R. Goutier

    1988-01-01

    Summary Quercetin is an effective inhibitor of human myeloperoxidase (MPO) activity, both with purified enzyme (IC50=3.5 ?M) and in a system using stimulated human neutrophils. Quercetin is significantly more potent than three other related compounds (rutin, rutin sulfate and troxerutin) and than methimazole, a previously-known myeloperoxidase inhibitor. The inhibitory activity of quercetin is of the competitive type. Moreover, quercetin is

  19. Evaluation of Crocus sativus L. stigma phenolic and flavonoid compounds and its antioxidant activity.

    PubMed

    Karimi, Ehsan; Oskoueian, Ehsan; Hendra, Rudi; Jaafar, Hawa Z E

    2010-09-01

    Saffron (Crocus sativus L.) belongs to the Iridaceae family. The stigma of saffron has been widely used as spice, medicinal plant, and food additive in the Mediterranean and Subtropical countries. Recently, attention has been paid to the identification of new sources of safe natural antioxidants for the food industry. The antioxidant activities of spices are mainly attributed to their phenolic and flavonoid compounds. Saffron is one of the spices believed to possess antioxidant properties, but information on its antioxidant activity and phenolic, flavonoids compound are rather limited, therefore this research was carried out to evaluate the antioxidant activity of saffron stigmas extracted with different solvents. The phenolic and flavonoid compounds of saffron were also examined using reversed phase (RP)-HPLC. Results showed that saffron stigma possess antioxidant activity. The free radical scavenging and ferric reducing power activities were higher for the methanolic extract of saffron stigma at a concentration of 300 ?g/mL, with values of 68.2% and 78.9%, respectively, as compared to the corresponding boiling water and ethanolic extracts, but the activities were lower than those of antioxidant standards such as BHT and ?-tocopherol. The obtained total phenolics value for methanolic saffron extract was 6.54 ± 0.02 mg gallic acid equivalent (GAE)/g dry weight (DW), and for total flavonoids, 5.88 ± 0.12 mg rutin equivalent/g DW, which were also higher than values obtained from the ethanolic and boiling water extracts. In addition, the RP-HPLC analyses indicated the presence of gallic acid and pyrogallol as two bioactive compounds. In summary, saffron stigmas showed antioxidant activity and methanol appeared to be the best solvent to extract the active components, among which the presence of gallic acid and pyrogallol might contribute towards the stigma's antioxidant properties. Hence, saffron stigma could be applied as a natural antioxidant source for industrial purposes. PMID:20877220

  20. Effects of various poisoning compounds on the activity and stereospecificity of heterogeneous Ziegler-Natta catalyst

    NASA Astrophysics Data System (ADS)

    Tangjituabun, Kitti; Kim, Sang Yull; Hiraoka, Yuichi; Taniike, Toshiaki; Terano, Minoru; Jongsomjit, Bunjerd; Praserthdam, Piyasan

    2008-04-01

    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.

  1. 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

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

    PubMed Central

    2011-01-01

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

  3. CYTOKININS: SYNTHESIS, MASS SPECTRA, AND BIOLOGICAL ACTIVITY OF COMPOUNDS RELATED TO ZEATIN*

    PubMed Central

    Leonard, Nelson J.; Hecht, Sidney M.; Skoog, Folke; Schmitz, Ruth Y.

    1969-01-01

    Compounds related to dihydrozeatin that define the influence of the location of the hydroxyl group along the side chain have been synthesized and tested for cytokinin activity. The compounds compared are in the series: 6-(X-hydroxy-3-methylbutylamino)purines and their ribosides, where X = 2, 3, and 4. Hydroxy substitution on the 4-position of the side chain enhances, but in the 2-, 3-, or 2- and 3- positions, decreases cytokinin activity as compared with the unsubstituted isopentyl (or isopentenyl) chains. This differential influence of the position of the hydroxyl group in the N6-chain holds also for the similarly related 9-?-D-ribofuranosides. The relatively higher activity of 3,4-dihydroxy as compared with 2,3-dihydroxy derivatives is consistent with this position effect. Compounds related to zeatin possessing side-chain ester moieties have also been synthesized and tested comparatively. Among these, 6-(4-acetoxy-3-methyl-trans-2-butenylamino)purine is at least as active as zeatin, the most active presently known cytokinin in the tobacco bioassay, whereas the analog, methyl 2-methyl-4-(purin-6-ylamino)-trans-crotonate, with the ester function effectively reversed, has vastly lower activity, and its riboside is practically inactive. PMID:16591745

  4. Xanthine Oxidase Inhibitor Activity of Terpenoid and Pyrrole Compounds Isolated from Snake Fruit (Salacca edulis Reinw.) cv. Bongkok

    NASA Astrophysics Data System (ADS)

    Herliani Afrianti Priyatno, Leni; Yulinah Sukandar, Elin; Ibrahim, Slamet; Ketut Adnyana, I.

    The compound of 3β-hydroxy-sitosterol (1) and 2-metylester-1-H-pyrrole-4-carboxilyc acid were isolated from ethyl acetate extract of snake fruit (Salacca edulis Reinw) cv. Bongkok, (2). Inhibition of xanthine oxidase by the two compounds were evaluated against enzyme of xanthine oxidase. Compound 1 could be regarded as inactive, while compound 2 was found to be active with IC50 value of 48.86 μg mL-1.

  5. Correlation of the genotoxic activation and kinetic properties of Salmonella enterica serovar Typhimurium nitroreductases SnrA and cnr with the redox potentials of nitroaromatic compounds and quinones.

    PubMed

    Salamanca-Pinzón, S G; Camacho-Carranza, R; Hernández-Ojeda, S L; Frontana-Uribe, B A; Espitia-Pinzón, C I; Espinosa-Aguirre, J J

    2010-05-01

    Bacterial nitroreductases (NRs) catalyse the oxygen-insensitive reduction of several nitro-substituted compounds and quinones. SnrA and cnr NRs have been previously identified in Salmonella enterica serovar Typhimurium; they reduce several environmental nitro compounds that display mutagenic activity in the Ames test. Although some of their biochemical properties have been reported, the substrate specificity of each protein over mutagenic nitro compounds is unknown; even more, the possible relationship between their capacity to activate nitro compounds into mutagens and the redox properties of putative substrates has been poorly investigated. We have purified SnrA and cnr and investigated their capacity to activate several mutagens in the Ames test as well as their kinetic parameters K(m) and V(max). Our results show that SnrA and cnr are able to activate 2,7-dinitrofluorene with the same efficiency and a similar mutagenic potency in the YG7132 tester strain; 1-nitropyrene and 1,3-dinitropyrene were efficiently activated by cnr, whereas 1,8-dinitropyrene, 1,6-dinitropyrene and 2-nitrofluorene were scarcely activated by either NR. The mutagenic potency of nitro compounds obtained in the presence of either enzyme correlates with their redox potential reported in the literature. On the other hand, a good correlation was obtained between the catalytic efficiency (V(max)/K(m)) of the purified cnr with the redox potential of eight molecules including nitro-substituted compounds and quinones. No correlation between redox potential and catalytic efficiency by SnrA was observed, suggesting that factors other than redox potential such as the structure of the compounds are involved in the catalytic efficiency of SnrA. PMID:20118186

  6. Biological activity of Pinus nigra terpenes--evaluation of FtsZ inhibition by selected compounds as contribution to their antimicrobial activity.

    PubMed

    Sarac, Zorica; Mateji?, Jelena S; Stojanovi?-Radi?, Zorica Z; Veselinovi?, Jovana B; Džami?, Ana M; Bojovi?, 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. PMID:25217763

  7. Assessment of flavonoids and volatile compounds in tea infusions of water lily flowers and their antioxidant activities.

    PubMed

    Yin, Dan-Dan; Yuan, Ru-Yu; Wu, Qian; Li, Shan-Shan; Shao, Shuai; Xu, Yan-Jun; Hao, Xiang-Hong; Wang, Liang-Sheng

    2015-11-15

    Water lily, a member of the Nymphaeaceae family, can be made into tea on the basis of outstanding fragrance characteristics and health care functions. In this study, 16 flavonoids were identified and quantified in tea infusions prepared from the petals of 33 water lily cultivars using HPLC-DAD and HPLC-ESI-MS/MS. The infusions were analyzed with HS-SPME coupled with GC-MS; 29 volatile compounds were detected, of which nine were found to be scent components. The cultivars were clustered into three clusters characterized according to scent components. The 'Conqueror' and 'Virginia' cultivars had the highest antioxidant activities. The concentrations of polyphenols and flavonoids showed significant positive correlations with antioxidant activity as measured by DPPH, ABTS(+), and FRAP assays. This study is valuable for a fuller understanding of this important tea and can also be used for the development of water lily. PMID:25976993

  8. The isolation and identification of two compounds with predominant radical scavenging activity in hempseed (seed of Cannabis sativa L.).

    PubMed

    Chen, Tianpeng; He, Jinfeng; Zhang, Jianchun; Li, Xiaohui; Zhang, Hua; Hao, Jianxiong; Li, Lite

    2012-09-15

    Forty samples were extracted from defatted kernels and hulls of two varieties of hempseed (Bama and Yunma No. 1) using 10 different polar solvent systems. The radical scavenging capacity of the extracts was evaluated using 2,2-diphenyl-1-pikrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays and the total phenolic content was determined by Folin-Ciocalteu's phenol reagent. The correlation analysis indicated that the antioxidants in hempseed belonged to phenolic and DPPH() assay was suitable for evaluating the radical scavenging activity. Two compounds, with predominant antiradical activity, were isolated in 60% ethanol extract of hempseed hull using macroporous resin absorption, LH-20 gel chromatography, and high performance liquid chromatography methods, which were identified as N-trans-caffeoyltyramine and cannabisin B by high-resolution mass spectra, nuclear magnetic resonance spectra, and ultraviolet data. The two compounds exhibited significant high DPPH() scavenging activity and protective effect against in vitro oxidation of human low-density lipoprotein compared with extracts from flaxseed, grape seed, and soybean. This suggests that hempseed hull extract is a potential source of natural antioxidants, which could be added to dietary supplements to help prevent oxidative stress. PMID:23107724

  9. Concentration of biologically active compounds extracted from Ilex paraguariensis St. Hil. by nanofiltration.

    PubMed

    Murakami, Aureanna Nairne Negrão; Amboni, Renata Dias de Mello Castanho; Prudêncio, Elane Schwinden; Amante, Edna Regina; Fritzen-Freire, Carlise Beddin; Boaventura, Brunna Cristina Bremer; Muñoz, Isabella de Bona; Branco, Catia Dos Santos; Salvador, Miriam; Maraschin, Marcelo

    2013-11-01

    The aim of this study was to characterise the bioactive compounds in mate (Ilex paraguariensis St. Hil) extract and in concentrated mate extract obtained by nanofiltration (NF). Also, the impact of NF on the antioxidant activity of both mate extracts was evaluated in vitro and using eukaryotic cells of Saccharomyces cerevisiae (yeast assay). The results showed a significant increase in the contents of total phenolics (338%), chlorogenic acid (483%), theobromine (323%), caffeine (251%), chlorophyll (321%), condensed tannins (278%) and saponins (211%) in the concentrated mate extract. The concentrated mate extract showed higher in vitro antioxidant activity than the mate extract. According to the results obtained, it can be stated that the use of nanofiltration membrane is a valid approach for the concentration of biologically active compounds in aqueous extract of mate. PMID:23768327

  10. Development of models for prediction of the antioxidant activity of derivatives of natural compounds.

    PubMed

    Martin?i?, Rok; Kuzmanovski, Igor; Wagner, Alain; Novi?, Marjana

    2015-04-01

    Antioxidants are important for maintaining the appropriate balance between oxidizing and reducing species in the body and thus preventing oxidative stress. Many natural compounds are being screened for their possible antioxidant activity. It was found that a mushroom pigment Norbadione A, which is a pulvinic acid derivative, shows an antioxidant activity; the same was found for other pulvinic acid derivatives and structurally related coumarines. Based on the results of in vitro studies performed on these compounds as a part of this study quantitative structure-activity relationship (QSAR) predictive models were constructed using multiple linear regression, counter-propagation artificial neural networks and support vector regression (SVR). The models have been developed in accordance with current QSAR guidelines, including the assessment of the models applicability domains. A new approach for the graphical evaluation of the applicability domain for SVR models is suggested. The developed models show sufficient predictive abilities for the screening of virtual libraries for new potential antioxidants. PMID:25813231

  11. Synthesis and antioxidant activities of some new triheterocyclic compounds containing benzimidazole, thiophene, and 1,2,4-triazole rings.

    PubMed

    Mente?e, Emre; Y?lmaz, Fatih; Balta?, Nimet; Bekircan, Olcay; Kahveci, Bahittin

    2014-09-01

    Abstract 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. PMID:25198894

  12. Acaricidal activity of constituents identified in Foeniculum vulgare fruit oil against Dermatophagoides spp. (Acari: Pyroglyphidae).

    PubMed

    Lee, Hoi-Seon

    2004-05-19

    Acaricidal activities of components derived from Foeniculum vulgare fruit oil against Dermatophagoides farinae and Dermatophagoides pteronyssinus were examined using direct contact application and compared with that of the commercial repellent benzyl benzoate. The major biologically active constituent of Foeniculum fruit oil was characterized as (+)-fenchone by spectroscopic analyses. On the basis of LD(50) values, the compound most toxic to D. farinae was p-anisaldehyde (11.3 mg/m(2)) followed by (+)-fenchone (38.9 mg/m(2)), (-)-fenchone (41.8 mg/m(2)), benzyl benzoate (89.2 mg/m(2)), thymol (90.3 mg/m(2)), and estragol (413.3 mg/m(2)). Against D. pteronyssinus, p-anisaldehyde (10.1 mg/m(2)) was much more effective than benzyl benzoate (67.5 mg/m(2)), thymol (68.5 mg/m(2)), and estragol (389.9 mg/m(2)). These results indicate that the acaricidal activity of F. vulgare fruit oil likely results from (+)-fenchone and p-anisaldehyde. (+)-Fenchone was 20.3 times more abundant in the oil than p-anisaldehyde. (+)-Fenchone and p-anisaldehyde merit further study as potential house dust mite control agents or as lead compounds. PMID:15137830

  13. Phenolic Compounds from the Leaves of Stewartia pseudocamellia Maxim. and their Whitening Activities

    PubMed Central

    Roh, Hyun Jung; Noh, Hye-Ji; Na, Chun Su; Kim, Chung Sub; Kim, Ki Hyun; Hong, Cheol Yi; Lee, Kang Ro

    2015-01-01

    The half-dried leaves of Stewartia. pseudocamellia were extracted with hot water (SPE) and partitioned with n-hexane (SPEH), dichloromethane (SPED), and ethyl acetate (SPEE) successively. SPE and SPEE showed significant inhibitory effects against melanogenesis and tyrosinase activities. By bioassay-guided isolation, ten phenolic compounds were isolated by column chromatography from SPEE. The whitening effect of the isolated compounds from SPEE were tested for the inhibitory activities against melanogenesis using B16 melanoma cells, in vitro inhibition of tyrosinase, and L-3,4-dihydorxy-indole-2-carboxylic acid (L-DOPA) auto-oxidation assay. A cytotoxic activity assay was done to examine the cellular toxicity in Raw 264.7 macrophage cells. Of the compounds isolated, gallic acid and quercetin revealed significant inhibitory activities against melanogenesis compared to arbutin. In particular, quercetin exhibited similar inhibitory activities against tyrosinase and L-DOPA oxidation without cytotoxicity. These results suggested that SPE could be used as a potential source of natural skin-whitening material in cosmetics as well as in food products. PMID:25995828

  14. Phenolic Compounds from the Leaves of Stewartia pseudocamellia Maxim. and their Whitening Activities.

    PubMed

    Roh, Hyun Jung; Noh, Hye-Ji; Na, Chun Su; Kim, Chung Sub; Kim, Ki Hyun; Hong, Cheol Yi; Lee, Kang Ro

    2015-05-01

    The half-dried leaves of Stewartia. pseudocamellia were extracted with hot water (SPE) and partitioned with n-hexane (SPEH), dichloromethane (SPED), and ethyl acetate (SPEE) successively. SPE and SPEE showed significant inhibitory effects against melanogenesis and tyrosinase activities. By bioassay-guided isolation, ten phenolic compounds were isolated by column chromatography from SPEE. The whitening effect of the isolated compounds from SPEE were tested for the inhibitory activities against melanogenesis using B16 melanoma cells, in vitro inhibition of tyrosinase, and L-3,4-dihydorxy-indole-2-carboxylic acid (L-DOPA) auto-oxidation assay. A cytotoxic activity assay was done to examine the cellular toxicity in Raw 264.7 macrophage cells. Of the compounds isolated, gallic acid and quercetin revealed significant inhibitory activities against melanogenesis compared to arbutin. In particular, quercetin exhibited similar inhibitory activities against tyrosinase and L-DOPA oxidation without cytotoxicity. These results suggested that SPE could be used as a potential source of natural skin-whitening material in cosmetics as well as in food products. PMID:25995828

  15. Comparison of odor-active compounds from six distinctly different rice flavor types.

    PubMed

    Yang, Dong Sik; Shewfelt, Robert L; Lee, Kyu-Seong; Kays, Stanley J

    2008-04-23

    Using a dynamic headspace system with Tenax trap, GC-MS, GC-olfactometry (GC-O), and multivariate analysis, the aroma chemistry of six distinctly different rice flavor types (basmati, jasmine, two Korean japonica cultivars, black rice, and a nonaromatic rice) was analyzed. A total of 36 odorants from cooked samples were characterized by trained assessors. Twenty-five odorants had an intermediate or greater intensity (odor intensity >or= 3) and were considered to be major odor-active compounds. Their odor thresholds in air were determined using GC-O. 2-Acetyl-1-pyrroline (2-AP) had the lowest odor threshold (0.02 ng/L) followed by 11 aldehydes (ranging from 0.09 to 3.1 ng/L), guaiacol (1.5 ng/L), and 1-octen-3-ol (2.7 ng/L). On the basis of odor thresholds and odor activity values (OAVs), the importance of each major odor-active compound was assessed. OAVs for 2-AP, hexanal, ( E)-2-nonenal, octanal, heptanal, and nonanal comprised >97% of the relative proportion of OAVs from each rice flavor type, even though the relative proportion varied among samples. Thirteen odor-active compounds [2-AP, hexanal, ( E)-2-nonenal, octanal, heptanal, nonanal, 1-octen-3-ol, ( E)-2-octenal, ( E, E)-2,4-nonadienal, 2-heptanone, ( E, E)-2,4-decadienal, decanal, and guaiacol] among the six flavor types were the primary compounds explaining the differences in aroma. Multivariate analysis demonstrated that the individual rice flavor types could be separated and characterized using these compounds, which may be of potential use in rice-breeding programs focusing on flavor. PMID:18363355

  16. Molecular docking study on platelet-activating factor antagonistic activity of bioactive compounds isolated from Guttiferae and Ardisia species.

    PubMed

    Jasamai, Malina; Jalil, Juriyati; Jantan, Ibrahim

    2015-06-01

    A handful of bioactive compounds from plants have been reported to possess platelet-activating factor (PAF) antagonist activity. However, their mode of action is not well understood. Selected bioactive compounds that exhibit PAF antagonist activity and synthetic PAF antagonists were subjected to docking simulations using the MOE 2007.09 software package. The docking study of PAF antagonists was carried out on the PAF receptor (PAFR) protein which involves in various pathological responses mediated by PAF. The docking results revealed that amentoflavone (3) showed good interactions with the PAFR model where the flavone and phenolic moieties were mostly involved in these interactions. Knowledge on PAF antagonists' interactions with the PAFR model is a useful screening tool of potential PAF antagonists prior to performing PAF inhibitory assay. PMID:25332053

  17. Phenotypic assays identify azoramide as a small-molecule modulator of the unfolded protein response with antidiabetic activity.

    PubMed

    Fu, Suneng; Yalcin, Abdullah; Lee, Grace Y; Li, Ping; Fan, Jason; Arruda, Ana Paula; Pers, Benedicte M; Yilmaz, Mustafa; Eguchi, Kosei; Hotamisligil, Gökhan S

    2015-06-17

    The endoplasmic reticulum (ER) plays a critical role in protein, lipid, and glucose metabolism as well as cellular calcium signaling and homeostasis. Perturbation of ER function and chronic ER stress are associated with many pathologies ranging from diabetes and neurodegenerative diseases to cancer and inflammation. Although ER targeting shows therapeutic promise in preclinical models of obesity and other pathologies, the available chemical entities generally lack the specificity and other pharmacological properties required for effective clinical translation. To overcome these challenges and identify new potential therapeutic candidates, we first designed and chemically and genetically validated two high-throughput functional screening systems that independently measure the free chaperone content and protein-folding capacity of the ER. With these quantitative platforms, we characterized a small-molecule compound, azoramide, that improves ER protein-folding ability and activates ER chaperone capacity to protect cells against ER stress in multiple systems. This compound also exhibited potent antidiabetic efficacy in two independent mouse models of obesity by improving insulin sensitivity and pancreatic ? cell function. Together, these results demonstrate the utility of this functional, phenotypic assay platform for ER-targeted drug discovery and provide proof of principle for the notion that specific ER modulators can be potential drug candidates for type 2 diabetes. PMID:26084805

  18. A QSAR, pharmacokinetic and toxicological study of new artemisinin compounds with anticancer activity.

    PubMed

    Vieira, Josinete B; Braga, Francinaldo S; Lobato, Cleison C; Santos, César F; Costa, Josivan S; Bittencourt, José Adolfo H M; Brasil, Davi S B; Silva, Jocivânia O; Hage-Melim, Lorane I S; Macêdo, Williams Jorge C; Carvalho, José Carlos T; Santos, Cleydson Breno R

    2014-01-01

    The Density Functional Theory (DFT) method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with different degrees of cytotoxicity against the human hepatocellular carcinoma HepG2 line. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were employed to select the most important descriptors related to anticancer activity. The significant molecular descriptors related to the compounds with anticancer activity were the ALOGPS_log, Mor29m, IC5 and GAP energy. The Pearson correlation between activity and most important descriptors were used for the regression partial least squares (PLS) and principal component regression (PCR) models built. The regression PLS and PCR were very close, with variation between PLS and PCR of R(2) = ± 0.0106, R(2)(ajust) = ± 0.0125, s = ± 0.0234, F(4,11) = ± 12.7802, Q(2) = ± 0.0088, SEV = ± 0.0132, PRESS = ± 0.4808 and SPRESS = ± 0.0057. These models were used to predict the anticancer activity of eight new artemisinin compounds (test set) with unknown activity, and for these new compounds were predicted pharmacokinetic properties: human intestinal absorption (HIA), cellular permeability (PCaCO2), cell permeability Maden Darby Canine Kidney (PMDCK), skin permeability (P(Skin)), plasma protein binding (PPB) and penetration of the blood-brain barrier (C(Brain/Blood)), and toxicological: mutagenicity and carcinogenicity. The test set showed for two new artemisinin compounds satisfactory results for anticancer activity and pharmacokinetic and toxicological properties. Consequently, further studies need be done to evaluate the different proposals as well as their actions, toxicity, and potential use for treatment of cancers. PMID:25061720

  19. Stoichiometry and kinetic of the aerobic oxidation of phenolic compounds by activated sludge.

    PubMed

    Lobo, Cintia C; Bertola, Nora C; Contreras, Edgardo M

    2013-05-01

    The aerobic degradation of phenol (PH), catechol (CA), resorcinol (RE), pyrogallol (PY), and hydroquinone (HY) by phenol-acclimated activated sludge was investigated. A Haldane-type dependence of the respiration rate on PH, RE, and HY was observed; CA and PY exhibited a biphasic respiration pattern. According to the initial biodegradation rate, tested compounds were ordered as follows: CA>PH>PYRE>HY. Also, they exhibited the following degree of toxicity to their own degradation: PY>CARE>PH>HY. Oxidation coefficients for PH, PY, RE, and HY were constant as a function of the consecutive additions of the compound. Conversely, an increase of YO/S from 1 to 1.5 molO2 molCA(-1) was observed during repeated additions of CA. The role of some enzymes involved in the aerobic degradation pathways of the tested compounds is discussed and related to the obtained results. PMID:23562772

  20. 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. PMID:25976793

  1. Comparison of the activity of subsurface and surface microorganisms and their anaerobic transformation of heterocyclic compounds

    SciTech Connect

    Bollag, J.-M.

    1991-02-01

    Our interest in this research was mainly to compare the physiological characteristics of microorganisms derived from subsurface and surface environments and their ability to transform heterocyclic aromatic chemicals. We selected essentially indole and pyridine compounds as representatives of heterocyclic compounds. The samples investigated originated from the subsurface drillings at the Savannah River Plant, from surface samples in Pennsylvania, from municipal sewage of State College, Pennsylvania, and from pyridine-contaminated sites at Indianapolis. At different physiological conditions (aerobic, denitrifying, sulfate-reducing or methanogenic), different groups of microorganisms are active. Not only the thermodynamics of microbial physiology vary, but different metabolic pathways are used by the various types of microbial processes. Therefore, it was important to determine under which physiological conditions a compound was metabolized, and to clarify the metabolic conditions under which intermediate(s) were produced. 29 refs.

  2. Antioxidant activity and characterization of phenolic compounds from bacaba (Oenocarpus bacaba Mart.) fruit by HPLC-DAD-MS(n).

    PubMed

    Abadio Finco, Fernanda D B; Kammerer, Dietmar R; Carle, Reinhold; Tseng, Wen-Hsin; Böser, Sabrina; Graeve, Lutz

    2012-08-01

    The phytochemicals in fruits have been shown to be major bioactive compounds with regard to health benefits. Bacaba (Oenocarpus bacaba Mart.) is a native palm fruit from the Brazilian savannah and Amazon rainforest that plays an important role in the diet of rural communities and is also a source of income for poor people. This paper reports the characterization and analyses of phenolics from bacaba fruit extract. The total phenolic content of bacaba fruit amounted to 1759.27 ± 1.01 mg GAE/100 g, the flavonoid content was 1134.32 ± 0.03 mg CTE/100 g, and the anthocyanin content was 34.69 ± 0.00 mg cyn-3-glc/100 g. The antioxidant activity was evaluated through different assays [ORAC, FRAP, DPPH, TEAC, and cellular antioxidant assay (CAA) assays] and revealed a significant antioxidant capacity for bacaba in comparison to the data available in the literature. The assignment of the phenolic compounds using HPLC-DAD-MS(n) was based on the evaluation of their UV-vis absorption maxima (?(max)) and mass spectral analyses, and 14 compounds were tentatively identified. The results suggest that bacaba fruits are a promising source of phenolics. PMID:22788720

  3. Adenosine, a hepato-protective component in active hexose correlated compound: its identification and iNOS suppression mechanism.

    PubMed

    Tanaka, Yoshito; Ohashi, Satomi; Ohtsuki, Aya; Kiyono, Tamami; Park, Eun Young; Nakamura, Yasushi; Sato, Kenji; Oishi, Masaharu; Miki, Hirokazu; Tokuhara, Katsuji; Matsui, Kosuke; Kaibori, Masaki; Nishizawa, Mikio; Okumura, Tadayoshi; Kwon, A-Hon

    2014-08-31

    Supplementation of active hexose correlated compound (AHCC) improved the prognosis of postoperative hepatocellular carcinoma patients. Excess production of nitric oxide (NO) by inducible NO synthase (iNOS) is an inflammatory biomarker in liver injury. AHCC suppressed iNOS induction in hepatocytes, suggesting that AHCC has a potential liver-protective effect. However, the active component in AHCC responsible for NO suppressive activities has not been identified. The objective of this study was to identify this NO suppressive component and to investigate its mechanisms of action. AHCC was subjected to fractionation by cation exchanger, size exclusion chromatography, and normal- and reversed-phase HPLC. Aliquots of the fractions were added to primary cultured rat hepatocytes stimulated with interleukin (IL)-1?, and NO production was assayed. By activity-guided fractionation and electron spray ionization mass spectrometry analysis, adenosine was identified as one of the NO suppressive components in AHCC. Adenosine inhibited NO production, and reduced the expression of iNOS protein and mRNA. It had no effects on I?B degradation, but it inhibited NF-?B activation. Adenosine also inhibited the upregulation of type I IL-1 receptor (IL-1RI). Experiments with iNOS promoter-luciferase constructs revealed that adenosine decreased the levels of iNOS mRNA at the promoter transactivation and mRNA stabilization steps. Adenosine decreased the expression of the iNOS gene antisense transcript, which is involved in iNOS mRNA stability. Adenosine in AHCC suppressed iNOS induction by blocking NF-?B activation and the upregulation of the IL-1RI pathways, resulting in the inhibition of NO production. PMID:24878381

  4. A Systematic Approach to Identify Markers of Distinctly Activated Human Macrophages

    PubMed Central

    Sudan, Bayan; Wacker, Mark A.; Wilson, Mary E.; Graff, Joel W.

    2015-01-01

    Polarization has been a useful concept for describing activated macrophage phenotypes and gene expression profiles. However, macrophage activation status within tumors and other settings are often inferred based on only a few markers. Complicating matters for relevance to human biology, many macrophage activation markers have been best characterized in mice and sometimes are not similarly regulated in human macrophages. To identify novel markers of activated human macrophages, gene expression profiles for human macrophages of a single donor subjected to 33 distinct activating conditions were obtained and a set of putative activation markers were subsequently evaluated in macrophages from multiple donors using integrated fluidic circuit (IFC)-based RT-PCR. Using unsupervised hierarchical clustering of the microarray screen, highly altered transcripts (>4-fold change in expression) sorted the macrophage transcription profiles into two major and 13 minor clusters. Among the 1874 highly altered transcripts, over 100 were uniquely altered in one major or two related minor clusters. IFC PCR-derived data confirmed the microarray results and determined the kinetics of expression of potential macrophage activation markers. Transcripts encoding chemokines, cytokines, and cell surface were prominent in our analyses. The activation markers identified by this study could be used to better characterize tumor-associated macrophages from biopsies as well as other macrophage populations collected from human clinical samples. PMID:26074920

  5. Feasibility studies on newly identified LiCrP2O7 compound for lithium insertion behavior

    NASA Astrophysics Data System (ADS)

    Gangulibabu; Bhuvaneswari, D.; Kalaiselvi, N.

    2009-08-01

    A new category of lithium intercalating cathode candidates, namely LiCrP2O7, was synthesized at 800°C using a citric acid assisted modified (CAM) sol-gel method and examined for possible lithium insertion behavior. The formation of a phase pure and monoclinic LiCrP2O7 compound with finer crystallite size was confirmed from the X-ray diffraction patterns. The presence of nano-sized particles as observed from a transmittance electron microscope image of LiCrP2O7 and the presence of a preferred local cation environment, evidenced from Fourier transform infra-red and 7Li nuclear magnetic resonance studies, are the added advantages of the present study. Further, cyclic voltametry study performed on 2016 coin cells consisting of the synthesized LiCrP2O7 cathode revealed an excellent cycling reversibility and structural stability. Hence, CAM sol-gel synthesized LiCrP2O7 is found to possess desirable physical as well as electrochemical properties, leading one to consider the same as a possible lithium intercalating cathode material.

  6. Specialized three-faceted information retrieval thesaurus as a means of indexing and retrieving biologically active compounds according to their biological effects

    Microsoft Academic Search

    V. V. Avidon; E. M. Mikhailovskii; L. A. Piruzyan

    1977-01-01

    The first stage in the screening of new chemical compounds for biological activity is the 'informational analysis' of these compounds [i], which consists in the comparison of the structures of the new compounds under test with those of compounds previously tested having established biological activity. The aim of informational analysis is to predict possible types of activity for new chemical

  7. Immersed effects of Ta and Zr compounds on activity of oxygen reduction reaction in sulfuric acid

    NASA Astrophysics Data System (ADS)

    Matsuzawa, Koichi; Nozawa, Kazuhiro; Yamauchi, Kyosuke; Ishihara, Akimitsu; Mitsushima, Shigenori; Ota, Ken-ichiro

    2013-03-01

    The immersed effects of Ta and Zr compounds (Ta-CNO and Zr-CNO) on the activity of oxygen reduction reaction (ORR) have been investigated in the sulfuric acid. The concentration of Zr on Zr-CNO was higher than that of Pt on Pt black. The concentration of Ta on Ta-CNO was almost the same as that of Pt on Pt black in sulfuric acid. The catalytic activity of Zr-CNO for the ORR decreased with time. In contrast, the catalytic activity of Ta-CNO for the ORR was maintained up to 1050 h in the sulfuric acid.

  8. Photo-activated luminescence sensor and method of detecting trichloroethylene and related volatile organochloride compounds

    DOEpatents

    Dinh, Tuan V. (Knoxville, TN)

    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.

  9. 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.

  10. Fungal proteins with mannanase activity identified directly from a Congo Red stained zymogram by mass spectrometry.

    PubMed

    Peterson, Robyn; Grinyer, Jasmine; Joss, Janice; Khan, Alamgir; Nevalainen, Helena

    2009-12-01

    Secreted fungal proteins with mannanase activity were identified by mass spectrometry of bands excised from a Congo Red stained zymogram containing locust bean gum as substrate. This technique circumvents the need to locate corresponding bands on a parallel gel without substrate and provides good accuracy in targeting proteins for identification. PMID:19854225

  11. Your Mission: (1) Identify 20 active faults in California (2) Identify the direction of fault motion and the slip rate for each fault

    E-print Network

    Smith-Konter, Bridget

    Your Mission: (1) Identify 20 active faults in California (2) Identify the direction of fault motion and the slip rate for each fault (3) Investigate recent earthquakes near your hometown (4) Use Microsoft Excel to plot a small set of earthquake data Your Supplies: California Faults map handout

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

    PubMed

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

    2014-12-01

    Organocatalysts, low-molecular mass organic compounds composed of nonmetallic elements, are often used in organic synthesis, but there have been no reports of organocatalysts of biological origin that function in vivo. Here, we report that actinorhodin (ACT), a natural product derived from Streptomyces coelicolor A3(2), acts as a biocatalyst. We purified ACT and assayed its catalytic activity in the oxidation of L-ascorbic acid and L-cysteine as substrates by analytical methods for enzymes. Our findings were as follows: (i) oxidation reactions producing H2O2 proceeded upon addition of ACT to the reaction mixture; (ii) ACT was not consumed during the reactions; and (iii) a small amount (catalytic amount) of ACT consumed an excess amount of the substrates. Even at room temperature, atmospheric pressure, and neutral pH, ACT showed catalytic activity in aqueous solution, and ACT exhibited substrate specificity in the oxidation reactions. These findings reveal ACT to be an organocatalyst. ACT is known to show antibiotic activity, but its mechanism of action remains unknown. On the basis of our results, we propose that ACT kills bacteria by catalyzing the production of toxic levels of H2O2. We also screened various other natural products of bacterial, plant, and animal origins and found that several of the compounds exhibited catalytic activity, suggesting that living organisms produce and use these compounds as biocatalysts in nature. PMID:25411318

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

    PubMed Central

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

    2014-01-01

    Organocatalysts, low-molecular mass organic compounds composed of nonmetallic elements, are often used in organic synthesis, but there have been no reports of organocatalysts of biological origin that function in vivo. Here, we report that actinorhodin (ACT), a natural product derived from Streptomyces coelicolor A3(2), acts as a biocatalyst. We purified ACT and assayed its catalytic activity in the oxidation of l-ascorbic acid and l-cysteine as substrates by analytical methods for enzymes. Our findings were as follows: (i) oxidation reactions producing H2O2 proceeded upon addition of ACT to the reaction mixture; (ii) ACT was not consumed during the reactions; and (iii) a small amount (catalytic amount) of ACT consumed an excess amount of the substrates. Even at room temperature, atmospheric pressure, and neutral pH, ACT showed catalytic activity in aqueous solution, and ACT exhibited substrate specificity in the oxidation reactions. These findings reveal ACT to be an organocatalyst. ACT is known to show antibiotic activity, but its mechanism of action remains unknown. On the basis of our results, we propose that ACT kills bacteria by catalyzing the production of toxic levels of H2O2. We also screened various other natural products of bacterial, plant, and animal origins and found that several of the compounds exhibited catalytic activity, suggesting that living organisms produce and use these compounds as biocatalysts in nature. PMID:25411318

  14. Antiparasitic compounds from Cupania cinerea with activities against Plasmodium falciparum and Trypanosoma brucei rhodesiense.

    PubMed

    Gachet, M Salomé; Kunert, Olaf; Kaiser, Marcel; Brun, Reto; Zehl, Martin; Keller, Walter; Muñoz, Ricardo A; Bauer, Rudolf; Schuehly, Wolfgang

    2011-04-25

    In a survey of plants from Ecuador with antiprotozoal activity, Cupania cinerea was found to show significant in vitro activity against the Plasmodium falciparum K1 strain and Trypanosoma brucei rhodesiense. Subsequently, activity-guided isolation of the n-hexane and dichloromethane extracts from the bark of C. cinerea afforded two diterpene glycosides (1 and 2), named cupacinoside and 6'-de-O-acetylcupacinoside, and a lactonized triterpene bearing an oxepin moiety named cupacinoxepin (3), together with the known compounds scopoletin (4), caryophyllene oxide (5), two bisabolane sesquiterpenes (6 and 7), lichexanthone (8), gustastatin (9), lupenone (10), betulone (11), 17?,21?-epoxyhopan-3-one (12), taraxerol (13), and taraxerone (14). For compound 3, X-ray crystallography was employed to elucidate the relative configuration. For cupacinosides (1) and (2) and cupacinoxepin (3), in vitro activities against the P. falciparum K1 strain (IC(50)1, 1.3; 2, 1.8; and 3, 8.7 ?M) and T. b. rhodesiense (IC(50)1, 4.5; 2, 15.8; and 3, 71.6 ?M) were found. Cytotoxicity toward L-6 cells is discussed for all the compounds isolated. PMID:21438586

  15. Implementation of a High-Throughput Screen for Identifying Small Molecules to Activate the Keap1-Nrf2-ARE Pathway

    E-print Network

    Wu, Kai Connie; McDonald, Peter R.; Liu, Jie Jerry; Chaguturu, Rathnam; Klaassen, Curtis D.

    2012-10-08

    compounds protect against oxidative/ electrophilic stress-induced toxicity, at least partially through activating Nrf2. For example, curcumin protects against focal ischemia of the cerebrum through upregulation of Nrf2 [16], and oltipraz protects against... pathway [18]. To date, a number of compounds with diverse chemical structures have been shown to activate Keap1- Nrf2, including oxidizable diphenols (tBHQ), dithiolethiones (oltipraz), isothiocyanates (sulforaphane), and Michael acceptors (curcumin...

  16. Development and Validation of Quantitative Structure-Activity Relationship Models for Compounds Acting on Serotoninergic Receptors

    PubMed Central

    ?ydek, Gra?yna; Brzezi?ska, El?bieta

    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 60F254 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 (R2 = 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. PMID:22619602

  17. Antibacterial activity of Pinus elliottii and its major compound, dehydroabietic acid, against multidrug-resistant strains.

    PubMed

    Leandro, Luís Fernando; Cardoso, Miguel Jorge Oliveira; Silva, Sandro Donizeti Caetano; Souza, Maria Gorete Mendes; Veneziani, Rodrigo Cassio Sola; Ambrosio, Sergio Ricardo; Martins, Carlos Henrique Gomes

    2014-12-01

    Antibiotic-resistant bacteria have emerged from the widespread use of antibiotics worldwide and have prompted the search for new sources of antimicrobial substances. Pinus spp. contain several bioactive compounds consisting mainly of terpenes, terpenoids and some other aromatic and aliphatic constituents. These compounds exert important biological effects, and pine oils have found wide application in the industry. In the present study, we have evaluated the potential activity of the resin-oil of Pinus elliottii and its major compound dehydroabietic acid (DA) against multiresistant bacteria by MIC, minimum bactericidal concentration and time-kill assays. The MIC of the resin-oil of P. elliottii varied between 25 and 100 µg ml(-1). As for DA, the MIC and minimum bactericidal concentration varied between 6.25 and 50 and between 6.25 and 100 µg ml(-1), respectively. The time-kill assay conducted with DA at 6.25 µg ml(-1) evidenced bactericidal activity against Staphylococcus epidermidis (American Type Culture Collection 14990) within 24 h. On the basis of these results, the resin-oil of P. elliottii and its major compound DA play an important part in the search for novel sources of agents that can act against multiresistant bacteria. PMID:25261060

  18. Pharmacophore based virtual screening, molecular docking and biological evaluation to identify novel PDE5 inhibitors with vasodilatory activity.

    PubMed

    Mittal, Anupama; Paliwal, Sarvesh; Sharma, Mukta; Singh, Aarti; Sharma, Swapnil; Yadav, Divya

    2014-07-15

    Prompted by the role of PDE5 and its closely associated cAMP and cGMP in hypertension, we have attempted to discover novel PDE5 inhibitors through ligand based virtual screening. Rigorously validated model comprising of one HBA, one HY and one RA was used as a query to search the NCI database leading to retrieval of many compounds which were screened on the basis of estimated activity, fit value and Lipinski's violation. Selected compounds were subjected to docking studies which resulted into visualization of potential interaction capabilities of NCI compounds in line to pharmacophoric features. Finally three compounds were subjected to in vitro evaluation using the isolated rat aortic model. The results showed that all three compounds are potent and novel PDE5 inhibitors with vasodilatory activity range from 10(-2) to 10(-5) M. PMID:24856068

  19. Identification strategy for unknown pollutants using high-resolution mass spectrometry: Androgen-disrupting compounds identified through effect-directed analysis

    Microsoft Academic Search

    Jana M. Weiss; Eszter Simon; Gerard J. Stroomberg; Ronald de Boer; Jacob de Boer; Sander C. van der Linden; Pim E. G. Leonards; Marja H. Lamoree

    2011-01-01

    Effect-directed analysis has been applied to a river sediment sample of concern to identify the compounds responsible for\\u000a the observed effects in an in vitro (anti-)androgenicity assay. For identification after non-target analysis performed on\\u000a a high-resolution LTQ-Orbitrap, we developed a de novo identification strategy including physico-chemical parameters derived\\u000a from the effect-directed analysis approach. With this identification strategy, we were able

  20. Salt reduction in slow fermented sausages affects the generation of aroma active compounds.

    PubMed

    Corral, Sara; Salvador, Ana; Flores, Mónica

    2013-03-01

    Slow fermented sausages with different salt content were manufactured: control (2.7% NaCl, S), 16% salt reduced (2.26% NaCl, RS) and 16% replaced by KCl (2.26% NaCl and 0.43% KCl, RSK). The effect of salt reduction on microbiology and chemical parameters, sensory characteristics, texture and volatile compounds was studied. The aroma compounds were identified by GC-MS and olfactometry analyses. Small salt reduction (16%) (RS) affected sausage quality producing a reduction in the acceptance of aroma, taste, juiciness and overall quality. The substitution by KCl (RSK) produced the same acceptability by consumers as for high salt (S) treatment except for the aroma that was not improved by KCl addition. The aroma was affected due to the reduction in sulfur and acids and the increase of aldehyde compounds. Aroma compounds that characterized the high salt treatment (S) were dimethyl trisulfide, 3-methyl thiophene, 2,3-butanedione, 2-nonanone and acetic acid. PMID:23261539

  1. 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. PMID:24964655

  2. 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

  3. Drug-repositioning screening identified piperlongumine as a direct STAT3 inhibitor with potent activity against breast cancer.

    PubMed

    Bharadwaj, U; Eckols, T K; Kolosov, M; Kasembeli, M M; Adam, A; Torres, D; Zhang, X; Dobrolecki, L E; Wei, W; Lewis, M T; Dave, B; Chang, J C; Landis, M D; Creighton, C J; Mancini, M A; Tweardy, D J

    2015-03-12

    Signal transducer and activator of transcription (STAT) 3 regulates many cardinal features of cancer including cancer cell growth, apoptosis resistance, DNA damage response, metastasis, immune escape, tumor angiogenesis, the Warburg effect and oncogene addiction and has been validated as a drug target for cancer therapy. Several strategies have been used to identify agents that target Stat3 in breast cancer but none has yet entered into clinical use. We used a high-throughput fluorescence microscopy search strategy to identify compounds in a drug-repositioning library (Prestwick library) that block ligand-induced nuclear translocation of Stat3 and identified piperlongumine (PL), a natural product isolated from the fruit of the pepper Piper longum. PL inhibited Stat3 nuclear translocation, inhibited ligand-induced and constitutive Stat3 phosphorylation, and modulated expression of multiple Stat3-regulated genes. Surface plasmon resonance assay revealed that PL directly inhibited binding of Stat3 to its phosphotyrosyl peptide ligand. Phosphoprotein antibody array analysis revealed that PL does not modulate kinases known to activate Stat3 such as Janus kinases, Src kinase family members or receptor tyrosine kinases. PL inhibited anchorage-independent and anchorage-dependent growth of multiple breast cancer cell lines having increased pStat3 or total Stat3, and induced apoptosis. PL also inhibited mammosphere formation by tumor cells from patient-derived xenografts. PL's antitumorigenic function was causally linked to its Stat3-inhibitory effect. PL was non-toxic in mice up to a dose of 30?mg/kg/day for 14 days and caused regression of breast cancer cell line xenografts in nude mice. Thus, PL represents a promising new agent for rapid entry into the clinic for use in treating breast cancer, as well as other cancers in which Stat3 has a role. PMID:24681959

  4. Isolation and identification of colourless caffeoyl compounds in purple sweet potato by HPLC-DAD-ESI/MS and their antioxidant activities.

    PubMed

    Zhao, Jin-Ge; Yan, Qian-Qian; Xue, Ren-Yu; Zhang, Jian; Zhang, Yu-Qing

    2014-10-15

    More than 10 red anthocyanins and related glucosides have been isolated and identified from purple sweet potato (Ipomoea batatas, Ayamurasaki) in the recent decades. This paper reports the isolation of colourless caffeoyl compounds from purple sweet potato using AB-8 macroresin absorption and semi-preparative HPLC-DAD. The structures of the five isolated monomers were identified as: 5-caffeoylquinic acid (1), 6-O-caffeoyl-?-d-fructofuranosyl-(2-1)-?-d-glucopyranoside (2) and trans-4,5-dicaffeoylquinic acid (3), 3,5-dicaffeoylquinic acid (4), 4,5-dicaffeoylquinic acid (5), and by ESI/MS and NMR. Compounds 1, 4 and 5 were reported previously in combination with anthocyanins in purple sweet potato, whereas 2 and 3 were found for the first time. In vitro antioxidant assay showed trans-4,5-dicaffeoylquinic acid has significant antioxidant activities. These results should lay the groundwork for further work identifying purple sweet potato as a healthy food. PMID:24837917

  5. Active Hexose Correlated Compound Inhibits the Expression of Proinflammatory Biomarker iNOS in Hepatocytes

    Microsoft Academic Search

    K. Matsui; T. Ozaki; M. Oishi; Y. Tanaka; M. Kaibori; M. Nishizawa; T. Okumura; A.-H. Kwon

    2011-01-01

    Background\\/Aims: Excess production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been implicated as proinflammatory biomarker in liver injury. The application of active hexose correlated compound (AHCC) as a functional food in complementary and alternative medicine has increased. The possibility that AHCC might inhibit iNOS induction was investigated as a potential liver-protective effect. Methods: Hepatocytes were isolated

  6. Supplementation with active hexose correlated compound increases survival following infectious challenge in mice.

    PubMed

    Ritz, Barry W

    2008-09-01

    Active hexose correlated compound (AHCC) is a fermented mushroom extract that is promoted for immune support. This review focuses on results from in vivo studies evaluating the effects of AHCC supplementation on survival and the immune response to a variety of infectious agents, including influenza virus, avian influenza virus, Klebsiella pneumoniae, Candida albicans, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. Supplementation with AHCC appears to modulate immunity and increase survival in response to acute infection and warrants further investigation. PMID:18752476

  7. Predicting Pharmacological and Toxicological Activity of Heterocyclic Compounds Using QSAR and Molecular Modeling

    Microsoft Academic Search

    Subhash C. Basak; Denise Mills; Brian Gute; Ramanathan Natarajan

    Heterocyclic compounds are important as drugs, toxicants, and agrochemicals. In this review,\\u000a we report the QSAR modeling of pharmacological activity, insect repellency, and environmental toxicity\\u000a for a few classes of heterocyclics from their structure. The calculated molecular descriptors\\u000a fall into four classes: topostructural (TS), topochemical (TC), 3-dimensional or geometrical (3D),\\u000a and quantum chemical (QC). The complexity and the computational time of

  8. Antiviral activity of Plantago major extracts and related compounds in vitro

    Microsoft Academic Search

    L. C Chiang; W Chiang; M. Y Chang; L. T Ng; C. C Lin

    2002-01-01

    Plantago major L., a popular traditional Chinese medicine, has long been used for treating various diseases varying from cold to viral hepatitis. The aim of present study was to examine the antiviral activity of aqueous extract and pure compounds of P. major. Studies were conducted on a series of viruses, namely herpesviruses (HSV-1, HSV-2) and adenoviruses (ADV-3, ADV-8, ADV-11). The

  9. 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.

  10. Adsorption from aqueous solutions of chlorinated organic compounds onto activated carbons

    Microsoft Academic Search

    Anna Bembnowska; Robert Pe?ech; Eugeniusz Milchert

    2003-01-01

    The adsorption capacities of five chlorinated organic compounds, chloroform (CHCl3), 1,1,2,2-tetrachloroethane (S-TET), 1,1,2,2-tetrachloroethylene (PER), 1,2-dichloropropane (DCP), and bis(1-chloroisopropyl) ether (BCIPE) for DTO, WD-EXTRA, and AG-5 activated carbons were investigated. Moreover, the effective molecular diameters of investigated chlorocompounds were calculated. The Freundlich and Langmuir equations of adsorption isotherms describe the experimental data with good correlation for each studied system. The equilibrium

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

    SciTech Connect

    Aziz, Gulzeb [Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo (Norway); Akselsen, Oyvind W.; Hansen, Trond V. [Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo (Norway); Paulsen, Ragnhild E., E-mail: r.e.paulsen@farmasi.uio.n [Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo (Norway)

    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.

  12. Glutathione S-transferase activity: enhancement by compounds inhibiting chemical carcinogenesis and by dietary constituents.

    PubMed

    Sparnins, V L; Venegas, P L; Wattenberg, L W

    1982-03-01

    Benzyl isothiocyanate, beta-naphthoflavone, coumarin, alpha-angelicalactone, disulfiram, indole-3-carbinol and indole-3-acetonitrile induced increased glutathione (GSH) S-transferase activity in the liver and small intestine in female ICR/Ha mice. All seven compounds are inhibitors of chemical carcinogenesis. In additional work, several dietary constituents increased GSH S-transferase activity. Consumption of diets containing dried powdered preparations of brussels sprouts, cabbage, coffee beans, or tea leaves resulted in increased GSH S-transferase activity. Mice fed an unrefined diet (Purina Rat Chow) had a higher GSH S-transferase activity than those fed a semipurified diet. The results of the present study indicated that the composition of the diet can alter the activity of an important enzyme system having the capacity to detoxify chemical carcinogens. PMID:6278195

  13. Antioxidant and antiacetylcholinesterase activities of some commercial essential oils and their major compounds.

    PubMed

    Aazza, Smail; Lyoussi, Badiâ; Miguel, Maria G

    2011-01-01

    The commercial essential oils of Citrus aurantium L., Cupressus sempervirens L., Eucalyptus globulus Labill., Foeniculum vulgare Mill. and Thymus vulgaris L., isolated by steam distillation by a company of Morocco were evaluated in terms of in vitro antioxidant activity through several methods. In vitro acetylcholinesterase inhibitory activity was also determined. Citrus limon (L.) Burm. f. oil was also studied, but it was obtained by peel expression. The best antioxidant was T. vulgaris oil, independent of the method used, mainly due to the presence of the phenolic monoterpenes thymol and carvacrol, which when studied as single compounds also presented the best activities. Concerning the acetylcholinesterase inhibition activity, E. globulus was the most effective. Nevertheless its main components 1,8-cineole and limonene were not the most active, a feature that corresponded to d-3-carene. PMID:21900869

  14. [Novel compounds increasing chaperone Hsp70 expression and their biological activity].

    PubMed

    Eremenko, E M; Antimonova, O I; Shekalova, O G; Polonik, S G; Margulis, B A; Guzhova, I V

    2010-01-01

    Hsp70 possesses chaperonic activity, the property associated with the protective function that was demonstrated in experiments on a great number of cell and animal models. Therefore, it seems important to search for the substances able to innocuously elevate the chaperone concentration in an organism cells and tissues. In our work, we screened of more that 60 compounds and found two chemicals, derivatives of shikonin and echinochrome that able to increase the chaperone level in a variety of human cells. It was shown that in human erythroleukemia K562 cells treated with the both substances concomitantly with elevation of Hsp70 level the absolute chaperonic activity was also increased; this can indicate mobilization of the whole cellular chaperonic machinery by above mentioned compounds. Estimating biological activity of the two substances, we demonstrated that treatments of cells by them prior to hard heat stress, hydrogen peroxide or staurosporine reduced cell mortality by 20-50 % depending on a cytotoxic factor. The results show that after simple chemical modifications these compounds might be taken as a basis of pharmaceuticals for therapy of wide range of disorders. PMID:20429301

  15. Phenylarsonic acid compounds with broad-spectrum and potent cytotoxic activity against human cancer cells.

    PubMed

    Uckun, Fatih M; D'Cruz, Osmond J; Liu, Xing-Ping; Narla, Rama Krishna

    2003-01-01

    The in vitro cytotoxic activity profile of nine novel phenylarsonic acid (CAS 98-05-5, PAA) compounds against 17 human cancer cell lines including (a) ovarian cancer cell lines ES-2, PA-1, CAOV-3, OVCAR-3, (b) testicular cancer cell lines Ntera-2, Tera-2, N2NICP, 833K, and 64CP, (c) multiple myeloma cell lines ARH77, HS-Sultan, RPMI-8226, and U266, and (d) acute lymphoblastic leukemia (ALL) cell lines NALM-6, MOLT-3, ALL-1, and RS4; 11, was determined by the MTT assay. The lead compounds, 2-methylthio-4-[(4'-aminophenylazo)-phenylarsonic acid] pyrimidine (PHI-370) and 2-methylthio-4-(4'-phenylarsonic acid)-aminopyrimidine (PHI-380) caused apoptotic death in all 17 cancer cell lines at low micromolar concentrations, as documented by TUNEL assays and confocal laser scanning microscopy. PHI-380 was also tested and found to be very active against primary tumor cells isolated from surgical biopsy specimens of 14 patients with therapy-refractory non-small cell lung cancer, breast cancer, colon cancer, lymphoma, hepatoblastoma, or Wilm's tumor as well. Because of their broad-spectrum and potent anticancer activity and ability to induce apoptosis in primary tumor cells from therapy-refractory cancer patients, PAA compounds such as PHI-370 and PHI-380 may provide the basis for effective salvage regimens for patients with recurrent cancer. PMID:12872614

  16. Electrospun nanofiber layers with incorporated photoluminescence indicator for chromatography and detection of ultraviolet-active compounds.

    PubMed

    Kampalanonwat, Pimolpun; Supaphol, Pitt; Morlock, Gertrud E

    2013-07-19

    For the first time, electrospun nanofiber phases were fabricated with manganese-activated zinc silicate as photoluminescent indicator (UV254) to transfer and enlarge its application to the field of UV-active compounds. By integration of such an indicator, UV-active compounds got visible on the chromatogram. The separation of 7 preservatives and a beverage sample were studied on the novel luminescent polyacrylonitrile layers. The mat thickness and mean fiber diameters were calculated for additions of different UV254 indicator concentrations. The separation efficiency on the photoluminescent layers was characterized by comparison to HPTLC layers and calculation of the plate numbers and resolutions. Some benefits were the reduction in migration distance (3cm), migration time (12min), analyte (10-nL volumes) and mobile phase volumes (1mL). As ultrathin stationary phase, such layers are suited for their integration into the Office Chromatography concept. For the first time, electrospun nanofiber layers were hyphenated with mass spectrometry and the confirmation of compounds was successfully performed using the elution-head based TLC-MS Interface. PMID:23764191

  17. 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 ?-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 ?-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

  18. Hydraphiles: A Rigorously Studied Class of Synthetic Channel Compounds with In Vivo Activity

    PubMed Central

    Negin, Saeedeh; Smith, Bryan A.; Unger, Alexandra; Leevy, W. Matthew; Gokel, George W.

    2013-01-01

    Hydraphiles are a class of synthetic ion channels that now have a twenty-year history of analysis and success. In early studies, these compounds were rigorously validated in a wide range of in vitro assays including liposomal ion flow detected by NMR or ion-selective electrodes, as well as biophysical experiments in planar bilayers. During the past decade, biological activity was observed for these compounds including toxicity to bacteria, yeast, and mammalian cells due to stress caused by the disruption of ion homeostasis. The channel mechanism was verified in cells using membrane polarity sensitive dyes, as well as patch clamping studies. This body of work has provided a solid foundation with which hydraphiles have recently demonstrated acute biological toxicity in the muscle tissue of living mice, as measured by whole animal fluorescence imaging and histological studies. Here we review the critical structure-activity relationships in the hydraphile family of compounds and the in vitro and in cellulo experiments that have validated their channel behavior. This report culminates with a description of recently reported efforts in which these molecules have demonstrated activity in living mice. PMID:23401675

  19. 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?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. PMID:24793354

  20. 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.

  1. Organic Compounds in the Environment Cotton Defoliant Runoff as a Function of Active Ingredient and Tillage

    Microsoft Academic Search

    Thomas L. Potter; Clint C. Truman; David D. Bosch; Craig W. Bednarz

    ants are used, how they are used, and when they are applied. Tank mixtures containing two or more active Cotton (Gossypium hirsutum L.) defoliant runoff was recently ingredients are favored. This overcomes problems with identified as an ecological risk. However, assessments are not sup- ported by field studies. Runoff potential of three defoliant active variation in efficacy due to crop

  2. Activity of South African medicinal plants against Listeria monocytogenes biofilms, and isolation of active compounds from Acacia karroo

    Microsoft Academic Search

    M. A. Nyila; C. M. Leonard; A. A. Hussein; N. Lall

    In South Africa, the antimicrobial activity of many indigenous plants has been investigated. In general, studies have focused on planktonic bacteria, with less attention given to bacterial biofilms. Many organisms, however, including the opportunistic pathogen Listeria monocytogenes occur more frequently as biofilms. The aim of this study was to identify and select plants that exhibit the best antilisterial activity, isolate

  3. Structure-activity relationship for quaternary ammonium compounds hybridized with poly(methyl methacrylate).

    PubMed

    Melo, Leticia D; Palombo, Renata R; Petri, Denise F S; Bruns, Michael; Pereira, Edla M A; Carmona-Ribeiro, Ana M

    2011-06-01

    Hybrid films from poly (methylmethacrylate) (PMMA) and dioctadecyldimethylammonium bromide (DODAB), cetyltrimethylammonium bromide (CTAB), or tetrapropylammonium bromide (TPAB) were characterized by determination of wettability, ellipsometry, atomic force microscopy, active compounds diffusion to water, X-ray photoelectron spectroscopy (XPS) with determination of atomic composition on the films surface, and biocidal activity against Pseudomonas aeruginosa or Staphylococcus aureus. QAC mobility in the films increased from DODAB to CTAB to TPAB. Diffusion and optimal hydrophobic-hydrophilic balance imparted the highest bioactivity to CTAB. DODAB sustained immobilization at the film surface killed bacteria upon contact. TPAB ability to diffuse was useless because of its unfavorable hydrophobic-hydrophilic balance for bioactivity. PMID:21591705

  4. 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. PMID:22205996

  5. Causal connection between detoxification enzyme activity and consumption of a toxic plant compound.

    PubMed

    Snyder, M J; Glendinning, J I

    1996-08-01

    Insect herbivores can increase their detoxification activities against a particular plant poison in response to prolonged ingestion of the same compound. For example, larval tobacco hornworms (Manduca sexta) experience a dramatic increase in cytochrome P450 activity against nicotine after ingesting nicotine. While it is generally assumed that this induction process permits increased consumption of toxic plant tissues, we are not aware of any direct experimental support for this assumption. Using a two-tiered approach, we examined the functional significance of P450 induction to M. sexta larvae ingesting a toxic but non-deterrent concentration of nicotine. First, we related the time-course of P450 induction in midgut microsomes to changes in nicotine consumption. When offered a nicotine diet, larvae failed to show a significant increase in consumption before 36 h, which was coincident with the time-course of the induction of midgut P450 activities against aldrin and nicotine. Second, we determined whether inhibiting the induced P450 activities affected nicotine consumption. We found that the increase in nicotine consumption following the induction of nicotine metabolism could be strongly inhibited by treatment with piperonyl butoxide, which by itself did not inhibit consumption. These results provide direct evidence for a causal connection between P450-mediated detoxification activity and consumption of a toxic plant compound. PMID:8765561

  6. Determination of some physicochemical characteristics, bioactive compounds and antioxidant activity of tropical fruits from Yucatan, Mexico.

    PubMed

    Moo-Huchin, Víctor M; Estrada-Mota, Iván; Estrada-León, Raciel; Cuevas-Glory, Luis; Ortiz-Vázquez, Elizabeth; Vargas y Vargas, María de Lourdes; Betancur-Ancona, David; Sauri-Duch, Enrique

    2014-01-01

    The aim to the study was to determine the physicochemical composition, bioactive compounds and antioxidant activity of fruits from Yucatan, Mexico such as star apple, cashew, mombin, mamey sapote, white sapote, sugar apple, sapodilla, dragon fruit, nance, ilama, custard apple, mamoncillo and black sapote. The physicochemical characteristics were different between fruits and were good sources of bioactive compounds. The edible part with the highest values of antioxidant activity were mamoncillo, star apple, mombin, cashew, white sapote, ilama, custard apple, sugar apple, and nance. Total soluble phenols content showed a correlation with antioxidant activity by ABTS (R=0.52, P?0.05) and DPPH (R=0.43, P?0.05). A high correlation was obtained between the two assays (ABTS and DPPH) used to measure antioxidant activity in the tropical fruit species under study (R=0.82, P?0.05). The results show promising perspectives for the exploitation and use of tropical fruits studied with significant levels of nutrients and antioxidant activity. PMID:24444968

  7. Assay development for identifying inhibitors of the mycobacterial FadD32 activity.

    PubMed

    Galandrin, Ségolène; Guillet, Valérie; Rane, Rajendra S; Léger, Mathieu; N, Radha; Eynard, Nathalie; Das, Kaveri; Balganesh, Tanjore S; Mourey, Lionel; Daffé, Mamadou; Marrakchi, Hedia

    2013-06-01

    FadD32, a fatty acyl-AMP ligase (FAAL32) involved in the biosynthesis of mycolic acids, major and specific lipid components of the mycobacterial cell envelope, is essential for the survival of Mycobacterium tuberculosis, the causative agent of tuberculosis. The protein catalyzes the conversion of fatty acid to acyl-adenylate (acyl-AMP) in the presence of adenosine triphosphate and is conserved in all the mycobacterial species sequenced so far, thus representing a promising target for the development of novel antituberculous drugs. Here, we describe the optimization of the protein purification procedure and the development of a high-throughput screening assay for FadD32 activity. This spectrophotometric assay measuring the release of inorganic phosphate was optimized using the Mycobacterium smegmatis FadD32 as a surrogate enzyme. We describe the use of T m (melting temperature) shift assay, which measures the modulation of FadD32 thermal stability, as a tool for the identification of potential ligands and for validation of compounds as inhibitors. Screening of a selected library of compounds led to the identification of five novel classes of inhibitors. PMID:23364516

  8. The effect of phase partitioning of semivolatile compounds on the measured CCN activity of aerosol particles

    NASA Astrophysics Data System (ADS)

    Romakkaniemi, S.; Jaatinen, A.; Laaksonen, A.; Nenes, A.; Raatikainen, T.

    2013-09-01

    The effect of inorganic semivolatile aerosol compounds on the CCN activity of aerosol particles was studied by using a computational model for a DMT-CCN counter, a cloud parcel model for condensation kinetics and experiments to quantify the modelled results. Concentrations of water vapour and semivolatiles as well as aerosol trajectories in the CCN column were calculated by a computational fluid dynamics model. These trajectories and vapour concentrations were then used as an input for the cloud parcel model to simulate mass transfer kinetics of water and semivolatiles between aerosol particles and the gas phase. Two different questions were studied: (1) how big fraction of semivolatiles is evaporated from particles before activation in the CCN counter? (2) How much the CCN activity can be increased due to condensation of semivolatiles prior to the maximum water supersaturation in the case of high semivolatile concentration in the gas phase? The results show that, to increase the CCN activity of aerosol particles, a very high gas phase concentration (as compared to typical ambient conditions) is needed. We used nitric acid as a test compound. A concentration of several ppb or higher is needed for measurable effect. In the case of particle evaporation, we used ammonium nitrate as a test compound and found that it partially evaporates before maximum supersaturation is reached in the CCN counter, thus causing an underestimation of CCN activity. The effect of evaporation is clearly visible in all supersaturations, leading to an underestimation of the critical dry diameter by 10 to 15 nanometres in the case of ammonium nitrate particles in different supersaturations. This result was also confirmed by measurements in supersaturations between 0.1 and 0.7%.

  9. Anti-ice nucleating activity of polyphenol compounds against silver iodide.

    PubMed

    Koyama, Toshie; Inada, Takaaki; Kuwabara, Chikako; Arakawa, Keita; Fujikawa, Seizo

    2014-10-01

    Freeze-avoiding organisms survive sub-zero temperatures without freezing in several ways, such as removal of ice nucleating agents (INAs), production of polyols, and dehydration. Another way is production of anti-ice nucleating agents (anti-INAs), such as has been reported for several antifreeze proteins (AFPs) and polyphenols, that inhibit ice nucleation by inactivating INAs. In this study, the anti-ice nucleating activity of five polyphenol compounds, including flavonoid and tannin compounds of both biological and synthetic origin, against silver iodide (AgI) was examined by measuring the ice nucleation temperature in emulsified polyphenol solutions containing AgI particles. The emulsified solutions eliminated the influence of contamination by unidentified INAs, thus enabling examination of the anti-ice nucleating activity of the polyphenols against AgI alone. Results showed that all five polyphenol compounds used here have anti-ice nucleating activities that are unique compared with other known anti-INAs, such as fish AFPs (type I and III) and synthetic polymers (poly(vinyl alcohol), poly(vinylpyrrolidone) and poly(ethylene glycol)). All five polyphenols completely inactivated the ice nucleating activity of AgI even at relatively low temperatures, and the first ice nucleation event was observed at temperatures between -14.1 and -19.4°C, compared with between -8.6 and -11.8°C for the fish AFPs and three synthetic polymers. These anti-ice nucleating activities of the polyphenols at such low temperatures are promising properties for practical applications where freezing should be prevented. PMID:25086201

  10. Activity-guided purification identifies lupeol, a pentacyclic triterpene, as a therapeutic agent multiple pathogenic factors of acne.

    PubMed

    Kwon, Hyuck Hoon; Yoon, Ji Young; Park, Seon Yong; Min, Seonguk; Kim, Yong-Il; Park, Ji Yong; Lee, Yun-Sang; Thiboutot, Diane M; Suh, Dae Hun

    2015-06-01

    Acne vulgaris is a nearly universal cutaneous disease characterized by multifactorial pathogenic processes. Because current acne medications have various side effects, investigating new pharmacologically active molecules is important for treating acne. As natural products generally provide various classes of relatively safe compounds with medicinal potentials, we performed activity-guided purification after a series of screenings from the extracts of five medicinal plants to explore alternative acne medications. Lupeol, a pentacyclic triterpene, from the hexane extract of Solanum melongena L. (SM) was identified after instrumental analysis. Lupeol targeted most of the major pathogenic features of acne with desired physicochemical traits. It strongly suppressed lipogenesis by modulating the IGF-1R/phosphatidylinositide 3 kinase (PI3K)/Akt/sterol response element-binding protein-1 (SREBP-1) signaling pathway in SEB-1 sebocytes, and reduced inflammation by suppressing the NF-?B pathway in SEB-1 sebocytes and HaCaT keratinocytes. Lupeol exhibited a marginal effect on cell viability and may have modulated dyskeratosis of the epidermis. Subsequently, histopathological analysis of human patients' acne tissues after applying lupeol for 4 weeks demonstrated that lupeol markedly attenuated the levels of both the number of infiltrated cells and major pathogenic proteins examined in vitro around comedones or sebaceous glands, providing solid evidence for suggested therapeutic mechanisms. These results demonstrate the clinical feasibility of applying lupeol for the treatment of acne. PMID:25647437

  11. Concept for a Compound Analysis in Active Learning for Remote Sensing

    NASA Astrophysics Data System (ADS)

    Wuttke, S.; Middelmann, W.; Stilla, U.

    2015-03-01

    Active learning reduces training costs for supervised classification by acquiring ground truth data only for the most useful samples. We present a new concept for the analysis of active learning techniques. Our framework is split into an outer and an inner view to facilitate the assignment of different influences. The main contribution of this paper is a concept of a new compound analysis in the active learning loop. It comprises three sub-analyses: structural, oracle, prediction. They are combined to form a hypothesis of the usefulness for each unlabeled training sample. Though the analysis is in an early stage, different extensions are highlighted. Further we show how variations inside the framework lead to many techniques from the active learning literature. In this work we focus on remote sensing, but the proposed method can be applied to other fields as well.

  12. Evaluation of anticandidal and antioxidant activities of phenolic compounds from Pyrostegia venusta (Ker Gawl.) Miers.

    PubMed

    Pereira, Ana Maria S; Hernandes, Camila; Pereira, Sarazete I V; Bertoni, Bianca W; França, Suzelei C; Pereira, Paulo S; Taleb-Contini, Silvia H

    2014-10-29

    We have investigated the in vitro anticandidal and antioxidant activities of phenolic compounds from Pyrostegia venusta flower extracts. We used the HPLC technique to purify the flavonoid (quercetin-3-O-?-l-rhamnopyranosyl-(1?6)-?-d-galactopyranoside) and two phenylpropanoid glycosides (verbascoside and isoverbascoside); we evaluated the antimicrobial activity of the extracts against Candida strains (Candidaalbicans; Candidakrusei ATCC 6258; and the clinical isolate strains of Candida sp. C. albicans, C. krusei, Candidatropicalis, Candidaparapsilosis, and Candidaguilhermondii). The P. venusta flower extracts displayed antimicrobial and antioxidant activities. The semi-purified fraction of the P. venusta flower extract and the phenylpropanoid glycoside verbascoside exhibited activity similar to that of amphotericin B, which denoted that they are potentially applicable as natural antioxidant and anticandidal agents in the pharmaceutical industries. PMID:25451592

  13. Antioxidant activities and determination of phenolic compounds isolated from oriental plums (Soldam, Oishiwase and Formosa)

    PubMed Central

    Kim, Mee-Ree; Cho, Soo-Muk; Kim, So-Young; Kim, Jung-Bong; Cho, Young-Sook

    2012-01-01

    The purposes of this study were to determine phenolic compounds and to evaluate antioxidant activities of plums (Soldam, Oishiwase and Formosa). Soldam contains the highest amount of total phenolics among cultivars (Formosa: 4.0%, Oishiwase: 3.3%, Soldam: 6.4% for total phenolic) as well as the total flavonoids of which constituents were mainly myricetin and anthocyanidin. The antioxidant activities were measured by DPPH, ABTS radical scavenging, and SOD-like activities. The DPPH radical scavenging activity of Korean plum extracts (200 µg/mL) showed more than 43%, and the Soldam turned out to be the highest : ID50 value: 160-177 µg/mL for Formosa and Oishiwase; 58-64 µg/mL for Soldam. The ABTS radical scavenging activity of Korean plum extracts (200 µg/mL) was found to be more than 50%. The SOD-like activity of Korean plum extracts (200 µg/mL) showed more than 70%. Among three kinds of cultivars, Soldam had the highest antioxidant activity. The nitrite scavenging activity of Soldam was 61.5%, which is the highest, compared with that of the other cultivars, about 50%. From these results, Korean plums turned out to be phytochemical rich fruit as well as to show high antioxidant activities. PMID:22977680

  14. The ruthenium compound KP1339 potentiates the anticancer activity of sorafenib in vitro and in vivo?

    PubMed Central

    Heffeter, Petra; Atil, Bihter; Kryeziu, Kushtrim; Groza, Diana; Koellensperger, Gunda; Körner, Wilfried; Jungwirth, Ute; Mohr, Thomas; Keppler, Bernhard K.; Berger, Walter

    2013-01-01

    KP1339 is a promising ruthenium-based anticancer compound in early clinical development. This study aimed to test the effects of KP1339 on the in vitro and in vivo activity of the multi-kinase inhibitor sorafenib, the current standard first-line therapy for advanced hepatoma. Anticancer activity of the parental compounds as compared to the drug combination was tested against a panel of cancer cell lines with a focus on hepatoma. Combination of KP1339 with sorafenib induced in the majority of all cases distinctly synergistic effects, comprising both sorafenib-resistant as well as sorafenib-responsive cell models. Several mechanisms were found to underlie these multifaceted synergistic activities. Firstly, co-exposure induced significantly enhanced accumulation levels of both drugs resulting in enhanced apoptosis induction. Secondly, sorafenib blocked KP1339-mediated activation of P38 signalling representing a protective response against the ruthenium drug. In addition, sorafenib treatment also abrogated KP1339-induced G2/M arrest but resulted in check point-independent DNA-synthesis block and a complete loss of the mitotic cell populations. The activity of the KP1339/sorafenib combination was evaluated in the Hep3B hepatoma xenograft. KP1339 monotherapy led to a 2.4-fold increase in life span and, thus, was superior to sorafenib, which induced a 1.9-fold prolonged survival. The combined therapy further enhanced the mean survival by 3.9-fold. Synergistic activity was also observed in the VM-1 melanoma xenograft harbouring an activating braf mutation. Together, our data indicate that the combination of KP1339 with sorafenib displays promising activity in vitro and in vivo especially against human hepatoma models. PMID:23790465

  15. The ruthenium compound KP1339 potentiates the anticancer activity of sorafenib in vitro and in vivo.

    PubMed

    Heffeter, Petra; Atil, Bihter; Kryeziu, Kushtrim; Groza, Diana; Koellensperger, Gunda; Körner, Wilfried; Jungwirth, Ute; Mohr, Thomas; Keppler, Bernhard K; Berger, Walter

    2013-10-01

    KP1339 is a promising ruthenium-based anticancer compound in early clinical development. This study aimed to test the effects of KP1339 on the in vitro and in vivo activity of the multi-kinase inhibitor sorafenib, the current standard first-line therapy for advanced hepatoma. Anticancer activity of the parental compounds as compared to the drug combination was tested against a panel of cancer cell lines with a focus on hepatoma. Combination of KP1339 with sorafenib induced in the majority of all cases distinctly synergistic effects, comprising both sorafenib-resistant as well as sorafenib-responsive cell models. Several mechanisms were found to underlie these multifaceted synergistic activities. Firstly, co-exposure induced significantly enhanced accumulation levels of both drugs resulting in enhanced apoptosis induction. Secondly, sorafenib blocked KP1339-mediated activation of P38 signalling representing a protective response against the ruthenium drug. In addition, sorafenib treatment also abrogated KP1339-induced G2/M arrest but resulted in check point-independent DNA-synthesis block and a complete loss of the mitotic cell populations. The activity of the KP1339/sorafenib combination was evaluated in the Hep3B hepatoma xenograft. KP1339 monotherapy led to a 2.4-fold increase in life span and, thus, was superior to sorafenib, which induced a 1.9-fold prolonged survival. The combined therapy further enhanced the mean survival by 3.9-fold. Synergistic activity was also observed in the VM-1 melanoma xenograft harbouring an activating braf mutation. Together, our data indicate that the combination of KP1339 with sorafenib displays promising activity in vitro and in vivo especially against human hepatoma models. PMID:23790465

  16. 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. PMID:11478248

  17. Synthesis and antiproliferative activity of novel polynuclear heterocyclic compounds derived from 2,3-diaminophenazine.

    PubMed

    Mahran, Asma M; Ragab, Sherif Sh; Hashem, Ahmed I; Ali, Mamdouh M; Nada, Afaf A

    2015-01-27

    2,3-Diaminophenazine 1 was used as a precursor for the preparation of some novel phenazine derivatives such as imidazo[4,5-b]phenazine-2-thione 2, its methylthio 3, ethyl 1-aryl-3H-[1,2,4]triazolo[2,3-a]imidazo[4,5-b]phenazines 8a-c, ethyl (2Z)-[3-aminophenazin-2-yl)amino](phenylhydrazono)ethanoate 9, pyrazino[2,3-b]phenazine derivatives 10, 12, 15-17, [1,4]diazepino[2,3-b]phenazine derivatives 13, 14, 2,3-dibenzoylaminophenazine 18, 1H-Imidazo[4,5-b]phenazine derivatives 20, 23a-c, 24, 25 and 4-[(E)-(3-amino phenazin-2-yl)diazenyl] derivatives 27-29. All compounds were tested as inhibitors of the proliferation of human lung carcinoma and colorectal cancer cell lines through inhibition of Tyrosine Kinases. Most of compounds exert good activity against the two cancer cell lines. Five compounds (1, 2, 3, 25 and 28) were found to possess the same activity as the standard drug Cisplatin. PMID:25497130

  18. Natural Compounds with Proteasome Inhibitory Activity for Cancer Prevention and Treatment

    PubMed Central

    Yang, H; Landis-Piwowar, KR.; Chen, D; Milacic, V; Dou, QP

    2012-01-01

    The proteasome is a multicatalytic protease complex that degrades most endogenous proteins including misfolded or damaged proteins to ensure normal cellular function. The ubiquitin-proteasome degradation pathway plays an essential role in multiuple cellular processes, including cell cycle progression, proliferation, apoptosis and angiogenesis. It has been shown that human cancer cells are more sensitive to proteasome inhibition than normal cells, indicating that a proteasome inhibitor could be used as a novel anticancer drug. Indeed, this idea has been supported by the encouraging results of the clinical trials using the proteasome inhibitor Bortezomib (Velcade, PS-341), a drug approved by the US Food and Drug Administration (FDA). Several natural compounds, including the microbial metabolite lactacystin, green tea polyphenols, and traditional medicinal triterpenes, have been shown to be potent proteasome inhibitors. These findings suggest the potential use of natural proteasome inhibitors as not only chemopreventive and chemotherapeutic agents, but also tumor sensitizers to conventional radiotherapy and chemotherapy. In this review, we will summarize the structure and biological activities of the proteasome and several natural compounds with proteasome inhibitory activity, and will discuss the potential use of these compounds for the prevention and treatment of human cancers. PMID:18537678

  19. Synthesis and "in Vitro" Trypanocidal Activity Evaluation of Some Organo-iron Compounds.

    PubMed

    E Silva, Máfircio L A; Neto, Alberto F; Cardoso, Silvia A; Albuquerque, Sérgio; Miller, Joseph

    2002-01-01

    Eight organo-iron ferrocene derivatives and arenocenium salts were prepared and evaluated by "in vitro" assay against one strain of Trypanosoma cruzi (Y). Six of the eight organo-iron compounds assayed, piperazinium diferrocenoate 1, eta(6)-(o-xylene)-eta(5)-(cyclopentadienyl) Iron(II) hexafluorophosphate 3, eta(6)-(mesitylene)-eta(5)-(cyclopentadienyl) iron(II) hexafluorphosphate 5, eta(6)-(durene)-eta(5)-(cyclopentadienyl) iron(II) hexafluorphosphate 6, eta(6)-(rho-chlorotoluene)-eta(5)-(cyclopentadienyl) Iron(II) hexafluorphosphate 7 and eta(6)-(chlorobenzene)-eta(5)-(cyclopentadienyl) iron(II) picrate 8 , were poorly active in the "in vitro" assays. Only two compounds 1,1'-(N-pyperidinocarbonyl) ferrocene 2(IC(50)=2.4 mug/mL) and eta(6)-(o-xylene)-eta(5)(cyclopentadienyl) iron(II) picrate 4 (IC(50)=12.08 mug/mL), were more active. Thus, some of the compounds are promising to be used against Chagas' disease as a prophylactic agents. PMID:18476014

  20. p-HPEA-EDA, a phenolic compound of virgin olive oil, activates AMP-activated protein kinase to inhibit carcinogenesis.

    PubMed

    Khanal, Prem; Oh, Won-Keun; Yun, Hyo Jeong; Namgoong, Gwang Mo; Ahn, Sang-Gun; Kwon, Seong-Min; Choi, Hoo-Kyun; Choi, Hong Seok

    2011-04-01

    Phenolic constituents of virgin olive oil are reported to have antitumor activity. However, the underlying molecular mechanisms and specific target proteins of virgin olive oil remain to be elucidated. Here, we report that dialdehydic form of decarboxymethyl ligstroside aglycone (p-HPEA-EDA), a phenolic compound of virgin olive oil, inhibits tumor promoter-induced cell transformation in JB6 Cl41 cells and suppress cyclooxygenase-2 (COX-2) and tumorigenicity by adenosine monophosphate-activated protein kinase (AMPK) activation in HT-29 cells. p-HPEA-EDA inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced phosphorylation of extracellular signal-regulated kinases 1/2 and p90RSK in JB6 Cl41 cells, resulting in the inhibition of cell proliferation, activator protein-1 transactivation and cell transformation promoted by TPA. Moreover, p-HPEA-EDA strongly inhibited the cell viability and COX-2 expression by activation of AMPK activity in HT-29 cells, resulted from depletion of intracellular adenosine triphosphate. p-HPEA-EDA-induced activation of caspase-3 and poly-adenosine diphosphate-ribose polymerase, phosphorylation of p53 (Ser15) and DNA fragmentation in HT-29 cells, leading to apoptosis. Importantly, p-HPEA-EDA suppressed the colony formation of HT-29 cells in soft agar. In contrast, Compound C, an AMPK inhibitor, and Z-DEVD-FMK, a caspase-3 inhibitor, blocked the p-HPEA-EDA-inhibited colony formation in HT-29 cells. In vivo chorioallantoic membrane assay also showed that p-HPEA-EDA-inhibited tumorigenicity of HT-29 cells. These findings revealed that targeted activation of AMPK and inhibition of COX-2 expression by p-HPEA-EDA contribute to the chemopreventive and chemotherapeutic potential of virgin olive oil against colon cancer cells. PMID:21216846

  1. Characteristic Chemical Components and Aroma-active Compounds of the Essential Oils from Ranunculus nipponicus var. submersus Used in Japanese Traditional Food.

    PubMed

    Nakaya, Satoshi; Usami, Atsushi; Yorimoto, Tomohito; Miyazawa, Mitsuo

    2015-06-01

    Ranunculus nipponicus var. submersus is an aquatic macrophyte; it is known as a wild edible plant in Japan for a long time. In this study, the essential oils from the fresh and dried aerial parts of R. nipponicus var. submersus were extracted by hydrodistillation and analyzed by gas chromatography (GC) and GC-mass spectrometry (GC-MS). Moreover, important aroma-active compounds were also detected in the oil using GC-olfactometry (GC-O) and aroma extract dilution analysis (AEDA). Thus, 98 compounds (accounting for 93.86%) of the oil were identified. The major compounds in fresh plant oil were phytol (41.94%), heptadecane (5.92%), and geranyl propionate (5.76%), while those of. Dried plant oil were ?-ionone (23.54%), 2-hexenal (8.75%), and dihydrobovolide (4.81%). The fresh and dried oils had the green-floral and citrus-floral odor, respectively. The GC-O and AEDA results show that phenylacetaldehyde (green, floral odor, FD-factor = 8) and ?-ionone (violet-floral odor, FD-factor = 8) were the most characteristic odor compounds of the fresh oils. ?-Cyclocitral (citrus odor, FD-factor = 64) and ?-ionone (violet-floral odor, FD-factor = 64) were the most characteristic odor compounds of the dried oil. These compounds are thought to contribute to the flavor of R. nipponicus var. submersus. PMID:25891110

  2. [Rough sets theory in the analysis of structure-activity relationships of quaternary quinolinium- and isoquinolinium compounds].

    PubMed

    Krysinski, J

    1991-11-01

    Relationship between chemical structure and antimicrobial activity of 72 quaternary quinolinium and isoquinolinium compounds is analyzed using the theory of rough sets. The compounds are described by 11 attributes concerning structure and are divided into 3 classes of activity. The description builds up on information system. Using the rough sets approach a smallest set of attributes significant for a high quality of classification has been found. A decision algorithm has been driven from the information system showing up important relations between structure and activity. This may be helpful in supporting decisions concerning synthesis of new antimicrobial compounds. PMID:1804057

  3. A c-Myc activation sensor-based high-throughput drug screening identifies an antineoplastic effect of nitazoxanide.

    PubMed

    Fan-Minogue, Hua; Bodapati, Sandhya; Solow-Cordero, David; Fan, Alice; Paulmurugan, Ramasamy; Massoud, Tarik F; Felsher, Dean W; Gambhir, Sanjiv S

    2013-09-01

    Deregulation of c-Myc plays a central role in the tumorigenesis of many human cancers. Yet, the development of drugs regulating c-Myc activity has been challenging. To facilitate the identification of c-Myc inhibitors, we developed a molecular imaging sensor-based high-throughput screening (HTS) system. This system uses a cell-based assay to detect c-Myc activation in a HTS format, which is established from a pure clone of a stable breast cancer cell line that constitutively expresses a c-Myc activation sensor. Optimization of the assay performance in the HTS format resulted in uniform and robust signals at the baseline. Using this system, we conducted a quantitative HTS against approximately 5,000 existing bioactive compounds from five different libraries. Thirty-nine potential hits were identified, including currently known c-Myc inhibitors. There are a few among the top potent hits that are not known for anti-c-Myc activity. One of these hits is nitazoxanide, a thiazolide for treating human protozoal infections. Validation of nitazoxanide in different cancer cell lines revealed a high potency for c-Myc inhibition with IC50 ranging between 10 and 500 nmol/L. Oral administration of nitazoxanide in breast cancer xenograft mouse models significantly suppressed tumor growth by inhibition of c-Myc and induction of apoptosis. These findings suggest a potential of nitazoxanide to be repurposed as a new antitumor agent for inhibition of c-Myc-associated neoplasia. Our work also demonstrated the unique advantage of molecular imaging in accelerating discovery of drugs for c-Myc-targeted cancer therapy. PMID:23825064

  4. Selected Compounds Structurally Related to Acyclic Sesquiterpenoids and Their Antibacterial and Cytotoxic Activity.

    PubMed

    Bonikowski, Rados?aw; ?witakowska, Paulina; Sienkiewicz, Monika; Zak?os-Szyda, Ma?gorzata

    2015-01-01

    By implementing a common and industrially used method, 30 compounds which are structurally related to geranyl acetone, nerolidol, farnesal, farnesol and farnesyl acetate were obtained. Their antimicrobial activity against Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii bacteria was investigated. Pharmacophore models were proposed based on the obtained results and 3D QSAR modelling. Cytotoxic effects against mainly human immortalised and normal cell lines of different origin (malignant melanoma MeWo, colorectal adenocarcinoma HT29, promyelocytic leukemia HL60, gingival fibroblasts HFIG, skin keratinocytes HaCaT and rat small intestine epithelium IEC6) were examined. The odour descriptions of newly synthesised compounds are given. PMID:26096434

  5. Antioxidant activity and bioactive compounds of lettuce improved by espresso coffee residues.

    PubMed

    Cruz, Rebeca; Gomes, Teresa; Ferreira, Anabela; Mendes, Eulália; Baptista, Paula; Cunha, Sara; Pereira, José Alberto; Ramalhosa, Elsa; Casal, Susana

    2014-02-15

    The antioxidant activity and individual bioactive compounds of lettuce, cultivated with 2.5-30% (v/v) of fresh or composted espresso spent coffee grounds, were assessed. A progressive enhancement of lettuce's antioxidant capacity, evaluated by radical scavenging effect and reducing power, was exhibited with the increment of fresh spent coffee amounts, while this pattern was not so clear with composted treatments. Total reducing capacity also improved, particularly for low spent coffee concentrations. Additionally, very significant positive correlations were observed for all carotenoids in plants from fresh spent coffee treatments, particularly for violaxanthin, evaluated by HPLC. Furthermore, chlorophyll a was a good discriminating factor between control group and all spent coffee treated samples, while vitamin E was not significantly affected. Espresso spent coffee grounds are a recognised and valuable source of bioactive compounds, proving herein, for the first time, to potentiate the antioxidant pool and quality of the vegetables produced. PMID:24128454

  6. Using fMRI Brain Activation to Identify Cognitive States Associated with Perception of Tools and Dwellings

    E-print Network

    Using fMRI Brain Activation to Identify Cognitive States Associated with Perception of Tools a simple cognitive state (such as the thought of a hammer) and the underlying brain activity. Moreover function uses machine learning techniques to identify the neural pattern of brain activity underlying

  7. Development of broad-spectrum antimicrobial latex paint surfaces employing active amphiphilic compounds.

    PubMed

    Fulmer, Preston A; Wynne, James H

    2011-08-01

    With the increase in antibiotic-resistant microbes, the production of self-decontaminating surfaces has become an area of research that has seen a surge of interest in recent years. Such surfaces, when incorporated into commercial products such as children's toys, medical devices and hospital surfaces could reduce the number of infections caused by pathogenic microorganisms. A number of active components for self-decontaminating surfaces have been investigated, including common antibiotics, metal ions, quaternary ammonium salts (QAS), and antimicrobial peptides (AMP). A recent research focus has been development of a wide range of amphiphilic antimicrobial additives that when combined with modern low volatile organic compound (VOC), water-based paints leads to a surface concentration of the active compounds as the coating cures. Herein we report the development of antimicrobial coatings containing a variety of additives, both QAS and AMP that are active against a broad-spectrum of potentially pathogenic bacteria (1-7 log kill), as well as enveloped viruses (2-7 log kill) and fungi (1-2 log kill). Additionally, these additives were compatible with water-dispersed acrylate coatings (latex paint) which have a broad range of real world applicability, and remained active for multiple challenges and when exposed to various cleaning scenarios in which they might encounter in real world situations. PMID:21770409

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

    PubMed Central

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

    2011-01-01

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

  9. A study of effect of the compound physical activity therapy on muscular strength in obese women.

    PubMed

    Kak, Hwang-Bo; Cho, Sung-Hyoun; Lee, Young-Hwa; Cho, Byung-Jun; Kim, Jin-Woo; Oh, Byoung-Don; Koh, Hyung-Woo

    2013-08-01

    [Purpose] The aim of this study was to determine how compound physical activity affects muscular strength of middle-aged obese women. [Subjects] The research subjects were 40-50?year-old middle-aged women with excess body fat (30%). [Methods] The subjects were randomly assigned to two group, the experimental group and the control group. The experimental group performed two types of exercise programs for 16 weeks. Aerobic physical activity was performed 5 times per week, and anaerobic physical activity was performed every two days, and the exercise program each day was composed of a warm-up, the main exercise, and cooldown. The type of exercise focused on walking at a quick pace, and the intensity of the exercise focused on long periods of exercise at low intensity with the level of HRmax being 40-60%. The weight training, which was useful for beginners, as a type of kinetic load exercise, was applied with a composition recommended by the ACSM for muscle fitness (intensity of 40-60% of 1 RM and 10-15 repetitions). SPSS version 16.0 was used to analyze the data by ANCOVA and the t-test. [Results] The chest, leg, and abdominal strengths were significantly increased in the experimental group, and this indicates that compound physical activity is effective for improvement of muscular strength. [Conclusion] In conclusion, there were significant differences between groups in terms of muscular strength. PMID:24259911

  10. From dynamic combinatorial ‘hit’ to lead: in vitro and in vivo activity of compounds targeting the pathogenic RNAs that cause myotonic dystrophy

    PubMed Central

    Ofori, Leslie O.; Hoskins, Jason; Nakamori, Masayuki; Thornton, Charles A.; Miller, Benjamin L.

    2012-01-01

    The myotonic dystrophies (DM) are human diseases in which the accumulation of toxic RNA (CUG or CCUG) repeats in the cell causes sequestration of splicing factors, including MBNL1, leading to clinical symptoms such as muscle wasting and myotonia. We previously used Dynamic Combinatorial Chemistry to identify the first compounds known to inhibit (CUG)-MBNL1 binding in vitro. We now report transformation of those compounds into structures with activity in vivo. Introduction of a benzo[g]quinoline substructure previously unknown in the context of RNA recognition, as well as other modifications, provided several molecules with enhanced binding properties, including compounds with strong selectivity for CUG repeats over CAG repeats or CAG–CUG duplex RNA. Compounds readily penetrate cells, and improve luciferase activity in a mouse myoblast assay in which enzyme function is coupled to a release of nuclear CUG–RNA retention. Most importantly, two compounds are able to partially restore splicing in a mouse model of DM1. PMID:22492623

  11. Significant Centers of Tectonic Activity as Identified by Wrinkle Ridges for the Western Hemisphere of Mars

    NASA Technical Reports Server (NTRS)

    Anderson, R.C.; Haldemann, A. F. C.; Golombek, M. P.; Franklin, B. J.; Dohm, J. M.; Lias, J.

    2000-01-01

    The western hemisphere region of Mars has been the site of numerous scientific investigations regarding its tectonic evolution. For this region of Mars, the dominant tectonic region is the Tharsis province. Tharsis is characterized by an enormous system of radiating grabens and a circumferential system of wrinkle ridges. Past investigations of grabens associated with Tharsis have identified specific centers of tectonic activity. A recent structural analysis of the western hemisphere region of Mars which includes the Tharsis region, utilized 25,000 structures to determine the history of local and regional centers of tectonic activity based primarily on the spatial and temporal relationships of extensional features. This investigation revealed that Tharsis is more structurally complex (heterogeneous) than has been previously identified: it consists of numerous regional and local centers of tectonic activity (some are more dominant and/or more long lived than others). Here we use the same approach as Anderson et al. to determine whether the centers of tectonic activity that formed the extensional features also contributed to wrinkle ridge (compressional) formation.

  12. Two ?-xylanases from Aspergillus terreus: characterization and influence of phenolic compounds on xylanase activity.

    PubMed

    de Souza Moreira, Leonora Rios; de Carvalho Campos, Marcela; de Siqueira, Pedro Henrique Vieira Martins; Silva, Luciano Paulino; Ricart, Carlos André Ornelas; Martins, Pedro Alves; Queiroz, Rayner Myr Lautherjung; Filho, Edivaldo Ximenes Ferreira

    2013-11-01

    Sugarcane bagasse was used as an inexpensive alternative carbon source for production of ?-xylanases from Aspergillus terreus. The induction profile showed that the xylanase activity was detected from the 6th day of cultivation period. Two low molecular weight enzymes, named Xyl T1 and Xyl T2 were purified to apparent homogeneity by ultrafiltration, gel filtration and ion exchange chromatographies and presented molecular masses of 24.3and 23.60 kDa, as determined by SDS-PAGE, respectively. Xyl T1 showed highest activity at 50 °C and pH 6.0, while Xyl T2 was most active at 45 °C and pH 5.0. Mass spectrometry analysis of trypsin digested Xyl T1 and Xyl T2 showed two different fingerprinting spectra, indicating that they are distinct enzymes. Both enzymes were specific for xylan as substrate. Xyl T1 was inhibited in greater or lesser degree by phenolic compounds, while Xyl T2 was very resistant to the inhibitory effect of all phenolic compounds tested. The apparent km values of Xyl T2, using birchwood xylan as substrate, decreased in the presence of six phenolic compounds. Both enzymes were inhibited by N-bromosuccinimide and Hg(2+) and activated by Mn(2+). Incubation of Xyl T1 and Xyl T2 with L-cysteine increased their half-lives up to 14 and 24 h at 50 °C, respectively. Atomic force microscopy showed a bimodal size distribution of globular particles for both enzymes, indicating that Xyl T1 is larger than Xyl T2. PMID:23892064

  13. Relationship between odour-active compounds and flavour perception in meat from lambs fed different diets.

    PubMed

    Resconi, Virginia C; Campo, M Mar; Montossi, Fabio; Ferreira, Vicente; Sañudo, Carlos; Escudero, Ana

    2010-08-01

    To identify the most important aroma compounds in 20d-aged meat from castrated heavy Corriedale lambs fed one of four diets, grilled loin samples were subjected to a dynamic headspace-solid phase extraction (DHS-SPE) and gas chromatography-olfactometry (GC-O). Most of the important odorants were aldehydes and ketones. To evaluate the effect of finishing diet on carbonyl compounds, a derivatization of the headspace carbonyls using o-[(2,3,4,5,6-pentafluorophenyl)methyl]hydroxylamine hydrochloride (PFBHA) and analysis by GC-MS was conducted. Diet did not affect aliphatic saturated aldehydes. The meat from lambs finished on pastures, without a concentrate supplement, had very low concentrations of lipid-derived unsaturated aldehydes and ketones and Strecker aldehydes, possibly because of the protective effect of antioxidants that occur in the diet naturally. Lamb flavour was related to the concentration of heptan-2-one and oct-1-en-3-one, but rancid or undesirable flavours were not related to the abundance of carbonyl compounds. PMID:20416794

  14. Antimicrobial activities of the methanol extract, fractions and compounds from Ficus polita Vahl. (Moraceae)

    PubMed Central

    2011-01-01

    Background Many plants of the family Moraceae are used in the treatment of infectious diseases. Ficus polita Vahl., an edible plant belonging to this family is used traditionally in case of dyspepsia, infectious diseases, abdominal pains and diarrhea. The present work was designed to assess the antimicrobial activity of the methanol extract from the roots of F. polita (FPR), as well as that of its fractions (FPR1-5) and two of the eight isolated compounds, namely euphol-3-O-cinnamate (1) and (E)-3,5,4'-trihydroxy-stilbene-3,5-O-?-D-diglucopyranoside (8). Methods The liquid microdilution assay was used in the determination of the minimal inhibitory concentration (MIC) and the minimal microbicidal concentration (MMC), against seven bacterial and one fungal species. Results The results of the MIC determination showed that the crude extract, fractions FPR1, FPR2 and compound 8 were able to prevent the growth of the eight tested microorganisms. Other samples showed selective activity. The lowest MIC value of 64 ?g/ml for the crude extract was recorded on 50% of the studied microbial species. The corresponding value for fractions of 32 ?g/ml was obtained on Salmonella typhi, Escherichia coli and Candida albicans ATCC strains. The MIC values recorded with compound 8 on the resistant Pseudomonas aeruginosa PA01 strain was equal to that of chloramphenicol used as reference antibiotic. Conclusion The obtained results highlighted the interesting antimicrobial potency of F. polita as well as that of compound 8, and provided scientific basis for the traditional use of this taxon in the treatment of microbial infections. PMID:21269424

  15. Theoretical and experimental study on lipophilicity and wound healing activity of ginger compounds

    PubMed Central

    Bakht, Mohammed Afroz; Alajmi, Mohammed F.; Alam, Perwez; Alam, Aftab; Alam, Prawez; Aljarba, Tariq Mohammed

    2014-01-01

    Objective To correlate the chromatographic and computational method to calculate lipophilicity of selected ginger compounds and to observe the effects of log P on wound healing. Methods Mixtures of acetonitrile and water with acetonitrile content between 95% and 50% v/v in 5% increments were kept separately in 10 different chromatographic chambers, saturated with solvent for 2 h. Spots were observed under UV light at ?=254 nm p-anisaldehyde used as a spraying reagent. Theoretical calculation was done using the Alogps 2.1 online program at www.vcclab.org/lab/alogps. For percentage wound contraction, five groups of animal (mice) (25-30 g) of either sex were selected. Wound were created on dorsal surface of animals using toothed forceps, scalpel and pointed scissors. The wound areas were calculated using vernier caliper. After making wound mice were orally administered 35 mg/kg 6-shogoal, 6-gingerol, 8-gingerol and 10-gingerol respectively. Group E as the control group received tap water. Results The lipophilicity values determined in thin layer chromatography were correlated with the theoretically calculated various log P by linear regression analysis. Significant correlations were found between log P values calculated by software program and the experimental reversed-phase thin-layer chromatography data. Order of wound healing property of ginger compounds is directly dependent on lipophilicity i.e. more lipophilic compound has highest activity. Conclusions Experimentally determined lipophilicity (RMO) values were correlated with log P determined by software's and found satisfactory. Lipophilicity (RMO) is a useful parameter for the determination and prediction of biological activity of ginger compounds. PMID:25182560

  16. Inhibitory effect of sulfur dioxide and other stress compounds in wine on the ATPase activity of Oenococcus oeni

    Microsoft Academic Search

    Ramon Carreté; M. Teresa Vidal; Albert Bordons; Magda Constant??

    2002-01-01

    Malolactic fermentation (MLF) is carried out by Oenococcus oeni under very harsh conditions. This paper shows that stress compounds in wine such as SO2, fatty acids and copper have an inhibitory effect on cell growth and MLF duration, and relates this effect to an inhibition of ATPase activity. Of the stress compounds, SO2 and dodecanoic acid had the strongest effect,

  17. COMPUTATIONAL MODELING OF SERUM BINDING PROTEINSAND CLEARANCE IN EXTRAPOLATIONS ACROSS LIFE-STAGES AND SPECIES FOR ENDOCRINE ACTIVE COMPOUNDS

    EPA Science Inventory

    One measure of the potency of compounds that lead to adverse 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. gen...

  18. A Stepwise Procedure for Assessment of the Microbial Respiratory Activity of Soil Samples Contaminated with Organic Compounds

    Microsoft Academic Search

    Adolf Eisentraeger; Gudrun Maxam; Jean-Paul Rila; Wolfgang Dott

    2000-01-01

    Soil respiration measurements are used frequently for the characterization of soil samples. Identical methods are used for the ecotoxicological characterization of contaminated soil samples as well as for quantification of the active microbial biomass in agriculturally used soils. In this study four soil samples contaminated with large amounts of volatile organic compounds, polyaromatic hydrocarbons, or nitroaromatic compounds are characterized after

  19. Accelerometer tags: detecting and identifying activities in fish and the effect of sampling frequency.

    PubMed

    Broell, Franziska; Noda, Takuji; Wright, Serena; Domenici, Paolo; Steffensen, John Fleng; Auclair, Jean-Pierre; Taggart, Christopher T

    2013-04-01

    Monitoring and measuring the behaviour and movement of aquatic animals in the wild is typically challenging, though micro-accelerometer (archival or telemetry) tags now provide the means to remotely identify and quantify behavioural states and rates such as resting, swimming and migrating, and to estimate activity and energy budgets. Most studies use low-frequency (?32 Hz) accelerometer sampling because of battery and data-archiving constraints. In this study we assessed the effect of sampling frequency (aliasing) on activity detection probability using the great sculpin (Myoxocephalus polyacanthoceaphalus) as a model species. Feeding strikes and escape responses (fast-start activities) and spontaneous movements among seven different great sculpin were triggered, observed and recorded using video records and a tri-axial accelerometer sampling at 100 Hz. We demonstrate that multiple parameters in the time and probability domains can statistically differentiate between activities with high detection (90%) and identification (80%) probabilities. Detection probability for feeding and escape activities decreased by 50% when sampling at <10 Hz. Our analyses illustrate additional problems associated with aliasing and how activity and energy-budget estimates can be compromised and misinterpreted. We recommend that high-frequency (>30 Hz) accelerometer sampling be used in similar laboratory and field studies. If battery and/or data storage is limited, we also recommend archiving the events via an on-board algorithm that determines the highest likelihood and subsequent archiving of the various event classes of interest. PMID:23197088

  20. Relationships between the Firing of Identified Striatal Interneurons and Spontaneous and Driven Cortical Activities In Vivo

    PubMed Central

    Sharott, Andrew; Doig, Natalie M.; Mallet, Nicolas; Magill, Peter J.

    2014-01-01

    The striatum is comprised of medium-sized spiny projection neurons (MSNs) and several types of interneuron, and receives massive glutamatergic input from the cerebral cortex. Understanding of striatal function requires definition of the electrophysiological properties of neurochemically identified interneurons sampled in the same context of ongoing cortical activity in vivo. To address this, we recorded the firing of cholinergic interneurons (expressing choline acetyltransferase; ChAT) and GABAergic interneurons expressing parvalbumin (PV) or nitric oxide synthase (NOS), as well as MSNs, in anesthetized rats during cortically defined brain states. Depending on the cortical state, these interneurons were partly distinguished from each other, and MSNs, on the basis of firing rate and/or pattern. During slow-wave activity (SWA), ChAT+ interneurons, and some PV+ and NOS+ interneurons, were tonically active; NOS+ interneurons fired prominent bursts but, contrary to investigations in vitro, these were not typical low-threshold spike bursts. Identified MSNs, and other PV+ and NOS+ interneurons, were phasically active. Contrasting with ChAT+ interneurons, whose firing showed poor brain state dependency, PV+ and NOS+ interneurons displayed robust firing increases and decreases, respectively, upon spontaneous or driven transitions from SWA to cortical activation. The firing of most neurons was phase locked to cortical slow oscillations, but only PV+ and ChAT+ interneurons also fired in time with cortical spindle and gamma oscillations. Complementing this diverse temporal coupling, each interneuron type exhibited distinct responses to cortical stimulation. Thus, these striatal interneuron types have distinct temporal signatures in vivo, including relationships to spontaneous and driven cortical activities, which likely underpin their specialized contributions to striatal microcircuit function. PMID:22993438

  1. In vitro and vivo antioxidant activities of daylily flowers and the involvement of phenolic compounds.

    PubMed

    Que, Fei; Mao, Linchun; Zheng, Xiaojie

    2007-01-01

    Daylily (Hemerocallis fulva Linn.) flowers were hot air-dried and freeze-dried after harvest. Antioxidant properties of water and ethanol extracts prepared from these dried flowers were evaluated in terms of total antioxidant activity, reducing capacity, and metal chelating activity. Extracts from daylily flowers exhibited strong antioxidant activity. Ethanol was more efficiency to extract antioxidants than water, and freeze-drying preserved higher activities than air-drying. Rutin, (+)-catechin, and gallic acid were identified in the extracts by HPLC, and were highly related to the antioxidant activities. The antioxidant activity was further evaluated by feeding mice with ethanol extract from freeze-dried daylily flowers for 60 days. The results demonstrated that the extract at dosage of 40-225 mg/100 g significantly increased the activity of SOD (superoxide dismutase) and reduced the lipid peroxidation in both blood and liver of rat. PMID:17392104

  2. Screening Assay for Promigratory\\/Antimigratory Compounds

    Microsoft Academic Search

    Will L. Rust; Janice L. Huff; George E. Plopper

    2000-01-01

    Large-scale screening strategies aimed at finding anticancer drugs traditionally focus on identifying cytotoxic compounds that attack actively dividing cells. Because progression to malignancy involves acquisition of an aggressively invasive phenotype in addition to hyperproliferation, simple and effective screening strategies for finding compounds that target the invasive aspects of cancer progression may prove valuable for identifying alternative and preventative cancer therapies.

  3. Enhancement of protocatechuate decarboxylase activity for the effective production of muconate from lignin-related aromatic compounds.

    PubMed

    Sonoki, Tomonori; Morooka, Miyuki; Sakamoto, Kimitoshi; Otsuka, Yuichiro; Nakamura, Masaya; Jellison, Jody; Goodell, Barry

    2014-12-20

    The decarboxylation reaction of protocatechuate has been described as a bottleneck and a rate-limiting step in cis,cis-muconate (ccMA) bioproduction from renewable feedstocks such as sugar. Because sugars are already in high demand in the development of many bio-based products, our work focuses on improving protocatechuate decarboxylase (Pdc) activity and ccMA production in particular, from lignin-related aromatic compounds. We previously had transformed an Escherichia coli strain using aroY, which had been used as a protocatechuate decarboxylase encoding gene from Klebsiella pneumoniae subsp. pneumoniae A170-40, and inserted other required genes from Pseudomonas putida KT2440, to allow the production of ccMA from vanillin. This recombinant strain produced ccMA from vanillin, however the Pdc reaction step remained a bottleneck during incubation. In the current study, we identify a way to increase protocatechuate decarboxylase activity in E. coli through enzyme production involving both aroY and kpdB; the latter which encodes for the B subunit of 4-hydroxybenzoate decarboxylase. This permits expression of Pdc activity at a level approximately 14-fold greater than the strain with aroY only. The expression level of AroY increased, apparently as a function of the co-expression of AroY and KpdB. Our results also imply that ccMA may inhibit vanillate demethylation, a reaction step that is rate limiting for efficient ccMA production from lignin-related aromatic compounds, so even though ccMA production may be enhanced, other challenges to overcome vanilate demethylation inhibition still remain. PMID:25449108

  4. Identifying induced seismicity in active tectonic regions: A case study of the San Joaquin Basin, California

    NASA Astrophysics Data System (ADS)

    Aminzadeh, F.; Göbel, T.

    2013-12-01

    Understanding the connection between petroleum-industry activities, and seismic event occurrences is essential to monitor, quantify, and mitigate seismic risk. While many studies identified anthropogenically-induced seismicity in intraplate regions where background seismicity rates are generally low, little is known about how to distinguish naturally occurring from induced seismicity in active tectonic regions. Further, it is not clear how different oil and gas operational parameters impact the frequency and magnitude of the induced seismic events. Here, we examine variations in frequency-size and spatial distributions of seismicity within the Southern Joaquin basin, an area of both active petroleum production and active fault systems. We analyze a newly available, high-quality, relocated earthquake catalog (Hauksson et al. 2012). This catalog includes many seismic events with magnitudes up to M = 4.5 within the study area. We start by analyzing the overall quality and consistence of the seismic catalog, focusing on temporal variations in seismicity rates and catalog completeness which could indicate variations in network sensitivity. This catalog provides relatively homogeneous earthquake recordings after 1981, enabling us to compare seismicity rates before and after the beginning of more pervasive petroleum-industry activities, for example, hydraulic-fracturing and waste-water disposals. We conduct a limited study of waste-water disposal wells to establish a correlation between seismicity statistics (i.e. rate changes, fractal dimension, b-value) within specific regions and anthropogenic influences. We then perform a regional study, to investigate spatial variations in seismicity statistics which are then correlated to oil field locations and well densities. In order to distinguish, predominantly natural seismicity from induced seismicity, we perform a spatial mapping of b-values and fractal dimensions of earthquake hypocenters. Seismic events in the proximity to active oil fields generally show different characteristics of frequency-magnitude distributions, higher fractal dimensions and higher b-values compared to natural seismicity. The estimated b-values vary between 0.7 close to the San Andreas fault up to 1.3 within the North-western corner of the Kern County. High b-values within this particular region are likely related to active petroleum production. The spatial differences in seismicity statistics delineate earthquakes related to active faults from distributed seismicity toward the center of the basin. Our results highlight, that the analysis of spatial and temporal variations in seismicity statistics may be a promising tool to identify induced seismicity in active tectonic regions.

  5. Ergosterol Is the Active Compound of Cultured Mycelium Cordyceps sinensis on Antiliver Fibrosis

    PubMed Central

    Peng, Yuan; Tao, Yanyan; Wang, Qinglan; Shen, Li; Yang, Tao; Liu, Zulong; Liu, Chenghai

    2014-01-01

    Cultured mycelium Cordyceps sinensis (CMCS) is a Chinese herbal medicine, which is widely used for a variety of diseases including liver injury in clinic. The current study aims to investigate the protective effects of CMCS against liver fibrosis and to exploit its active antifibrotic substances in vivo and in vitro. For evaluating the antifibrotic effect of CMCS and ergosterol, male C57BL/6 mice were injected intraperitoneally with carbon tetrachloride (CCl4) and treated with CMCS (120?mg/kg/d) or ergosterol (50?mg/kg/d). Four weeks later, serum liver function, hepatic hydroxyproline (Hyp) content, liver inflammation, collagen deposition, and expression of alpha smooth muscle actin (?-SMA) in liver tissue were evaluated. Besides, toxicological effects of active compounds of CMCS on hepatocytes and hepatic stellate cells (HSCs) were detected and expressions of permeability of the lysosomal membrane, EdU, F-actin, and ?-SMA of activated HSCs were analyzed to screen the antifibrotic substance in CMCS in vitro. Our results showed that CMCS could significantly alleviate levels of serum liver functions, attenuate hepatic inflammation, decrease collagen deposition, and relieve levels of ?-SMA in liver, respectively. Ergosterol, the active compound in CMCS that was detected by HPLC, played a dose-dependent inhibition role on activated HSCs via upregulating expressions of permeability of the lysosomal membrane and downregulating levels of EdU, F-actin, and ?-SMA on activated HSCs in vitro. Moreover, ergosterol revealed the antifibrotic effect alike in vivo. In conclusion, CMCS is effective in alleviating liver fibrosis induced by CCl4 and ergosterol might be the efficacious antifibrotic substance in CMCS in vivo and in vitro. PMID:25386220

  6. Ergosterol Is the Active Compound of Cultured Mycelium Cordyceps sinensis on Antiliver Fibrosis.

    PubMed

    Peng, Yuan; Tao, Yanyan; Wang, Qinglan; Shen, Li; Yang, Tao; Liu, Zulong; Liu, Chenghai

    2014-01-01

    Cultured mycelium Cordyceps sinensis (CMCS) is a Chinese herbal medicine, which is widely used for a variety of diseases including liver injury in clinic. The current study aims to investigate the protective effects of CMCS against liver fibrosis and to exploit its active antifibrotic substances in vivo and in vitro. For evaluating the antifibrotic effect of CMCS and ergosterol, male C57BL/6 mice were injected intraperitoneally with carbon tetrachloride (CCl4) and treated with CMCS (120?mg/kg/d) or ergosterol (50?mg/kg/d). Four weeks later, serum liver function, hepatic hydroxyproline (Hyp) content, liver inflammation, collagen deposition, and expression of alpha smooth muscle actin (?-SMA) in liver tissue were evaluated. Besides, toxicological effects of active compounds of CMCS on hepatocytes and hepatic stellate cells (HSCs) were detected and expressions of permeability of the lysosomal membrane, EdU, F-actin, and ?-SMA of activated HSCs were analyzed to screen the antifibrotic substance in CMCS in vitro. Our results showed that CMCS could significantly alleviate levels of serum liver functions, attenuate hepatic inflammation, decrease collagen deposition, and relieve levels of ?-SMA in liver, respectively. Ergosterol, the active compound in CMCS that was detected by HPLC, played a dose-dependent inhibition role on activated HSCs via upregulating expressions of permeability of the lysosomal membrane and downregulating levels of EdU, F-actin, and ?-SMA on activated HSCs in vitro. Moreover, ergosterol revealed the antifibrotic effect alike in vivo. In conclusion, CMCS is effective in alleviating liver fibrosis induced by CCl4 and ergosterol might be the efficacious antifibrotic substance in CMCS in vivo and in vitro. PMID:25386220

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

    PubMed

    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)-? 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. PMID:26028482

  8. Antimicrobial activity of essential oils and five terpenoid compounds against Campylobacter jejuni in pure and mixed culture experiments.

    PubMed

    Kurekci, Cemil; Padmanabha, Jagadish; Bishop-Hurley, Sharon L; Hassan, Errol; Al Jassim, Rafat A M; McSweeney, Christopher S

    2013-09-16

    The aim of this study was to examine the antimicrobial potential of three essential oils (EOs: tea tree oil, lemon myrtle oil and Leptospermum oil), five terpenoid compounds (?-bisabolol, ?-terpinene, cineole, nerolidol and terpinen-4-ol) and polyphenol against two strains of Campylobacter jejuni (ACM 3393 and the poultry isolate C338), Campylobacter coli and other Gram negative and Gram positive bacteria. Different formulations of neem oil (Azadirachta indica) with these compounds were also tested for synergistic interaction against all organisms. Antimicrobial activity was determined by the use of disc diffusion and broth dilution assays. All EOs tested were found to have strong antimicrobial activity against Campylobacter spp. with inhibitory concentrations in the range 0.001-1% (v/v). Among the single compounds, terpinen-4-ol showed the highest activity against Campylobacter spp. and other reference strains. Based on the antimicrobial activity and potential commerciality of these agents, lemon myrtle oil, ?-tops (?-terpineol+cineole+terpinen-4-ol) and terpinen-4-ol were also evaluated using an in vitro fermentation technique to test antimicrobial activity towards C. jejuni in the microbiota from the chicken-caecum. EO compounds (terpinen-4-ol and ?-tops) were antimicrobial towards C. jejuni at high doses (0.05%) without altering the fermentation profile. EOs and terpenoid compounds can have strong anti-Campylobacter activity without adversely affecting the fermentation potential of the chicken-caeca microbiota. EOs and their active compounds may have the potential to control C. jejuni colonisation and abundance in poultry. PMID:24041998

  9. ESTROGENICITY OF ALKYLPHENOLIC COMPOUNDS: A 3-D STRUCTURE-ACTIVITY OF GENE ACTIVATION

    EPA Science Inventory

    A SAR evaluation of alkylphenol potency in activating a human estrogen receptor (hER) reporter gene construct was done using the Common REactivity Pattern (COREPA) approach and its modification COREPA-C....

  10. An Automated High-Throughput Cell-Based Multiplexed Flow Cytometry Assay to Identify Novel Compounds to Target Candida albicans Virulence-Related Proteins

    PubMed Central

    Bernardo, Stella M.; Allen, Christopher P.; Waller, Anna; Young, Susan M.; Oprea, Tudor; Sklar, Larry A.; Lee, Samuel A.

    2014-01-01

    Although three major classes of systemic antifungal agents are clinically available, each is characterized by important limitations. Thus, there has been considerable ongoing effort to develop novel and repurposed agents for the therapy of invasive fungal infections. In an effort to address these needs, we developed a novel high-throughput, multiplexed screening method that utilizes small molecules to probe candidate drug targets in the opportunistic fungal pathogen Candida albicans. This method is amenable to high-throughput automated screening and is based upon detection of changes in GFP levels of individually tagged target proteins. We first selected four GFP-tagged membrane-bound proteins associated with virulence or antifungal drug resistance in C. albicans. We demonstrated proof-of-principle that modulation of fluorescence intensity can be used to assay the expression of specific GFP-tagged target proteins to inhibitors (and inducers), and this change is measurable within the HyperCyt automated flow cytometry sampling system. Next, we generated a multiplex of differentially color-coded C. albicans strains bearing C-terminal GFP-tags of each gene encoding candidate drug targets incubated in the presence of small molecules from the Prestwick Chemical Library in 384-well microtiter plate format. Following incubation, cells were sampled through the HyperCyt system and modulation of protein levels, as indicated by changes in GFP-levels of each strain, was used to identify compounds of interest. The hit rate for both inducers and inhibitors identified in the primary screen did not exceed 1% of the total number of compounds in the small-molecule library that was probed, as would be expected from a robust target-specific, high-throughput screening campaign. Secondary assays for virulence characteristics based on null mutant strains were then used to further validate specificity. In all, this study presents a method for the identification and verification of new antifungal drugs targeted to fungal virulence proteins using C. albicans as a model fungal pathogen. PMID:25350399

  11. [Influence of transition metal compounds on superoxide dismutase activity of sulfur reducing Desulfuromonas acetoxidans bacteria].

    PubMed

    Vasyliv, O M; Hnatush, S O

    2013-01-01

    Superoxide dismutase, as one of the enzymes of cells' antioxidant defensive system, catalyzes superoxide anion-radical (O2-) dismutation with O2 and H2O2 forming. The influence of such transition metal compounds, as FeSO4, FeCl3, MnCl2, NiCl2, and CoCl2 on superoxide dismutase activity of sulfur-reducing Desulfuromonas acetoxidans bacteria has been investigated. Maximal activity of the investigated enzyme has been observed accordingly under the influence of 1.0 mM of NiCl2, 2.0 mM of CoCl2 and MnCl2 on the second day and under the influence of 1.0 mM of FeCl3 and FeSO4 respectively, on the third day of growth in comparison with control samples. An increase of incubation time and concentration of metal compound in the medium caused the inhibition of superoxide dismutase activity. PMID:23720962

  12. The study of interactions between active compounds of coffee and willow (Salix sp.) bark water extract.

    PubMed

    Durak, Agata; Gawlik-Dziki, Urszula

    2014-01-01

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

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

    PubMed

    Fra?ková, Adéla; Marounek, Milan; Mozrová, V?ra; Weber, Jaroslav; Klou?ek, Pavel; Lukešová, Daniela

    2014-10-01

    Abstract Cronobacter sakazakii and C. malonaticus are opportunistic pathogens that cause infections in children and immunocompromised adults. In the present study, the antibacterial activity of 19 plant-derived compounds, 5 essential oils, and an extract of propolis were assessed against C. sakazakii and C. malonaticus. The effects of most of these antimicrobials have not been reported previously. Both strains were susceptible to thymol, carvacrol, thymoquinone, p-cymene, linalool, camphor, citral, eugenol, and trans-cinnamaldehyde as well as cinnamon, lemongrass, oregano, clove, and laurel essential oils; their minimum inhibitory concentrations varied between 0.1 and 2.0?mg/mL. As an alternative treatment method, vapors of the volatiles were tested as an indirect treatment. Vapors of trans-cinnamaldehyde, eugenol, oregano, and cinnamon essential oils inhibited both tested strains, while vapors of linalool were only active against C. sakazakii. To our knowledge, this study is the first time that the inhibitory activity of the vapors of these compounds and essential oils has been reported against Cronobacter spp. PMID:25062020

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

    PubMed Central

    Durak, Agata; Gawlik-Dziki, Urszula

    2014-01-01

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

  15. Structure-activity relationships of tea compounds against human cancer cells.

    PubMed

    Friedman, Mendel; Mackey, Bruce E; Kim, Hyun-Jeong; Lee, In-Seon; Lee, Kap-Rang; Lee, Seung-Un; Kozukue, Etsuko; Kozukue, Nobuyuki

    2007-01-24

    The content of the biologically active amino acid theanine in 15 commercial black, green, specialty, and herbal tea leaves was determined as the 2,4-dinitrophenyltheanine derivative (DNP-theanine) by a validated HPLC method. To define relative anticarcinogenic potencies of tea compounds and teas, nine green tea catechins, three black tea theaflavins, and theanine as well as aqueous and 80% ethanol/water extracts of the same tea leaves were evaluated for their ability to induce cell death in human cancer and normal cells using a tetrazolium microculture (MTT) assay. Compared to untreated controls, most catechins, theaflavins, theanine, and all tea extracts reduced the numbers of the following human cancer cell lines: breast (MCF-7), colon (HT-29), hepatoma (liver) (HepG2), and prostate (PC-3) as well as normal human liver cells (Chang). The growth of normal human lung (HEL299) cells was not inhibited. The destruction of cancer cells was also observed visually by reverse phase microscopy. Statistical analysis of the data showed that (a) the anticarcinogenic effects of tea compounds and of tea leaf extracts varied widely and were concentration dependent over the ranges from 50 to 400 microg/mL of tea compound and from 50 to 400 microg/g of tea solids; (b) the different cancer cells varied in their susceptibilities to destruction; (c) 80% ethanol/water extracts with higher levels of flavonoids determined by HPLC were in most cases more active than the corresponding water extracts; and (d) flavonoid levels of the teas did not directly correlate with anticarcinogenic activities. The findings extend related observations on the anticarcinogenic potential of tea ingredients and suggest that consumers may benefit more by drinking both green and black teas. PMID:17227049

  16. Enantioselective synthesis and vanilloid activity evaluation of 1-beta-(p-methoxycinnamoyl)polygodial, an antinociceptive compound from Drymis winteri barks.

    PubMed

    Della Monica, Carmela; De Petrocellis, Luciano; Di Marzo, Vincenzo; Landi, Raffaella; Izzo, Irene; Spinella, Aldo

    2007-12-01

    A simple strategy is outlined for preparation of the antinociceptive 1-beta-(p-methoxycinnamoyl)polygodial, isolated from Drymis winteri barks. The synthesized compound showed vanilloid activity. PMID:17951058

  17. Chemical composition and major odor-active compounds of essential oil from PINELLIA TUBER (dried rhizome of Pinellia ternata) as crude drug.

    PubMed

    Iwasa, Megumi; Iwasaki, Toshiki; Ono, Toshirou; Miyazawa, Mitsuo

    2014-01-01

    The chemical composition of the essential oil from PINELLIA TUBER (Japanese name: Hange), the dried rhizome of Pinellia ternata, was investigated by capillary gas chromatography (GC) and GC-mass spectrometry (MS) analyses. The oil obtained from Pinellia tuber was revealed the presence of 114 compounds, representing 90.6% of the total oil identified. This colorless oil had a spicy and woody odor. The main components of the oil were ?-cubebene (8.8%), atractylon (7.8%), methyl eugenol (6.2%), and ?-cadinene (5.3%). Fifteen major odor-active compounds were identified in the essential oil from PINELLIA TUBER by the GC-olfactometry (GC-O) and aroma extract dilution analysis (AEDA). Among these, safrole (spicy) and ?-vatirenene (woody) showed the highest flavor dilution (FD) factor (128), followed by paeonol (FD = 64; woody, spicy), ?-humulene (FD = 64; woody), and ?-phenylnaphthalene (FD = 64; spicy). PMID:24500103

  18. The activity of identified supraoptic neurones and their response to acetylcholine applied by iontophoresis

    PubMed Central

    Dreifuss, J. J.; Kelly, J. S.

    1972-01-01

    1. In urethane/pentobarbitone anaesthetized male rats, the hypothalamus and pituitary stalk were exposed by a transpharyngeal approach. Cells recorded with glass micro-electrodes from the ventral hypothalamus near the bifurcation of the internal carotid artery were identified as supraoptic neurones only when their antidromic action potential evoked at constant latency by stimulation of the pituitary stalk was cancelled by collision with a spontaneously occurring action potential. 2. More than 80% of the identified cells were spontaneously active. The frequency of firing was often slow (under 1 Hz) and rather irregular. More than half the cells, however, had a more distinctive firing pattern which recurred every 1-3 min and consisted of a period of low or absent activity alternating with periods of quite marked discharge which occasionally exceeded 20 Hz. This periodicity was retained when the over-all activity was enhanced by an intracarotid injection of 0·2 ml. 5% (w/v) NaCl. 3. Of fifty-two cells tested, thirty-six were excited by acetylcholine applied by iontophoresis from a multibarrelled micropipette with average ejection currents of 35 ± 5 nA (S.D. of thirty-six observations). Ten of these cells were also excited by nicotine applied with similar currents. PMID:5059232

  19. Antifeedant Compounds from Three Species of Apiaceae Active Against the Field Slug, Deroceras reticulatum (Muller)

    Microsoft Academic Search

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

    2004-01-01

    Extracts of volatiles from foliage of three plants in the Apiaceae, Conium maculatumL. (hemlock), Coriandrum sativum L. (coriander), and Petroselinum crispum Mill. (Nym.) (parsley), previously shown to exhibit antifeedant activity in assays with the field slug, Deroceras reticulatum (Muller) (Limacidae: Pulmonata), were studied further to identify the active components. Coupled gas chromatography–mass spectrometry (GC–MS) and neurophysiological assays using tentacle nerve

  20. Historic volatile organic compounds (VOCS) emissions estimates and activity data (for microcomputers). Data file

    SciTech Connect

    Mobley, J.D.; Gschwandtner, G.

    1988-03-31

    Lotus spreadsheets containing the data presented in Appendix B of the EPA report Historic Emissions of Volatile Organic Compounds (VOC) in the United States from 1900 to 1985 are provided on three 5 1/4 floppy diskettes. VOC emissions and activity data are given for the United States; Alabama-Florida; Georgia-Louisiana; Maine-Montana; Nebraska-North Dakota; Ohio-Tennessee; and Texas-Wyoming. The data file is in the LOTUS 1-2-3 format using the DOS 3.10 operating system.

  1. Lasing properties of active medium based on sulforhodamine 101 incorporated into commercial polyurethane compound

    SciTech Connect

    Nikolaev, S V; Pozhar, V V; Dzyubenko, M I [A.Ya. Usikov Institute of Radiophysics and Electronics, National Academy of Sciences of Ukraine, Khar'kov (Ukraine)

    2011-01-24

    The lasing properties of polymer matrices based on commercial polyurethane compound activated by sulforhodamine 101 dye are studied. Lasing with an efficiency of 26 % and pulse energy of 76 mJ is obtained using microsecond transverse pumping at a wavelength of 587 nm. The service life (time of operation to a decrease in the output energy by 50 % upon excitation by 0.3 J cm{sup -2} pulses) amounts to 2500 pulses. A particular attention is given to the bichromatic lasing spectra of the samples tested. Based on the experimental data a model explaining the two-band emission spectrum is proposed and discussed. (lasers and amplifiers)

  2. Highly selective palladium–benzothiazole carbene-catalyzed allylation of active methylene compounds under neutral conditions

    PubMed Central

    Cotugno, Pietro; Zambonin, Carlo Giorgio; Ciminale, Francesco

    2015-01-01

    Summary The Pd–benzothiazol-2-ylidene complex I was found to be a chemoselective catalyst for the Tsuji–Trost allylation of active methylene compounds carried out under neutral conditions and using carbonates as allylating agents. The proposed protocol consists in a simplified procedure adopting an in situ prepared catalyst from Pd2dba3 and 3-methylbenzothiazolium salt V as precursors. A comparison of the performance of benzothiazole carbene with phosphanes and an analogous imidazolium carbene ligand is also proposed. PMID:26199653

  3. Reduction of pharmaceutically active compounds by a lagoon wetland wastewater treatment system in Southeast Louisiana.

    PubMed

    Conkle, Jeremy L; White, John R; Metcalfe, Chris D

    2008-12-01

    A number of pharmaceutically active compounds (PhACs) have been detected in the aquatic environment as a result of discharges of municipal wastewater. In the state of Louisiana, USA, many municipalities treat wastewater using natural systems, such as lagoons and wetlands, rather than conventional wastewater treatment technologies. Nearly all research to date has focused on the fate of PhACs in conventional treatment plants, not constructed and natural wetlands. In the wastewater treatment plant (WWTP) for Mandeville, Louisiana, USA, wastewater flows of 7600 m(3)d(-1) are treated in a series of aeration lagoons (basins), followed by a constructed wetland and UV disinfection, before being discharged into a natural forested wetland (i.e. Bayou Chinchuba) and eventually, Lake Pontchartrain. Thirteen out of the 15PhACs investigated were detected in the wastewater inflow to the treatment plant. Only 9 of the 13 compounds were above the detection limits at the treatment plant effluent. The concentrations of most compounds were reduced by greater than 90% within the plant, while carbamazepine and sotalol were only reduced by 51% and 82%, respectively. The percent reductions observed in the Mandeville system were greater than reduction rates reported for conventional WWTPs; perhaps due to the longer treatment time ( approximately 30 days). Most target PhACs were not completely removed before discharge into Lake Pontchartrain, although their collective annual loading was reduced to less than 1kg and down to ppb with significant potential for dilution in the large lake. PMID:18977010

  4. Polyphenolic compounds and antioxidant activities of the leaves of Glochidion hypoleucum.

    PubMed

    Anantachoke, Natthinee; Kitphati, Worawan; Mangmool, Supachoke; Bunyapraphatsara, Nuntavan

    2015-03-01

    Bioassay-guided fractionation of the methanol extract of Glochidion hypoleucum (Miq.) Boerl leaves led to the isolation of five polyphenolic compounds, methyl gallate, gallic acid, apigenin-8-C-?-D-glucopyranoside (vitexin), luteolin-8-C-?-D-glucopyranoside (orientin), and luteolin-6-C-?-D-glucopyranoside (isoorientin). The chemical structures of the isolated compounds were determined using spectroscopic (NMR, UV-Vis, IR) and mass spectrometric techniques. The antioxidative properties of the methanol extract and isolated polyphenols were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) for radical scavenging activity and 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) to measure the level of reactive oxygen species (ROS). With the exception of vitexin, the crude methanol extract and the polyphenolic compounds inhibited DPPH radicals with IC50 values ranging from 2.46 ± 0.05 to 40.0 ± 0.3 ?g/mL. In addition, the crude methanol extract attenuated H202-induced intracellular ROS production in a dose-dependent manner in HEK-293 cells. Gallic acid and isoorientin significantly reduced the ROS level in HEK-293 cells at a concentration of 20 ?M. PMID:25924533

  5. Silver Oxynitrate, an Unexplored Silver Compound with Antimicrobial and Antibiofilm Activity.

    PubMed

    Lemire, Joe A; Kalan, Lindsay; Bradu, Alexandru; Turner, Raymond J

    2015-07-01

    Historically it has been accepted, and recent research has established, that silver (Ag) is an efficacious antimicrobial agent. A dwindling pipeline of new antibiotics, combined with an increase in the number of antibiotic-resistant infections, is bringing Ag to the fore as a therapeutic compound to treat infectious diseases. Currently, many formulations of Ag are being deployed for commercial and medical purposes, with various degrees of effectiveness at killing microbial cells. Here, we evaluated the antimicrobial and antibiofilm capacity of our lead compound, silver oxynitrate [Ag(Ag3O4)2NO3 or Ag7NO11], against other metal compounds with documented antimicrobial activity, including Ag2SO4, AgNO3, silver sulfadiazine (AgSD), AgO, Ag2O, and CuSO4. Our findings reveal that Ag7NO11 eradicates biofilm and planktonic populations of Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, uropathogenic Escherichia coli (UPEC), fluoroquinolone-resistant Pseudomonas aeruginosa (FQRP), and methicillin-resistant Staphylococcus aureus (MRSA) at lower concentrations than those of the other tested metal salts. Altogether, our results demonstrate that Ag7NO11 has an enhanced efficacy for the treatment of biofilm-forming pathogens. PMID:25918137

  6. Comprehensive profiling analysis of actively resorbing osteoclasts identifies critical signaling pathways regulated by bone substrate

    PubMed Central

    Purdue, P. Edward; Crotti, Tania N.; Shen, Zhenxin; Swantek, Jennifer; Li, Jun; Hill, Jonathan; Hanidu, Adedayo; Dimock, Janice; Nabozny, Gerald; Goldring, Steven R.; McHugh, Kevin P.

    2014-01-01

    As the only cells capable of efficiently resorbing bone, osteoclasts are central mediators of both normal bone remodeling and pathologies associates with excessive bone resorption. However, despite the clear evidence of interplay between osteoclasts and the bone surface in vivo, the role of the bone substrate in regulating osteoclast differentiation and activation at a molecular level has not been fully defined. Here, we present the first comprehensive expression profiles of osteoclasts differentiated on authentic resorbable bone substrates. This analysis has identified numerous critical pathways coordinately regulated by osteoclastogenic cytokines and bone substrate, including the transition from proliferation to differentiation, and sphingosine-1-phosphate signaling. Whilst, as expected, much of this program is dependent upon integrin beta 3, the pre-eminent mediator of osteoclast-bone interaction, a surprisingly significant portion of the bone substrate regulated expression signature is independent of this receptor. Together, these findings identify an important hitherto underappreciated role for bone substrate in osteoclastogenesis. PMID:25534583

  7. Pine Bark and Green Tea Concentrated Extracts: Antioxidant Activity and Comprehensive Characterization of Bioactive Compounds by HPLC–ESI-QTOF-MS

    PubMed Central

    Cádiz-Gurrea, María de la Luz; Fernández-Arroyo, Salvador; Segura-Carretero, Antonio

    2014-01-01

    The consumption of polyphenols has frequently been associated with low incidence of degenerative diseases. Most of these natural antioxidants come from fruits, vegetables, spices, grains and herbs. For this reason, there has been increasing interest in identifying plant extract compounds. Polymeric tannins and monomeric flavonoids, such as catechin and epicatechin, in pine bark and green tea extracts could be responsible for the higher antioxidant activities of these extracts. The aim of the present study was to characterize the phenolic compounds in pine bark and green tea concentrated extracts using high-performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC–ESI-QTOF-MS). A total of 37 and 35 compounds from pine bark and green tea extracts, respectively, were identified as belonging to various structural classes, mainly flavan-3-ol and its derivatives (including procyanidins). The antioxidant capacity of both extracts was evaluated by three complementary antioxidant activity methods: Trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC). Higher antioxidant activity values by each method were obtained. In addition, total polyphenol and flavan-3-ol contents, which were determined by Folin–Ciocalteu and vanillin assays, respectively, exhibited higher amounts of gallic acid and (+)-catechin equivalents. PMID:25383680

  8. Bioactive Compounds and Prebiotic Activity in Thailand-Grown Red and White Guava Fruit (Psidium guajava L.)

    Microsoft Academic Search

    W. Thuaytong; P. Anprung

    2011-01-01

    This research involves the comparison of bioactive compounds, volatile compounds and prebiotic activity of white guava (Psidium guajava L.) cv. Pansithong and red guava cv. Samsi. The antioxidant activity values determined by 2-diphenyl-1-picryhydrazyl (DPPH) free radical scavenging and ferric reducing antioxidant power (FRAP) assays were 10.28 µg fresh weight (fw)\\/µg DPPH and 78.56 µg Trolox equivalent (TE)\\/g fw for white

  9. Antioxidative activity and total phenolic compounds of leaf, root and petiole of four accessions of Centella asiatica (L.) Urban

    Microsoft Academic Search

    M. K Zainol; A Abd-Hamid; S Yusof; R Muse

    2003-01-01

    Antioxidative activity and total phenolic compounds of root, leaf and petiole of four accessions of Centella asiatica (L.) Urban, namely CA 01, CA 05, CA 08 and CA 11, were evaluated. Antioxidative activity of the extracts was measured using the ferric thiocyanate (FTC) method and thiobarbituric acid (TBA) test. The antioxidative activities were then compared with that of ?-tocopherol (natural

  10. Determination of phenolic compounds and their antioxidant activity in fruits and cereals.

    PubMed

    Stratil, P; Klejdus, B; Kubán, V

    2007-03-15

    Three methods, FCM (with Folin-Ciocalteu reagent), PBM (Price and Butler) and AAPM (with 4-aminoantipyrine) for assessment of phenolic compounds and three commonly used methods, TEAC (Trolox equivalent antioxidant capacity), DPPH (with diphenyl-picrylhydrazyl radical), and FRAP (ferric reducing antioxidant power) for evaluation of antioxidant capacity, were modified to a semimicroscale (total volume 1ml) with minimum consumption (to 100mul) of a sample and thereby applicable for fast screening. Appropriate standards and extracts of 17 kinds of fruit and six kinds of cereal were assessed for total content of phenolic compounds and total antioxidant capacity by each of these methods. The results of analyses of commonly used standards (gallic, caffeic and ferulic acids, (+)-catechin, Trolox, fenol and FeSO(4)) for these methods and identical plant extract showed different reactivity of principal reagent of the methods with individual standards and therefore with phenolic substances of extracts as well. However, the trends of the measured values of extracts could be compared, though their absolute values differ proportionally. At assessments of phenolic compounds it is important to determine content of ascorbic acid at roughly the same time and correct the obtained values according to its contribution to the increase in absorbance calculated on the basis of absorbance equations, especially for samples with a higher content. The same is true for reducing saccharides; they can significantly "elevate" values of contents of phenolic compounds and antioxidant activities (by even more than 50%), especially in samples of sweeter fruits. The saccharides should therefore be removed or a correction applied reflecting their concentration. PMID:19071517

  11. Analysis of the Bacterial Response to Ru(CO)3Cl(Glycinate) (CORM-3) and the Inactivated Compound Identifies the Role Played by the Ruthenium Compound and Reveals Sulfur-Containing Species as a Major Target of CORM-3 Action

    PubMed Central

    Begg, Ronald; Jesse, Helen E.; Mann, Brian E.; Sanguinetti, Guido; Poole, Robert K.

    2013-01-01

    Abstract Aims: Carbon monoxide (CO)-releasing molecules (CO-RMs) are being developed with the ultimate goal of safely utilizing the therapeutic potential of CO clinically. One such application is antimicrobial activity; therefore, we aimed to characterize and compare the effects of the CO-RM, CORM-3, and its inactivated counterpart, where all labile CO has been removed, at the transcriptomic and cellular level. Results: We found that both compounds are able to penetrate the cell, but the inactive form is not inhibitory to bacterial growth under conditions where CORM-3 is. Transcriptomic analyses revealed that the bacterial response to inactivated CORM-3 (iCORM-3) is much lower than to the active compound and that a wide range of processes appear to be affected by CORM-3 and to a lesser extent iCORM-3, including energy metabolism, membrane transport, motility, and the metabolism of many sulfur-containing species, including cysteine and methionine. Innovation: This work has demonstrated that both CORM-3 and its inactivated counterpart react with cellular functions to yield a complex response at the transcriptomic level. A full understanding of the actions of both compounds is vital to understand the toxic effects of CO-RMs. Conclusion: This work has furthered our understanding of how CORM-3 behaves at the cellular level and identifies the responses that occur when the host is exposed to the Ru compound as well as those that result from the released CO. This is a vital step in laying the groundwork for future development of optimized CO-RMs for eventual use in antimicrobial therapy. Antioxid. Redox Signal. 19, 1999–2012. PMID:23472713

  12. Bioactivity of tomato hybrid powder: antioxidant compounds and their biological activities.

    PubMed

    Tommonaro, Giuseppina; De Prisco, Rocco; Abbamondi, Gennaro Roberto; Nicolaus, Barbara

    2013-04-01

    The antioxidant and cytotoxic activities and the polyphenolic and anthocyanin contents of tomato hybrid powders were studied. Tomato powders were obtained, starting from the fresh fruits that had undergone an industrial process of drying and pulverization at two different temperatures. Antioxidant activities were evaluated in different extracts by using spectrophotometric assays: 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid and N,N-dimethyl-p-phenylenediamine dihydrochloride cation radical inhibition for lipophilic and hydrophilic extracts, respectively, and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay for polyphenolic extracts. Moreover, polyphenolic and anthocyanin contents were also carried out to detect the presence of these bioactive compounds. The effect of cytotoxic activity in vitro of tomato hybrid powder extracts on T47D (human breast carcinoma) cells was also evaluated. Results showed good antioxidant activities in lipophilic, polyphenolic, and hydrophilic extracts of samples that were obtained at a lower temperature. Extracts of the sample obtained at a higher temperature presented moderate antioxidant activity, lower than the extracts of other samples, which was probably due to the loss of labile antioxidant compounds during the industrial process. Very interesting was the presence of anthocyanins in both samples, even if in traces, and also a moderate cytotoxicity of a lipophilic extract on T47D cells. Therefore, tomato hybrid powders, on the basis of their multifunctional properties, could have a biotechnological application in agri-food or cosmetic industries as an additive for improving nutritional and/or bioactive qualities of commercial products used in daily nutrition and cosmetics. PMID:23472745

  13. The antimicrobial activity, hydrophobicity and toxicity of sulfonium compounds, and their relationship.

    PubMed

    Hirayama, Michiasa

    2011-03-01

    The sulfonium compound is a kind of cationic surfactant as well as a quaternary ammonium which has been used widely around the globe. This study investigated the antimicrobial activity, the hydrophobicity, the toxicity of several sulfoniums and their relationship with the aim of clarifying their antimicrobial activity and toxicity, and, furthermore, of predicting their usefulness availability as antimicrobials. As a result, the antimicrobial activity, expressed as the minimum inhibitory concentration (MIC) of the sulfoniums examined in this study, tended to decrease with the increase of their hydrophobicity, estimated by ClogP, and their antimicrobial activity against the gram-positive bacteria was higher than that against the gram-negative bacteria used in this study. The antimicrobial activities of several sulfoniums against the gram-positive bacteria were higher than those of some common cationic antimicrobials including quaternary ammoniums such as cetylpyridinium chloride (CPC) and benzalkonium chloride (BKC). In contrast, the antimicrobial activities of the sulfoniums against the gram-negative bacteria were lower than those of some common cationic antimicrobials. Meanwhile the toxicity, in particular, the acute dermal irritation/corrosion of the sulfoniums, tended to be lower than that of common cationic antimicrobials which were toxic in many cases indices. These results suggest that the sulfoniums might become useful antimicrobials which are less hazardous to human health than common cationic antimicrobials. PMID:21467626

  14. Fumigant activity of (E)-anethole identified in Illicium verum fruit against Blattella germanica.

    PubMed

    Chang, Kyu-Sik; Ahn, Young-Joon

    2002-02-01

    The insecticidal activities of materials derived from the fruit of star anise, Illicium verum, against adults of Blattella germanica were examined by direct contact application and fumigation methods, and compared with those of DDVP, deltamethrin and hydramethylnon. The biologically active constituent of the Illicium fruit was characterized as the phenylpropene, (E)-anethole, by spectroscopic analysis. In a filter paper diffusion test with females, (E)-anethole caused 80.3% mortality at 0.159 mg cm-2 at 1 and 3 days after treatment (DAT), whereas 16.7% mortality at 3 DAT was achieved at 0.079 mg cm-2. DDVP and deltamethrin gave > 90% mortality at 0.019 mg cm-2 at 1 DAT. At 0.009 mg cm-2, DDVP and deltamethrin showed 73.3 and 60% mortality at 1 DAT, respectively, but 93.3 and 76.7% mortality at 3 DAT. Hydramethylnon exhibited 0 and 93.3% mortality at 0.159 mg cm-2 at 1 and 3 DAT, respectively, whereas 6.7% mortality at 3 DAT was observed at 0.079 mg cm-2. In a fumigation test with females, (E)-anethole was much more effective in closed cups than in open ones, indicating that the insecticidal activity of the compound was largely attributable to fumigant action. (E)-Anethole and DDVP caused 100% mortality at 0.398 and 0.051 mg cm-2 4 and 1 h after treatment, respectively. (E)-Anethole showed 46.7% mortality at 0.199 mg cm-2 at 3 DAT, whereas deltamethrin and hydramethylnon at 0.796 mg cm-2 was ineffective for 3-day period. As naturally occurring insect-control agents, the I verum fruit-derived materials described could be useful for managing populations of B germanica. PMID:11852640

  15. Activated by Combined Magnrtic Field Gravitropic Reaction Reply on Nanodose of Biologicaly Active Compounds

    NASA Astrophysics Data System (ADS)

    Sheykina, Nadezhda; Bogatina, Nina

    The new science direction nanotechnologies initiated a big jump in the pharmacology and medicine. This leads to the big development of homeopathy. The most interest appeared while investigating of the reaction of biological object on the nano dose of iologically substances. The changing of concentration (in nmol/l) of biologically active material is also possible during weak energy action. For instance, weak combined magnetic field may change a little the concentration of ions that are oriented parallel to the external magnetic field and, by the analogy with said above, lead to the similar effects. Simple estimations give the value for the threshold to the magnetic field by two orders smaller than the geomagnetic field. By this investigation we wanted to understand whether the analogy in the action of nano dose of biologically active substances and weak combined magnetic field presents and whether the action of one of these factors may be replaced by other one. The effect of one of biologically active substances NPA (Naphtyl-Phtalame Acid) solution with the concentration 0.01 mol/l on the gravitropic reaction of cress roots was investigated. It was shown that its effect was the inhibition of cress roots gravitropic reaction. The same inhibition was achieved by the combined magnetic field action on the cress roots, germinated in water. The alternative component of the combined magnetic field coincided formally with the cyclotron frequency of NPA ions. So the analogy in the action of nano dose of biologically active substances and weak combined magnetic field was shown. The combined magnetic field using allows to decrease sufficiently the dose of biologically active substances. This fact can be of great importance in pharmacy and medicine.

  16. Ginsenoside Rb1 and its metabolite compound K inhibit IRAK-1 activation--the key step of inflammation.

    PubMed

    Joh, Eun-Ha; Lee, In-Ah; Jung, Il-Hoon; Kim, Dong-Hyun

    2011-08-01

    In the preliminary study, ginsenoside Rb1, a main constituent of the root of Panax ginseng (family Araliaceae), and its metabolite compound K inhibited a key factor of inflammation, nuclear transcription factor ?B (NF-?B) activation, in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages. When ginsenoside Rb1 or compound K were orally administered to 2,4,6-trinitrobenzene sulfuric acid (TNBS)-induced colitic mice, these agents inhibited colon shortening, macroscopic score, and colonic thickening. Furthermore, treatment with ginsenoside Rb1 or compound K at 20mg/kg inhibited colonic myeloperoxidase activity by 84% and 88%, respectively, as compared with TNBS alone (p<0.05), and also potently inhibited the expression of tumor necrosis factor-?, interleukin (IL)-1? and IL-6, but increased the expression of IL-10. Both ginsenoside Rb1 and compound K blocked the TNBS-induced expressions of COX-2 and iNOS and the activation of NF-?B in mice. When ginsenoside Rb1 or compound K was treated in LPS-induced murine peritoneal macrophages, these agents potently inhibited the expression of the proinflammatory cytokines. Ginsenoside Rb1 and compound K also significantly inhibited the activation of interleukin-1 receptor-associated kinase-1 (IRAK-1), IKK-?, NF-?B, and MAP kinases (ERK, JNK, and p-38); however, interaction between LPS and Toll-like receptor-4, IRAK-4 activation and IRAK-2 activation were unaffected. Furthermore, compound K inhibited the production of proinflammatory cytokines more potently than did those of ginsenoside Rb1. On the basis of these findings, ginsenosides, particularly compounds K, could be used to treat inflammatory diseases, such as colitis, by targeting IRAK-1 activation. PMID:21600888

  17. Heart rate biofeedback fails to enhance children's ability to identify time spent in moderate to vigorous physical activity

    Microsoft Academic Search

    Marguerite M. Conley; Paul B. Gastin; Helen Brown; Christine Shaw

    2011-01-01

    Physical activity recommendations for children in several countries advise that all young people should accumulate at least 60min of moderate to vigorous physical activity every day. Perceiving physical activity intensity, however, can be a difficult task for children and it is not clear whether children can identify their levels of moderate to vigorous physical activity in accordance with the recommended

  18. Novel compound heterozygous mutations in the MYO15A gene in autosomal recessive hearing loss identified by whole-exome sequencing

    PubMed Central

    2013-01-01

    Background Inherited genetic defects play an important role in congenital hearing loss, contributing to about 60% of deafness occurring in infants. Hereditary nonsyndromic hearing loss is highly heterogeneous, and most patients with a presumed genetic etiology lack a specific molecular diagnosis. Methods By whole exome sequencing, we identified responsible gene of family 4794 with autosomal recessively nonsyndromic hearing loss (ARNSHL). We also used DNA from 56 Chinese familial patients with ARNSHL (autosomal recessive nonsyndromic hearing loss) and 108 ethnicity-matched negative samples to perform extended variants analysis. Results We identified MYO15A c.IVS25?+?3G?>?A and c.8375 T?>?C (p.V2792A) as the disease-causing mutations. Both mutations co-segregated with hearing loss in family 4794, but were absent in the 56 index patients and 108 ethnicity-matched controls. Conclusions Our results demonstrated that the hearing loss of family 4794 was caused by novel compound heterozygous mutations in MYO15A. PMID:24206587

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

    PubMed

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

    2014-01-01

    Endocrine-disrupting compounds (EDCs) are chemical compounds with the ability to alter the hormonal systems of organisms. Such compounds are used in several industrial and domestic activities and reach the aquatic environment via wastewater discharge. The aim of this study is to assess the occurrence of 30 EDCs and related compounds in the surface waters of central Spain and to determine the overall estrogenic activity of environmental samples. This study analyzed a large number of EDCs and other emergent or suspected compounds with endocrine-disrupting activity. The results have shown the presence of 19 EDCs at concentrations ranging from 2 to 5928 ng L(-1). Organophosphorus-based flame retardants, alkylphenolic compounds and anticorrosives were found at the highest concentrations. Furthermore, although insufficient data are available to calculate an average over time, these preliminary results show the need to monitor the waters in both rivers studied. Alkylphenolic compounds, particularly nonylphenol, were the main contributors to overall estrogenicity. A higher concentration of the compounds studied was detected in the river Jarama, although the estrogenicity expressed as estradiol equivalents (EEQs) was higher in the river Manzanares due to a higher concentration of nonylphenol. However, the total estrogenicity did not exceed 1 ng L(-1) (EEQ), which is the level that may cause estrogenic effects in aquatic organisms, in any of the samples. In conclusion, the potential estrogenic risk in both rivers is low, although organophosphorus-based flame retardants may increase this risk as they were found at high levels in all samples. Unfortunately, these compounds could not be taken into account when calculating the estrogenic activity due to the lack of activity data for them. For future investigations, it will be important to assess the estrogenicity provided by these flame retardants. Due to the significant concentrations of EDCs detected in both rivers, further studies in this region are required. PMID:23978587

  20. An experimental method to identify neurogenic and myogenic active mechanical states of intestinal motility

    PubMed Central

    Costa, Marcello; Wiklendt, Lukasz; Arkwright, John W.; Spencer, Nicholas J.; Omari, Taher; Brookes, Simon J. H.; Dinning, Phil G.

    2013-01-01

    Excitatory and inhibitory enteric neural input to intestinal muscle acting on ongoing myogenic activity determines the rich repertoire of motor patterns involved in digestive function. The enteric neural activity cannot yet be established during movement of intact intestine in vivo or in vitro. We propose the hypothesis that is possible to deduce indirectly, but reliably, the state of activation of the enteric neural input to the muscle from measurements of the mechanical state of the intestinal muscle. The fundamental biomechanical model on which our hypothesis is based is the “three-element model” proposed by Hill. Our strategy is based on simultaneous video recording of changes in diameters and intraluminal pressure with a fiber-optic manometry in isolated segments of rabbit colon. We created a composite spatiotemporal map (DPMap) from diameter (DMap) and pressure changes (PMaps). In this composite map rhythmic myogenic motor patterns can readily be distinguished from the distension induced neural peristaltic contractions. Plotting the diameter changes against corresponding pressure changes at each location of the segment, generates “orbits” that represent the state of the muscle according to its ability to contract or relax actively or undergoing passive changes. With a software developed in MatLab, we identified twelve possible discrete mechanical states and plotted them showing where the intestine actively contracted and relaxed isometrically, auxotonically or isotonically, as well as where passive changes occurred or was quiescent. Clustering all discrete active contractions and relaxations states generated for the first time a spatio-temporal map of where enteric excitatory and inhibitory neural input to the muscle occurs during physiological movements. Recording internal diameter by an impedance probe proved equivalent to measuring external diameter, making possible to further develop similar strategy in vivo and humans. PMID:23596400