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Sample records for identify active compounds

  1. Microtubule inhibitors: structure-activity analyses suggest rational models to identify potentially active compounds.

    PubMed Central

    Callahan, H L; Kelley, C; Pereira, T; Grogl, M

    1996-01-01

    Trifluralin, a dinitroaniline microtubule inhibitor currently in use as an herbicide, has been shown to inhibit the proliferation of Plasmodium falciparum, Trypanosoma brucei, and several species of Leishmania, in vitro. As a topical formulation, trifluralin is also effective in vivo (in BALB/c mice) against Leishmania major and Leishmania mexicana. Although trifluralin and other dinitroaniline herbicides show significant activity as antiparasitic compounds, disputed indications of potential carcinogenicity will probably limit advanced development of these substances. However, researchers have suggested that the activity of trifluralin is due to an impurity or contaminant, not to trifluralin itself. We have pursued this lead and identified the structure of the active impurity. This compound, chloralin, is 100 times more active than trifluralin. On the basis of its structure, we developed a rational structure-activity model for chloralin. Using this model, we have successfully predicted and tested active analogs in a Leishmania promastigote assay; thus, we have identified the putative mechanism of action of this class of drugs in Leishmania species. Potentially, this will allow the design of noncarcinogenic, active drugs. PMID:8849257

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

    PubMed Central

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

    2015-01-01

    Candida species have emerged as important and common opportunistic human pathogens, particularly in immunocompromised individuals. The current antifungal therapies either have toxic side effects or are insufficiently effect. The aim of this study is develop new small-molecule antifungal compounds by library screening methods using Candida albicans, and to evaluate their antifungal effects on Candida biofilms and cytotoxic effects on human cells. Wild-type C. albicans strain SC5314 was used in library screening. To identify antifungal compounds, we screened a small-molecule library of 1,280 pharmacologically active compounds (LOPAC1280TM) using an antifungal susceptibility test (AST). To investigate the antifungal effects of the hit compounds, ASTs were conducted using Candida strains in various growth modes, including biofilms. We tested the cytotoxicity of the hit compounds using human gingival fibroblast (hGF) cells to evaluate their clinical safety. Only 35 compounds were identified by screening, which inhibited the metabolic activity of C. albicans by >50%. Of these, 26 compounds had fungistatic effects and nine compounds had fungicidal effects on C. albicans. Five compounds, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate, ellipticine and CV-3988, had strong fungicidal effects and could inhibit the metabolic activity of Candida biofilms. However, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine were cytotoxic to hGF cells at low concentrations. CV-3988 showed no cytotoxicity at a fungicidal concentration. Four of the compounds identified, BAY11-7082, BAY11-7085, sanguinarine chloride hydrate and ellipticine, had toxic effects on Candida strains and hGF cells. In contrast, CV-3988 had fungicidal effects on Candida strains, but low cytotoxic effects on hGF cells. Therefore, this screening reveals agent, CV-3988 that was previously unknown to be antifungal agent, which could be a novel therapies for superficial mucosal candidiasis. PMID:26733987

  3. Calcium Imaging of Neuronal Activity in Drosophila Can Identify Anticonvulsive Compounds

    PubMed Central

    Streit, Anne K.; Fan, Yuen Ngan; Masullo, Laura; Baines, Richard A.

    2016-01-01

    Although there are now a number of antiepileptic drugs (AEDs) available, approximately one-third of epilepsy patients respond poorly to drug intervention. The reasons for this are complex, but are probably reflective of the increasing number of identified mutations that predispose individuals to this disease. Thus, there is a clear requirement for the development of novel treatments to address this unmet clinical need. The existence of gene mutations that mimic a seizure-like behaviour in the fruit fly, Drosophila melanogaster, offers the possibility to exploit the powerful genetics of this insect to identify novel cellular targets to facilitate design of more effective AEDs. In this study we use neuronal expression of GCaMP, a potent calcium reporter, to image neuronal activity using a non-invasive and rapid method. Expression in motoneurons in the isolated CNS of third instar larvae shows waves of calcium-activity that pass between segments of the ventral nerve cord. Time between calcium peaks, in the same neurons, between adjacent segments usually show a temporal separation of greater than 200 ms. Exposure to proconvulsants (picrotoxin or 4-aminopyridine) reduces separation to below 200 ms showing increased synchrony of activity across adjacent segments. Increased synchrony, characteristic of epilepsy, is similarly observed in genetic seizure mutants: bangsenseless1 (bss1) and paralyticK1270T (paraK1270T). Exposure of bss1 to clinically-used antiepileptic drugs (phenytoin or gabapentin) significantly reduces synchrony. In this study we use the measure of synchronicity to evaluate the effectiveness of known and novel anticonvulsive compounds (antipain, isethionate, etopiside rapamycin and dipyramidole) to reduce seizure-like CNS activity. We further show that such compounds also reduce the Drosophila voltage-gated persistent Na+ current (INaP) in an identified motoneuron (aCC). Our combined assays provide a rapid and reliable method to screen unknown compounds for potential to function as anticonvulsants. PMID:26863447

  4. Yeast-Based High-Throughput Screens to Identify Novel Compounds Active against Brugia malayi

    PubMed Central

    Bilsland, Elizabeth; Bean, Daniel M.; Devaney, Eileen; Oliver, Stephen G.

    2016-01-01

    Background Lymphatic filariasis is caused by the parasitic worms Wuchereria bancrofti, Brugia malayi or B. timori, which are transmitted via the bites from infected mosquitoes. Once in the human body, the parasites develop into adult worms in the lymphatic vessels, causing severe damage and swelling of the affected tissues. According to the World Health Organization, over 1.2 billion people in 58 countries are at risk of contracting lymphatic filariasis. Very few drugs are available to treat patients infected with these parasites, and these have low efficacy against the adult stages of the worms, which can live for 7–15 years in the human body. The requirement for annual treatment increases the risk of drug-resistant worms emerging, making it imperative to develop new drugs against these devastating diseases. Methodology/Principal Findings We have developed a yeast-based, high-throughput screening system whereby essential yeast genes are replaced with their filarial or human counterparts. These strains are labeled with different fluorescent proteins to allow the simultaneous monitoring of strains with parasite or human genes in competition, and hence the identification of compounds that inhibit the parasite target without affecting its human ortholog. We constructed yeast strains expressing eight different Brugia malayi drug targets (as well as seven of their human counterparts), and performed medium-throughput drug screens for compounds that specifically inhibit the parasite enzymes. Using the Malaria Box collection (400 compounds), we identified nine filarial specific inhibitors and confirmed the antifilarial activity of five of these using in vitro assays against Brugia pahangi. Conclusions/Significance We were able to functionally complement yeast deletions with eight different Brugia malayi enzymes that represent potential drug targets. We demonstrated that our yeast-based screening platform is efficient in identifying compounds that can discriminate between human and filarial enzymes. Hence, we are confident that we can extend our efforts to the construction of strains with further filarial targets (in particular for those species that cannot be cultivated in the laboratory), and perform high-throughput drug screens to identify specific inhibitors of the parasite enzymes. By establishing synergistic collaborations with researchers working directly on different parasitic worms, we aim to aid antihelmintic drug development for both human and veterinary infections. PMID:26812604

  5. Identifying biologically active compound classes using phenotypic screening data and sampling statistics.

    PubMed

    Klekota, Justin; Brauner, Erik; Schreiber, Stuart L

    2005-01-01

    Scoring the activity of compounds in phenotypic high-throughput assays presents a unique challenge because of the limited resolution and inherent measurement error of these assays. Techniques that leverage the structural similarity of compounds within an assay can be used to improve the hit-recovery rate from screening data. A technique is presented that uses clustering and sampling statistics to predict likely compound activity by scoring entire structural classes. A set of phenotypic assays performed against a commercially available compound library was used as a test set. Using the class-scoring technique, the resultant activity prediction scores were more reproducible than individual assay measurements, and class scoring recovered known active compounds more efficiently than individual assay measurements because class scoring had fewer false positives. Known biologically active compounds were recovered 87% of the time using class scores, suggesting a low false-negative rate that compared well to individual assay measurements. In addition, many weak and potentially novel classes of active compounds, overlooked by individual assay measurements, were suggested. PMID:16309290

  6. 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

  7. Screening of Transient Receptor Potential Canonical Channel Activators Identifies Novel Neurotrophic Piperazine Compounds.

    PubMed

    Sawamura, Seishiro; Hatano, Masahiko; Takada, Yoshinori; Hino, Kyosuke; Kawamura, Tetsuya; Tanikawa, Jun; Nakagawa, Hiroshi; Hase, Hideharu; Nakao, Akito; Hirano, Mitsuru; Rotrattanadumrong, Rachapun; Kiyonaka, Shigeki; Mori, Masayuki X; Nishida, Motohiro; Hu, Yaopeng; Inoue, Ryuji; Nagata, Ryu; Mori, Yasuo

    2016-03-01

    Transient receptor potential canonical (TRPC) proteins form Ca(2+)-permeable cation channels activated upon stimulation of metabotropic receptors coupled to phospholipase C. Among the TRPC subfamily, TRPC3 and TRPC6 channels activated directly by diacylglycerol (DAG) play important roles in brain-derived neurotrophic factor (BDNF) signaling, promoting neuronal development and survival. In various disease models, BDNF restores neurologic deficits, but its therapeutic potential is limited by its poor pharmacokinetic profile. Elucidation of a framework for designing small molecules, which elicit BDNF-like activity via TRPC3 and TRPC6, establishes a solid basis to overcome this limitation. We discovered, through library screening, a group of piperazine-derived compounds that activate DAG-activated TRPC3/TRPC6/TRPC7 channels. The compounds [4-(5-chloro-2-methylphenyl)piperazin-1-yl](3-fluorophenyl)methanone (PPZ1) and 2-[4-(2,3-dimethylphenyl)piperazin-1-yl]-N-(2-ethoxyphenyl)acetamide (PPZ2) activated, in a dose-dependent manner, recombinant TRPC3/TRPC6/TRPC7 channels, but not other TRPCs, in human embryonic kidney cells. PPZ2 activated native TRPC6-like channels in smooth muscle cells isolated from rabbit portal vein. Also, PPZ2 evoked cation currents and Ca(2+) influx in rat cultured central neurons. Strikingly, both compounds induced BDNF-like neurite growth and neuroprotection, which were abolished by a knockdown or inhibition of TRPC3/TRPC6/TRPC7 in cultured neurons. Inhibitors of Ca(2+) signaling pathways, except calcineurin, impaired neurite outgrowth promotion induced by PPZ compounds. PPZ2 increased activation of the Ca(2+)-dependent transcription factor, cAMP response element-binding protein. These findings suggest that Ca(2+) signaling mediated by activation of DAG-activated TRPC channels underlies neurotrophic effects of PPZ compounds. Thus, piperazine-derived activators of DAG-activated TRPC channels provide important insights for future development of a new class of synthetic neurotrophic drugs. PMID:26733543

  8. Use of thermal desorption gas chromatography-olfactometry/mass spectrometry for the comparison of identified and unidentified odor active compounds emitted from building products containing linseed oil.

    PubMed

    Clausen, P A; Knudsen, H N; Larsen, K; Kofoed-Sørensen, V; Wolkoff, P; Wilkins, C K

    2008-11-14

    The emission of odor active volatile organic compounds (VOCs) from a floor oil based on linseed oil, the linseed oil itself and a low-odor linseed oil was investigated by thermal desorption gas chromatography combined with olfactometry and mass spectrometry (TD-GC-O/MS). The oils were applied to filters and conditioned in the micro emission cell, FLEC, for 1-3days at ambient temperature, an air exchange rate of 26.9h(-1) and a 30% relative humidity. These conditions resulted in dynamic headspace concentrations and composition of the odor active VOCs that may be similar to real indoor setting. Emission samples for TD-GC-O/MS analysis from the FLEC were on Tenax TA. Although many volatile VOCs were detected by MS, only the odor active VOCs are reported here. In total, 142 odor active VOCs were detected in the emissions from the oils. About 50 of the odor active VOCs were identified or tentatively identified by GC-MS. While 92 VOCs were detected from the oil used in the floor oil, only 13 were detected in the low-odor linseed oil. The major odor active VOCs were aldehydes and carboxylic acids. Spearmen rank correlation of the GC-O profiles showed that the odor profile of the linseed oil likely influenced the odor profile of the floor oil based on this linseed oil. PMID:18922536

  9. Antifungal chemical compounds identified using a C. elegans pathogenicity assay.

    PubMed

    Breger, Julia; Fuchs, Beth Burgwyn; Aperis, George; Moy, Terence I; Ausubel, Frederick M; Mylonakis, Eleftherios

    2007-02-01

    There is an urgent need for the development of new antifungal agents. A facile in vivo model that evaluates libraries of chemical compounds could solve some of the main obstacles in current antifungal discovery. We show that Candida albicans, as well as other Candida species, are ingested by Caenorhabditis elegans and establish a persistent lethal infection in the C. elegans intestinal track. Importantly, key components of Candida pathogenesis in mammals, such as filament formation, are also involved in nematode killing. We devised a Candida-mediated C. elegans assay that allows high-throughput in vivo screening of chemical libraries for antifungal activities, while synchronously screening against toxic compounds. The assay is performed in liquid media using standard 96-well plate technology and allows the study of C. albicans in non-planktonic form. A screen of 1,266 compounds with known pharmaceutical activities identified 15 (approximately 1.2%) that prolonged survival of C. albicans-infected nematodes and inhibited in vivo filamentation of C. albicans. Two compounds identified in the screen, caffeic acid phenethyl ester, a major active component of honeybee propolis, and the fluoroquinolone agent enoxacin exhibited antifungal activity in a murine model of candidiasis. The whole-animal C. elegans assay may help to study the molecular basis of C. albicans pathogenesis and identify antifungal compounds that most likely would not be identified by in vitro screens that target fungal growth. Compounds identified in the screen that affect the virulence of Candida in vivo can potentially be used as "probe compounds" and may have antifungal activity against other fungi. PMID:17274686

  10. Inhibitors of Tubulin Assembly Identified through Screening a Compound Library

    PubMed Central

    Morgan, Rachel E.; Ahn, Sunjoo; Nzimiro, Sandra; Fotie, Jean; Phelps, Mitch A.; Cotrill, Jeffrey; Yakovich, Adam J.; Sackett, Dan L.; Dalton, James T.; Werbovetz, Karl A.

    2013-01-01

    Tubulin is the proposed target for drugs against cancer and helminths and is also a validated target in kinetoplastid parasites. With the aim of identifying new lead compounds against Leishmania sp., tubulin isolated from L. tarentolae was used to screen a 10 000 compound library. One compound, Chembridge No. 7992831 (5), displayed an IC50 of 13 ?m against Leishmania tubulin in an in vitro assembly assay and showed a greater than threefold selectivity over mammalian tubulin. Another compound, Chembridge No. 9067250 (8), exhibited good activity against mammalian tubulin (IC50 = 5.0 ?m). This compound was also toxic to several cancer cell lines with IC50 values in the region of 1 ?M. Subsequent testing of analogues of 8 contained within the library identified two compounds with greater potency against mammalian tubulin (IC50 values of 1.1 and 2.8 ?M). The more potent antitubulin agent also showed promising activity against cancer cell lines in vitro, with IC50 values ranging from 0.18 to 0.73 ?M. PMID:19090918

  11. The Development, Validation, and Use of Quantitative Structure Activity Relationship Models of 5-Hydroxytryptamine (2B) Receptor Ligands to Identify Novel Receptor Binders and Putative Valvulopathic Compounds among Common Drugs

    PubMed Central

    Hajjo, Rima; Grulke, Christopher; Golbraikh, Alexander; Setola, Vincent; Huang, Xi-Ping; Roth, Bryan L.; Tropsha, Alexander

    2012-01-01

    Some antipsychotic drugs are known to cause valvular heart disease by activating serotonin 5-HT2B receptors. We have developed and validated binary classification QSAR models capable of predicting potential 5-HT2B binders. The classification accuracies of the models to discriminate 5-HT2B actives from the inactives were as high as 80% for the external test set. These models were used to screen in silico 59,000 compounds included in the World Drug Index and 122 compounds were predicted as actives with high confidence. Ten of them were tested in radioligand binding assays and nine were found active suggesting a success rate of 90%. All validated binders were then tested in functional assays and one compound was identified as a true 5-HT2B agonist. We suggest that the QSAR models developed in this study could be used as reliable predictors to flag drug candidates that are likely to cause valvulopathy. PMID:20958049

  12. Odor-active compounds in cardboard.

    PubMed

    Czerny, Michael; Buettner, Andrea

    2009-11-11

    The odor-active compounds of cardboard were identified by aroma extract dilution analysis and HRGC-MS analysis. In total, 36 compounds were detected with medium to high intensities during HRGC-olfactometry. The highest odor intensities were evaluated for vanillin, (E)-non-2-enal, (R/S)-gamma-nonalactone, 2-methoxyphenol, (R/S)-delta-decalactone, p-anisaldehyde, 3-propylphenol, and a woody-smelling unknown compound. Most of the identified compounds were described as odor-active cardboard constituents for the first time. Sensory experiments demonstrated that extensive release of odor-active compounds occurred upon moistening of the cardboard. Accordingly, data indicated that the odorants are present in cardboard in relatively high amounts. In a further sensory study, a transfer of the released odor to food was demonstrated in a model experiment showing that cardboards with high odor potential can cause unwanted flavor changes in foods. PMID:19817420

  13. 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...

  14. A Novel Way To Identify Precursors That Degrade To Perfluourinated Compounds In Activated Sludge Using Ion-Trap Time-Of-Flight Mass Spectrometer

    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, the fate and transport of PFCs are little under...

  15. Natural compounds with Wnt signal modulating activity.

    PubMed

    Fuentes, Rolly G; Arai, Midori A; Ishibashi, Masami

    2015-12-19

    Covering: up to 2015 The Wnt signalling pathway is essential in many biological processes. The Wnt signal is associated with several diseases, particularly cancer and neurodegenerative diseases. Recently, high-throughput screening systems have been developed to rapidly identify compounds, including natural compounds, that target the Wnt signal. Some studies on natural modulators of the Wnt signal have also suggested their possible target. This review highlights some important natural compounds reported to regulate Wnt activity and describes their possible mechanism of action. PMID:26395516

  16. 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

  17. IDENTIFYING COMPOUNDS DESPITE CHROMATOGRAPHY LIMITATIONS: ORGANOPHOSPHATES IN TREATED SEWAGE

    EPA Science Inventory

    Highly concentrated extracts of sewage treatment plant (STP) effluents contain detectable
    levels of dozens of compounds resulting from human activities. Recent concern over use and
    disposal of Pharmaceuticals and Personal Care Products (PPCPS) (1) has stimulated interest ...

  18. Gintonin, Newly Identified Compounds from Ginseng, Is Novel Lysophosphatidic Acids-Protein Complexes and Activates G Protein-Coupled Lysophosphatidic Acid Receptors with High Affinity

    PubMed Central

    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

    2012-01-01

    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 inhibitor Y-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

  19. High-throughput screening identifies compounds that enhance lentiviral transduction.

    PubMed

    Johnston, J M; Denning, G; Moot, R; Whitehead, D; Shields, J; Le Doux, J M; Doering, C B; Spencer, H T

    2014-12-01

    A difficulty in the field of gene therapy is the need to increase the susceptibility of hematopoietic stem cells (HSCs) to ex vivo genetic manipulation. To overcome this obstacle a high-throughput screen was performed to identify compounds that could enhance the transduction of target cells by lentiviral vectors. Of the 1280 compounds initially screened using the myeloid-erythroid-leukemic K562 cell line, 30 were identified as possible enhancers of viral transduction. Among the positive hits were known enhancers of transduction (camptothecin, etoposide and taxol), as well as the previously unidentified phorbol 12-myristate 13-acetate (PMA). The percentage of green fluorescent protein (GFP)-positive-expressing K562 cells was increased more than fourfold in the presence of PMA. In addition, the transduction of K562 cells with a lentiviral vector encoding fVIII was four times greater in the presence of PMA as determined by an increase in the levels of provirus in genetically modified cells. PMA did not enhance viral transduction of all cell types (for example, sca-1(+) mouse hematopoietic cells) but did enhance viral transduction of human bone marrow-derived CD34(+) cells. Notably, the percentage of GFP-positive CD34(+) cells was increased from 7% in the absence of PMA to greater than 22% in the presence of 1?nM PMA. PMA did not affect colony formation of CD34(+) cells or the expression of the hematopoietic markers CD34 and CD45. These data demonstrate that high-throughput screening can be used to identify compounds that increase the transduction efficiency of lentiviral vectors, identifying PMA as a potential enhancer of lentiviral HSC transduction. PMID:25231175

  20. 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

  1. Odour-active compounds in banana fruit cv. Giant Cavendish.

    PubMed

    Pino, Jorge A; Febles, Yanet

    2013-11-15

    Application of solid-phase microextraction, simultaneous distillation-extraction and liquid-liquid extraction, combined with GC-FID, GC-MS, aroma extract dilution analysis, and odour activity value were used to analyse volatile compounds from banana fruit cv. Giant Cavendish and to estimate the most odour-active compounds. The analyses led to the identification of 146 compounds, 124 of them were positively identified. Thirty-one odourants were considered as odour-active compounds and contribute to the typical banana aroma, eleven of them are reported for the first time as odour-active compounds. PMID:23790849

  2. Structure-based drug design identifies polythiophenes as antiprion compounds.

    PubMed

    Herrmann, Uli S; Schtz, Anne K; Shirani, Hamid; Huang, Danzhi; Saban, Dino; Nuvolone, Mario; Li, Bei; Ballmer, Boris; slund, Andreas K O; Mason, Jeffrey J; Rushing, Elisabeth; Budka, Herbert; Nystrm, Sofie; Hammarstrm, Per; Bckmann, Anja; Caflisch, Amedeo; Meier, Beat H; Nilsson, K Peter R; Hornemann, Simone; Aguzzi, Adriano

    2015-08-01

    Prions cause transmissible spongiform encephalopathies for which no treatment exists. Prions consist of PrP(Sc), a misfolded and aggregated form of the cellular prion protein (PrP(C)). We explore the antiprion properties of luminescent conjugated polythiophenes (LCPs) that bind and stabilize ordered protein aggregates. By administering a library of structurally diverse LCPs to the brains of prion-infected mice via osmotic minipumps, we found that antiprion activity required a minimum of five thiophene rings bearing regularly spaced carboxyl side groups. Solid-state nuclear magnetic resonance analyses and molecular dynamics simulations revealed that anionic side chains interacted with complementary, regularly spaced cationic amyloid residues of model prions. These findings allowed us to extract structural rules governing the interaction between LCPs and protein aggregates, which we then used to design a new set of LCPs with optimized binding. The new set of LCPs showed robust prophylactic and therapeutic potency in prion-infected mice, with the lead compound extending survival by >80% and showing activity against both mouse and hamster prions as well as efficacy upon intraperitoneal administration into mice. These results demonstrate the feasibility of targeted chemical design of compounds that may be useful for treating diseases of aberrant protein aggregation such as prion disease. PMID:26246168

  3. Identifying organic nitrogen compounds in Rocky Mountain National Park aerosols

    NASA Astrophysics Data System (ADS)

    Beem, K. B.; Desyaterik, Y.; Ozel, M. Z.; Hamilton, J. F.; Collett, J. L.

    2010-12-01

    Nitrogen deposition is an important issue in Rocky Mountain National Park (RMNP). While inorganic nitrogen contributions to the ecosystems in this area have been studied, the sources of organic nitrogen are still largely unknown. To better understand the potential sources of organic nitrogen, filter samples were collected and analyzed for organic nitrogen species. Samples were collected in RMNP using a Thermo Fisher Scientific TSP (total suspended particulate) high-volume sampler with a PM2.5 impactor plate from April - November of 2008. The samples presented the opportunity to compare two different methods for identification of individual organic nitrogen species. The first type of analysis was performed with a comprehensive two dimensional gas chromatography (GCxGC) system using a nitrogen chemiluminescence detector (NCD). The filter samples were spiked with propanil in dichloromethane to use as an internal standard and were then extracted in water followed by solid phase extraction. The GCxGC system was comprised of a volatility based separation (DB5 column) followed by a polarity based separation (RXI-17 column). A NCD was used to specifically detect nitrogen compounds and remove the complex background matrix. Individual standards were used to identify peaks by comparing retention times. This method has the added benefit of an equimolar response for nitrogen so only a single calibration is needed for all species. In the second analysis, a portion of the same filter samples were extracted in DI water and analyzed with liquid chromatography coupled with mass spectroscopy (LC/MS). The separation was performed using a C18 column and a water-methanol gradient elution. Electrospray ionization into a time of flight mass spectrometer was used for detection. High accuracy mass measurement allowed unambiguous assignments of elemental composition of resulting ions. Positive and negative polarities were used since amines tend to show up in positive mode and nitrates in negative. The differences in the number of species and what species are identified between these two methods are important for planning future analyses of organic nitrogen compounds. In addition, these data provide new insight into the potential source of organic nitrogen in RMNP. Using the GCxGC method, 39 organic nitrogen species were detected and 20 were identified. Identified species include several types of amines and phenols. The LC/MS method identified several types of cresols, amines, and nitrates.

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

    PubMed Central

    Gergely, Szabolcs; Heged?s, Csaba; Lakatos, Petra; Kovcs, Katalin; Gspr, Renta; Csont, Tams; Virg, Lszl

    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

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

    PubMed

    Gergely, Szabolcs; Heged?s, Csaba; Lakatos, Petra; Kovcs, Katalin; Gspr, Renta; Csont, Tams; Virg, Lszl

    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

  6. A Chemical Screen Identifies Novel Compounds That Overcome Glial-Mediated Inhibition Of Neuronal Regeneration

    PubMed Central

    Usher, Lynn C.; Johnstone, Andrea; Ertürk, Ali; Hu, Ying; Strikis, Dinara; Wanner, Ina B.; Moorman, Sanne; Lee, Jae-Wook; Min, Jaeki; Ha, Hyung-Ho; Duan, Yuanli; Hoffman, Stanley; Goldberg, Jeffrey L.; Bradke, Frank; Chang, Young-Tae; Lemmon, Vance P.; Bixby, John L.

    2010-01-01

    A major barrier to regeneration of central nervous system (CNS) axons is the presence of growth-inhibitory proteins associated with myelin and the glial scar. To identify chemical compounds with the ability to overcome the inhibition of regeneration, we screened a novel triazine library, based on the ability of compounds to increase neurite outgrowth from cerebellar neurons on inhibitory myelin substrates. The screen produced 4 “hit compounds”, which act with nM potency on several different neuronal types, and on several distinct substrates relevant to glial inhibition. Moreover, the compounds selectively overcome inhibition rather than promote growth in general. The compounds do not affect neuronal cAMP levels, PKC activity, or EGFR activation. Interestingly, one of the compounds alters microtubule dynamics and increases microtubule density in both fibroblasts and neurons. This same compound promotes regeneration of dorsal column axons after acute lesions, and potentiates regeneration of optic nerve axons after nerve crush in vivo. These compounds should provide insight into the mechanisms through which glial-derived inhibitors of regeneration act, and could lead to the development of novel therapies for CNS injury. PMID:20357120

  7. Identifying Sexual Harassment: A Classroom Activity

    ERIC Educational Resources Information Center

    Madson, Laura; Shoda, Jennifer

    2002-01-01

    We created a classroom activity to illustrate the complexity involved in identifying sexual harassment. In the activity, students decided whether 6 fictional scenarios constituted sexual harassment. The activity stimulates animated discussion, and evaluation data indicate that it received positive feedback from students and refined students'

  8. Nematicidal activities of acetylene compounds from Coreopsis lanceolata L.

    PubMed

    Kimura, Yasuo; Hiraoka, Kensuke; Kawano, Tsuyoshi; Fujioka, Shozo; Shimada, Atsumi

    2008-01-01

    1-Phenylhepta-1,3,5-triyne (1), 5-phenyl-2-(1'-propynyl)-thiophene (2), and 2-(3'-acetoxy-1'-propynyl)-5-phenylthiophene (3) were isolated from Coreopsis lanceolata L., and their structures identified by spectroscopic methods. Compounds 1 and 2 showed effective nematicidal activities against Bursaphelenchus xylophilus and Caenorhabditis elegans, but had hardly any effect against Pratylenchus penetrans. Compound 3 did not show any effective nematicidal activity. PMID:19227832

  9. Activities of dicationic compounds against Trichomonas vaginalis.

    PubMed

    Crowell, Andrea L; Stephens, Chad E; Kumar, Arvind; Boykin, David W; Secor, W Evan

    2004-09-01

    We evaluated 44 novel cationic compounds for activity against metronidazole-sensitive and -resistant Trichomonas vaginalis isolates. Six compounds in three different structural classes demonstrated 50% inhibitory concentrations as low as 1 microM against both sensitive and resistant isolates, suggesting a mode of action independent of parasite biochemical pathways that confer resistance to 5-nitroimidazoles. PMID:15328138

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

    PubMed

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

    2014-07-01

    A new biflavonoid, named asteryomenin (1), as well as six known phenolic compounds, esculetin (2), 4-O-?-D-glucopyranoside-3-hydroxy methyl benzoate (3), caffeic acid (4), isoquercitrin (5), isorhamnetin-3-O-glucoside (6), and apigenin (7) were isolated from the aerial parts of Aster yomena. The structures of compounds (1-7) were identified based on 1D and 2D NMR, including (1)H-(1)H COSY, HSQC, HMBC and NOESY spectroscopic analyses. Compounds 2-7 were isolated from this plant for the first time. For these isolates, the inhibitory activity of IL-6 production in the TNF-? stimulated MG-63 cell was examined. Among these isolates, compounds 4 and 7 appeared to have potent inhibitory activity of IL-6 production in the TNF-? stimulated MG-63 cell, while compounds 1-3 and 5-6 showed moderate activity. PMID:24014305

  11. Differential nuclear staining assay for high-throughput screening to identify cytotoxic compounds

    PubMed Central

    LEMA, Carolina; VARELA-RAMIREZ, Armando; AGUILERA, Renato J.

    2016-01-01

    As large quantities of novel synthetic molecules continue to be generated there is a challenge to identify therapeutic agents with cytotoxic activity. Here we introduce a Differential Nuclear Staining (DNS) assay adapted to live-cell imaging for high throughput screening (HTS) that utilizes two fluorescent DNA intercalators, Hoechst 33342 and Propidium iodide (PI). Since Hoechst can readily cross cell membranes to stain DNA of living and dead cells, it was used to label the total number of cells. In contrast, PI only enters cells with compromised plasma membranes, thus selectively labeling dead cells. The DNS assay was successfully validated by utilizing well known cytotoxic agents with fast or slow cytotoxic activities. The assay was found to be suitable for HTS with Z′ factors ranging from 0.86 to 0.60 for 96 and 384-well formats, respectively. Furthermore, besides plate-to-plate reproducibility, assay quality performance was evaluated by determining ratios of signal-to-noise and signal-to-background, as well as coefficient of variation, which resulted in adequate values and validated the assay for HTS initiatives. As proof of concept, eighty structurally diverse compounds from a small molecule library were screened in a 96-well plate format using the DNS assay. Using this DNS assay, six hits with cytotoxic properties were identified and all of them were also successfully identified by using the commercially available MTS assay (CellTiter 96® Cell Proliferation Assay). In addition, the DNS and a flow cytometry assay were used to validate the activity of the cytotoxic compounds. The DNS assay was also used to generate dose-response curves and to obtain CC50 values. The results indicate that the DNS assay is reliable and robust and suitable for primary and secondary screens of compounds with potential cytotoxic activity.

  12. Multiplexing high-content flow (HCF) and quantitative high-throughput screening (qHTS) to identify compounds capable of decreasing cell viability, activating caspase 3/7, expressing annexin V, and changing mitochondrial membrane integrity.

    PubMed

    Mathews, Lesley A; Keller, Jonathan M; McKnight, Crystal; Michael, Sam; Shinn, Paul; Liu, Dongbo; Staudt, Louis M; Thomas, Craig J; Ferrer, Marc

    2013-01-01

    High-content flow (HCF) screening systems, such as the iQue Screener and HTFC Screening System from IntelliCyt, have facilitated the implementation of flow cytometry assays for high-throughput screening. HCF screening systems enable the use of smaller sample volumes and multiplexed assays to simultaneously assess different cellular parameters from a single well. This becomes invaluable when working with cells or compounds that are available in limited quantities or when conducting large-scale screens. When assays can be miniaturized to a 384- or 1536-well microplate format, it is possible to implement dose-response-based high-throughput screens, also known as quantitative HTS or qHTS. This article describes how qHTS at the new National Center for Advancing Translational Science (NCATS) has been systematically coupled with the HTFC Screening System and Multimetric Apoptosis Screening Kit from IntelliCyt to biologically validate active compounds from primary cell proliferation screens using a model of diffuse large B cell lymphoma (DLBCL). PMID:24391083

  13. Antifungal Activity of Isothiocyanates and Related Compounds

    PubMed Central

    Drobnica, Ľ.; Zemanová, M.; Nemec, P.; Antoš, K.; Kristián, P.; Štullerová, A.; Knoppová, V.; Nemec, P.

    1967-01-01

    Data are presented concerning the antifungal activity of 11 natural isothiocyanates and 27 synthetized analogues in Aspergillus niger, Penicillium cyclopium, and Rhizopus oryzae, as well as in 13 additional saprophytic and parasitic fungi. A remarkable antifungal activity was observed in some analogues of benzylisothiocyanate and β-phenylethylisothiocyanate. The latter-mentioned compounds have not been described previously. In the group of benzylisothiocyanates, a correlation, which was inversely proportional, was detected between ed100 values for A. niger and R. oryzae and the corresponding molar solubilities of compounds in water. In contradistinction, no relationship was observed between antifungal activity and chemical reactivity of investigated derivatives. PMID:6049294

  14. Artificial neural network cascade identifies multi-P450 inhibitors in natural compounds

    PubMed Central

    Li, Zhangming; Li, Yan; Sun, Lu; Tang, Yun; Liu, Lanru

    2015-01-01

    Substantial evidence has shown that most exogenous substances are metabolized by multiple cytochrome P450 (P450) enzymes instead of by merely one P450 isoform. Thus, multi-P450 inhibition leads to greater drug-drug interaction risk than specific P450 inhibition. Herein, we innovatively established an artificial neural network cascade (NNC) model composed of 23 cascaded networks in a ladder-like framework to identify potential multi-P450 inhibitors among natural compounds by integrating 12 molecular descriptors into a P450 inhibition score (PIS). Experimental data reporting in vitro inhibition of five P450 isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) were obtained for 8,148 compounds from the Cytochrome P450 Inhibitors Database (CPID). The results indicate significant positive correlation between the PIS values and the number of inhibited P450 isoforms (Spearman’s ρ = 0.684, p < 0.0001). Thus, a higher PIS indicates a greater possibility for a chemical to inhibit the enzyme activity of at least three P450 isoforms. Ten-fold cross-validation of the NNC model suggested an accuracy of 78.7% for identifying whether a compound is a multi-P450 inhibitor or not. Using our NNC model, 22.2% of the approximately 160,000 natural compounds in TCM Database@Taiwan were identified as potential multi-P450 inhibitors. Furthermore, chemical similarity calculations suggested that the prevailing parent structures of natural multi-P450 inhibitors were alkaloids. Our findings show that dissection of chemical structure contributes to confident identification of natural multi-P450 inhibitors and provides a feasible method for virtually evaluating multi-P450 inhibition risk for a known structure. PMID:26719820

  15. 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

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

    PubMed Central

    2014-01-01

    Background In Chinese traditional medicine, Agrimonia pilosa Ledeb (APL) exhibits great effect on treatment of type 2 diabetes mellitus (T2DM), however its mechanism is still unknown. Considering that T2DM are correlated with postprandial hyperglycemia and oxidative stress, we investigated the α-glucosidase inhibitory activity and the antioxidant activity of flavonoid compound (FC) and triterpenoid compound (TC) from APL. Methods Entire plants of APL were extracted using 95% ethanol and 50% ethanol successively. The resulting extracts were partitioned and isolated by applying liquid chromatography using silica gel column and Sephadex LH 20 column to give FC and TC. The content of total flavonoids in FC and the content of total triterpenoids in TC were determined by using UV spectrophotometry. HPLC analysis was used to identify and quantify the monomeric compound in FC and TC. The α-glucosidase inhibitory activities were determined using the chromogenic method with p-nitrophenyl-α-D-glucopyranoside as substrate. Antioxidant activities were assessed through three kinds of radical scavenging assays (DPPH radical, ABTS radical and hydroxyl radical) & β-carotene-linoleic acid assay. Results The results indicate FC is abundant of quercitrin, and hyperoside, and TC is abundant of 1β, 2β, 3β, 19α-tetrahydroxy-12-en-28-oic acid (265.2 mg/g) and corosolic acid (100.9 mg/g). The FC & the TC have strong α-glucosidase inhibitory activities with IC50 of 8.72 μg/mL and 3.67 μg/mL, respectively. We find that FC show competitive inhibition against α-glucosidase, while the TC exhibits noncompetitive inhibition. Furthermore, The FC exhibits significant radical scavenging activity with the EC50 values of 7.73 μg/mL, 3.64 μg/mL and 5.90 μg/mL on DPPH radical, hydroxyl radical and ABTS radical, respectively. The FC also shows moderate anti-lipid peroxidation activity with the IC50 values of 41.77 μg/mL on inhibiting β-carotene bleaching. Conclusion These results 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 α-glucosidase inhibitors exhibiting remarkable potential value for the therapy of T2DM. PMID:24410924

  17. Identifying crucial parameter correlations maintaining bursting activity.

    PubMed

    Doloc-Mihu, Anca; Calabrese, Ronald L

    2014-06-01

    Recent experimental and computational studies suggest that linearly correlated sets of parameters (intrinsic and synaptic properties of neurons) allow central pattern-generating networks to produce and maintain their rhythmic activity regardless of changing internal and external conditions. To determine the role of correlated conductances in the robust maintenance of functional bursting activity, we used our existing database of half-center oscillator (HCO) model instances of the leech heartbeat CPG. From the database, we identified functional activity groups of burster (isolated neuron) and half-center oscillator model instances and realistic subgroups of each that showed burst characteristics (principally period and spike frequency) similar to the animal. To find linear correlations among the conductance parameters maintaining functional leech bursting activity, we applied Principal Component Analysis (PCA) to each of these four groups. PCA identified a set of three maximal conductances (leak current, [Formula: see text]Leak; a persistent K current, [Formula: see text]K2; and of a persistent Na+ current, [Formula: see text]P) that correlate linearly for the two groups of burster instances but not for the HCO groups. Visualizations of HCO instances in a reduced space suggested that there might be non-linear relationships between these parameters for these instances. Experimental studies have shown that period is a key attribute influenced by modulatory inputs and temperature variations in heart interneurons. Thus, we explored the sensitivity of period to changes in maximal conductances of [Formula: see text]Leak, [Formula: see text]K2, and [Formula: see text]P, and we found that for our realistic bursters the effect of these parameters on period could not be assessed because when varied individually bursting activity was not maintained. PMID:24945358

  18. Identifying natural images from human brain activity

    PubMed Central

    Kay, Kendrick N.; Naselaris, Thomas; Prenger, Ryan J.; Gallant, Jack L.

    2013-01-01

    A challenging goal in neuroscience is to be able to read out, or decode, mental content from brain activity. Recent functional magnetic resonance imaging (fMRI) studies have decoded orientation1,2, position3, and object category4,5 from activity in visual cortex. However, these studies typically used relatively simple stimuli (e.g. gratings) or images drawn from fixed categories (e.g. faces, houses), and decoding was based on prior measurements of brain activity evoked by those same stimuli or categories. To overcome these limitations, we develop a decoding method based on quantitative receptive field models that characterize the relationship between visual stimuli and fMRI activity in early visual areas. These models describe the tuning of individual voxels for space, orientation, and spatial frequency, and are estimated directly from responses evoked by natural images. We show that these receptive field models make it possible to identify, from a large set of completely novel natural images, which specific image was seen by an observer. Identification is not a mere consequence of the retinotopic organization of visual areas; simpler receptive field models that describe only spatial tuning yield much poorer identification performance. Our results suggest that it may soon be possible to reconstruct a picture of a persons visual experience from brain activity measurements alone. PMID:18322462

  19. 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

  20. Identifying bioaccumulative halogenated organic compounds using a nontargeted analytical approach: seabirds as sentinels.

    PubMed

    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 (GCGC/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

  1. Compounds identified in-flight by ROSETTA-COSIMA before the comet encounter

    NASA Astrophysics Data System (ADS)

    Hilchenbach, M.; Fischer, H.; Krger, H.; Thirkell, L.; Ryn, J.

    2013-09-01

    Secondary ion mass spectrometry (SIMS) is a laboratory surface analyzing technique and, with the COSIMA instrument onboard ROSETTA, it will be applied for the first time to in-situ measurements of cometary grains, once ROSETTA encounters its target comet, 67P/Churyumov-Gerasimenko, in the September 2014. The COmetary Secondary Ion Mass analyzer (COSIMA) onboard ROSETTA will expose metal targets, collect cometary dust grains in the inner coma and analyze these with an optical microscope as well as secondary ion mass spectrometry [1]. The COSIMA instrument has been operated in-flight for commissioning in the first months after launch in March 2004 and on a regular basis during the passive and active spacecraft check-out time intervals up to ROSETTA hibernation from June 2011 onwards. The secondary ion mass spectra background and /or contamination level of the COSIMA metal targets has been identified prior to launch and these had been selected accordingly to avoid masking of single elements or compounds by carrying different metal targets for cometary grain collection. The main compounds identified in-flight are silicon polymers and hydrocarbons. We will discuss the surface analysis results with COSIMA, carried out far off any comet or asteroid in interplanetary space, their time evolution and their potential sources within ROSETTA.

  2. A Virtual Screening Approach For Identifying Plants with Anti H5N1 Neuraminidase Activity

    PubMed Central

    2016-01-01

    Recent outbreaks of highly pathogenic and occasional drug-resistant influenza strains have highlighted the need to develop novel anti-influenza therapeutics. Here, we report computational and experimental efforts to identify influenza neuraminidase inhibitors from among the 3000 natural compounds in the Malaysian-Plants Natural-Product (NADI) database. These 3000 compounds were first docked into the neuraminidase active site. The five plants with the largest number of top predicted ligands were selected for experimental evaluation. Twelve specific compounds isolated from these five plants were shown to inhibit neuraminidase, including two compounds with IC50 values less than 92 ?M. Furthermore, four of the 12 isolated compounds had also been identified in the top 100 compounds from the virtual screen. Together, these results suggest an effective new approach for identifying bioactive plant species that will further the identification of new pharmacologically active compounds from diverse natural-product resources. PMID:25555059

  3. 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...

  4. 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...

  5. Selenium compounds activate early barriers of tumorigenesis.

    PubMed

    Wu, Min; Kang, Mandy M; Schoene, Norberta W; Cheng, Wen-Hsing

    2010-04-16

    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 test this hypothesis, we treated normal and cancerous cells with a gradient concentration of sodium selenite, methylseleninic acid and methylselenocysteine for 48 h, followed by a recovery of 1-7 days. Here we show that selenium compounds at doses of activated, which in turn initiates a cascade of DNA damage response. We found that the ATM pathway is activated by the selenium compounds, and the kinase activity is required for the selenium-induced senescence response. Pretreatment of the MRC-5 non-cancerous cells with the antioxidant N-acetylcysteine or 2,2,6,6-tetramethylpiperidine-1-oxyl suppresses the selenium-induced ATM activation and senescence. Taken together, the results suggest a novel role of selenium in the activation of early tumorigenesis barriers specific in non-cancerous cells, whereby selenium induces an ATM-dependent senescence response that depends on reactive oxygen species. PMID:20157118

  6. Systemically and topically active antinociceptive neurotensin compounds.

    PubMed

    Rossi, Grace C; Matulonis, Joshua E; Richelson, Elliott; Barbut, Denise; Pasternak, Gavril W

    2010-09-01

    Neurotensin is a neurotransmitter/modulator with a wide range of actions. Using a series of 10 stable analogs, we have examined neurotensin antinociception in mice. By incorporating (2S)-2-amino-3-(1H-4-indoyl)propanoic acid (l-neoTrp), a series of neurotensin analogs have been synthesized that are stable in serum and are systemically active in vivo. When administered in mice, they all were antinociceptive in the radiant heat tail-flick assay. Time-action curves revealed a peak effect at 30 min and a duration of action ranging from 2 to 4 h. Dose-response curves revealed that two compounds were partial agonists with maximal responses below 75%, whereas all of the remaining compounds displayed a full response. Overall, the compounds were quite potent, with ED(50) values similar to those of opioids. At peak effect, the ED(50) values ranged from 0.91 to 9.7 mg/kg s.c. Two of the analogs were active topically. Together, these studies support the potential of neurotensin analogs as analgesics. They are active systemically and by using them topically, it may be possible to avoid problematic side effects, such as hypothermia and hypotension. PMID:20576795

  7. 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

  8. 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

  9. A cell-based screening for TAZ activators identifies ethacridine, a widely used antiseptic and abortifacient, as a compound that promotes dephosphorylation of TAZ and inhibits adipogenesis in C3H10T1/2 cells.

    PubMed

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

    2015-11-01

    Transcriptional co-activator with PSD-95/Dlg-A/ZO-1 (PDZ)-binding motif (TAZ) regulates in cell proliferation and differentiation. In mesenchymal stem cells it promotes osteogenesis and myogenesis, and suppresses adipogenesis. TAZ activators are expected to prevent osteoporosis, obesity and muscle atrophy. TAZ activation induces epithelial-mesenchymal transition, confers stemness to cancer cells and leads to poor clinical prognosis in cancer patients. In this point of view, TAZ inhibitors should contribute to cancer therapy. Thus, TAZ attracts attention as a two-faced drug target. We screened for TAZ modulators by using human lung cancer A549 cells expressing the fluorescent reporter. Through this assay, we obtained TAZ activator candidates. We unexpectedly found that ethacridine, a widely used antiseptic and abortifacient, enhances the interaction of TAZ and protein phosphatases and increases unphosphorylated and nuclear TAZ. Ethacridine inhibits adipogenesis in mesenchymal C3H10T1/2 cells through the activation of TAZ. This finding suggests that ethacridine is a bona fide TAZ activator and supports that our assay is useful to discover TAZ activators. PMID:25979969

  10. Natural products as a resource for biologically active compounds

    SciTech Connect

    Hanke, F.J.

    1986-01-01

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

  11. 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

  12. Antioxidant activity of phenylpropanoid esters isolated and identified from Platycodon grandiflorum A. DC.

    PubMed

    Lee, Ji-Young; Yoon, Jae-Wook; Kim, Cheong-Tae; Lim, Seung-Taik

    2004-11-01

    Platycodon grandiflorum A. DC (Campanulaceae) is used as a traditional oriental medicine and also as a food in Korea. Here we investigated its antioxidant activity, and isolated and identified its active compounds. Petroleum ether extracts from the whole root of P. grandiflorum were fractionated by silica gel column chromatography using a solvent gradient (petroleum ether:diethyl ether, v/v; 9:1-5:5). The 8:2 fraction showed a higher radical scavenging activity than the other fractions, and active compounds were purified from this fraction by reversed-phased HPLC. Two active compounds were identified as coniferyl alcohol esters of palmitic and oleic acids by FAB-MS, UV, IR and NMR spectroscopy. The antioxidant activities of these two compounds, which were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide and nitric oxide radical scavenging capacity, were found to be as high as those of BHT or BHA. PMID:15504438

  13. Identifying physical activity gender differences among youth

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Physical activity (PA) is an important part of a healthy lifestyle and reduces risk of certain chronic diseases. Many youth do not currently meet PA guidelines; evidence suggests that girls are less active than boys are at all ages. PA differences need to be understood, so that gender-specific inter...

  14. A framework for identifying characteristic odor compounds in municipal wastewater effluent.

    PubMed

    Agus, Eva; Zhang, Lifeng; Sedlak, David L

    2012-11-15

    Municipal wastewater often contains trace amounts of organic compounds that can compromise aesthetics of drinking water and undermine public confidence if a small amount of effluent enters the raw water source of a potable water supply. To efficiently identify compounds responsible for odors in wastewater effluent, an analytical framework consisting of gas chromatography with mass spectrometry (GC-MS) and gas chromatography with olfactometry detection (GC-Olf) coupled with flavor profile analysis (FPA) was used to identify and monitor compounds that could affect the aesthetics of drinking water. After prioritizing odor peaks detected in wastewater effluent by GC-Olf, the odorous components were tentatively identified using retention indices, mass spectra and odor descriptors. Wastewater effluent samples were typically dominated by earthy-musty odors with additional odors in the amine, sulfidic and fragrant categories. 2,4,6-trichloroanisole (246TCA), geosmin and 2-methylisoborneol (2MIB) were the main sources of the earthy/musty odors in wastewater effluent. The other odors were attributable to a suite of compounds, which were detected in some but not all of the wastewater effluents at levels well in excess of their odor thresholds. In most cases, the identities of odorants were confirmed using authentic standards. The fate of these odorous compounds, including 2-pyrrolidone, methylnaphthalenes, vanillin and 5-hydroxyvanillin (5-OH-vanillin), should be considered in future studies of water systems that receive effluent from upstream sources. PMID:22981490

  15. A Yeast/Drosophila Screen to Identify New Compounds Overcoming Frataxin Deficiency

    PubMed Central

    Seguin, Alexandra; Monnier, Véronique; Palandri, Amandine; Bihel, Frédéric; Rera, Michael; Schmitt, Martine; Camadro, Jean-Michel; Tricoire, Hervé; Lesuisse, Emmanuel

    2015-01-01

    Friedreich's ataxia (FA) is a rare neurodegenerative disease which is very debilitating for the patients who progressively lose their autonomy. The lack of efficient therapeutic treatment of the disease strongly argues for urgent need to search for new active compounds that may stop the progression of the disease or prevent the appearance of the symptoms when the genetic defect is diagnosed early enough. In the present study, we used a yeast strain with a deletion of the frataxin homologue gene as a model of FA cells in a primary screen of two chemical libraries, a fraction of the French National Chemical Library (5500 compounds) and the Prestwick collection (880 compounds). We ran a secondary screen on Drosophila melanogaster flies expressing reduced levels of frataxin during larval development. Half of the compounds selected in yeast appeared to be active in flies in this developmental paradigm, and one of the two compounds with highest activities in this assay partially rescued the heart dilatation phenotype resulting from heart specific depletion of frataxin. The unique complementarity of these two frataxin-deficient models, unicellular and multicellular, appears to be very efficient to select new compounds with improved selectivity, bringing significant perspectives towards improvements in FA therapy. PMID:26523199

  16. Antileishmanial Activity of Compounds Isolated from Sassafras albidum.

    PubMed

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

    2015-07-01

    Leishmaniasis is a neglected tropical disease caused by Leishmania parasitic protozoa, which currently lacks efficient treatment. Natural products have shown promise as a potential source for antiprotozoal drugs. This work focuses on the antileishmanial potential of Sassafras albidum (Lauraceae) bark extract. The crude bark extract of S. albidum showed excellent antileishmanial activity with an IC50 value less than 12.5 μg/mL against promastigotes of L. amazonensis. The chloroform stem bark extract of S. albidum was subjected to preparative column chromatography. Five compounds were isolated, purified by recrystallization, and identified as sesamin, spinescin, β-sitosterol, hexatriacontanal, and 1-triacontanol. Antileishmanial and cytotoxic screening were performed on these compounds. Sesamin exhibited the best activity against L. amazonensis with an IC50 of 15.8 μg/mL and was not cytotoxic to mouse macrophage cells (CC50 > 100 μg/mL). PMID:26411017

  17. 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...

  18. ION COMPOSITION ELUCIDATION (ICE): A HIGH RESOLUTION MASS SPECTROMETRIC TECHNIQUE FOR IDENTIFYING COMPOUNDS IN COMPLEX MIXTURES

    EPA Science Inventory

    When tentatively identifying compounds in complex mixtures using mass spectral libraries, multiple matches or no plausible matches due to a high level of chemical noise or interferences can occur. Worse yet, most analytes are not in the libraries. In each case, Ion Composition El...

  19. 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...

  20. 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

  1. Identifying Creative Activities in Preschool Children.

    ERIC Educational Resources Information Center

    Keily, Margaret Mary

    This study compared the creative self-direction, creative behavior, and creative activities of preschool children to determine if students and teachers trained in the creative process and in observation techniques can, with reliability, observe the creative potential of young children. Creative abilities of 155 children from four preschool centers

  2. Profiling of the Tox21 Chemical Collection for Mitochondrial Function to Identify Compounds that Acutely Decrease Mitochondrial Membrane Potential

    PubMed Central

    Attene-Ramos, Matias S.; Huang, Ruili; Michael, Sam; Witt, Kristine L.; Richard, Ann; Tice, Raymond R.; Simeonov, Anton; Austin, Christopher P.

    2014-01-01

    Background: Mitochondrial dysfunction has been implicated in the pathogenesis of a variety of disorders including cancer, diabetes, and neurodegenerative and cardiovascular diseases. Understanding whether different environmental chemicals and druglike molecules impact mitochondrial function represents an initial step in predicting exposure-related toxicity and defining a possible role for such compounds in the onset of various diseases. Objectives: We sought to identify individual chemicals and general structural features associated with changes in mitochondrial membrane potential (MMP). Methods: We used a multiplexed [two end points in one screen; MMP and adenosine triphosphate (ATP) content] quantitative high throughput screening (qHTS) approach combined with informatics tools to screen the Tox21 library of 10,000 compounds (~ 8,300 unique chemicals) at 15 concentrations each in triplicate to identify chemicals and structural features that are associated with changes in MMP in HepG2 cells. Results: Approximately 11% of the compounds (913 unique compounds) decreased MMP after 1 hr of treatment without affecting cell viability (ATP content). In addition, 309 compounds decreased MMP over a concentration range that also produced measurable cytotoxicity [half maximal inhibitory concentration (IC50) in MMP assay/IC50 in viability assay ? 3; p < 0.05]. More than 11% of the structural clusters that constitute the Tox21 library (76 of 651 clusters) were significantly enriched for compounds that decreased the MMP. Conclusions: Our multiplexed qHTS approach allowed us to generate a robust and reliable data set to evaluate the ability of thousands of drugs and environmental compounds to decrease MMP. The use of structure-based clustering analysis allowed us to identify molecular features that are likely responsible for the observed activity. Citation: Attene-Ramos MS, Huang R, Michael S, Witt KL, Richard A, Tice RR, Simeonov A, Austin CP, Xia M. 2015. Profiling of the Tox21 chemical collection for mitochondrial function to identify compounds that acutely decrease mitochondrial membrane potential. Environ Health Perspect 123:4956;?http://dx.doi.org/10.1289/ehp.1408642 PMID:25302578

  3. Insilico studies of organosulfur-functional active compounds in garlic.

    PubMed

    Singh, Yogendra P; Singh, Ram A

    2010-01-01

    Garlic has been used medicinally since antiquity because of its antimicrobial activity, anticancer activity, antioxidant activity, ability to reduce cardiovascular diseases, improving immune functions, and antidiabetic activities and also in reducing cardiovascular diseases and improving immune functions. Recent studies identify that the wide variety of medicinal functions are attributed to the sulfur compounds present in garlic. Epidemiological observations and laboratory studies in animal models have also showed anticarcinogenic potential of organosulfur compounds of garlic. In this study, in silico analysis of organosulfur compounds is reported using the methods of theoretical chemistry to elucidate the molecular properties of garlic as it is more time and cost efficient, reduces the number of wet experiments, and offers the possibility of replacing some animal tests with suitable in silico models. The analysis of molecular descriptors defined by Lipinski has been done. The solubility of drug in water has been determined as it is of useful importance in the process of drug discovery from molecular design to pharmaceutical formulation and biopharmacy. All toxicities associated with candidate drug have been calculated. P-Glycoprotein expressed in normal tissues as a cause of drug pharmacokinetics and pharmacodynamics has been examined. Drug-plasma protein binding and volume of distribution have also been calculated. To avoid rejection of drugs, it is becoming more important to determine pK(a), absorption, polar surface area, and other physiochemical properties associated with a drug, before synthetic work is undertaken. The present in silico study is aimed at examining these compounds of garlic to evaluate its possible efficacy and toxicity under conditions of actual use in humans. PMID:20641079

  4. Antibacterial and Cytotoxic Activity of Compounds Isolated from Flourensia oolepis

    PubMed Central

    Joray, Mariana Belén; Trucco, Lucas Daniel; González, María Laura; Napal, Georgina Natalia Díaz; Palacios, Sara María; Bocco, José Luis; Carpinella, María Cecilia

    2015-01-01

    The antibacterial and cytotoxic effects of metabolites isolated from an antibacterial extract of Flourensia oolepis were evaluated. Bioguided fractionation led to five flavonoids, identified as 2′,4′-dihydroxychalcone (1), isoliquiritigenin (2), pinocembrin (3), 7-hydroxyflavanone (4), and 7,4′-dihydroxy-3′-methoxyflavanone (5). Compound 1 showed the highest antibacterial effect, with minimum inhibitory concentration (MIC) values ranging from 31 to 62 and 62 to 250 μg/mL, against Gram-positive and Gram-negative bacteria, respectively. On further assays, the cytotoxic effect of compounds 1–5 was determined by MTT assay on acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) cell lines including their multidrug resistant (MDR) phenotypes. Compound 1 induced a remarkable cytotoxic activity toward ALL cells (IC50 = 6.6–9.9 μM) and a lower effect against CML cells (IC50 = 27.5–30.0 μM). Flow cytometry was used to analyze cell cycle distribution and cell death by PI-labeled cells and by Annexin V/PI staining, respectively. Upon treatment, 1 induced cell cycle arrest in the G2/M phase accompanied by a strong induction of apoptosis. These results describe for the first time the antibacterial metabolites of F. oolepis extract, with 1 being the most effective. This chalcone also emerges as a selective cytotoxic agent against sensitive and resistant leukemic cells, highlighting its potential as a lead compound. PMID:26819623

  5. Is the toxicity of pesticide mixtures on river biofilm accounted for solely by the major compounds identified?

    PubMed

    Kim Tiam, Sandra; Morin, Soizic; Bonet, Berta; Guasch, Helena; Feurtet-Mazel, Agns; Eon, Mlissa; Gonzalez, Patrice; Mazzella, Nicolas

    2015-03-01

    Comparative effects of long-term exposure to Polar Organic Chemical Integrative Sampler (POCIS) extracts (PE) and to a reconstituted mixture based on the major compounds quantified in the PE were evaluated on river biofilm communities. The study aimed to characterize the effects of long-term and low-dose exposure to pesticides on natural biofilm communities and to evaluate if the effects due to PE exposure could be explained solely by the major compounds identified in the extracts. Biofilms from an uncontaminated site were exposed in artificial channels to realistic environmental concentrations using diluted PE, with the 12 major compounds quantified in the extracts (Mix) or with water not containing pesticides (Ctr). Significant differences between biofilms exposed to pesticides or not were observed with regard to diatom density, biomass (dry weight and ash-free dry mass), photosynthetic efficiency (?psII) and antioxidant enzyme activities. After 14days of exposure to the different treatments, the observed trend towards a decrease of mean diatom cell biovolumes in samples exposed to pesticides was related to the control biofilms' higher relative abundance of large species like Cocconeis placentula or Amphora copulata and lower relative abundance of small species like Eolimna minima compared to the contaminated ones. Principal component analyses clearly separated contaminated (PE and Mix) from non-contaminated (Ctr) biofilms; on the contrary, the analyses did not reveal separation between biofilms exposed to PE or to the 12 major compounds identified in the extract. PMID:25077658

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

    PubMed

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

    2013-01-01

    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

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

    PubMed Central

    Kraft, Robert; Kahn, Allon; Medina-Franco, Jos L.; Orlowski, Mikayla L.; Baynes, Cayla; Lpez-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

  8. 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

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

    PubMed

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

    2015-01-01

    Speed, a relatively low requirement for computational resources and high effectiveness of the evaluation of the bioactivity of compounds have caused a rapid growth of interest in the application of machine learning methods to virtual screening tasks. However, due to the growth of the amount of data also in cheminformatics and related fields, the aim of research has shifted not only towards the development of algorithms of high predictive power but also towards the simplification of previously existing methods to obtain results more quickly. In the study, we tested two approaches belonging to the group of so-called 'extremely randomized methods'-Extreme Entropy Machine and Extremely Randomized Trees-for their ability to properly identify compounds that have activity towards particular protein targets. These methods were compared with their 'non-extreme' competitors, i.e., Support Vector Machine and Random Forest. The extreme approaches were not only found out to improve the efficiency of the classification of bioactive compounds, but they were also proved to be less computationally complex, requiring fewer steps to perform an optimization procedure. PMID:26569196

  10. A Clinical Drug Library Screen Identifies Tosufloxacin as Being Highly Active against Staphylococcus aureus Persisters

    PubMed Central

    Niu, Hongxia; Cui, Peng; Yee, Rebecca; Shi, Wanliang; Zhang, Shuo; Feng, Jie; Sullivan, David; Zhang, Wenhong; Zhu, Bingdong; Zhang, Ying

    2015-01-01

    To identify effective compounds that are active against Staphylococcus aureus (S. aureus) persisters, we screened a clinical drug library consisting of 1524 compounds and identified six drug candidates that had anti-persister activity: tosufloxacin, clinafloxacin, sarafloxacin, doxycycline, thiostrepton, and chlorosalicylanilide. Among them, tosufloxacin had the highest anti-persister activity, which could completely eradicate S. aureus persisters within 2 days in vitro. Clinafloxacin ranked the second with very few persisters surviving the drug exposure. Interestingly, we found that both tosufloxacin and trovafloxacin that had high activity against persisters contained at the N-1 position the 2,4-difluorophenyl group, which is absent in other less active quinolones and may be associated with the high anti-persister activity. Further studies are needed to evaluate tosufloxacin in animal models and to explain its unique activity against bacterial persisters. Our findings may have implications for improved treatment of persistent bacterial infections.

  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. Biologically active compounds of semi-metals.

    PubMed

    Rezanka, Toms; 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

  14. High-Throughput Screening Using a Whole-Cell Virus Replication Reporter Gene Assay to Identify Inhibitory Compounds against Rift Valley Fever Virus Infection.

    PubMed

    Islam, Md Koushikul; Baudin, Maria; Eriksson, Jonas; Öberg, Christopher; Habjan, Matthias; Weber, Friedemann; Överby, Anna K; Ahlm, Clas; Evander, Magnus

    2016-04-01

    Rift Valley fever virus (RVFV) is an emerging virus that causes serious illness in humans and livestock. There are no approved vaccines or treatments for humans. The purpose of the study was to identify inhibitory compounds of RVFV infection without any preconceived idea of the mechanism of action. A whole-cell-based high-throughput drug screening assay was developed to screen 28,437 small chemical compounds targeting RVFV infection. To accomplish both speed and robustness, a replication-competent NSs-deleted RVFV expressing a fluorescent reporter gene was developed. Inhibition of fluorescence intensity was quantified by spectrophotometry and related to virus infection in human lung epithelial cells (A549). Cell toxicity was assessed by the Resazurin cell viability assay. After primary screening, 641 compounds were identified that inhibited RVFV infection by ≥80%, with ≥50% cell viability at 50 µM concentration. These compounds were subjected to a second screening regarding dose-response profiles, and 63 compounds with ≥60% inhibition of RVFV infection at 3.12 µM compound concentration and ≥50% cell viability at 25 µM were considered hits. Of these, six compounds with high inhibitory activity were identified. In conclusion, the high-throughput assay could efficiently and safely identify several promising compounds that inhibited RVFV infection. PMID:26762502

  15. Analogue Experiments Identify Possible Precursor Compounds for Chlorohydrocarbons Detected in SAM

    NASA Astrophysics Data System (ADS)

    Miller, K.; Summons, R. E.; Eigenbrode, J. L.; Freissinet, C.; Glavin, D. P.; Martin, M. G.; Team, M.

    2013-12-01

    Since landing at Gale Crater on August 6, 2012, the Sample Analysis at Mars (SAM) instrument suite, aboard the Curiosity Rover, has conducted multiple analyses of scooped and drilled samples and has identified a suite of chlorohydrocarbons including chloromethane, dichloromethane, trichloromethane, chloromethylpropene, and chlorobenzene (Glavin et al., 2013; Leshin et al., 2013). These compounds were identified after samples were pyrolysed at temperatures up to ~835C through a combination of Evolved Gas Analysis (EGA) and Gas Chromatography Mass Spectrometry (GCMS). Since these chlorinated species were well above the background levels determined by empty cup blanks analyzed prior to solid sample analyses, thermal degradation of oxychlorine phases, such as perchlorate, present in the Martian soil, are the most likely source of chlorine needed to generate these chlorohydrocarbons. Laboratory analogue experiments show that terrestrial organics internal to SAM, such as N-methyl-N(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA), a derivatization agent, can react with perchlorates to produce all of the chlorohydrocarbons detected by SAM. However, in pyrolysis-trap-GCMS laboratory experiments with MTBSTFA, C4 compounds are the predominant chlorohydrocarbon observed, whereas on SAM the C1 chlorohydrocarbons dominate (Glavin et al., 2013). This, in addition to the previous identification of chloromethane and dichloromethane by the 1976 Viking missions (Biemann et al., 1977), suggest that there could be another, possibly Martian, source of organic carbon contributing to the formation of the C1 chlorohydrocarbons, or other components of the solid samples analyzed by SAM are having a catalytic effect on chlorohydrocarbon generation. Laboratory analogue experiments investigated a suite of organic compounds that have the potential to accumulate on Mars (Benner et al., 2000) and thus serve as sources of carbon for the formation of chlorohydrocarbons detected by the SAM and Viking GCMS instruments. Experiments were conducted under SAM-like conditions using a commercial pyroprobe equipped with a SAM-like hydrocarbon trap and coupled to a GCMS. In general, when pyrolyzed with 1 wt.% calcium perchlorate, the C1 organic compounds (e.g. methanol, formic acid, and formaldehyde) produced only C1 chlorinated compounds while propanol and butyric acid formed only C3 chlorinated compounds. All of the pyrolysis experiments produced chlorobenzene, suggesting that it forms from chlorine, released during calcium perchlorate decomposition, reacting with benzene and toluene, released from the Tenax component of the hydrocarbon trap. Pyrolysis of phthalic acid however, produces a higher abundance of chlorobenzene than could be attributed to the Tenax alone and also forms C1 chlorohydrocarbons. Additional analogue experiments to identify potential precursor compounds for the chlorohydrocarbons detected by SAM are ongoing. Benner et al., 2000, PNAS, 97(6), 2425-2430 Biemann et al., 1977, JGR, 82(28), 4641-4658 Glavin et al., 2013, JGR-Planets, accepted for publication Leshin et al., 2013, Science, in press

  16. 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 μM, 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  19. Compounds with species and cell type specific toxicity identified in a 2,000 compound drug screen of neural stem cells and rat mixed cortical neurons

    PubMed Central

    Malik, Nasir; Efthymiou, Anastasia G.; Mather, Karly; Chester, Nathaniel; Wang, Xiantao; Nath, Avindra; Rao, Mahendra S.; Steiner, Joseph P.

    2015-01-01

    Human primary neural tissue is a vital component for the quick and simple determination of chemical compound neurotoxicity in vitro. In particular, such tissue would be ideal for high-throughput screens that can be used to identify novel neurotoxic or neurotherapeutic compounds. We have previously established a high-throughput screening platform using human induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) and neurons. In this study, we conducted a 2,000 compound screen with human NSCs and rat cortical cells to identify compounds that are selectively toxic to each group. Approximately 100 of the tested compounds showed specific toxicity to human NSCs. A secondary screen of a small subset of compounds from the primary screen on human iPSCs, NSC-derived neurons, and fetal astrocytes validated the results from >80% of these compounds with some showing cell specific toxicity. Amongst those compounds were several cardiac glycosides, all of which were selectively toxic to the human cells. As the screen was able to reliably identify neurotoxicants, many with species and cell-type specificity, this study demonstrates the feasibility of this NSC-driven platform for higher-throughput neurotoxicity screens. PMID:25454721

  20. A novel 3D high-content assay identifies compounds that prevent fibroblast invasion into tissue surrogates.

    PubMed

    Wenzel, Carsten; Otto, Saskia; Prechtl, Stefan; Parczyk, Karsten; Steigemann, Patrick

    2015-11-15

    Invasion processes underlie or accompany several pathological processes but only a limited number of high-throughput capable phenotypic models exist to test anti-invasive compounds in vitro. We here evaluated 3D co-cultures as a high-content phenotypic screening system for fibrotic invasive processes. 3D multicellular spheroids were used as living tissue surrogates in co-culture with fluorescently labeled lung fibroblasts to monitor invasion processes by automated microscopy. This setup was used to screen a compound library containing 480 known bioactive substances. Identified hits prevented fibroblast invasion and could be subdivided into two hit classes. First, Prostaglandins were shown to prevent fibroblast invasion, most likely mediated by the prostaglandin EP2 receptor and generation of cAMP. Additionally, Rho-associated protein kinase (ROCK) inhibitors prevented fibroblast invasion, possibly by inactivation of myosin II. Importantly, both Prostaglandins and ROCK inhibitors are potential treatment options shown to be effective in in vitro and in vivo models of fibrotic diseases. This validates the presented novel phenotypic screening approach for the evaluation of potential inhibitors and the identification of novel compounds with activity in diseases that are associated with fibroblast invasion. PMID:26475730

  1. Feasibility of Active Machine Learning for Multiclass Compound Classification.

    PubMed

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

    2016-01-25

    A common task in the hit-to-lead process is classifying sets of compounds into multiple, usually structural classes, which build the groundwork for subsequent SAR studies. Machine learning techniques can be used to automate this process by learning classification models from training compounds of each class. Gathering class information for compounds can be cost-intensive as the required data needs to be provided by human experts or experiments. This paper studies whether active machine learning can be used to reduce the required number of training compounds. Active learning is a machine learning method which processes class label data in an iterative fashion. It has gained much attention in a broad range of application areas. In this paper, an active learning method for multiclass compound classification is proposed. This method selects informative training compounds so as to optimally support the learning progress. The combination with human feedback leads to a semiautomated interactive multiclass classification procedure. This method was investigated empirically on 15 compound classification tasks containing 86-2870 compounds in 3-38 classes. The empirical results show that active learning can solve these classification tasks using 10-80% of the data which would be necessary for standard learning techniques. PMID:26740007

  2. 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

  3. Thin-layer Chromatographic (TLC) Separations and Bioassays of Plant Extracts to Identify Antimicrobial Compounds

    PubMed Central

    Kagan, Isabelle A.; Flythe, Michael D.

    2014-01-01

    A common screen for plant antimicrobial compounds consists of separating plant extracts by paper or thin-layer chromatography (PC or TLC), exposing the chromatograms to microbial suspensions (e.g. fungi or bacteria in broth or agar), allowing time for the microbes to grow in a humid environment, and visualizing zones with no microbial growth. The effectiveness of this screening method, known as bioautography, depends on both the quality of the chromatographic separation and the care taken with microbial culture conditions. This paper describes standard protocols for TLC and contact bioautography with a novel application to amino acid-fermenting bacteria. The extract is separated on flexible (aluminum-backed) silica TLC plates, and bands are visualized under ultraviolet (UV) light. Zones are cut out and incubated face down onto agar inoculated with the test microorganism. Inhibitory bands are visualized by staining the agar plates with tetrazolium red. The method is applied to the separation of red clover (Trifolium pratense cv. Kenland) phenolic compounds and their screening for activity against Clostridium sticklandii, a hyper ammonia-producing bacterium (HAB) that is native to the bovine rumen. The TLC methods apply to many types of plant extracts and other bacterial species (aerobic or anaerobic), as well as fungi, can be used as test organisms if culture conditions are modified to fit the growth requirements of the species. PMID:24747583

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

    PubMed

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

    2011-09-01

    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 capability 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. 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...

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

    PubMed

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

    2011-09-01

    Coffee is one of the most widely consumed beverages worldwide. Evidence of the health benefits and the important contribution of coffee brew to the intake of anti-oxidants in the diet has increased coffee consumption. Chlorogenic acid (ChA) and caffeic acid (CaA) are the major phenolic compounds in coffee. However, phenolic compounds, which are generally effective anti-oxidants, can become pro-oxidants in the presence of Cu(2+) to induce DNA damage under certain conditions. On the other hand, sodium nitrite (NaNO(2)) is widely used as a food additive to preserve and tinge color on cured meat and fish. It is possible that phenolic compounds react with NaNO(2) under acidic conditions, such as gastric juice. In this study, we identified compounds produced by the reaction between ChA or CaA in coffee and NaNO(2) in artificial gastric juice. The identified phenolic compounds and nitrated phenolic compounds were assessed for their anti-oxidant, pro-oxidant, and nitration activities by performing an in vitro assay. The nitrated phenolic compounds seemed to show increased anti-oxidant activity and decreased pro-oxidant activity. However, one nitrated CaA compound that has a furoxan ring showed the ability to release NO(2)(-) in the neutral condition. PMID:21723849

  8. Polyketide and benzopyran compounds of an endophytic fungus isolated from Cinnamomum mollissimum: biological activity and structure

    PubMed Central

    Santiago, Carolina; Sun, Lin; Munro, Murray Herbert Gibson; Santhanam, Jacinta

    2014-01-01

    Objective To study bioactivity and compounds produced by an endophytic Phoma sp. fungus isolated from the medicinal plant Cinnamomum mollissimum. Methods Compounds produced by the fungus were extracted from fungal broth culture with ethyl acetate. This was followed by bioactivity profiling of the crude extract fractions obtained via high performance liquid chromatography. The fractions were tested for cytotoxicity to P388 murine leukemic cells and antimicrobial activity against bacteria and pathogenic fungi. Compounds purified from active fractions which showed antibacterial, antifungal and cytotoxic activities were identified using capillary nuclear magnetic resonance analysis, mass spectrometry and admission to AntiMarin database. Results Three known compounds, namely 4-hydroxymellein, 4,8-dihydroxy-6-methoxy-3-methyl-3,4-dihydro-1H-isochromen-1-one and 1-(2,6-dihydroxyphenyl) ethanone, were isolated from the fungus. The polyketide compound 4-hydroxymellein showed high inhibitory activity against P388 murine leukemic cells (94.6%) and the bacteria Bacillus subtilis (97.3%). Meanwhile, 4,8-dihydroxy-6-methoxy-3-methyl-3,4-dihydro-1H-isochromen-1-one, a benzopyran compound, demonstrated moderate inhibitory activity against P388 murine leukemic cells (48.8%) and the fungus Aspergillus niger (56.1%). The second polyketide compound, 1 (2,6-dihydroxyphenyl) ethanone was inactive against the tested targets. Conclusions These findings demonstrate the potential of endophytes as producers of pharmacologically important compounds, including polyketides which are major secondary metabolites in fungi. PMID:25183332

  9. 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.

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

    PubMed

    Camacho-Muoz, Dolores; Martn, 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

  11. New pyridin-3-ylmethyl carbamodithioic esters activate pyruvate kinase M2 and potential anticancer lead compounds.

    PubMed

    Zhang, Yu; Liu, Bin; Wu, Xingyu; Li, Ridong; Ning, Xianling; Liu, Yu; Liu, Zhenming; Ge, Zemei; Li, Runtao; Yin, Yuxin

    2015-08-01

    Pyruvate kinase M2 (PKM2) is a key protein responsible for cancer's Warburg effect. Activation of PKM2 may alter aberrant metabolism in cancer cells, which suggests PKM2 as a tumor selective therapeutic target. In this paper, the lead compound 8 was first discovered as a new kind of PKM2 activator from a random screening of an in-house compound library. Then, a series of lead compound 8 analogs were designed, synthesized and evaluated for their activation of PKM2 and anticancer activities. 7-Azaindole analog 32 was identified as the most potent PKM2 activator. Compounds with potent enzyme activity also exhibited selective anti-proliferation activity on cancer cell lines HCT116, Hela and H1299 compared with non-tumor cell line BEAS-2B. The structure-activity relationships of these compounds were supported by molecular docking results. Preliminary pharmacological studies also showed that compound 32 arrests the cell cycle at the G2/M phase in HCT116 cell line. PMID:26081759

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

    PubMed Central

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

    2015-01-01

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

  13. Studying a Drug-like, RNA-Focused Small Molecule Library Identifies Compounds That Inhibit RNA Toxicity in Myotonic Dystrophy.

    PubMed

    Rzuczek, Suzanne G; Southern, Mark R; Disney, Matthew D

    2015-12-18

    There are many RNA targets in the transcriptome to which small molecule chemical probes and lead therapeutics are desired. However, identifying compounds that bind and modulate RNA function in cellulo is difficult. Although rational design approaches have been developed, they are still in their infancies and leave many RNAs "undruggable". In an effort to develop a small molecule library that is biased for binding RNA, we computationally identified "drug-like" compounds from screening collections that have favorable properties for binding RNA and for suitability as lead drugs. As proof-of-concept, this collection was screened for binding to and modulating the cellular dysfunction of the expanded repeating RNA (r(CUG)(exp)) that causes myotonic dystrophy type 1. Hit compounds bind the target in cellulo, as determined by the target identification approach Competitive Chemical Cross-Linking and Isolation by Pull-down (C-ChemCLIP), and selectively improve several disease-associated defects. The best compounds identified from our 320-member library are more potent in cellulo than compounds identified by high-throughput screening (HTS) campaigns against this RNA. Furthermore, the compound collection has a higher hit rate (9% compared to 0.01-3%), and the bioactive compounds identified are not charged; thus, RNA can be "drugged" with compounds that have favorable pharmacological properties. Finally, this RNA-focused small molecule library may serve as a useful starting point to identify lead "drug-like" chemical probes that affect the biological (dys)function of other RNA targets by direct target engagement. PMID:26414664

  14. Different phenolic compounds activate distinct human bitter taste receptors.

    PubMed

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

    2013-02-20

    Bitterness is a major sensory attribute of several common foods and beverages rich in polyphenol compounds. These compounds are reported as very important for health as chemopreventive compounds, but they are also known to taste bitter. In this work, the activation of the human bitter taste receptors, TAS2Rs, by six polyphenol compounds was analyzed. The compounds chosen are present in a wide range of plant-derived foods and beverages, namely, red wine, beer, tea, and chocolate. Pentagalloylglucose (PGG) is a hydrolyzable tannin, (-)-epicatechin is a precursor of condensed tannins, procyanidin dimer B3 and trimer C2 belong to the condensed tannins, and malvidin-3-glucoside and cyanidin-3-glucoside are anthocyanins. The results show that the different compounds activate different combinations of the ~25 TAS2Rs. (-)-Epicatechin activated three receptors, TAS2R4, TAS2R5, and TAS2R39, whereas only two receptors, TAS2R5 and TAS2R39, responded to PGG. In contrast, malvidin-3-glucoside and procyanidin trimer stimulated only one receptor, TAS2R7 and TAS2R5, respectively. Notably, tannins are the first natural agonists found for TAS2R5 that display high potency only toward this receptor. The catechol and/or galloyl groups appear to be important structural determinants that mediate the interaction of these polyphenolic compounds with TAS2R5. Overall, the EC(50) values obtained for the different compounds vary 100-fold, with the lowest values for PGG and malvidin-3-glucoside compounds, suggesting that they could be significant polyphenols responsible for the bitterness of fruits, vegetables, and derived products even if they are present in very low concentrations. PMID:23311874

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

    PubMed

    Dimova, Dilyana; Stumpfe, Dagmar; Bajorath, Jrgen

    2015-11-01

    A systematic search for active small molecules shared by orthologous targets was carried out, leading to the identification of 803 compound-based orthologous target pairs covering a total of 938 orthologues, 358 unique targets and 98 organisms. Many orthologous target pairs were found to have substantial compound coverage, enabling the introduction of an orthologous target pairs classification including 'organism cliffs' and 'potency-retaining' pairs. A total of 158 orthologous target pairs involving human orthologues were identified, which were typically associated with drug discovery-relevant targets, organism combinations and compound data. Orthologous target pairs with human orthologues included 83 potency-retaining orthologous target pairs covering a variety of targets and organisms. On the basis of these orthologous target pairs, the compound search was further extended and 1149 potent compounds were identified that only had reported activities for non-human orthologues of 48 therapeutic targets, but not their human counterparts, hence providing a large pool of candidate compounds for further evaluation. The complete set of orthologous target pairs identified in our analysis, the orthologous target pairs classification including associated data and all candidate compounds are made freely available. PMID:25931211

  16. A simple and predictive phenotypic High Content Imaging assay for Plasmodium falciparum mature gametocytes to identify malaria transmission blocking compounds.

    PubMed

    Lucantoni, Leonardo; Silvestrini, Francesco; Signore, Michele; Siciliano, Giulia; Eldering, Maarten; Dechering, Koen J; Avery, Vicky M; Alano, Pietro

    2015-01-01

    Plasmodium falciparum gametocytes, specifically the mature stages, are the only malaria parasite stage in humans transmissible to the mosquito vector. Anti-malarial drugs capable of killing these forms are considered essential for the eradication of malaria and tools allowing the screening of large compound libraries with high predictive power are needed to identify new candidates. As gametocytes are not a replicative stage it is difficult to apply the same drug screening methods used for asexual stages. Here we propose an assay, based on high content imaging, combining "classic" gametocyte viability readout based on gametocyte counts with a functional viability readout, based on gametocyte activation and the discrimination of the typical gamete spherical morphology. This simple and rapid assay has been miniaturized to a 384-well format using acridine orange staining of wild type P. falciparum 3D7A sexual forms, and was validated by screening reference antimalarial drugs and the MMV Malaria Box. The assay demonstrated excellent robustness and ability to identify quality hits with high likelihood of confirmation of transmission reducing activity in subsequent mosquito membrane feeding assays. PMID:26553647

  17. A simple and predictive phenotypic High Content Imaging assay for Plasmodium falciparum mature gametocytes to identify malaria transmission blocking compounds

    PubMed Central

    Lucantoni, Leonardo; Silvestrini, Francesco; Signore, Michele; Siciliano, Giulia; Eldering, Maarten; Dechering, Koen J.; Avery, Vicky M.; Alano, Pietro

    2015-01-01

    Plasmodium falciparum gametocytes, specifically the mature stages, are the only malaria parasite stage in humans transmissible to the mosquito vector. Anti-malarial drugs capable of killing these forms are considered essential for the eradication of malaria and tools allowing the screening of large compound libraries with high predictive power are needed to identify new candidates. As gametocytes are not a replicative stage it is difficult to apply the same drug screening methods used for asexual stages. Here we propose an assay, based on high content imaging, combining “classic” gametocyte viability readout based on gametocyte counts with a functional viability readout, based on gametocyte activation and the discrimination of the typical gamete spherical morphology. This simple and rapid assay has been miniaturized to a 384-well format using acridine orange staining of wild type P. falciparum 3D7A sexual forms, and was validated by screening reference antimalarial drugs and the MMV Malaria Box. The assay demonstrated excellent robustness and ability to identify quality hits with high likelihood of confirmation of transmission reducing activity in subsequent mosquito membrane feeding assays. PMID:26553647

  18. 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, ...

  19. 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

  20. Cdc25B Dual-Specificity Phosphatase Inhibitors Identified in a High-Throughput Screen of the NIH Compound Library

    PubMed Central

    Foster, Caleb A.; Tierno, Marni Brisson; Shun, Tong Ying; Shinde, Sunita N.; Paquette, William D.; Brummond, Kay M.; Wipf, Peter; Lazo, John S.

    2009-01-01

    Abstract The University of Pittsburgh Molecular Library Screening Center (Pittsburgh, PA) conducted a screen with the National Institutes of Health compound library for inhibitors of in vitro cell division cycle 25 protein (Cdc25) B activity during the pilot phase of the Molecular Library Screening Center Network. Seventy-nine (0.12%) of the 65,239 compounds screened at 10 μM met the active criterion of ≥50% inhibition of Cdc25B activity, and 25 (31.6%) of these were confirmed as Cdc25B inhibitors with 50% inhibitory concentration (IC50) values <50 μM. Thirteen of the Cdc25B inhibitors were represented by singleton chemical structures, and 12 were divided among four clusters of related structures. Thirteen (52%) of the Cdc25B inhibitor hits were quinone-based structures. The Cdc25B inhibitors were further characterized in a series of in vitro secondary assays to confirm their activity, to determine their phosphatase selectivity against two other dual-specificity phosphatases, mitogen-activated protein kinase phosphatase (MKP)-1 and MKP-3, and to examine if the mechanism of Cdc25B inhibition involved oxidation and inactivation. Nine Cdc25B inhibitors did not appear to affect Cdc25B through a mechanism involving oxidation because they did not generate detectable amounts of H2O2 in the presence of dithiothreitol, and their Cdc25B IC50 values were not significantly affected by exchanging the dithiothreitol for β-mercaptoethanol or reduced glutathione or by adding catalase to the assay. Six of the nonoxidative hits were selective for Cdc25B inhibition versus MKP-1 and MKP-3, but only the two bisfuran-containing hits, PubChem substance identifiers 4258795 and 4260465, significantly inhibited the growth of human MBA-MD-435 breast and PC-3 prostate cancer cell lines. To confirm the structure and biological activity of 4260465, the compound was resynthesized along with two analogs. Neither of the substitutions to the two analogs was tolerated, and only the resynthesized hit 26683752 inhibited Cdc25B activity in vitro (IC50 = 13.83 ± 1.0 μM) and significantly inhibited the growth of the MBA-MD-435 breast and PC-3 prostate cancer cell lines (IC50 = 20.16 ± 2.0 μM and 24.87 ± 2.25 μM, respectively). The two bis-furan-containing hits identified in the screen represent novel nonoxidative Cdc25B inhibitor chemotypes that block tumor cell proliferation. The availability of non-redox active Cdc25B inhibitors should provide valuable tools to explore the inhibition of the Cdc25 phosphatases as potential mono- or combination therapies for cancer. PMID:19530895

  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. 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. Prediction of Antifungal Activity of Gemini Imidazolium Compounds

    PubMed Central

    Pa?kowski, ?ukasz; B?aszczy?ski, Jerzy; Skrzypczak, Andrzej; B?aszczak, Jan; Nowaczyk, Alicja; Wrblewska, 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

  4. Identification of active compounds in vegetal extracts based on correlation between activity and HPLC-MS data.

    PubMed

    Roldán, Cristina; de la Torre, Angel; Mota, Sonia; Morales-Soto, Aránzazu; Menéndez, Javier; Segura-Carretero, Antonio

    2013-01-15

    We propose a method identifying candidates for active compounds in vegetal extracts. From a collection of samples, the method requires, for each sample, a HPLC-MS analysis and a measurement of the activity. By applying a correlation analysis between the activity and the chromatographic area for each interval of elution time and m/z ratio, the peaks corresponding to candidates for active compounds can be identified. Additionally, when peaks are identified, a model can be estimated to predict the activity in new samples. Both methods are evaluated in one experiment involving the phenolic extract (PE) from 22 samples of extra virgin olive oil (EVOO) where the activity is a cytotoxicity index against JIMT-1 breast cancer cells. In this experiment, the samples were separated into two disjunct partitions: one was used for training (identification of candidates and estimation of prediction model), while the other was used for validation (by comparing the predicted and the measured activities). Three compounds were identified as candidates to be responsible for the cytotoxicity of the EVOO-PE against JIMT-1 cells. The prediction model provided an accurate estimation of the activity. PMID:23122076

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

    PubMed Central

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

    2014-01-01

    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

  6. Identifying Clusters of Active Transportation Using Spatial Scan Statistics

    PubMed Central

    Huang, Lan; Stinchcomb, David G.; Pickle, Linda W.; Dill, Jennifer; Berrigan, David

    2009-01-01

    Background There is an intense interest in the possibility that neighborhood characteristics influence active transportation such as walking or biking. The purpose of this paper is to illustrate how a spatial cluster identification method can evaluate the geographic variation of active transportation and identify neighborhoods with unusually high/low levels of active transportation. Methods Self-reported walking/biking prevalence, demographic characteristics, street connectivity variables, and neighborhood socioeconomic data were collected from respondents to the 2001 California Health Interview Survey (CHIS; N=10,688) in Los Angeles County (LAC) and San Diego County (SDC). Spatial scan statistics were used to identify clusters of high or low prevalence (with and without age-adjustment) and the quantity of time spent walking and biking. The data, a subset from the 2001 CHIS, were analyzed in 20072008. Results Geographic clusters of significantly high or low prevalence of walking and biking were detected in LAC and SDC. Structural variables such as street connectivity and shorter block lengths are consistently associated with higher levels of active transportation, but associations between active transportation and socioeconomic variables at the individual and neighborhood levels are mixed. Only one cluster with less time spent walking and biking among walkers/bikers was detected in LAC, and this was of borderline significance. Age-adjustment affects the clustering pattern of walking/biking prevalence in LAC, but not in SDC. Conclusions The use of spatial scan statistics to identify significant clustering of health behaviors such as active transportation adds to the more traditional regression analysis that examines associations between behavior and environmental factors by identifying specific geographic areas with unusual levels of the behavior independent of predefined administrative units. PMID:19589451

  7. New Compound Sets Identified from High Throughput Phenotypic Screening Against Three Kinetoplastid Parasites: An Open Resource

    PubMed Central

    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

  8. Identifying new small molecule anti-invasive compounds for glioma treatment

    PubMed Central

    Munson, Jennifer; Bonner, Michael; Fried, Levi; Hofmekler, Jonathan; Arbiser, Jack; Bellamkonda, Ravi

    2013-01-01

    Glioblastoma is a disease with poor survival rates after diagnosis. Treatment of the disease involves debulking of the tumor, which is limited by the degree of invasiveness of the disease. Therefore, a treatment to halt the invasion of glioma is desirable for clinical implementation. There have been several candidate compounds targeting specific aspects of invasion, including cell adhesions, matrix degradation, and cytoskeletal rearrangement, but they have failed clinically for a variety of reasons. New targets against glioma invasion include upstream mediators of these classical targets in an effort to better inhibit invasion with more specificity for cancer. Included in these treatments is a new class of compounds inhibiting the generation of reactive oxygen species by targeting the NADPH oxidases. These compounds stand to inhibit multiple pathways, including nuclear factor kappa B and Akt. By conducting a screen of compounds thought to inhibit these pathways, a new compound to halt invasion was found that may have a beneficial effect against glioma, based on recent publications. Further, there are still limitations to the treatment of glioblastoma regardless of the discovery of new targets and compounds that should be addressed to better the therapies against this deadly cancer. PMID:24067366

  9. 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 transcriptionpolymerase 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

  10. 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...

  11. Byrsonima fagifolia Niedenzu Apolar Compounds with Antitubercular Activity

    PubMed Central

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

    2011-01-01

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

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

    PubMed

    Rusetskaya, N Y; Borodulin, V B

    2015-01-01

    Possible mechanisms of the antitoxic action of organoselenium compounds in heavy metal poisoning have been considered. Heavy metal toxicity associated with intensification of free radical oxidation, suppression of the antioxidant system, damage to macromolecules, mitochondria and the genetic material can cause apoptotic cell death or the development of carcinogenesis. Organic selenium compounds are effective antioxidants during heavy metal poisoning; they exhibit higher bioavailability in mammals than inorganic ones and they are able to activate antioxidant defense, bind heavy metal ions and reactive oxygen species formed during metal-induced oxidative stress. One of promising organoselenium compounds is diacetophenonyl selenide (DAPS-25), which is characterized by antioxidant and antitoxic activity, under conditions including heavy metal intoxication. PMID:26350735

  13. 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.

  14. Discovery of compounds that protect tyrosine hydroxylase activity through different mechanisms.

    PubMed

    Hole, Magnus; Underhaug, Jarl; Diez, Hector; Ying, Ming; Rhr, smund Kjendseth; Jorge-Finnigan, Ana; Fernndez-Castillo, Nolia; Garca-Cazorla, Angels; Andersson, K Kristoffer; Teigen, Knut; Martinez, Aurora

    2015-09-01

    Pharmacological chaperones are small compounds that correct the folding of mutant proteins, and represent a promising therapeutic strategy for misfolding diseases. We have performed a screening of 10,000 compounds searching for pharmacological chaperones of tyrosine hydroxylase (TH), the tetrahydrobiopterin (BH4)-dependent enzyme that catalyzes the rate-limiting step in the synthesis of catecholamines. A large number of compounds bound to human TH, isoform 1 (hTH1), but only twelve significantly protected wild-type (hTH1-wt) and mutant TH-R233H (hTH1-p.R202H), associated to the rare neurological disorder TH deficiency (THD), from time-dependent loss of activity. Three of them (named compounds 2, 4 and 5) were subjected to detailed characterization of their functional and molecular effects. Whereas compounds 2 and 4 had a characteristic pharmacological chaperone (stabilizing) effect, compound 5 protected the activity in a higher extent than expected from the low conformational stabilization exerted on hTH1. Compounds 4 and 5 were weak competitive inhibitors with respect to the cofactor BH4 and, as seen by electron paramagnetic resonance, they induced small changes to the first coordination sphere of the catalytic iron. Molecular docking also indicated active-site location with coordination to the iron through a pyrimidine nitrogen atom. Interestingly, compound 5 increased TH activity in cells transiently transfected with either hTH1-wt or the THD associated mutants p.L205P, p.R202H and p.Q381K without affecting the steady-state TH protein levels. This work revealed different mechanisms for the action of pharmacological chaperones and identifies a subtype of compounds that preserve TH activity by weak binding to the catalytic iron. This article is part of a Special Issue entitled: Cofactor-dependent proteins: Evolution, chemical diversity and bio-applications. PMID:25960279

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

    PubMed

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

    2015-07-01

    Essential oil derived from the fresh leaves of Polygonum odoratum Lour was tested for their effects on a foodborne bacterium Salmonella choleraesuis subsp. choleraesuis ATCC 35640 using a broth dilution method. This essential oil showed a significant antibacterial activity against S. choleraesuis at the concentration of 200 µg/mL. Twenty-five volatile compounds were characterized from this essential oil by GC-MS, and aldehyde compounds were found abundant and accounted for more than three-fourths of the essential oil. Among the compounds characterized, dodecanal (C12 ) was the most abundant (55.5%), followed by decanal (C10 ) (11.6%). Both alkanals were effective against S. choleraesuis with the minimum growth inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 100 µg/mL. The most potent antibacterial activity against this bacterium was found with two minor compounds, dodecanol (lauryl alcohol) and 2E-dodecenal, both with each MBC of 6.25 µg/mL. Their primary antibacterial action against S. choleraesuis provably comes from their ability to function as nonionic surface-active agents (surfactants), disrupting the native function of integral membrane proteins nonspecifically. Thus, the antibacterial activity is mediated by biophysical processes. In the case of 2E-alkenals, a biochemical mechanism is also somewhat involved, depending on their alkyl chain length. PMID:25870012

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

    PubMed Central

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

    2013-01-01

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

  17. Callicarpenal and Intermedeol: Two Natural Arthropod Feeding Deterrent and Repellent Compounds Identified from the Southern Folk Remedy Plant, Callicarpa americana

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In previous studies on the American beautyberry (Callicarpa americana), it was demonstrated that callicarpenal and intermedeol were responsible for the arthropod repellent and feeding deterrent activity of this folk remedy. Both compounds showed significant bite-deterring activity against Aedes aeg...

  18. Machine learning models identify molecules active against the Ebola virus in vitro

    PubMed Central

    Ekins, Sean; Freundlich, Joel S.; Clark, Alex M.; Anantpadma, Manu; Davey, Robert A.; Madrid, Peter

    2016-01-01

    The search for small molecule inhibitors of Ebola virus (EBOV) has led to several high throughput screens over the past 3 years. These have identified a range of FDA-approved active pharmaceutical ingredients (APIs) with anti-EBOV activity in vitro and several of which are also active in a mouse infection model. There are millions of additional commercially-available molecules that could be screened for potential activities as anti-EBOV compounds. One way to prioritize compounds for testing is to generate computational models based on the high throughput screening data and then virtually screen compound libraries. In the current study, we have generated Bayesian machine learning models with viral pseudotype entry assay and the EBOV replication assay data. We have validated the models internally and externally. We have also used these models to computationally score the MicroSource library of drugs to select those likely to be potential inhibitors. Three of the highest scoring molecules that were not in the model training sets, quinacrine, pyronaridine and tilorone, were tested in vitro and had EC 50 values of 350, 420 and 230 nM, respectively. Pyronaridine is a component of a combination therapy for malaria that was recently approved by the European Medicines Agency, which may make it more readily accessible for clinical testing. Like other known antimalarial drugs active against EBOV, it shares the 4-aminoquinoline scaffold. Tilorone, is an investigational antiviral agent that has shown a broad array of biological activities including cell growth inhibition in cancer cells, antifibrotic properties, α7 nicotinic receptor agonist activity, radioprotective activity and activation of hypoxia inducible factor-1. Quinacrine is an antimalarial but also has use as an anthelmintic. Our results suggest data sets with less than 1,000 molecules can produce validated machine learning models that can in turn be utilized to identify novel EBOV inhibitors in vitro. PMID:26834994

  19. Pharmacophore modeling, molecular docking, and molecular dynamics simulation approaches for identifying new lead compounds for inhibiting aldose reductase 2.

    PubMed

    Sakkiah, Sugunadevi; Thangapandian, Sundarapandian; Lee, Keun Woo

    2012-07-01

    Aldose reductase 2 (ALR2), which catalyzes the reduction of glucose to sorbitol using NADP as a cofactor, has been implicated in the etiology of secondary complications of diabetes. A pharmacophore model, Hypo1, was built based on 26 compounds with known ALR2-inhibiting activity values. Hypo1 contains important chemical features required for an ALR2 inhibitor, and demonstrates good predictive ability by having a high correlation coefficient (0.95) as well as the highest cost difference (128.44) and the lowest RMS deviation (1.02) among the ten pharmacophore models examined. Hypo1 was further validated by Fisher's randomization method (95%), test set (r = 0.91), and the decoy set shows the goodness of fit (0.70). Furthermore, during virtual screening, Hypo1 was used as a 3D query to screen the NCI database, and the hit leads were sorted by applying Lipinski's rule of five and ADME properties. The best-fitting leads were subjected to docking to identify a suitable orientation at the ALR2 active site. The molecule that showed the strongest interactions with the critical amino acids was used in molecular dynamics simulations to calculate its binding affinity to the candidate molecules. Thus, Hypo1 describes the key structure-activity relationship along with the estimated activities of ALR2 inhibitors. The hit molecules were searched against PubChem to find similar molecules with new scaffolds. Finally, four molecules were found to satisfy all of the chemical features and the geometric constraints of Hypo1, as well as to show good dock scores, PLPs and PMFs. Thus, we believe that Hypo1 facilitates the selection of novel scaffolds for ALR2, allowing new classes of ALR2 inhibitors to be designed. PMID:22249747

  20. Phenotypic Approaches to Identify Inhibitors of B Cell Activation.

    PubMed

    Rex, Elizabeth B; Kim, Suzie; Wiener, Jake; Rao, Navin L; Milla, Marcos E; DiSepio, Daniel

    2015-08-01

    An EPIC label-free phenotypic platform was developed to explore B cell receptor (BCR) and CD40R-mediated B cell activation. The phenotypic assay measured the association of RL non-Hodgkin's lymphoma B cells expressing lymphocyte function-associated antigen 1 (LFA-1) to intercellular adhesion molecule 1 (ICAM-1)-coated EPIC plates. Anti-IgM (immunoglobulin M) mediated BCR activation elicited a response that was blocked by LFA-1/ICAM-1 specific inhibitors and a panel of Bruton's tyrosine kinase (BTK) inhibitors. LFA-1/ICAM-1 association was further increased on coapplication of anti-IgM and mega CD40L when compared to individual application of either. Anti-IgM, mega CD40L, or the combination of both displayed distinct kinetic profiles that were inhibited by treatment with a BTK inhibitor. We also established a FLIPR-based assay to measure B cell activation in Ramos Burkitt's lymphoma B cells and an RL cell line. Anti-IgM-mediated BCR activation elicited a robust calcium response that was inhibited by a panel of BTK inhibitors. Conversely, CD40R activation did not elicit a calcium response in the FLIPR assay. Compared to the FLIPR, the EPIC assay has the propensity to identify inhibitors of both BCR and CD40R-mediated B cell activation and may provide more pharmacological depth or novel mechanisms of action for inhibition of B cell activation. PMID:25948491

  1. Phenotypic Approaches to Identify Inhibitors of B Cell Activation

    PubMed Central

    Kim, Suzie; Wiener, Jake; Rao, Navin L.; Milla, Marcos E.; DiSepio, Daniel

    2015-01-01

    An EPIC label-free phenotypic platform was developed to explore B cell receptor (BCR) and CD40R-mediated B cell activation. The phenotypic assay measured the association of RL non-Hodgkins lymphoma B cells expressing lymphocyte function-associated antigen 1 (LFA-1) to intercellular adhesion molecule 1 (ICAM-1)-coated EPIC plates. Anti-IgM (immunoglobulin M) mediated BCR activation elicited a response that was blocked by LFA-1/ICAM-1 specific inhibitors and a panel of Brutons tyrosine kinase (BTK) inhibitors. LFA-1/ICAM-1 association was further increased on coapplication of anti-IgM and mega CD40L when compared to individual application of either. Anti-IgM, mega CD40L, or the combination of both displayed distinct kinetic profiles that were inhibited by treatment with a BTK inhibitor. We also established a FLIPR-based assay to measure B cell activation in Ramos Burkitts lymphoma B cells and an RL cell line. Anti-IgM-mediated BCR activation elicited a robust calcium response that was inhibited by a panel of BTK inhibitors. Conversely, CD40R activation did not elicit a calcium response in the FLIPR assay. Compared to the FLIPR, the EPIC assay has the propensity to identify inhibitors of both BCR and CD40R-mediated B cell activation and may provide more pharmacological depth or novel mechanisms of action for inhibition of B cell activation. PMID:25948491

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

    PubMed Central

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

    2016-01-01

    To determine whether a C. elegans bioassay could predict mammalian developmental activity, we selected diverse compounds known and known not to elicit such activity and measured their effect on C. elegans egg viability. 89% of compounds that reduced C. elegans egg viability also had mammalian developmental activity. Conversely only 25% of compounds found not to reduce egg viability in C. elegans were also inactive in mammals. We conclude that the C. elegans egg viability assay is an accurate positive predictor, but an inaccurate negative predictor, of mammalian developmental activity. We then evaluated C. elegans as a tool to identify mechanisms affecting toxicological outcomes among related compounds. The difference in developmental activity of structurally related fungicides in C. elegans correlated with their rate of metabolism. Knockdown of the cytochrome P450s cyp-35A3 and cyp-35A4 increased the toxicity to C. elegans of the least developmentally active compounds to the level of the most developmentally active. This indicated that these P450s were involved in the greater rate of metabolism of the less toxic of these compounds. We conclude that C. elegans based approaches can predict mammalian developmental activity and can yield plausible hypotheses for factors affecting the biological potency of compounds in mammals. PMID:26987796

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

    PubMed

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

    2016-01-01

    To determine whether a C. elegans bioassay could predict mammalian developmental activity, we selected diverse compounds known and known not to elicit such activity and measured their effect on C. elegans egg viability. 89% of compounds that reduced C. elegans egg viability also had mammalian developmental activity. Conversely only 25% of compounds found not to reduce egg viability in C. elegans were also inactive in mammals. We conclude that the C. elegans egg viability assay is an accurate positive predictor, but an inaccurate negative predictor, of mammalian developmental activity. We then evaluated C. elegans as a tool to identify mechanisms affecting toxicological outcomes among related compounds. The difference in developmental activity of structurally related fungicides in C. elegans correlated with their rate of metabolism. Knockdown of the cytochrome P450s cyp-35A3 and cyp-35A4 increased the toxicity to C. elegans of the least developmentally active compounds to the level of the most developmentally active. This indicated that these P450s were involved in the greater rate of metabolism of the less toxic of these compounds. We conclude that C. elegans based approaches can predict mammalian developmental activity and can yield plausible hypotheses for factors affecting the biological potency of compounds in mammals. PMID:26987796

  4. A review on antimicrobial activity of mushroom (Basidiomycetes) extracts and isolated compounds.

    PubMed

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

    2012-11-01

    Despite the huge diversity of antibacterial compounds, bacterial resistance to first-choice antibiotics has been drastically increasing. Moreover, the association between multiresistant microorganisms and nosocomial infections highlight the problem, and the urgent need for solutions. Natural resources have been exploited in the last years and among them, mushrooms could be an alternative source of new antimicrobials. In this review, we present an overview of the antimicrobial properties of mushroom extracts and highlight some of the active compounds identified, including low- and high-molecular weight (LMW and HMW, respectively) compounds. LMW compounds are mainly secondary metabolites, such as sesquiterpenes and other terpenes, steroids, anthraquinones, benzoic acid derivatives, and quinolines, but also primary metabolites such as oxalic acid. HMW compounds are mainly peptides and proteins. Data available from the literature indicate a higher antimicrobial activity of mushroom extracts against gram-positive bacteria. Among all the mushrooms, Lentinus edodes is the most studied species and seems to have a broad antimicrobial action against both gram-positive and gram-negative bacteria. Plectasin peptide, obtained from Pseudoplectania nigrella, is the isolated compound with the highest antimicrobial activity against gram-positive bacteria, while 2-aminoquinoline, isolated from Leucopaxillus albissimus, presents the highest antimicrobial activity against gram-negative bacteria. PMID:23023950

  5. 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...

  6. Vanillin-derived antiproliferative compounds influence Plk1 activity.

    PubMed

    Carrasco-Gomez, Roberto; Keppner-Witter, Sarah; Hieke, Martina; Lange, Lisa; Schneider, Gisbert; Schubert-Zsilavecz, Manfred; Proschak, Ewgenij; Spnkuch, Birgit

    2014-11-01

    We synthesized a series of vanillin-derived compounds and analyzed them in HeLa cells for their effects on the proliferation of cancer cells. The molecules are derivatives of the lead compound SBE13, a potent inhibitor of the inactive conformation of human polo-like kinase 1 (Plk1). Some of the new designs were able to inhibit cancer cell proliferation to a similar extent as the lead structure. Two of the compounds ((({4-[(6-chloropyridin-3-yl)methoxy]-3-methoxyphenyl}methyl)(pyridin-4-ylmethyl)amine) and (({4-[(4-chlorophenyl)methoxy]-3-methoxyphenyl}methyl)(pyridin-4-ylmethyl)amine)) were much stronger in their capacity to reduce HeLa cell proliferation and turned out to potently induce apoptosis and reduce Plk1 kinase activity in vitro. PMID:25304894

  7. Hybrid energy storage systems utilizing redox active organic compounds

    DOEpatents

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

    2015-09-08

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

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

    PubMed

    Stumpfe, Dagmar; Dimova, Dilyana; Bajorath, Jrgen

    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

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

    NASA Astrophysics Data System (ADS)

    Kos, G.; Ariya, P. A.

    2004-05-01

    The occurrence of VOCs in snow has been observed and can be related to anthropogenic emissions and biological activity. Photochemistry and microorganisms play a major role in the transformation of compounds in different compartments of the global ecosystem. Studies so far focused on the determination of single analytes or a class of compounds - mainly of anthropogenic origin (e.g. halogenated aromatic hydrocarbons) - that were considered important with regard to health and environmental concerns. Broader studies that describe a range of different compounds with different functionalities are relatively rare, especially for those of biological origin. The presented study investigated the formation of VOCs in snow samples and their connection with microbiological activity. The main aim was to pre-concentrate, identify and quantify volatile organic compounds. Snow samples were collected in an urban environment (Montreal, Canada) with sterilized containers. Samples were transferred into a heated reaction flask, where the sample was melted. A two-trap system was employed for pre-concentration: The first trap was used for water removal. The second trap was used for the collection of expected analytes by removing volatiles from the circulating air. Circulation was maintained with a pump at atmospheric pressure. Adsorption to glass walls of the reaction flask was prevented with halocarbon wax coating. Different sterilization methods were employed to suppress microbiological activity in order to collect background data and identify compounds of biological origin. VOC concentration and compound identification was performed with gas chromatography and mass spectrometric detection (GC-MS) by taking a sample with a gas-tight syringe through a septum-port. The sample was directly injected into the GC system. Compounds were identified by their respective mass spectra and included aldehydes and alcohols.

  10. Structure-activity relationship of aliphatic compounds for nematicidal activity against pine wood nematode (Bursaphelenchus xylophilus).

    PubMed

    Seo, Seon-Mi; Kim, Junheon; Kim, Eunae; Park, Hye-Mi; Kim, Young-Joon; Park, Il-Kwon

    2010-02-10

    Nematicidal activity of aliphatic compounds was tested to determine a structure-activity relationship. There was a significant difference in nematicidal activity among functional groups. In a test with alkanols and 2E-alkenols, compounds with C(8)-C(11) chain length showed 100% nematicidal activity against pine wood nematode, Bursaphelenchus xylophilus , at 0.5 mg/mL concentration. C(6)-C(10) 2E-alkenals exhibited >95% nematicidal activity, but the other compounds with C(11)-C(14) chain length showed weak activity. Nematicidal activity of alkyl acetates with C(7)-C(11) chain length was strong. Compounds belonging to hydrocarbons, alkanals, and alkanoic acetates showed weak activity at 0.5 mg/mL concentration. Nematicidal activity of active compounds was determined at lower concentrations. At 0.25 mg/mL concentration, whole compounds except C(8) alkanol, C(8) 2E-alkenol, and C(7) alkanoic acid showed >80% nematicidal activity. C(9)-C(11) alkanols, C(10)-C(11) 2E-alkenols, C(8)-C(9) 2E-alkenals, and C(9)-C(10) alkanoic acids showed >80% nematicidal activity at 0.125 mg/mL concentration. Only C(11) alkanol exhibited strong nematicidal activity at 0.0625 mg/mL concentration, the lowest concentration that was tested. PMID:20055406

  11. Historical trends in organochlorine compounds in river basins identified using sediment cores from reservoirs

    USGS Publications Warehouse

    Van Metre, P.C.; Callender, E.; Fuller, C.C.

    1997-01-01

    This study used chemical analyses of dated sediment cores from reservoirs to define historical trends in water quality in the influent river basins. This work applies techniques from paleolimnology to reservoirs, and in the process, highlights differences between sediment-core interpretations for reservoirs and natural lakes. Sediment cores were collected from six reservoirs in the central and southeastern United States, sectioned, and analyzed for 137Cs and organochlorine compounds. 137Cs analyses were used to demonstrate limited post-depositional mixing, to indicate sediment deposition dates, and to estimate sediment focusing factors. Relative lack of mixing, high sedimentation rates, and high focusing factors distinguish reservoir sediment cores from cores collected in natural lakes. Temporal trends in concentrations of PCBs, total DDT (DDT + DDD + DDE), and chlordane reflect historical use and regulation of these compounds and differences in land use between reservoir drainages. PCB and total DDT core burdens, normalized for sediment focusing, greatly exceed reported cumulative regional atmospheric fallout of PCBs and total DDT estimated using cores from peat hogs and natural lakes, indicating the dominance of fluvial inputs of both groups of compounds to the reservoirs.This study used chemical analyses of dated sediment cores from reservoirs to define historical trends in water quality in the influent river basins. This work applies techniques from paleolimnology to reservoirs, and in the process, highlights differences between sediment-core interpretations for reservoirs and natural lakes. Sediment cores were collected from six reservoirs in the central and southeastern United States, sectioned, and analyzed for 137Cs and organochlorine compounds. 137Cs analyses were used to demonstrate limited post-depositional mixing, to indicate sediment deposition dates, and to estimate sediment focusing factors. Relative lack of mixing, high sedimentation rates, and high focusing factors distinguish reservoir sediment cores from cores collected in natural lakes. Temporal trends in concentrations of PCBs, total DOT (DDT+DDD+DDE), and chlordane reflect historical use and regulation of these compounds and differences in land use between reservoir drainages. PCB and total DDT core burdens, normalized for sediment focusing, greatly exceed reported cumulative regional atmospheric fallout of PCBs and total DDT estimated using cores from peat bogs and natural lakes, indicating the dominance of fluvial inputs of both groups of compounds to the reservoirs.

  12. Large-Scale Chemical Similarity Networks for Target Profiling of Compounds Identified in Cell-Based Chemical Screens

    PubMed Central

    Lo, Yu-Chen; Senese, Silvia; Li, Chien-Ming; Hu, Qiyang; Huang, Yong; Damoiseaux, Robert; Torres, Jorge Z.

    2015-01-01

    Target identification is one of the most critical steps following cell-based phenotypic chemical screens aimed at identifying compounds with potential uses in cell biology and for developing novel disease therapies. Current in silico target identification methods, including chemical similarity database searches, are limited to single or sequential ligand analysis that have limited capabilities for accurate deconvolution of a large number of compounds with diverse chemical structures. Here, we present CSNAP (Chemical Similarity Network Analysis Pulldown), a new computational target identification method that utilizes chemical similarity networks for large-scale chemotype (consensus chemical pattern) recognition and drug target profiling. Our benchmark study showed that CSNAP can achieve an overall higher accuracy (>80%) of target prediction with respect to representative chemotypes in large (>200) compound sets, in comparison to the SEA approach (6070%). Additionally, CSNAP is capable of integrating with biological knowledge-based databases (Uniprot, GO) and high-throughput biology platforms (proteomic, genetic, etc) for system-wise drug target validation. To demonstrate the utility of the CSNAP approach, we combined CSNAP's target prediction with experimental ligand evaluation to identify the major mitotic targets of hit compounds from a cell-based chemical screen and we highlight novel compounds targeting microtubules, an important cancer therapeutic target. The CSNAP method is freely available and can be accessed from the CSNAP web server (http://services.mbi.ucla.edu/CSNAP/). PMID:25826798

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

    PubMed Central

    Tiwari, Vishvanath; Roy, Ranita; Tiwari, Monalisa

    2015-01-01

    Bacterial pathogens cause a number of lethal diseases. Opportunistic bacterial pathogens grouped into ESKAPE pathogens that are linked to the high degree of morbidity, mortality and increased costs as described by Infectious Disease Society of America. Acinetobacter baumannii is one of the ESKAPE pathogens which cause respiratory infection, pneumonia and urinary tract infections. The prevalence of this pathogen increases gradually in the clinical setup where it can grow on artificial surfaces, utilize ethanol as a carbon source and resists desiccation. Carbapenems, a β-lactam, are the most commonly prescribed drugs against A. baumannii. The high level of acquired and intrinsic carbapenem resistance mechanisms acquired by these bacteria makes their eradication difficult. The pharmaceutical industry has no solution to this problem. Hence, it is an urgent requirement to find a suitable alternative to carbapenem, a commonly prescribed drug for Acinetobacter infection. In order to do this, here we have made an effort to review the active compounds of plants that have potent antibacterial activity against many bacteria including carbapenem resistant strain of A. baumannii. We have also briefly highlighted the separation and identification methods used for these active compounds. This review will help researchers involved in the screening of herbal active compounds that might act as a replacement for carbapenem. PMID:26150810

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

    PubMed

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

    2014-09-17

    In this study, we evaluated the nematicidal activity of natural ester compounds against the pine wood nematode, Bursaphelenchus xylophilus, to identify candidates for the development of novel, safe nematicides. We also tested the nematicidal activity of synthesized analogues of these ester compounds to determine the structure-activity relationship. Among 28 ester compounds tested, isobutyl 2-methylbutanoate, 3-methylbutyl 2-methylbutanoate, 3-methylbutyl tiglate, 3-methyl-2-butenyl 2-methylbutanoate, and pentyl 2-methylbutanoate showed strong nematicidal activity against the pine wood nematode at a 1 mg/mL concentration. The other ester compounds showed weak nematicidal activity. The LC50 values of 3-methylbutyl tiglate, isobutyl 2-methylbutanoate, 3-methylbutyl 2-methylbutanoate, 3-methyl-2-butenyl 2-methylbutanoate, and pentyl 2-methylbutanoate were 0.0218, 0.0284, 0.0326, 0.0402, and 0.0480 mg/mL, respectively. The ester compounds described herein merit further study as potential nematicides for pine wood nematode control. PMID:25153339

  15. Selective CB2 receptor agonists. Part 2: Structure-activity relationship studies and optimization of proline-based compounds.

    PubMed

    Riether, Doris; Zindell, Renee; Wu, Lifen; Betageri, Raj; Jenkins, James E; Khor, Someina; Berry, Angela K; Hickey, Eugene R; Ermann, Monika; Albrecht, Claudia; Ceci, Angelo; Gemkow, Mark J; Nagaraja, Nelamangala V; Romig, Helmut; Sauer, Achim; Thomson, David S

    2015-02-01

    Through a ligand-based pharmacophore model (S)-proline based compounds were identified as potent cannabinoid receptor 2 (CB2) agonists with high selectivity over the cannabinoid receptor 1 (CB1). Structure-activity relationship investigations for this compound class lead to oxo-proline compounds 21 and 22 which combine an impressive CB1 selectivity profile with good pharmacokinetic properties. In a streptozotocin induced diabetic neuropathy model, 22 demonstrated a dose-dependent reversal of mechanical hyperalgesia. PMID:25556092

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

    PubMed

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

    2014-12-01

    Recent therapeutic successes have renewed interest in drug combinations, but experimental screening approaches are costly and often identify only small numbers of synergistic combinations. The DREAM consortium launched an open challenge to foster the development of in silico methods to computationally rank 91 compound pairs, from the most synergistic to the most antagonistic, based on gene-expression profiles of human B cells treated with individual compounds at multiple time points and concentrations. Using scoring metrics based on experimental dose-response curves, we assessed 32 methods (31 community-generated approaches and SynGen), four of which performed significantly better than random guessing. We highlight similarities between the methods. Although the accuracy of predictions was not optimal, we find that computational prediction of compound-pair activity is possible, and that community challenges can be useful to advance the field of in silico compound-synergy prediction. PMID:25419740

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

    PubMed Central

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

    2015-01-01

    Recent therapeutic successes have renewed interest in drug combinations, but experimental screening approaches are costly and often identify only small numbers of synergistic combinations. The DREAM consortium launched an open challenge to foster the development of in silico methods to computationally rank 91 compound pairs, from the most synergistic to the most antagonistic, based on gene-expression profiles of human B cells treated with individual compounds at multiple time points and concentrations. Using scoring metrics based on experimental dose-response curves, we assessed 32 methods (31 community-generated approaches and SynGen), four of which performed significantly better than random guessing. We highlight similarities between the methods. Although the accuracy of predictions was not optimal, we find that computational prediction of compound-pair activity is possible, and that community challenges can be useful to advance the field of in silico compound-synergy prediction. PMID:25419740

  18. 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

  19. High-throughput screening and whole genome sequencing identifies an antimicrobially active inhibitor of Vibrio cholerae

    PubMed Central

    2014-01-01

    Background Pathogenic serotypes of Vibrio cholerae cause the life-threatening diarrheal disease cholera. The increasing development of bacterial resistances against the known antibiotics necessitates the search for new antimicrobial compounds and targets for this pathogen. Results A high-throughput screening assay with a Vibrio cholerae reporter strain constitutively expressing green fluorescent protein (GFP) was developed and applied in the investigation of the growth inhibitory effect of approximately 28,300 structurally diverse natural compounds and synthetic small molecules. Several compounds with activities in the low micromolar concentration range were identified. The most active structure, designated vz0825, displayed a minimal inhibitory concentration (MIC) of 1.6?M and a minimal bactericidal concentration (MBC) of 3.2?M against several strains of V. cholerae and was specific for this pathogen. Mutants with reduced sensitivity against vz0825 were generated and whole genome sequencing of 15 pooled mutants was carried out. Comparison with the genome of the wild type strain identified the gene VC_A0531 (GenBank: AE003853.1) as the major site of single nucleotide polymorphisms in the resistant mutants. VC_A0531 is located on the small chromosome of V. cholerae and encodes the osmosensitive K+-channel sensor histidine kinase (KdpD). Nucleotide exchange of the major mutation site in the wild type strain confirmed the sensitive phenotype. Conclusion The reporter strain MO10 pG13 was successfully used for the identification of new antibacterial compounds against V. cholerae. Generation of resistant mutants and whole genome sequencing was carried out to identify the histidine kinase KdpD as a novel antimicrobial target. PMID:24568688

  20. Antifungal activities of compounds isolated from Piper abutiloides Kunth.

    PubMed

    Johann, S; Cota, B B; Souza-Fagundes, E M; Pizzolatti, M G; Resende, M A; Zani, C L

    2009-11-01

    Piperaceae is a family of tropical plants known to have antifungal, antibacterial, tumour-inhibitory, antiviral, antioxidant, molluscicidal and leishmanicidal activities. In this work, extracts and fractions from aerial parts of Piper abutiloides (Piperaceae), a traditional medicinal plant, were evaluated against the fungal species Candida albicans, C. parapsilosis, C. krusei, C. glabrata, C. tropicalis, Cryptococcus neoformans and Sporothrix schenckii. The results have shown that the antifungal activity of this plant can be concentrated in the hexanic fraction after partitioning its hydroalcoholic extract between hexane and 90% aqueous methanol. The chromatographic fractionation of the bioactive part was monitored with a bioautographic assay using C. glabrata, and allowed the isolation of three antifungal compounds: pseudodillapiol, eupomatenoid-6 and conocarpan. These compounds presented different potencies against the fungi tested, with the strongest effect being observed for eupomatenoid-6 against C. glabrata, which presented a minimal inhibitory concentration value of 0.3 microg spot(-1). Conocarpan showed antifungal activity without apparent cytotoxic effect on normal human lymphocytes, as assessed by the proliferation assay with human peripheral blood mononuclear cells stimulated with phytohaemaglutinin. This work reveals for the first time the occurrence of these compounds in P. abutiloides and justifies further studies to clarify their mechanisms of action. PMID:19076283

  1. Global Proteome Analysis Identifies Active Immunoproteasome Subunits in Human Platelets*

    PubMed Central

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

    2014-01-01

    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

  2. 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

  3. 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

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

    PubMed Central

    Thi, Nhuan Do; Hwang, Eun-Sun

    2014-01-01

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

  5. 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

  6. Small Molecule Activation by Constrained Phosphorus Compounds: Insights from Theory.

    PubMed

    Pal, Amrita; Vanka, Kumar

    2016-01-19

    An exciting new development in main group chemistry has been the use of a constrained, "flat", phosphorus-based complex to mediate in reactions such as the dehydrogenation of ammonia borane (AB), and the activation of the N-H bond in primary amines. Its importance is based on the fact that it shows that main group compounds, when properly designed, can be as effective as transition metal complexes for doing significant chemical transformations. What the current computational study, employing density functional theory (DFT), reveals is that a common, general mechanism exists that accounts for the behavior of the flat phosphorus compound in the different reactions that have been experimentally reported to date. This mechanism, which involves the mediation by a base as a proton transfer agent, is simpler and energetically more favorable than the previous mechanisms that have been proposed for the same reactions in the literature. It is likely that the knowledge gained from the current work about the chemical behavior of this phosphorus compound can be utilized to design new constrained phosphorus-based compounds. PMID:26700074

  7. 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

  8. Problems for risk assessment of endocrine-active estrogenic compounds.

    PubMed

    Safe, Stephen H; Pallaroni, Lea; Yoon, Kyungsil; Gaido, Kevin; Ross, Susan; McDonnell, Donald

    2002-12-01

    Estrogenic industrial compounds such as bisphenol A (BPA) and nonylphenol typically bind estrogen receptor (ER) alpha and ERBeta and induce transactivation of estrogen-responsive genes/reporter genes, but their potencies are usually greater than or equal to 1,000-fold lower than observed for 17Beta-estradiol. Risk assessment of estrogenic compounds on the basis of their potencies in simple reporter gene or binding assays may be inappropriate. For example, selective ER modulators (SERMs) represent another class of synthetic estrogens being developed for treatment of hormone-dependent problems. SERMs differentially activate wild-type ERalpha and variant forms expressing activation function 1 (ER-AF1) and AF2 (ER-AF2) in human HepG2 hepatoma cells transfected with an estrogen-responsive complement C3 promoter-luciferase construct, and these in vitro differences reflect their unique in vivo biologies. The HepG2 cell assay has also been used in our laboratories to investigate the estrogenic activities of the following structurally diverse synthetic and phytoestrogens: 4 -hydroxytamoxifen; BPA; 2 ,4 ,6 -trichloro-4-biphenylol; 2 ,3 ,4 ,5 -tetrachloro-4-biphenylol; p-t-octylphenol; p-nonylphenol; naringenin; kepone; resveratrol; and 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane. The results show that synthetic and phytoestrogens are weakly estrogenic but induce distinct patterns of ER agonist/antagonist activities that are cell context- and promoter-dependent, suggesting that these compounds will induce tissue-specific (in vivo(ER agonist or antagonist activities. These results suggest that other receptors, such as the aryl hydrocarbon receptor, that also bind structurally diverse ligands may exhibit unique responses in vivo that are not predicted by standard in vitro bioassays. PMID:12634121

  9. Problems for risk assessment of endocrine-active estrogenic compounds.

    PubMed Central

    Safe, Stephen H; Pallaroni, Lea; Yoon, Kyungsil; Gaido, Kevin; Ross, Susan; McDonnell, Donald

    2002-01-01

    Estrogenic industrial compounds such as bisphenol A (BPA) and nonylphenol typically bind estrogen receptor (ER) alpha and ERBeta and induce transactivation of estrogen-responsive genes/reporter genes, but their potencies are usually greater than or equal to 1,000-fold lower than observed for 17Beta-estradiol. Risk assessment of estrogenic compounds on the basis of their potencies in simple reporter gene or binding assays may be inappropriate. For example, selective ER modulators (SERMs) represent another class of synthetic estrogens being developed for treatment of hormone-dependent problems. SERMs differentially activate wild-type ERalpha and variant forms expressing activation function 1 (ER-AF1) and AF2 (ER-AF2) in human HepG2 hepatoma cells transfected with an estrogen-responsive complement C3 promoter-luciferase construct, and these in vitro differences reflect their unique in vivo biologies. The HepG2 cell assay has also been used in our laboratories to investigate the estrogenic activities of the following structurally diverse synthetic and phytoestrogens: 4 -hydroxytamoxifen; BPA; 2 ,4 ,6 -trichloro-4-biphenylol; 2 ,3 ,4 ,5 -tetrachloro-4-biphenylol; p-t-octylphenol; p-nonylphenol; naringenin; kepone; resveratrol; and 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane. The results show that synthetic and phytoestrogens are weakly estrogenic but induce distinct patterns of ER agonist/antagonist activities that are cell context- and promoter-dependent, suggesting that these compounds will induce tissue-specific (in vivo(ER agonist or antagonist activities. These results suggest that other receptors, such as the aryl hydrocarbon receptor, that also bind structurally diverse ligands may exhibit unique responses in vivo that are not predicted by standard in vitro bioassays. PMID:12634121

  10. Compounded bioidentical hormone therapy: identifying use trends and knowledge gaps among US women

    PubMed Central

    Pinkerton, JoAnn V.; Santoro, Nanette

    2015-01-01

    Abstract Objective: Two surveys (Harris and Rose surveys) were conducted to quantify the use of compounded hormone therapy (CHT; or bioidentical hormone therapy) among perimenopausal and postmenopausal women in the United States, to assess women's knowledge of CHT versus Food and Drug Administration (FDA)–approved hormone therapy, and to gather information on menopausal experience. Methods: The Harris survey was administered to 801 women aged 45 to 60 years who had experienced at least one menopausal symptom. The Rose survey was administered to 2,044 women aged 40 years or older who were ever users of hormone therapy. Women were queried about menopausal symptoms, hormone therapy use, and knowledge of CHT. Findings from the Rose survey were extrapolated using US Census Bureau data and prescription claims for FDA-approved hormone therapy to estimate the prevalence of CHT use. Results: According to extrapolations using Rose data, up to 2.5 million US women aged 40 years or older may use CHT annually, accounting for 28% to 68% of hormone therapy prescriptions. Harris data showed that 86% of women surveyed were unaware that CHT products are not FDA-approved. The Rose survey asked a subset of 1,771 women whether their hormone therapy had been personalized based on hormone levels; 21% (378) answered “yes” whereas 27% (476) did not know. In both surveys, most hormone therapy users stated that their physician had recommended the treatment. Conclusions: We estimate that 1 million to 2.5 million US women aged 40 years or older use CHT. The data suggest that many women are unaware that compounded hormones have not been evaluated or approved by the FDA. Providers have an educational opportunity to ensure that women considering hormone therapy understand the risks and benefits of inadequately regulated CHT. PMID:25692877

  11. Use of dermal equivalent and skin equivalent models for identifying phototoxic compounds in vitro.

    PubMed

    Augustin, C; Collombel, C; Damour, O

    1997-01-01

    Phototoxicity inducing in vivo photoirritation, a reversible inflammatory reaction of the skin after chemical contact and UVA radiation exposure, is increasingly observed as a side effect associated with the use of both cosmetics and systemic drugs. In order to systematically screen for the phototoxic potential of new compounds, we propose two three-dimensional models suitable for in vitro testing: a dermal equivalent (DE) and a skin equivalent (SE) model. The DE model includes a collagen-glycosaminoglycans-chitosan porous matrix populated by normal human fibroblasts. The SE model is made by seeding normal human keratinocytes onto the DE, leading to a fully differentiated epidermis. The objectives of this pilot study are: 1) to compare the deleterious effects of UVA radiation on the two models and 2) to evaluate to what extent the in vitro results can predict the in vivo phototoxicity caused by well-known photoirritant compounds, included in the COLIPA validation phototoxicity reference chemical list. Dilutions of thiourea, sulisobenzone, promethazine, chlorpromazine and tetracycline were applied (20 microliters) onto DEs and SEs (n = 6) and incubated for 1 h (or 15 h) at 37 degrees C. Irradiated samples received 3 J/cm2 UVA. The 24 h post-irradiation residual cellular viability was measured using the MTT test on treated and untreated tissues and IL-1 alpha release measurement in collected SE culture media. A concordance in terms of photoirritant/non-photoirritant was obtained between the in vivo data and the in vitro results, suggesting that the DE and the SE models could be integrated, after a complete validation study, into a protocol for in vitro testing of the photoirritant potential of new molecules. PMID:9361126

  12. Phenolic compounds from leaves of Casimiroa edulis showed adipogenesis activity.

    PubMed

    Nagai, Hiroyuki; Tanaka, Toshiyuki; Goto, Tsuyoshi; Kusudo, Tatsuya; Takahashi, Nobuyuki; Kawada, Teruo

    2014-01-01

    Casimiroa edulis is known as cochitzapotl, and it belongs to a species of tropical fruiting tree in the family Rutaceae, native to eastern Mexico and Central America south to Costa Rica. In this study, we isolated two furocoumarins and two polymethoxyflavones from leaves of C. edulis and evaluated the functions of glucose and lipid metabolism activity with 3T3-L1 adipocytes. We discovered that the addition of furocoumarins increased glucose uptake and lipid accumulation in 3T3-L1 adipocyte. These results suggest that furocoumarin compounds can be used as functional food-derived compounds, to regulate adipocyte functioning for the management of metabolic syndrome, which is associated with dysfunctions of glucose and lipid metabolism. PMID:25036684

  13. Cytotoxic activity of compounds from the lichen: Cladonia convoluta.

    PubMed

    Bzivin, Carine; Tomasi, Sophie; Rouaud, Isabelle; Delcros, Jean-Guy; Boustie, Jol

    2004-09-01

    The depsidone 9'-( O-methyl)protocetraric acid was isolated from the lichen Cladonia convoluta (Lam.) Anders along with the known (-)-usnic acid and fumarprotocetraric acid. The complete structure of 9'-( O-methyl)protocetraric acid was elucidated using HSQC and HMBC spectral data. (-)-Usnic acid was the only compound to display a moderate cytotoxic activity on various cancer cell lines (IC (50) = 6, 12.1, 15.8, 17.8, 8.2 and 6.8 microg/mL on L1210, 3LL, DU145, MCF7, K-562 and U251, respectively). This compound was also shown to induce apoptosis of murine leukaemia L1210 cells in a dose- and time-dependent manner. PMID:15386197

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

    PubMed Central

    Balunas, Marcy J.; Kinghorn, A. Douglas

    2010-01-01

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

  15. Quantitative structure-activity relationships of phenolic compounds causing apoptosis.

    PubMed

    Hansch, Corwin; Bonavida, Benjamin; Jazirehi, Ali R; Cohen, J John; Milliron, Cheri; Kurup, Alka

    2003-02-20

    A study of a variety of phenolic compounds (simple phenols, estradiol, bisphenol A, diethylstilbesterol) on their action on L1210 leukemia cells led to the formulation of the following QSAR for apoptosis:log 1/C=-3.16 Clog P+2.77 CMR-3.76n=11, r(2)=0.939, s=0.630, q(2)=0.892C is the molar concentration causing 25% apoptosis, Clog P is the calculated octanol/water partition coefficient and CMR is the calculated molecular refractivity. Our results imply the significance of characterization of the phenolic compounds with apoptotic activity and the development of new agents for cancer therapy. PMID:12538027

  16. Antiviral Activities and Putative Identification of Compounds in Microbial Extracts from the Hawaiian Coastal Waters

    PubMed Central

    Tong, Jing; Trapido-Rosenthal, Hank; Wang, Jun; Wang, Youwei; Li, Qing X.; Lu, Yuanan

    2012-01-01

    Marine environments are a rich source of significant bioactive compounds. The Hawaiian archipelago, located in the middle of the Pacific Ocean, hosts diverse microorganisms, including many endemic species. Thirty-eight microbial extracts from Hawaiian coastal waters were evaluated for their antiviral activity against four mammalian viruses including herpes simplex virus type one (HSV-1), vesicular stomatitis virus (VSV), vaccinia virus and poliovirus type one (poliovirus-1) using in vitro cell culture assay. Nine of the 38 microbial crude extracts showed antiviral potencies and three of these nine microbial extracts exhibited significant activity against the enveloped viruses. A secosteroid, 5?(H),17?(H),(20R)-beta-acetoxyergost-8(14)-ene was putatively identified and confirmed to be the active compound in these marine microbial extracts. These results warrant future in-depth tests on the isolation of these active elements in order to explore and validate their antiviral potential as important therapeutic remedies. PMID:22611351

  17. Identification of the main odor-active compounds in musts from French and Romanian hybrids by three olfactometric methods.

    PubMed

    Serot, T; Prost, C; Visan, L; Burcea, M

    2001-04-01

    Three olfactometric methods (frequency of detection, time--intensity method, and aroma extract dilution analysis) were used to evaluate the main odorants of three musts obtained from French--Romanian hybrids (Valerien, Admira, and Brumariu). The three methods allow detection of the same odor-active compounds. The results obtained from these methods were closely related. Nineteen odor-active compounds were detected, and 13 were identified. The three methods showed the importance of an unidentified compound with a grape and grape juice aroma note in the three musts. Among the other compounds, 3-hexen-1-al, (E,Z)-2,6-nonadien-1-ol, and 1-ccten-3-one seemed to contribute actively to the odor of Valerien must. 3-(Methylthio)propanal and hexanal were contributors to the Admira and Brumariu odor. Phenylacetaldehyde was one of the main odor-active compounds in must from Admira. PMID:11308345

  18. Antibiofilm Activity, Compound Characterization, and Acute Toxicity of Extract from a Novel Bacterial Species of Paenibacillus

    PubMed Central

    Alasil, Saad Musbah; Omar, Rahmat; Yusof, Mohd Yasim

    2014-01-01

    The effectiveness of many antimicrobial agents is currently decreasing; therefore, it is important to search for alternative therapeutics. Our study was carried out to assess the in vitro antibiofilm activity using microtiter plate assay, to characterize the bioactive compounds using Ultra Performance Liquid Chromatography-Diode Array Detection and Liquid Chromatography-Mass Spectrometry and to test the oral acute toxicity on Sprague Dawley rats of extract derived from a novel bacterial species of Paenibacillus strain 139SI. Our results indicate that the crude extract and its three identified compounds exhibit strong antibiofilm activity against a broad range of clinically important pathogens. Three potential compounds were identified including an amino acid antibiotic C8H20N3O4P (MW 253.237), phospholipase A2 inhibitor C21H36O5 (MW 368.512), and an antibacterial agent C14H11N3O2 (MW 253.260). The acute toxicity test indicates that the mortality rate among all rats was low and that the biochemical parameters, hematological profile, and histopathology examination of liver and kidneys showed no significant differences between experimental groups (P > 0.05). Overall, our findings suggest that the extract and its purified compounds derived from novel Paenibacillus sp. are nontoxic exhibiting strong antibiofilm activity against Gram-positive and Gram-negative pathogens that can be useful towards new therapeutic management of biofilm-associated infections. PMID:24790603

  19. 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 (>100M) 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 M 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

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

    PubMed Central

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  2. 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

  3. In vitro Cytotoxic Activities and Molecular Mechanisms of Angelica shikokiana Extract and its Isolated Compounds

    PubMed Central

    Mira, Amira; Shimizu, Kuniyoshi

    2015-01-01

    Background: Angelica shikokiana is a Japanese medicinal herb that is included among food and drug preparations protecting against cancer; however, there is no previous report about the cytotoxicity of A. shikokiana or its bioactive compounds. Objective: This study was designed to investigate the cytotoxic activities of A. shikokiana methanol extract (AME) and its isolated compounds and to identify the molecular mechanisms of the cytotoxicity. Materials and Methods: Cytotoxicity and selectivity was investigated by measuring the IC50 values on five cancer cell lines; human hepatocellular carcinoma, rhabdomyosarcoma (RD), colorectal carcinoma, human epithelioma and human breast adenocarcinoma and one normal cell line; human lung fibroblasts. The effects on tubulin polymerization and histone deacetylase 8 (HDAC8), were examined to determine the mechanism of cytotoxicity. Docking study was designed to examine the binding affinity to the target molecules. Results: Methanol extract and some of its isolated coumarins and flavonoids showed potent, selective cytotoxicity against cancer cell lines. AME and all isolated compounds inhibited tubulin polymerization. Angelicin and kaempferol-3-O-rutinoside were the most active compounds. Phenolic compounds and furanocoumarins showed binding affinity to colchicine binding site rather than the vinblastine binding site of tubulin microtubules. On the other side, quercetin, kaempferol, luteolin, chlorogenic acid, and methyl chlorogenate exhibited the strongest activity against HDAC8 and the highest affinity to trichostatin A binding site. Conclusion: These findings provide the first scientific evidence of the cytotoxicity of AME through inhibition of tubulin polymerization and HDAC8 activity through its coumarin and flavonoid content. SUMMARY The present study provides for the first time a clue for the cytotoxic activities of the AME. Our results indicate that the cytotoxic activities are partially related to the ability of AME to inhibit tubulin polymerization and HDAC8 activity. Isolated compounds; Angelicin and kaempferol-3-O-rutinoside showed the strongest inhibition of tubulin polymerization through binding to colchicine binding domain of tubulin microtubules. Phenolic compounds; quercetin, luteolin, kaempferol, chlorogenic acid and methyl chlorogenate exhibited a strong inhibition of HDAC8 through binding to TSA binding site. This, however, further detailed pharmacological and in vivo studies should be the next step in evaluating the cytotoxic activities of AME and its active compounds that are currently ongoing. Abbreviations used: AME: Methanol extract of the aerial part of A. shikokiana, HDACs: Histone deacetylases,HDAC8: Histone deacetylase 8 PMID:27013795

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

    PubMed

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

    2015-07-01

    Infections with Cryptococcus are invasive mycoses associated with significant morbidity and mortality, mainly in immunosuppressed patients. Several drugs have been introduced to combat these opportunistic infections. However, resistance of this organism to antifungal drugs has increased, causing difficulties in the treatment. The goal of this work was to evaluate the antifungal activity of ethanol extracts from endophytic fungi isolated from plants collected from different Brazilian ecosystems and to perform the fractionation of the most promising extract. Four-hundred fungal extracts were investigated by microdilution broth assays against Cryptococcus neoformans and Cryptococcus gattii at a concentration of 500 μg ml(-1). Among them, the extract of Mycosphaerella sp. UFMGCB 2032, an endophytic fungus isolated from the plant Eugenia bimarginata DC. (Myrtaceae) exhibited outstanding antifungal activity against C. neoformans and C. gattii, with MIC values of 31.2 μg ml(-1) and 7.8 μg ml(-1), respectively. The fractionation of this extract using liquid-liquid partitioning and semi-preparative HPLC afforded two eicosanoic acids with antifungal activity, compound 1, (2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-(hydroxymethyl)-14-oxoeicos-6,12-dienoic acid with MIC values ranging from 1.3-2.50 μg ml(-1), and compound 2, known as myriocin, with MIC values of 0.5 μg ml(-1) against C. neoformans and C. gattii. These compounds are reported for the first time in the Mycosphaerella genus. PMID:25712396

  5. Laboratory Infrared Spectroscopy to Identify New Compounds on Icy Moon Surfaces

    NASA Astrophysics Data System (ADS)

    Wray, James J.; Young, Cindy L.; Hand, Kevin P.; Poston, Michael J.; Carlson, Robert W.; Clark, Roger N.; Spencer, John R.; Jennings, Donald E.

    2014-11-01

    We are exploring the value of mid-infrared spectroscopy for identifying non-H2O constituents of icy moon surfaces. Recently we reported evidence for a new emissivity feature identified on Iapetus using Cassini’s Composite Infrared Spectrometer [1]. This 11.7 μm feature is consistent with emissivity minima (transparency features) of very fine-grained silicates. Its position and shape may be diagnostic of silicate type, but most lab data at these wavelengths have been acquired using coarser grains and/or at Earth surface pressures and temperatures. Infrared spectra can change substantially under low-temperature, vacuum conditions [e.g., 2,3].We prepared sieved (<0.4 mm) and very fine-grained (few μm) powders of six different silicates and measured their VNIR (0.35-2.5 μm) reflectance spectra under ambient air, and mid-IR (1.2-20 μm) spectra in a purged N2 glovebox. All silicates exhibited mid-IR transparency features (and loss of other features) in micronized form that were not observed for the coarser grain sizes. Muscovite, a phyllosilicate mineral possibly similar to those tentatively identified on Europa [4], provided the closest match to Iapetus in the mid-IR--although clear VNIR features of muscovite have not been identified on Iapetus [5]--and therefore we measured muscovite across the same wavelength range under Iapetus-like conditions (T=125 K, P<3x10^-8 torr). We will report on our ongoing analysis and plans for additional future measurements in JPL’s Icy Worlds Simulation Lab. [1] Young, C.L., et al. (2014), Workshop on the Habitability of Icy Worlds, Abstract #4038.[2] Logan, L.M., et al. (1973), J. Geophys. Res., 78(23), 4983-5003.[3] Donaldson Hanna, K.L., et al. (2012), J. Geophys. Res., 117, E00H05.[4] Shirley, J.H., et al. (2013), AGU Fall Meeting, Abstract #P54A-07.[5] Clark, R.N., et al. (2012), Icarus, 218, 831-860.

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

    PubMed Central

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

    2014-01-01

    STUDY QUESTION Can we identify compound(s) with reported phosphodiesterase inhibitor (PDEI) activity that could be added to human spermatozoa in vitro to enhance their motility without compromising other sperm functions? SUMMARY ANSWER We have identified several compounds that produce robust and effective stimulation of sperm motility and, importantly, have a positive response on patient samples. WHAT IS KNOWN ALREADY For >20 years, the use of non-selective PDEIs, such as pentoxifylline, has been known to influence the motility of human spermatozoa; however, conflicting results have been obtained. It is now clear that human sperm express several different phosphodiesterases and these are compartmentalized at different regions of the cells. By using type-specific PDEIs, differential modulation of sperm motility may be achieved without adversely affecting other functions such as the acrosome reaction (AR). STUDY DESIGN, SIZE, DURATION This was a basic medical research study examining sperm samples from normozoospermic donors and subfertile patients attending the Assisted Conception Unit (ACU), Ninewells Hospital Dundee for diagnostic semen analysis, IVF and ICSI. Phase 1 screened 43 commercially available compounds with reported PDEI activity to identify lead compounds that stimulate sperm motility. Samples were exposed (20 min) to three concentrations (1, 10 and 100 M) of compound, and selected candidates (n = 6) progressed to Phase 2, which provided a more comprehensive assessment using a battery of in vitro sperm function tests. PARTICIPANTS/MATERIALS, SETTING, METHODS All healthy donors and subfertile patients were recruited at the Medical Research Institute, University of Dundee and ACU, Ninewells Hospital Dundee (ethical approval 08/S1402/6). In Phase 1, poor motility cells recovered from the 40% interface of the discontinuous density gradient were used as surrogates for patient samples. Pooled samples from three to four different donors were utilized in order to reduce variability and increase the number of cells available for simultaneous examination of multiple compounds. During Phase 2 testing, semen samples from 23 patients attending for either routine diagnostic andrology assessment or IVF/ICSI were prepared and exposed to selected compounds. Additionally, 48 aliquots of prepared samples, surplus to clinical use, were examined from IVF (n = 32) and ICSI (n = 16) patients to further determine the effects of selected compounds under clinical conditions of treatment. Effects of compounds on sperm motility were assessed by computer-assisted sperm analysis. A modified Kremer test using methyl cellulose was used to assess sperm functional ability to penetrate into viscous media. Sperm acrosome integrity and induction of apoptosis were assessed using the acrosomal content marker PSA-FITC and annexin V kit, respectively. MAIN RESULTS AND THE ROLE OF CHANCE In Phase 1, six compounds were found to have a strong effect on poor motility samples with a magnitude of response of ?60% increase in percentage total motility. Under capacitating and non-capacitating conditions, these compounds significantly (P ? 0.05) increased the percentage of total and progressive motility. Furthermore, these compounds enhanced penetration into a cervical mucus substitute (P ? 0.05). Finally, the AR was not significantly induced and these compounds did not significantly increase the externalization of phosphatidylserine (P = 0.6, respectively). In general, the six compounds maintained the stimulation of motility over long periods of time (180 min) and their effects were still observed after their removal. In examinations of clinical samples, there was a general observation of a more significant stimulation of sperm motility in samples with lower baseline motility. In ICSI samples, compounds #26, #37 and #38 were the most effective at significantly increasing total motility (88, 81 and 79% of samples, respectively) and progressive motility (94, 93 and 81% of samples, respectively). In conclusion, using a two-phased

  7. A high content screen identifies novel compounds that inhibit stress-induced TDP-43 cellular aggregation and associated cytotoxicity

    PubMed Central

    Zauur, Nava; Liu, Min; Concannon, John; Ebata, Atsushi; Wolozin, Benjamin; Glicksman, Marcie A.

    2014-01-01

    TDP-43 is an RNA binding protein found to accumulate in the cytoplasm of brain and spinal cord from patients affected with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Nuclear TDP-43 protein regulates transcription through several mechanisms, and under stressed conditions it forms cytoplasmic aggregates that co-localize with stress granule (SG) proteins in cell culture. These granules are also found in the brain and spinal cord of patients affected with ALS and FTLD. The mechanism through which TDP-43 might contribute to neurodegenerative diseases is poorly understood. In order to investigate the pathophysiology of TDP-43 aggregation and to isolate potential therapeutic targets, we screened a chemical library of 75,000 compounds using high content analysis with PC12 cells that inducibly express human TDP-43 tagged with GFP. The screen identified 16 compounds that dose-dependently decreased the TDP-43 inclusions without significant cellular toxicity or changes in total TDP-43 expression levels. To validate the effect of the compounds, we tested compounds by Western Blot analysis and in a model that replicates some of the relevant disease phenotypes. The hits from this assay will be useful for elucidating regulation of TDP-43, stress granule response, and possible ALS therapeutics. PMID:24019256

  8. Spectral library validation to identify ingredients of compound feedingstuffs by near infrared reflectance microscopy.

    PubMed

    Fernndez-Ibez, V; Fearn, T; Soldado, A; de la Roza-Delgado, B

    2009-11-15

    To guarantee feed quality and safety the development and improvement of analytical methods for feed authentication and detection of contaminants is fundamental. Near infrared reflectance microscopy (NIRM) has been investigated as an alternative method to contribute to control systems for feed materials. The major task is the need to build NIRM reference spectral libraries that must represent the variability in feed ingredients. The aim of the present work was to evaluate the performance of a NIRM reference spectral library on animal feed, with external samples of animal feed ingredients and possible contaminants such as processed animal proteins, and in particular to assess its ability to identify ingredients in mixtures. Three external sample sets were used: (A) artificial mixtures, (B) synthetic mixtures and (C) synthetic binary mixtures. The prediction and repeatability results for set A, in which the spectra are from pure ingredients, were very good for both animal and vegetable ingredients and confirm that the spectral library is very good at identifying spectra from pure ingredients. For sets B and C, in which the spectra were measured on mixtures, the prediction results were very disappointing compared with the artificial samples. This means that a strategy that tries to match the spectra taken from a mixture with those of pure ingredients is unlikely to meet with much success. It is possible that an interpolation between pure ingredients for suitably chosen spectral ranges may provide a way to extend this system to mixtures, including mixtures of several ingredients. PMID:19782192

  9. 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

  10. Effects of compounds found in propolis on Streptococcus mutans growth and on glucosyltransferase activity.

    PubMed

    Koo, Hyun; Rosalen, Pedro L; Cury, Jaime A; Park, Yong K; Bowen, William H

    2002-05-01

    Propolis, a resinous bee product, has been shown to inhibit the growth of oral microorganisms and the activity of bacterium-derived glucosyltransferases (GTFs). Several compounds, mainly polyphenolics, have been identified in this natural product. The present study evaluated the effects of distinct chemical groups found in propolis on the activity of GTF enzymes in solution and on the surface of saliva-coated hydroxyapatite (sHA) beads. Thirty compounds, including flavonoids, cinnamic acid derivatives, and terpenoids, were tested for the ability to inhibit GTFs B, C, and D from Streptococcus mutans and GTF from S. sanguinis (GTF Ss). Flavones and flavonols were potent inhibitors of GTF activity in solution; lesser effects were noted on insolubilized enzymes. Apigenin, a 4',5,7-trihydroxyflavone, was the most effective inhibitor of GTFs, both in solution (90.5 to 95% inhibition at a concentration of 135 microg/ml) and on the surface of sHA beads (30 to 60% at 135 microg/ml). Antibacterial activity was determined by using MICs, minimum bactericidal concentrations (MBCs), and time-kill studies. Flavanones and some dihydroflavonols, as well as the sesquiterpene tt-farnesol, inhibited the growth of S. mutans and S. sobrinus; tt-farnesol was the most effective antibacterial compound (MICs of 14 to 28 microg/ml and MBCs of 56 to 112 microg/ml). tt-Farnesol (56 to 112 microg/ml) produced a 3-log-fold reduction in the bacterial population after 4 h of incubation. Cinnamic acid derivatives had negligible biological activities. Several of the compounds identified in propolis inhibit GTF activities and bacterial growth. Apigenin is a novel and potent inhibitor of GTF activity, and tt-farnesol was found to be an effective antibacterial agent. PMID:11959560

  11. How Can We Identify Ictal and Interictal Abnormal Activity?

    PubMed Central

    Fisher, Robert S.; Scharfman, Helen E.; deCurtis, Marco

    2015-01-01

    The International League Against Epilepsy (ILAE) defined a seizure as “a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.” This definition has been used since the era of Hughlings Jackson, and does not take into account subsequent advances made in epilepsy and neuroscience research. The clinical diagnosis of a seizure is empirical, based upon constellations of certain signs and symptoms, while simultaneously ruling out a list of potential imitators of seizures. Seizures should be delimited in time, but the borders of ictal (during a seizure), interictal (between seizures) and postictal (after a seizure) often are indistinct. EEG recording is potentially very helpful for confirmation, classification and localization. About a half-dozen common EEG patterns are encountered during seizures. Clinicians rely on researchers to answer such questions as why seizures start, spread and stop, whether seizures involve increased synchrony, the extent to which extra-cortical structures are involved, and how to identify the seizure network and at what points interventions are likely to be helpful. Basic scientists have different challenges in use of the word ‘seizure,’ such as distinguishing seizures from normal behavior, which would seem easy but can be very difficult because some rodents have EEG activity during normal behavior that resembles spike-wave discharge or bursts of rhythmic spiking. It is also important to define when a seizure begins and stops so that seizures can be quantified accurately for pre-clinical studies. When asking what causes seizures, the transition to a seizure and differentiating the pre-ictal, ictal and post-ictal state is also important because what occurs before a seizure could be causal and may warrant further investigation for that reason. These and other issues are discussed by three epilepsy researchers with clinical and basic science expertise. PMID:25012363

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

    PubMed

    Kusuda, Ai; Kitayama, Mikito; Ohta, Yoshio

    2013-12-01

    The advanced oxidation process (AOP), chemical oxidation using aqueous ozone in the presence of appropriate catalysts to generate highly reactive oxygen species, offers an attractive option for removing poorly biodegradable pollutants. Using the commercial zeolite powders with various Si/Al ratios and crystal structures, their catalytic activities for decomposing aqueous ozone were evaluated by continuously flowing ozone to water containing the zeolite powders. The hydrophilic zeolites (low Si/Al ratio) with alkali cations in the crystal structures were found to possess high catalytic activity for decomposing aqueous ozone. The hydrophobic zeolite compounds (high Si/Al ratio) were found to absorb ozone very well, but to have no catalytic activity for decomposing aqueous ozone. Their catalytic activities were also evaluated by using the fixed bed column method. When alkali cations were removed by acid rinsing or substituted by alkali-earth cations, the catalytic activities was significantly deteriorated. These results suggest that the metal cations on the crystal surface of the hydrophilic zeolite would play a key role for catalytic activity for decomposing aqueous ozone. PMID:25078817

  13. [Development of fluorescence imaging based assay for screening compounds with anti-migration activity].

    PubMed

    Nie, Xiao-Jing; Zhao, Xiao-Ping; Wang, Yi

    2011-07-01

    In the present study, A fluorescent imaging-based high-throughput screening method was developed for identifying anti-migratory compounds with 96-well Transwell plates. The correlation, precision and stability of this method were examined and the incubation time of dye Hoechst 33342 in addition to migration time was optimized. In addition, The inhibitory activity of anti-cancer drug paclitaxel on tumor cell migration was assayed and an IC50 value of 0.717 micromol x L(-1) was obtained. Using this method, 24 components from Rhizoma Alismatis were screened and one component with anti-migration activity was found. These results show that the new proposed method with good precision, stability and linear range has the potential to assay the inhibitory activity of anticancer compounds. PMID:22010348

  14. Identification of major phenolic compounds of Chinese water chestnut and their antioxidant activity.

    PubMed

    You, Yanli; Duan, Xuewu; Wei, Xiaoyi; Su, Xinguo; Zhao, Mouming; Sun, Jian; Ruenroengklin, Neungnapa; Jiang, Yueming

    2007-01-01

    Chinese water chestnut (CWC) is one of the most popular foods among Asian people due to its special taste and medical function. Experiments were conducted to test the antioxidant activity and then determine the major phenolic compound components present in CWC. CWC phenolic extract strongly inhibited linoleic acid oxidation and exhibited a dose-dependent free-radical scavenging activity against alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radicals, superoxide anions and hydroxyl radicals, which was superior to ascorbic acid and butylated hydroxytoluene (BHT), two commercial used antioxidants. Furthermore, the CWC extract was found to have a relatively higher reducing power, compared with BHT. The major phenolic compounds present in CWC tissues were extracted, purified and identified by high-performance liquid chromatograph (HPLC) as (-)-gallocatechin gallate, (-)-epicatechin gallate and (+)-catechin gallate. This study suggests that CWC tissues exhibit great potential for antioxidant activity and may be useful for their nutritional and medicinal functions. PMID:17851436

  15. Bio-active compounds from Euphorbia cornigera Boiss.

    PubMed

    Baloch, Imam Bakhsh; Baloch, Musa Kaleem; Baloch, Ahmad Khan

    2009-08-01

    Euphorbia cornigera Boiss. (Euphorbiaceae) roots extracted in various organic solvents were tested against Biomphalaria glabrata snails as molluscicide using Bayluscide as a control. Among these, acetone extract was found to be the most active (LC(50)=17.5 microg L(-1)) as compared to Bayluscide. The application of HPLC fractionation yielded ten (1-10) N-(2-aminobenzoyl)anthraniloy esters. Structure and the relative configuration of all the compounds were established through spectroscopic (UV, IR (1)H, (13)C NMR, 2-D NMR, HSQC, HMQC, HMBC, COSY-45 degrees , TOCSY, HOHAHA, HOESY, ROESY, NOESY, SECSY, NOE and mass measurements) techniques. On these basis the esters are named as: 3-O-[N-(2-aminobenzoyl)]-5-O-acetyl-20-O-angelylingenol (1), 3-O-[N-(2-aminobenzoyl)]anthraniloyl-5-O-angelyl-20-O-acetylingenol (2), 3-O-acetyl-5-O-[N-(2-aminobenzoyl)]anthraniloyl-20-O-angelylingenol (3), 3-O-acetyl-5-O-angelyl-20-O-[N-(2-aminobenzoyl)]anthraniloylingenol (4), 3-O-angelyl-5-O-acetyl-20-O-[N-(2-aminobenzoyl)]-anthraniloylingenol (5), 3-O-angelyl-5-O-[N-(2-aminobenzoyl)]anthraniloyl-20-O-acetylingenol (6), 3,20-O-diacetyl-5-O-[N-(2-aminobenzoyl)]anthraniloylingenol (7), 5,20-O-diacetyl-3-O-[N-(2-aminobenzoyl)]anthraniloylingenol (8), 3-O-[N-(2-aminobenzoyl)]anthraniloyl-20-O-acetylingenol (9) and 20-O-[N-(2-aminobenzoyl)]anthraniloyl-3-O-acetylingenol (10). The literature reveals that compounds 1-8 are new from plant kingdom, whereas 9 and 10 are known but not reported from this source earlier. Their molluscicidal activity (in terms of LC(50)) showed that all the compounds were 1.3-2.2 times more toxic than Bayluscide except 5 and 6. PMID:19376614

  16. Protein Folding Activity of the Ribosome (PFAR) A Target for Antiprion Compounds

    PubMed Central

    Banerjee, Debapriya; Sanyal, Suparna

    2014-01-01

    Prion diseases are fatal neurodegenerative diseases affecting mammals. Prions are misfolded amyloid aggregates of the prion protein (PrP), which form when the alpha helical, soluble form of PrP converts to an aggregation-prone, beta sheet form. Thus, prions originate as protein folding problems. The discovery of yeast prion(s) and the development of a red-/white-colony based assay facilitated safe and high-throughput screening of antiprion compounds. With this assay three antiprion compounds; 6-aminophenanthridine (6AP), guanabenz acetate (GA), and imiquimod (IQ) have been identified. Biochemical and genetic studies reveal that these compounds target ribosomal RNA (rRNA) and inhibit specifically the protein folding activity of the ribosome (PFAR). The domain V of the 23S/25S/28S rRNA of the large ribosomal subunit constitutes the active site for PFAR. 6AP and GA inhibit PFAR by competition with the protein substrates for the common binding sites on the domain V rRNA. PFAR inhibition by these antiprion compounds opens up new possibilities for understanding prion formation, propagation and the role of the ribosome therein. In this review, we summarize and analyze the correlation between PFAR and prion processes using the antiprion compounds as tools. PMID:25341659

  17. Protein folding activity of the ribosome (PFAR) -- a target for antiprion compounds.

    PubMed

    Banerjee, Debapriya; Sanyal, Suparna

    2014-10-01

    Prion diseases are fatal neurodegenerative diseases affecting mammals. Prions are misfolded amyloid aggregates of the prion protein (PrP), which form when the alpha helical, soluble form of PrP converts to an aggregation-prone, beta sheet form. Thus, prions originate as protein folding problems. The discovery of yeast prion(s) and the development of a red-/white-colony based assay facilitated safe and high-throughput screening of antiprion compounds. With this assay three antiprion compounds; 6-aminophenanthridine (6AP), guanabenz acetate (GA), and imiquimod (IQ) have been identified. Biochemical and genetic studies reveal that these compounds target ribosomal RNA (rRNA) and inhibit specifically the protein folding activity of the ribosome (PFAR). The domain V of the 23S/25S/28S rRNA of the large ribosomal subunit constitutes the active site for PFAR. 6AP and GA inhibit PFAR by competition with the protein substrates for the common binding sites on the domain V rRNA. PFAR inhibition by these antiprion compounds opens up new possibilities for understanding prion formation, propagation and the role of the ribosome therein. In this review, we summarize and analyze the correlation between PFAR and prion processes using the antiprion compounds as tools. PMID:25341659

  18. Phenotypic assays to identify agents that induce reactive gliosis: a counter-screen to prioritize compounds for preclinical animal studies.

    PubMed

    Beckerman, Samuel R; Jimenez, Joaquin E; Shi, Yan; Al-Ali, Hassan; Bixby, John L; Lemmon, Vance P

    2015-09-01

    Astrocyte phenotypes change in a process called reactive gliosis after traumatic central nervous system (CNS) injury. Astrogliosis is characterized by expansion of the glial fibrillary acidic protein (GFAP) cytoskeleton, adoption of stellate morphologies, and differential expression of some extracellular matrix molecules. The astrocytic response immediately after injury is beneficial, but in the chronic injury phase, reactive astrocytes produce inhibitory factors (i.e., chondroitin sulfate proteoglycans [CSPGs]) that limit the regrowth of injured axons. There are no drugs that promote axon regeneration or functional recovery after CNS trauma in humans. To develop novel therapeutics for the injured CNS, we screened various libraries in a phenotypic assay to identify compounds that promote neurite outgrowth. However, the effects these compounds have on astrocytes are unknown. Specifically, we were interested in whether compounds could alter astrocytes in a manner that mimics the glial reaction to injury. To test this hypothesis, we developed cell-based phenotypic bioassays to measure changes in (1) GFAP morphology/localization and (2) CSPG expression/immunoreactivity from primary astrocyte cultures. These assays were optimized for six-point dose-response experiments in 96-well plates. The GFAP morphology assay is suitable for counter-screening with a Z-factor of 0.44±0.03 (mean±standard error of the mean; N=3 biological replicates). The CSPG assay is reproducible and informative, but does not satisfy common metrics for a "screenable" assay. As proof of principle, we tested a small set of hit compounds from our neurite outgrowth bioassay and identified one that can enhance axon growth without exacerbating the deleterious characteristics of reactive gliosis. PMID:26230074

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  1. Activity of 2,4-Diaminoquinazoline Compounds against Candida species

    PubMed Central

    Castaldo, Robert A.; Gump, Dieter W.; McCormack, John J.

    1979-01-01

    Forty recent clinical isolates of three different Candida sp. were tested in the microtiter system for susceptibility to two new 2,4-diaminoquinazoline (DAQ) compounds, amphotericin B and flucytosine. The two DAQ preparations showed activity similar to amphotericin B and flucytosine. The geometric mean minimal inhibitory concentrations for these four drugs were as follows: DAQ 1A, 0.64 ?g/ml; DAQ 2A, 1.39 ?g/ml; amphotericin B, 1.03 ?g/ml; and flucytosine, 0.72 ?g/ml. An additional seven DAQ compounds were tested but showed less or no activity against 17 Candida isolates. Forty-eight-hour viability studies with DAQ 2A alone or in combination with amphotericin B, flucytosine, or sulfamethoxazole were carried out with one isolate of intermediate susceptibility to each of these agents except sulfamethoxazole. For this isolate the combination of DAQ 2A and sulfamethoxazole was synergistic, and the combination of DAQ 2A and AMB was either synergistic or additive, whereas the combination of DAQ 2A and flucytosine was antagonistic. Although regrowth of cultures exposed to DAQ 2A was noted over a 48-h period, neither degradation of the drug nor development of resistance to the drug could be detected. Swiss white mice receiving DAQ 1A at a dose of 6 mg/kg for 5 days showed no obvious signs of toxicity, including weight loss. PMID:426507

  2. 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, 000000. PMID:22900955

  3. Systematic Repurposing Screening in Xenograft Models Identifies Approved Drugs with Novel Anti-Cancer Activity

    PubMed Central

    Roix, Jeffrey J.; Harrison, S. D.; Rainbolt, Elizabeth A.; Meshaw, Kathryn R.; McMurry, Avery S.; Cheung, Peter; Saha, Saurabh

    2014-01-01

    Approved drugs target approximately 400 different mechanisms of action, of which as few as 60 are currently used as anti-cancer therapies. Given that on average it takes 1015 years for a new cancer therapeutic to be approved, and the recent success of drug repurposing for agents such as thalidomide, we hypothesized that effective, safe cancer treatments may be found by testing approved drugs in new therapeutic settings. Here, we report in-vivo testing of a broad compound collection in cancer xenograft models. Using 182 compounds that target 125 unique target mechanisms, we identified 3 drugs that displayed reproducible activity in combination with the chemotherapeutic temozolomide. Candidate drugs appear effective at dose equivalents that exceed current prescription levels, suggesting that additional pre-clinical efforts will be needed before these drugs can be tested for efficacy in clinical trials. In total, we suggest drug repurposing is a relatively resource-intensive method that can identify approved medicines with a narrow margin of anti-cancer activity. PMID:25093583

  4. Systematic repurposing screening in xenograft models identifies approved drugs with novel anti-cancer activity.

    PubMed

    Roix, Jeffrey J; Harrison, S D; Rainbolt, Elizabeth A; Meshaw, Kathryn R; McMurry, Avery S; Cheung, Peter; Saha, Saurabh

    2014-01-01

    Approved drugs target approximately 400 different mechanisms of action, of which as few as 60 are currently used as anti-cancer therapies. Given that on average it takes 10-15 years for a new cancer therapeutic to be approved, and the recent success of drug repurposing for agents such as thalidomide, we hypothesized that effective, safe cancer treatments may be found by testing approved drugs in new therapeutic settings. Here, we report in-vivo testing of a broad compound collection in cancer xenograft models. Using 182 compounds that target 125 unique target mechanisms, we identified 3 drugs that displayed reproducible activity in combination with the chemotherapeutic temozolomide. Candidate drugs appear effective at dose equivalents that exceed current prescription levels, suggesting that additional pre-clinical efforts will be needed before these drugs can be tested for efficacy in clinical trials. In total, we suggest drug repurposing is a relatively resource-intensive method that can identify approved medicines with a narrow margin of anti-cancer activity. PMID:25093583

  5. Mutations in a translation initiation factor identify target of a memory-enhancing compound

    PubMed Central

    Sekine, Yusuke; Zyryanova, Alisa; Crespillo-Casado, Ana; Fischer, Peter M.; Harding, Heather P.; Ron, David

    2015-01-01

    The integrated stress response (ISR) modulates mRNA translation to regulate the mammalian unfolded protein response (UPR), immunity and memory formation. A chemical ISR inhibitor, ISRIB, enhances cognitive function and modulates the UPR in vivo. To explore mechanisms involved in ISRIB action we screened cultured mammalian cells for somatic mutations that reversed its effect on the ISR. Clustered missense mutations were found at the N-terminal portion of the delta subunit of guanine nucleotide exchange factor (GEF) eIF2B. When reintroduced by CRISPR-Cas9 gene editing of wildtype cells, these mutations reversed both ISRIB-mediated inhibition of the ISR and its stimulatory effect on eIF2B GEF activity towards its substrate, eIF2, in vitro. Thus ISRIB targets an interaction between eIF2 and eIF2B that lies at the core of the ISR. PMID:25858979

  6. Compounds Released from Biomass Deconstruction: Understanding Their Effect on Cellulose Enzyme Hydrolysis and Their Biological Activity

    NASA Astrophysics Data System (ADS)

    Djioleu, Angele Mezindjou

    The effect of compounds produced during biomass pretreatment on cellulolytic enzyme was investigated. Liquid prehydrolyzates were prepared by pretreating switchgrass using 24 combinations of temperature, time, and sulfuric acid concentration based on a full factorial design. Temperature was varied from 140°C to 180°C; time ranged from 10 to 40 min; and the sulfuric acid concentrations were 0.5% or 1% (v/v). Identified products in the prehydrolyzates included xylose, glucose, hydroxymethylfurfural (HMF), furfural, acetic acid, formic acid, and phenolic compounds at concentration ranging from 0 to 21.4 g/L. Pretreatment conditions significantly affected the concentrations of compounds detected in prehydrolyzates. When assayed in the presence of switchgrass prehydrolyzates against model substrates, activities of cellulase, betaglucosidase, and exoglucanase, were significantly reduced by at least 16%, 31.8%, and 57.8%, respectively, as compared to the control. A strong positive correlation between inhibition of betaglucosidase and concentration of glucose, acetic acid, and furans in prehydrolyzate was established. Exoglucanase inhibition correlated with the presence of phenolic compounds and acetic acid. The prehydrolyzate, prepared at 160°C, 30 min, and 1% acid, was fractionated by centrifugal partition chromatography (CPC) into six fractions; the inhibition effect of these fractions on betaglucosidase and exoglucanase was determined. The initial hydrolysis rate of cellobiose by betaglucosidase was significantly reduced by the CPC sugar-rich fraction; however, exoglucanase was deactivated by the CPC phenolic-rich fraction. Finally, biological activities of water-extracted compounds from sweetgum bark and their effect on cellulase was investigated. It was determined that 12% of solid content of the bark extract could be accounted by phenolic compounds with gallic acid identified as the most concentrated phytochemical. Sweetgum bark extract inhibited Staphylococcus aureus growth and copper-induced peroxidation of human low-density lipoprotein, confirming antimicrobial and antioxidant activities of the extract. On the other hand, bark extract inhibited cellulase cocktail activity by reducing cellulose hydrolysis by 82.32% after 48 h of incubation. Overall, phenolic compounds generated from biomass fractionation are important players in cellulolytic enzyme inhibition; removal of biomass extractives prior to pretreatment could reduce inhibitory compounds in prehydrolyzate while generating phytochemicals with societal benefits.

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

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

    A wealth of recent laboratory and field experiments demonstrate that organic aerosol composition evolves with time in the atmosphere, leading to changes in the influence of the organic fraction to cloud condensation nuclei (CCN) spectra. There is a need for tools that can realistically represent the evolution of CCN activity to better predict indirect effects of organic aerosol on clouds and climate. This work describes a model to predict the CCN activity of organic compounds from functional group composition. The model combines Khler theory with semi-empirical group contribution methods to estimate molar volumes, activity coefficients and liquid-liquid phase boundaries to predict the effective hygroscopicity parameter, kappa. Model evaluation against a selected database of published laboratory measurements demonstrates that kappa can be predicted within a factor of two. Simulation of homologous series is used to identify the relative effectiveness of different functional groups in increasing the CCN activity of weakly functionalized organic compounds. Hydroxyl, carboxyl, aldehyde, hydroperoxide, carbonyl, and ether moieties promote CCN activity while methylene and nitrate moieties inhibit CCN activity. The model can be incorporated into scale-bridging testbeds such as the Generator of Explicit Chemistry and Kinetics of Organics in the Atmosphere to evaluate the evolution of kappa for a complex mix of organic compounds and to develop suitable parameterizations of CCN evolution for larger scale models.

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

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

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

  9. 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 110(-4)M or 610(-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

  10. 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; Frdrich, 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

  11. 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

  12. Rapid, Semiquantitative Assay To Discriminate among Compounds with Activity against Replicating or Nonreplicating Mycobacterium tuberculosis.

    PubMed

    Gold, Ben; Roberts, Julia; Ling, Yan; Quezada, Landys Lopez; Glasheen, Jou; Ballinger, Elaine; Somersan-Karakaya, Selin; Warrier, Thulasi; Warren, J David; Nathan, Carl

    2015-10-01

    The search for drugs that can kill replicating and nonreplicating Mycobacterium tuberculosis faces practical bottlenecks. Measurement of CFU and discrimination of bacteriostatic from bactericidal activity are costly in compounds, supplies, labor, and time. Testing compounds against M. tuberculosis under conditions that prevent the replication of M. tuberculosis often involves a second phase of the test in which conditions are altered to permit the replication of bacteria that survived the first phase. False-positive determinations of activity against nonreplicating M. tuberculosis may arise from carryover of compounds from the nonreplicating stage of the assay that act in the replicating stage. We mitigate these problems by carrying out a 96-well microplate liquid MIC assay and then transferring an aliquot of each well to a second set of plates in which each well contains agar supplemented with activated charcoal. After 7 to 10 days-about 2 weeks sooner than required to count CFU-fluorometry reveals whether M. tuberculosis bacilli in each well have replicated extensively enough to reduce a resazurin dye added for the final hour. This charcoal agar resazurin assay (CARA) distinguishes between bacterial biomasses in any two wells that differ by 2 to 3 log10 CFU. The CARA thus serves as a pretest and semiquantitative surrogate for longer, more laborious, and expensive CFU-based assays, helps distinguish bactericidal from bacteriostatic activity, and identifies compounds that are active under replicating conditions, nonreplicating conditions, or both. Results for 14 antimycobacterial compounds, including tuberculosis (TB) drugs, revealed that PA-824 (pretomanid) and TMC207 (bedaquiline) are largely bacteriostatic. PMID:26239979

  13. Rapid, Semiquantitative Assay To Discriminate among Compounds with Activity against Replicating or Nonreplicating Mycobacterium tuberculosis

    PubMed Central

    Roberts, Julia; Ling, Yan; Quezada, Landys Lopez; Glasheen, Jou; Ballinger, Elaine; Somersan-Karakaya, Selin; Warrier, Thulasi; Warren, J. David; Nathan, Carl

    2015-01-01

    The search for drugs that can kill replicating and nonreplicating Mycobacterium tuberculosis faces practical bottlenecks. Measurement of CFU and discrimination of bacteriostatic from bactericidal activity are costly in compounds, supplies, labor, and time. Testing compounds against M. tuberculosis under conditions that prevent the replication of M. tuberculosis often involves a second phase of the test in which conditions are altered to permit the replication of bacteria that survived the first phase. False-positive determinations of activity against nonreplicating M. tuberculosis may arise from carryover of compounds from the nonreplicating stage of the assay that act in the replicating stage. We mitigate these problems by carrying out a 96-well microplate liquid MIC assay and then transferring an aliquot of each well to a second set of plates in which each well contains agar supplemented with activated charcoal. After 7 to 10 days—about 2 weeks sooner than required to count CFU—fluorometry reveals whether M. tuberculosis bacilli in each well have replicated extensively enough to reduce a resazurin dye added for the final hour. This charcoal agar resazurin assay (CARA) distinguishes between bacterial biomasses in any two wells that differ by 2 to 3 log10 CFU. The CARA thus serves as a pretest and semiquantitative surrogate for longer, more laborious, and expensive CFU-based assays, helps distinguish bactericidal from bacteriostatic activity, and identifies compounds that are active under replicating conditions, nonreplicating conditions, or both. Results for 14 antimycobacterial compounds, including tuberculosis (TB) drugs, revealed that PA-824 (pretomanid) and TMC207 (bedaquiline) are largely bacteriostatic. PMID:26239979

  14. Activation tag screening to identify novel genes for trichothecene resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The goal of our research is to identify plant genes which enhance trichothecene resistance and, ultimately, Fusarium Head Blight resistance in wheat and barley. We are taking a two pronged approach using Arabidopsis to identify plant genes which confer resistance to trichothecenes. The first approac...

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

  17. Antioxidant activities and phenolic compounds of date plum persimmon ( Diospyros lotus L.) fruits.

    PubMed

    Gao, Hui; Cheng, Ni; Zhou, Juan; Wang, Bini; Deng, Jianjun; Cao, Wei

    2014-05-01

    In the present study, phenolic compounds are extracted from the date plum persimmon fruits using water, methanol and acetone as solvents. Antioxidant activities of the phenolic extracts are measured using four different tests, namely, DPPH, hydroxyl radical scavenging activities, chelating and reducing power assays. All the extracts show dose dependent DPPH radical scavenging activity, reducing and chelating powers and moreover, they are well correlated with the total phenolic and total flavonoid substances, suggesting direct contribution of phenolic compounds to these activities. In further, the extracts are identified and quantified by HPLC-ECD. Results show that gallic acid is the most abundant phenolic compound, with amounts ranging between 45.49and 287.47 μg/g dry sample. Myricetin is the dominant flavonoid in all extracts. Its level varied from 2.75 μg/g dry sample in acetone extract to 5.28 μg/g dry sample in water extract. On the basis of the results obtained, the date plum persimmon fruits phenolic extract is a potential source of natural antioxidants owing to its significant antioxidant activities. PMID:24803703

  18. Natural Compounds' Activity against Cancer Stem-Like or Fast-Cycling Melanoma Cells

    PubMed Central

    Majchrzak, Kinga; Hartman, Mariusz; Czyz, Malgorzata

    2014-01-01

    Background Accumulating evidence supports the concept that melanoma is highly heterogeneous and sustained by a small subpopulation of melanoma stem-like cells. Those cells are considered as responsible for tumor resistance to therapies. Moreover, melanoma cells are characterized by their high phenotypic plasticity. Consequently, both melanoma stem-like cells and their more differentiated progeny must be eradicated to achieve durable cure. By reevaluating compounds in heterogeneous melanoma populations, it might be possible to select compounds with activity not only against fast-cycling cells but also against cancer stem-like cells. Natural compounds were the focus of the present study. Methods We analyzed 120 compounds from The Natural Products Set II to identify compounds active against melanoma populations grown in an anchorage-independent manner and enriched with cells exerting self-renewing capacity. Cell viability, cell cycle arrest, apoptosis, gene expression, clonogenic survival and label-retention were analyzed. Findings Several compounds efficiently eradicated cells with clonogenic capacity and nanaomycin A, streptonigrin and toyocamycin were effective at 0.1 M. Other anti-clonogenic but not highly cytotoxic compounds such as bryostatin 1, siomycin A, illudin M, michellamine B and pentoxifylline markedly reduced the frequency of ABCB5 (ATP-binding cassette, sub-family B, member 5)-positive cells. On the contrary, treatment with maytansine and colchicine selected for cells expressing this transporter. Maytansine, streptonigrin, toyocamycin and colchicine, even if highly cytotoxic, left a small subpopulation of slow-dividing cells unaffected. Compounds selected in the present study differentially altered the expression of melanocyte/melanoma specific microphthalmia-associated transcription factor (MITF) and proto-oncogene c-MYC. Conclusion Selected anti-clonogenic compounds might be further investigated as potential adjuvants targeting melanoma stem-like cells in the combined anti-melanoma therapy, whereas selected cytotoxic but not anti-clonogenic compounds, which increased the frequency of ABCB5-positive cells and remained slow-cycling cells unaffected, might be considered as a tool to enrich cultures with cells exhibiting melanoma stem cell characteristics. PMID:24595456

  19. Isolation and antimicrobial activity of two phenolic compounds from Pulicaria odora L.

    PubMed

    Ezoubeiri, A; Gadhi, C A; Fdil, N; Benharref, A; Jana, M; Vanhaelen, M

    2005-06-01

    The essential oil of Pulicaria odora, a Moroccan medicinal plant; was analyzed by GC-MS, and subjected to column chromatography on silica gel. Two major constituents were isolated and identified as 2-isopropyl-4-methylphenol (1) and isobutyric acid 2-isopropyl-4-methylphenylester (2), by analysis of spectroscopic data (MS, 1H NMR, 13C NMR, DEPT, COSY, HMQC and HMBC experiments). The isolated compounds are reported for the first time from Pulicaria genus. The essential oil and its major constituents (compounds 1 and 2) were examined for antibacterial and antifungal activity in vitro using the diffusion and dilution methods. Results showed that the essential oil and the 2-isopropyl-4-methylphenol (1) exhibited a very significant antibacterial and antifungal activity, while the isobutyric acid 2-isopropyl-4-methylphenylester (2) was inactive for all tested strains. PMID:15894140

  20. 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.

  1. Rejection of pharmaceutically active compounds and endocrine disrupting compounds by clean and fouled nanofiltration membranes.

    PubMed

    Yangali-Quintanilla, V; Sadmani, A; McConville, M; Kennedy, M; Amy, G

    2009-05-01

    Rejections of 9 pharmaceuticals and 5 endocrine disruptors by clean and fouled nanofiltration membranes were investigated in this study. Waters containing a cocktail of compounds were filtered by clean and pre-fouled membranes. The rejection of hydrophilic neutral compounds by the clean NF-200 membrane varied from 35 to 70% under steady state conditions while that of NF-90 membrane was in the range of 62-96%. The clean NF-90 membrane rejected nearly all of the hydrophobic neutral compounds (95-98%) predominantly due to size exclusion. Nevertheless, electrostatic repulsion was the main mechanism of rejection of ionic compounds by both membranes (71-94% by NF-200 and 99% by NF-90). Fouling with sodium alginate deteriorated the performance of the NF-200 membrane in rejecting hydrophilic neutral compounds as well as hydrophilic and hydrophobic ionic compounds. In contrast, rejections of hydrophobic neutral compounds by the fouled NF-200 membrane increased by 5-38%. This may be attributed to the incipient interaction of the solutes with the membrane foulant layer resulting in less partitioning and diffusion across the membrane surface. On the other hand, rejections of hydrophobic compounds by NF-90 were not observed to be affected by fouling; however, hydrophilic neutral compounds showed increased rejections by 7-30%. PMID:19303127

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

    PubMed

    Bankova, Vassya; Popova, Milena; Trusheva, Boryana

    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

  3. 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

  4. Ensemble docking and molecular dynamics identify knoevenagel curcumin derivatives with potent anti-EGFR activity.

    PubMed

    Yadav, Inderjit S; Nandekar, Prajwal P; Srivastavaa, Shambhavi; Shrivastava, Shambhavi; Sangamwar, Abhay; Chaudhury, Ashok; Agarwal, Subhash Mohan

    2014-04-10

    Epidermal growth factor receptor tyrosine kinase (EGFR-TK) is an attractive target for cancer therapy. Despite a number of effective EGFR inhibitors that are constantly expanding and different methods being employed to obtain novel compounds, the search for newer EGFR inhibitors is still a major scientific challenge. In the present study, a molecular docking and molecular dynamics investigation has been carried out with an ensemble of EGFR-TK structures against a synthetically feasible library of curcumin analogs to discover potent EGFR inhibitors. To resolve protein flexibility issue we have utilized 5 EGFR wild type crystal structures during docking as this gives improved possibility of identifying an active compound as compared to using a single crystal structure. We then identified five curcumin analogs representing different scaffolds that can serve as lead molecules. Finally, the 5 ns molecular dynamics simulation shows that knoevenagel condensate of curcumin specifically C29 and C30 can be used as starting blocks for developing effective leads capable of inhibiting EGFR. PMID:24491504

  5. Screening Compounds with a Novel High-Throughput ABCB1-Mediated Efflux Assay Identifies Drugs with Known Therapeutic Targets at Risk for Multidrug Resistance Interference

    PubMed Central

    Ansbro, Megan R.; Shukla, Suneet; Ambudkar, Suresh V.; Yuspa, Stuart H.; Li, Luowei

    2013-01-01

    ABCB1, also known as P-glycoprotein (P-gp) or multidrug resistance protein 1 (MDR1), is a membrane-associated multidrug transporter of the ATP-binding cassette (ABC) transporter family. It is one of the most widely studied transporters that enable cancer cells to develop drug resistance. Reliable high-throughput assays that can identify compounds that interact with ABCB1 are crucial for developing new therapeutic drugs. A high-throughput assay for measuring ABCB1-mediated calcein AM efflux was developed using a fluorescent and phase-contrast live cell imaging system. This assay demonstrated the time- and dose-dependent accumulation of fluorescent calcein in ABCB1-overexpressing KB-V1 cells. Validation of the assay was performed with known ABCB1 inhibitors, XR9576, verapamil, and cyclosporin A, all of which displayed dose-dependent inhibition of ABCB1-mediated calcein AM efflux in this assay. Phase-contrast and fluorescent images taken by the imaging system provided additional opportunities for evaluating compounds that are cytotoxic or produce false positive signals. Compounds with known therapeutic targets and a kinase inhibitor library were screened. The assay identified multiple agents as inhibitors of ABCB1-mediated efflux and is highly reproducible. Among compounds identified as ABCB1 inhibitors, BEZ235, BI 2536, IKK 16, and ispinesib were further evaluated. The four compounds inhibited calcein AM efflux in a dose-dependent manner and were also active in the flow cytometry-based calcein AM efflux assay. BEZ235, BI 2536, and IKK 16 also successfully inhibited the labeling of ABCB1 with radiolabeled photoaffinity substrate [125I]iodoarylazidoprazosin. Inhibition of ABCB1 with XR9576 and cyclosporin A enhanced the cytotoxicity of BI 2536 to ABCB1-overexpressing cancer cells, HCT-15-Pgp, and decreased the IC50 value of BI 2536 by several orders of magnitude. This efficient, reliable, and simple high-throughput assay has identified ABCB1 substrates/inhibitors that may influence drug potency or drug-drug interactions and predict multidrug resistance in clinical treatment. PMID:23593196

  6. Analytical methodology for the profiling and characterization of androgen receptor active compounds in human placenta.

    PubMed

    Indiveri, Paolo; Horwood, Julia; Abdul-Sada, Alaa; Arrebola, Juan P; Olea, Nicolas; Hill, Elizabeth M

    2014-08-01

    The exposure to endocrine disrupting chemicals during foetal development has been proposed to cause reproductive dysfunctions in the neonate or later life. In order to support such studies, an analytical method was developed to profile the receptor mediated (anti)androgenic activities present in extracts of placenta samples. Placenta samples from women giving birth to healthy male neonates were extracted and fractionated by HPLC. Fractions containing androgen receptor (AR) activity were detected using an in vitro yeast-based human androgen receptor transcription screen. GC-MS analyses of receptor active fractions resulted in detection of chemical contaminants including antimicrobial and cosmetic compounds which exhibited AR antagonist activity in the yeast screen, and endogenously derived steroids which contributed to both the agonist and antagonistic activity in the samples. The bioassay-directed fractionation methodology developed in this study revealed the potential to identify mixtures of chemical contaminants that should be investigated for potential effects on the reproductive system. PMID:24972338

  7. Separation and Identification of Four New Compounds with Antibacterial Activity from Portulaca oleracea L.

    PubMed

    Lei, Xia; Li, Jianmin; Liu, Bin; Zhang, Ning; Liu, Haiyang

    2015-01-01

    The Portulaca oleracea L. (P. oleracea) has been used to treat bacillary dysentery for thousands of years in China. Pharmacology studies on P. oleracea have also showed its significant antibacterial effects on the enteropathogenic bacteria, which might reveal the treatment of P. oleracea in cases of bacillary dysentery to some extent. To date, however, the therapeutic basis of P. oleracea treating on bacillary dysentery remains unknown. We determined the antibacterial effective fraction of P. oleracea in a previous study. The current study, which is based on our previous study, was first designed to isolate, identify and screen antibacterial active constituents from P. oleracea. As a result, four new compounds (1-4), portulacerebroside B (1), portulacerebroside C (2), portulacerebroside D (3) and portulaceramide A (4) along with five known compounds (5-9) were isolated, and structures were established by their physico-chemical constants and spectroscopic analysis. The antibacterial activities against common enteropathogenic bacteria were evaluated for all compounds and the new compounds 1-4 showed significant antibacterial effect on enteropathogenic bacteria in vitro, which might contribute to revealing the treatment of P. oleracea in cases of bacillary dysentery. PMID:26378504

  8. Antioxidative Activities and Active Compounds of Extracts from Catalpa Plant Leaves

    PubMed Central

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

    2014-01-01

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

  9. Identification of Novel p53 Pathway Activating Small-Molecule Compounds Reveals Unexpected Similarities with Known Therapeutic Agents

    PubMed Central

    Peltonen, Karita; Colis, Laureen; Liu, Hester; Jmaa, Sari; Moore, Henna M.; Enbck, Juulia; Laakkonen, Pirjo; Vaahtokari, Anne; Jones, Richard J.; af Hllstrm, Taija M.; Laiho, Marikki

    2010-01-01

    Manipulation of the activity of the p53 tumor suppressor pathway has demonstrated potential benefit in preclinical mouse tumor models and has entered human clinical trials. We describe here an improved, extensive small-molecule chemical compound library screen for p53 pathway activation in a human cancer cell line devised to identify hits with potent antitumor activity. We uncover six novel small-molecule lead compounds, which activate p53 and repress the growth of human cancer cells. Two tested compounds suppress in vivo tumor growth in an orthotopic mouse model of human B-cell lymphoma. All compounds interact with DNA, and two activate p53 pathway in a DNA damage signaling-dependent manner. A further screen of a drug library of approved drugs for medicinal uses and analysis of gene-expression signatures of the novel compounds revealed similarities to known DNA intercalating and topoisomerase interfering agents and unexpected connectivities to known drugs without previously demonstrated anticancer activities. These included several neuroleptics, glycosides, antihistamines and adrenoreceptor antagonists. This unbiased screen pinpoints interference with the DNA topology as the predominant mean of pharmacological activation of the p53 pathway and identifies potential novel antitumor agents. PMID:20885994

  10. Surface comparison of active and inactive protein kinases identifies a conserved activation mechanism

    PubMed Central

    Kornev, Alexandr P.; Haste, Nina M.; Taylor, Susan S.; Ten Eyck, Lynn F.

    2006-01-01

    The surface comparison of different serinethreonine and tyrosine kinases reveals a set of 30 residues whose spatial positions are highly conserved. The comparison between active and inactive conformations identified the residues whose positions are the most sensitive to activation. Based on these results, we propose a model of protein kinase activation. This model explains how the presence of a phosphate group in the activation loop determines the position of the catalytically important aspartate in the Asp-Phe-Gly motif. According to the model, the most important feature of the activation is a spine formation that is dynamically assembled in all active kinases. The spine is comprised of four hydrophobic residues that we detected in a set of 23 eukaryotic and prokaryotic kinases. It spans the molecule and plays a coordinating role in activated kinases. The spine is disordered in the inactive kinases and can explain how stabilization of the whole molecule is achieved upon phosphorylation. PMID:17095602

  11. Management Development Program. Preliminary Organizing Structure for Identifying Educational Activities.

    ERIC Educational Resources Information Center

    Cloud, Sherrill

    The Management Development Program, which was designed to address the needs of executive-level administrators of higher education, is described. The program was developed by the National Center for Higher Education Management Systems (NCHEMS). Seven limitations of executive-level administrators are identified, along with the capabilities of NCHEMS

  12. Antimicrobial activity and cytotoxic effects of Magnolia dealbata and its active compounds.

    PubMed

    Jacobo-Salcedo, Maria del Rosario; Gonzalez-Espindola, Luis Angel; Alonso-Castro, Angel Josabad; Gonzalez-Martinez, Marisela del Rocio; Domnguez, Fabiola; Garcia-Carranca, Alejandro

    2011-08-01

    Multi-drug resistance is of great concern for public health worldwide and necessitates the search for new antimicrobials from sources such as plants. Several Magnolia (Magnoliaceae) species have been reported to exert antimicrobial effects on sensitive and multidrug-resistant microorganisms. However, the antimicrobial properties of Magnolia dealbata have not been experimentally evaluated. The antimicrobial effects of an ethanol extract of Magnolia dealbata seeds (MDE) and its active compounds honokiol (HK) and magnolol (MG) were tested against the phytopathogen Clavibacter michiganensis subsp. michiganensis and several human multi-drug resistant pathogens using the disk-diffusion assay. The effects of MDE and its active compounds on the viability of human peripheral blood mononuclear cells (PBMC) were evaluated using MTT assay. MDE and its active compounds had antimicrobial activity (inhibition zone > 10 mm) against C. michiganensis, Pseudomonas aeruginosa, Acinetobacter baumannii, Acinetobacter lwoffii, Candida albicans, Candida tropicalis and Trichosporon belgeii. The results suggest that M. dealbata and its active compounds have selective antimicrobial effects against drug-resistant fungal and Gram (-) bacteria and exert minimal toxic effects on human PMBC. PMID:21922914

  13. Pomegranate Fruit as a Rich Source of Biologically Active Compounds

    PubMed Central

    Sreekumar, Sreeja; Sithul, Hima; Muraleedharan, Parvathy; Azeez, Juberiya Mohammed; Sreeharshan, Sreeja

    2014-01-01

    Pomegranate is a widely used plant having medicinal properties. In this review, we have mainly focused on the already published data from our laboratory pertaining to the effect of methanol extract of pericarp of pomegranate (PME) and have compared it with other relevant literatures on Punica. Earlier, we had shown its antiproliferative effect using human breast (MCF-7, MDA MB-231), and endometrial (HEC-1A), cervical (SiHa, HeLa), and ovarian (SKOV3) cancer cell lines, and normal breast fibroblasts (MCF-10A) at concentration of 20–320 μg/mL. The expressions of selected estrogen responsive genes (PR, pS2, and C-Myc) were downregulated by PME. Unlike estradiol, PME did not increase the uterine weight and proliferation in bilaterally ovariectomized Swiss-Albino mice models and its cardioprotective effects were comparable to that of 17β-estradiol. We had further assessed the protective role of PME on skeletal system, using MC3T3-E1 cells. The results indicated that PME (80 μg/mL) significantly increased ALP (Alkaline Phosphatase) activity, supporting its suggested role in modulating osteoblastic cell differentiation. The antiosteoporotic potential of PME was also evaluated in ovariectomized (OVX) rodent model. The results from our studies and from various other studies support the fact that pomegranate fruit is indeed a source of biologically active compounds. PMID:24818149

  14. 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

  15. Using perturbations to identify the brain circuits underlying active vision

    PubMed Central

    Wurtz, Robert H.

    2015-01-01

    The visual and oculomotor systems in the brain have been studied extensively in the primate. Together, they can be regarded as a single brain system that underlies active vision—the normal vision that begins with visual processing in the retina and extends through the brain to the generation of eye movement by the brainstem. The system is probably one of the most thoroughly studied brain systems in the primate, and it offers an ideal opportunity to evaluate the advantages and disadvantages of the series of perturbation techniques that have been used to study it. The perturbations have been critical in moving from correlations between neuronal activity and behaviour closer to a causal relation between neuronal activity and behaviour. The same perturbation techniques have also been used to tease out neuronal circuits that are related to active vision that in turn are driving behaviour. The evolution of perturbation techniques includes ablation of both cortical and subcortical targets, punctate chemical lesions, reversible inactivations, electrical stimulation, and finally the expanding optogenetic techniques. The evolution of perturbation techniques has supported progressively stronger conclusions about what neuronal circuits in the brain underlie active vision and how the circuits themselves might be organized. PMID:26240420

  16. Using perturbations to identify the brain circuits underlying active vision.

    PubMed

    Wurtz, Robert H

    2015-09-19

    The visual and oculomotor systems in the brain have been studied extensively in the primate. Together, they can be regarded as a single brain system that underlies active vision--the normal vision that begins with visual processing in the retina and extends through the brain to the generation of eye movement by the brainstem. The system is probably one of the most thoroughly studied brain systems in the primate, and it offers an ideal opportunity to evaluate the advantages and disadvantages of the series of perturbation techniques that have been used to study it. The perturbations have been critical in moving from correlations between neuronal activity and behaviour closer to a causal relation between neuronal activity and behaviour. The same perturbation techniques have also been used to tease out neuronal circuits that are related to active vision that in turn are driving behaviour. The evolution of perturbation techniques includes ablation of both cortical and subcortical targets, punctate chemical lesions, reversible inactivations, electrical stimulation, and finally the expanding optogenetic techniques. The evolution of perturbation techniques has supported progressively stronger conclusions about what neuronal circuits in the brain underlie active vision and how the circuits themselves might be organized. PMID:26240420

  17. 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, Jrgen; 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

  18. 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

  19. In silico inhibition of GABARAP activity using antiepileptic medicinal derived compounds

    PubMed Central

    Mathew, Shilu; Faheem, Muhammad; Al-Malki, Abdulrahman L; Kumosani, Taha A; Qadri, Ishtiaq

    2015-01-01

    Epilepsy is a neurological disorder affecting more than 50 million people worldwide. It can be controlled by antiepileptic drugs (AEDs) but more than 30% patients are still resistant to AEDs. To overcome this problem, researchers are trying to develop novel approaches to treat epilepsy including the use of herbal medicines. The ?-amino butyric acid type-A receptor associated protein (GABARAP) is ubiquitin-like modifier implicated in the intracellular trafficking of GABAAR. An in silico mutation was created at 116 amino acid position G116A, and an in silico study was carried out to identify the potential binding inhibitors (with antiepileptic properties) against the active sites of GABARAP. Five different plant derived compounds namely (a) Aconitine (b) Berberine (c) Montanine (d) Raubasine (e) Safranal were selected, and their quantitative structure-activity relationships (QSAR) have been conducted to search the inhibitory activity of the selected compounds. The results have shown maximum number of hydrogen bond (H-bond) interactions of Raubasine with highest interaction energy among all of the five compounds. So, Raubasine could be the best fit ligand of GABARAP but in vitro, and in vivo studies are necessary for further confirmation. PMID:26124559

  20. Evaluation of Biologically Active Compounds from Calendula officinalis Flowers using Spectrophotometry

    PubMed Central

    2012-01-01

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

  1. Liquid-phase adsorption of organic compounds by granular activated carbon and activated carbon fibers

    SciTech Connect

    Lin, S.H.; Hsu, F.M.

    1995-06-01

    Liquid-phase adsorption of organic compounds by granular activated carbon (GAC) and activated carbon fibers (ACFs) is investigated. Acetone, isopropyl alcohol (IPA), phenol, and tetrahydrofuran (THF) were employed as the model compounds for the present study. It is observed from the experimental results that adsorption of organic compounds by GAC and ACF is influenced by the BET (Brunauer-Emmett-Teller) surface area of adsorbent and the molecular weight, polarity, and solubility of the adsorbate. The adsorption characteristics of GAC and ACFs were found to differ rather significantly. In terms of the adsorption capacity of organic compounds, the time to reach equilibrium adsorption, and the time for complete desorption, ACFs have been observed to be considerably better than GAC. For the organic compounds tested here, the GAC adsorptions were shown to be represented well by the Langmuir isotherm while the ACF adsorption could be adequately described by the Langmuir or the Freundlich isotherm. Column adsorption tests indicated that the exhausted ACFs can be effectively regenerated by static in situ thermal desorption at 150 C, but the same regeneration conditions do not do as well for the exhausted GAC.

  2. A bitter melon extract inhibits the P-glycoprotein activity in intestinal Caco-2 cells: monoglyceride as an active compound.

    PubMed

    Konishi, Tomoko; Satsu, Hideo; Hatsugai, Yasuo; Aizawa, Koichi; Inakuma, Takahiro; Nagata, Shinji; Sakuda, Sho-hei; Nagasawa, Hiromichi; Shimizu, Makoto

    2004-01-01

    P-glycoprotein (P-gp) is a 170 kDa membrane protein that belongs to the ATP-binding cassette (ABC) transporter superfamily. In normal tissues, P-gp functions as an ATP-dependent efflux pump that excretes highly hydrophobic xenobiotic compounds, playing an important role in protecting the cells/tissues from xenobiotics. In the present study, chemical substances that could directly modulate the intestinal P-gp activity were searched in vegetables and fruits. By using human intestinal epithelial Caco-2 cells as a model of the small intestinal cells, we observed that a bitter melon fraction extracted from 40% methanol showed the greatest increase of the rhodamine-123 accumulation by Caco-2 cells. Inhibitory compounds in the bitter melon fraction were then isolated by HPLC using Pegasil C4 and Pegasil ODS columns. The HPLC fraction having the highest activity was analyzed by (1)H-NMR and FAB-MS, and the active compound was identified as 1-monopalmitin. It is interesting that certain types of monoglyceride might be involved in the drug bioavailability by specifically inhibiting the efflux mediated by P-gp. PMID:15630255

  3. 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...

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

    SciTech Connect

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

    2008-12-01

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

  5. Predicting health effects of exposures to compounds with estrogenic activity: methodological issues.

    PubMed Central

    Rudel, R

    1997-01-01

    Many substances are active in in vitro tests for estrogenic activity, but data from multigenerational and other toxicity studies are not available for many of those substances. Controversy has arisen, therefore, concerning the likelihood of adverse health effects. Based on a toxic equivalence factor risk assessment approach, some researchers have concluded that exposure to environmental estrogens is not associated with estrogen receptor (ER)-mediated health effects. Their rationale cites the low potency of these compounds in in vitro assays relative to estradiol, and the widespread exposure to pharmaceutical, endogenous, and dietary estrogens. This reasoning relies on two assumptions: that the relative estrogenic potency in in vitro assays is predictive of the relative potency for the most sensitive in vivo estrogenic effect; and that all estrogens act via the same mechanism to produce the most sensitive in vivo estrogenic effect. Experimental data reviewed here suggest that these assumptions may be inappropriate because diversity in both mechanism and effect exists for estrogenic compounds. Examples include variations in ER-ligand binding to estrogen response elements, time course of nuclear ER accumulation, patterns of gene activation, and other mechanistic characteristics that are not reflected in many in vitro assays, but may have significance for ER-mediated in vivo effects. In light of these data, this report identifies emerging methodological issues in risk assessment for estrogenic compounds: the need to address differences in in vivo end points of concern and the associated mechanisms; pharmacokinetics; the crucial role of timing and duration of exposure; interactions; and non-ER-mediated activities of estrogenic compounds. PMID:9168010

  6. Biological surface-active compounds from marine bacteria.

    PubMed

    Dang, Nga Phuong; Landfald, Bjarne; Willassen, Nils Peder

    2016-05-01

    Surface-active compounds (SACs) are widely used in different industries as well as in many daily consumption products. However, with the increasing concern for their environmental acceptability, attention has turned towards biological SACs which are biodegradable, less toxic and more environmentally friendly. In this work, 176 marine hydrocarbon-degrading bacterial isolates from petroleum-contaminated sites along the Norwegian coastline were isolated and screened for their capacity to produce biological SACs. Among them, 18 isolates were capable of reducing the surface tension of the culture medium by at least 20 mN m(-1) and/or capable of maintaining more than 40% of the emulsion volume after 24 h when growing on glucose or kerosene as carbon and energy source. These isolates were members of the genera Pseudomonas, Pseudoalteromonas, Rhodococcus, Catenovulum, Cobetia, Glaciecola, Serratia, Marinomonas and Psychromonas. Two isolates, Rhodococcus sp. LF-13 and Rhodococcus sp. LF-22, reduced surface tension of culture medium by more than 40 mN m(-1) when growing on kerosene, n-hexadecane or rapeseed oil. The biosurfactants were produced by resting cells of the two Rhodococcus strains suggesting the biosynthesis of the biosurfactants was not necessarily associated with their growth on hydrocarbons. PMID:26506920

  7. Fate of selected pharmaceutically active compounds during simulated riverbank filtration.

    PubMed

    D'Alessio, Matteo; Yoneyama, Bunnie; Ray, Chittaranjan

    2015-02-01

    The objective of this study was to investigate the effect of temperature, oxygen, and organic matter on the removal of selected pharmaceutically active compounds (PhACs) during simulated riverbank filtration (RBF). The behavior of six PhACs (caffeine, carbamazepine, 17-? estradiol [E2], estrone [E1], gemfibrozil, and phenazone) was evaluated by small flow-through column experiments. Results from our study showed that RBF can be used to treat many of the PhACs found in environmental waters. Local conditions at the RBF site, however, can affect the removal of PhACs and should be investigated. Biodegradation and sorption represented the predominant mechanisms involved during the removal of the selected PhACs. All selected PhACs showed limited and slower removal during the winter. Phenazone was highly impacted by the level of oxygen; complete depletion of phenazone below the analytical limit occurred only under aerobic conditions (dissolved oxygen >8 mg L(-1)). Caffeine and E2 were highly impacted by the presence of humic acid in the feed water. Caffeine and E2 were depleted below the detection limit in the presence of humic acid regardless of the temperature and the level of oxygen. E1 was impacted by the different environmental conditions and depletion below the detection limit occurred only during the summer under aerobic conditions. Carbamazepine (10%) and gemfibrozil (<30%) showed limited removal regardless of the different levels of temperature, oxygen and humic acid. PMID:25461064

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

    PubMed

    Moo-Huchin, Vctor M; Moo-Huchin, Mariela I; Estrada-Len, Raciel J; Cuevas-Glory, Luis; Estrada-Mota, Ivn A; Ortiz-Vzquez, 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, Mxico: 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

  9. 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 (17β-estradiol and alkylphenolpolyethoxylates, respectively) was quantified. The distance required for 17β-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.

  10. Activation of HIV-1 with Nanoparticle-Packaged Small-Molecule Protein Phosphatase-1-Targeting Compound

    PubMed Central

    Smith, Kahli A.; Lin, Xionghao; Bolshakov, Oleg; Griffin, James; Niu, Xiaomei; Kovalskyy, Dmytro; Ivanov, Andrey; Jerebtsova, Marina; Taylor, Robert E.; Akala, Emmanuel; Nekhai, Sergei

    2015-01-01

    Complete eradication of HIV-1 infection is impeded by the existence of latent HIV-1 reservoirs in which the integrated HIV-1 provirus is transcriptionally inactive. Activation of HIV-1 transcription requires the viral Tat protein and host cell factors, including protein phosphatase-1 (PP1). We previously developed a library of small compounds that targeted PP1 and identified a compound, SMAPP1, which induced HIV-1 transcription. However, this compound has a limited bioavailability in vivo and may not be able to reach HIV-1-infected cells and induce HIV-1 transcription in patients. We packaged SMAPP1 in polymeric polyethylene glycol polymethyl methacrylate nanoparticles and analyzed its release and the effect on HIV-1 transcription in a cell culture. SMAPP1 was efficiently packaged in the nanoparticles and released during a 120-hr period. Treatment of the HIV-1-infected cells with the SMAPP1-loaded nanoparticles induced HIV-1 transcription. Thus, nanoparticles loaded with HIV-1-targeting compounds might be useful for future anti-HIV-1 therapeutics. PMID:26839837

  11. 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

  12. Mutagenic and genotoxic activity of chosen dyes and surface active compounds used in the textile industry.

    PubMed

    Przybojewska, B; Bara?ski, B; Spiechowicz, E; Szymczak, W

    1989-01-01

    This study was designed to investigate the mutagenic and genotoxic properties of ten dyes and four surface active compounds using Salmonella/microsome assay and the micronucleus test. Five of the investigated dyes (Acid Blue 7, Acid Green 16, Direct Black 19:1, Basic Red 22, Basic Orange 28) possessed mutagenic activity with regard to test strains of Salmonella. In addition, all of them increased the frequency of micronucleated polychromatic erythrocytes in the bone marrow of mice. Three other compounds (Acid Blue 62, Direct Yellow 12, Direct Red 81), which were not mutagenic in the Salmonella/microsome assay, were genotoxic in the micronucleus test. The other two dyes (Reactive Blue 13, Acid Red 213), as well as tested surface active compounds, did not exert mutagenic and genotoxic effects, and therefore, it is most probable that they do not have carcinogenic properties. Besides, it was noted that Acid Blue 62, Direct Black 19:1, Direct Red 81 and Basic Orange 28 cause a significant decrease in the ratio polychromatic to normochromatic erythrocytes in the bone marrow of mice, which means that, at the doses used in the experiment, they are toxic to the erythrocyte series cells of bone marrow. The other compounds under consideration have no such effect. PMID:2489422

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  15. JV Task 86 - Identifying the Source of Benzene in Indoor Air Using Different Compound Classes from TO-15 Data

    SciTech Connect

    Steven B. Hawthorne

    2007-04-15

    Volatile organic compound (VOC) data that had already been collected using EPA method TO-15 at four different sites under regulatory scrutiny (a school, strip mall, apartment complex, and business/residential neighborhood) were evaluated to determine whether the source of indoor air benzene was outdoor air or vapor intrusion from contaminated soil. Both the use of tracer organics characteristic of different sources and principal component statistical analysis demonstrated that the source of indoor air at virtually all indoor sampling locations was a result of outdoor air, and not contaminated soil in and near the indoor air-sampling locations. These results show that proposed remediation activities to remove benzene-contaminated soil are highly unlikely to reduce indoor air benzene concentrations. A manuscript describing these results is presently being prepared for submission to a peer-reviewed journal.

  16. 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

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

    PubMed

    Arajo, Sthfane 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

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

    PubMed Central

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

    2015-01-01

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

  19. High-throughput screen identifies small molecule inhibitors targeting acetyltransferase activity of Mycobacterium tuberculosis GlmU.

    PubMed

    Rani, Chitra; Mehra, Rukmankesh; Sharma, Rashmi; Chib, Reena; Wazir, Priya; Nargotra, Amit; Khan, Inshad Ali

    2015-12-01

    N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) is a pivotal bifunctional enzyme, its N and C terminal domains catalyzes uridyltransferase and acetyltransferase activities, respectively. Final product of GlmU catalyzed reaction, uridine-diphospho-N-acetylglucosamine (UDP-GlcNAc), acts as sugar donor providing GlcNAc residues in the synthesis of peptidoglycan and a disaccharide linker (D-N-GlcNAc-1-rhamnose), the key structural components of Mycobacterium tuberculosis (M. tuberculosis) cell wall. In the present study, we have searched new inhibitors against acetyltransferase activity of M. tuberculosis GlmU. A subset of 1607 synthetic compounds, selected through dual approach i.e., in-silico and whole cell screen against 20,000 compounds from ChemBridge library, was further screened using an in-vitro high throughput bioassay to identify inhibitors of acetyltransferase domain of M. tuberculosis GlmU. Four compounds were found to inhibit GlmU enzyme specific to acetyltransferase activity, with IC50 values ranging from 9 to 70 μM. Two compounds (6624116, 5655606) also exhibited whole cell activity against drug susceptible as well as drug resistant M. tuberculosis. These two compounds also exhibited increased anti-TB activity when tested in combination with rifampicin, isoniazid and ethambutol, however 5655606 was cytotoxic to eukaryotic cell line. These results demonstrate that identified chemical scaffolds can be used as inhibitors of M. tuberculosis cell wall enzyme after optimizations for future anti-TB drug development program. PMID:26318557

  20. The novel antibacterial compound walrycin A induces human PXR transcriptional activity

    PubMed Central

    Berthier, Alexandre; Oger, Frdrik; Gheeraert, Cline; Boulahtouf, Abdel; Le Guvel, Rmy; Balaguer, Patrick; Staels, Bart; Salbert, Gilles; Lefebvre, Philippe

    2012-01-01

    The human pregnane X receptor (PXR) is a ligand-regulated transcription factor belonging to the nuclear receptor superfamily. PXR is activated by a large, structurally diverse, set of endogenous and xenobiotic compounds, and coordinates the expression of genes central to metabolism and excretion of potentially harmful chemicals and therapeutic drugs in humans. Walrycin A is a novel antibacterial compound targeting the WalK/WalR two-component signal transduction system of Gram (+) bacteria. Here we report that, in hepatoma cells, walrycin A potently activates a gene set known to be regulated by the xenobiotic sensor PXR. Walrycin A was as efficient as the reference PXR agonist rifampicin to activate PXR in a transactivation assay at non cytoxic concentrations. Using a limited proteolysis assay, we show that walrycin A induces conformational changes at a concentration which correlates with walrycin A ability to enhance the expression of prototypic target genes, suggesting that walrycin A interacts with PXR. The activation of the canonical human PXR target gene CYP3A4 by walrycin A is dose- and PXR-dependent. Finally, in silico docking experiments suggest that the walrycin A oxidation product Russigs blue is the actual a ligand for PXR. Taken together, these results identify walrycin A as novel human PXR activator. PMID:22314385

  1. Identifying Physical Activity Profiles in COPD Patients Using Topic Models.

    PubMed

    Spina, Gabriele; Casale, Pierluigi; Albert, Paul S; Alison, Jennifer; Garcia-Aymerich, Judith; Costello, Richard W; Hernandes, Nidia A; van Gestel, Arnoldus J R; Leuppi, Jrg D; Mesquita, Rafael; Singh, Sally J; Smeenk, Frank W J M; Tal-Singer, Ruth; Wouters, Emiel F M; Spruit, Martijn A; den Brinker, Albertus C

    2015-09-01

    With the growing amount of physical activity (PA) measures, the need for methods and algorithms that automatically analyze and interpret unannotated data increases. In this paper, PA is seen as a combination of multimodal constructs that can cooccur in different ways and proportions during the day. The design of a methodology able to integrate and analyze them is discussed, and its operation is illustrated by applying it to a dataset comprising data from COPD patients and healthy subjects acquired in daily life. The method encompasses different stages. The first stage is a completely automated method of labeling low-level multimodal PA measures. The information contained in the PA labels are further structured using topic modeling techniques, a machine learning method from the text processing community. The topic modeling discovers the main themes that pervade a large set of data. In our case, topic models discover PA routines that are active in the assessed days of the subjects under study. Applying the designed algorithm to our data provides new learnings and insights. As expected, the algorithm discovers that PA routines for COPD patients and healthy subjects are substantially different regarding their composition and moments in time in which transitions occur. Furthermore, it shows consistent trends relating to disease severity as measured by standard clinical practice. PMID:25974957

  2. The cell competition-based high-throughput screening identifies small compounds that promote the elimination of RasV12-transformed cells from epithelia

    PubMed Central

    Yamauchi, Hajime; Matsumaru, Takanori; Morita, Tomoko; Ishikawa, Susumu; Maenaka, Katsumi; Takigawa, Ichigaku; Semba, Kentaro; Kon, Shunsuke; Fujita, Yasuyuki

    2015-01-01

    Recent studies have revealed that cell competition can occur between normal and transformed epithelial cells; normal epithelial cells recognize the presence of the neighboring transformed cells and actively eliminate them from epithelial tissues. Here, we have established a brand-new high-throughput screening platform that targets cell competition. By using this platform, we have identified Rebeccamycin as a hit compound that specifically promotes elimination of RasV12-transformed cells from the epithelium, though after longer treatment it shows substantial cytotoxic effect against normal epithelial cells. Among several Rebeccamycin-derivative compounds, we have found that VC1-8 has least cytotoxicity against normal cells but shows the comparable effect on the elimination of transformed cells. This cell competition-promoting activity of VC1-8 is observed both in vitro and ex vivo. These data demonstrate that the cell competition-based screening is a promising tool for the establishment of a novel type of cancer preventive medicine. PMID:26480891

  3. ION COMPOSITION ELUCIDATION (ICE): A HIGH RESOLUTION MASS SPECTROMETRIC TOOL FOR IDENTIFYING ORGANIC COMPOUNDS IN COMPLEX EXTRACTS OF ENVIRONMENTAL SAMPLES

    EPA Science Inventory


    Unidentified Organic Compounds. For target analytes, standards are purchased, extraction and clean-up procedures are optimized, and mass spectra and retention times for the chromatographic separation are obtained for comparison to the target compounds in environmental sample ...

  4. Annotated compound data for modulators of detergent-solubilised or lipid-reconstituted respiratory type II NADH dehydrogenase activity obtained by compound library screening.

    PubMed

    Dunn, Elyse A; Cook, Gregory M; Heikal, Adam

    2016-03-01

    The energy-generating membrane protein NADH dehydrogenase (NDH-2), a proposed antibacterial drug target (see "Inhibitors of type II NADH:menaquinone oxidoreductase represent a class of antitubercular drugs" Weinstein et al.2005 [1]), was screened for modulators of activity in either detergent-solublised or lipid reconstituted (proteolipsome) form. Here we present an annotated list of compounds identified in a small-scale screen against NDH-2. The dataset contains information regarding the libraries screened, the identities of hit compounds and the physicochemical properties governing solubility and permeability. The implications of these data for future antibiotic discovery are discussed in our associated report, "Comparison of lipid and detergent enzyme environments for identifying inhibitors of membrane-bound energy-transducing proteins" [2]. PMID:26862571

  5. Annotated compound data for modulators of detergent-solubilised or lipid-reconstituted respiratory type II NADH dehydrogenase activity obtained by compound library screening

    PubMed Central

    Dunn, Elyse A.; Cook, Gregory M.; Heikal, Adam

    2015-01-01

    The energy-generating membrane protein NADH dehydrogenase (NDH-2), a proposed antibacterial drug target (see Inhibitors of type II NADH:menaquinone oxidoreductase represent a class of antitubercular drugs Weinstein et al.2005 [1]), was screened for modulators of activity in either detergent-solublised or lipid reconstituted (proteolipsome) form. Here we present an annotated list of compounds identified in a small-scale screen against NDH-2. The dataset contains information regarding the libraries screened, the identities of hit compounds and the physicochemical properties governing solubility and permeability. The implications of these data for future antibiotic discovery are discussed in our associated report, Comparison of lipid and detergent enzyme environments for identifying inhibitors of membrane-bound energy-transducing proteins [2].

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

    PubMed Central

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

    2014-01-01

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

  7. Determination of the cytostatic and cytocidal activities of antimalarial compounds and their combination interactions.

    PubMed

    Sherlach, Katy S; Roepe, Paul D

    2014-01-01

    Determining the antiplasmodial activity of candidate antimalarial drugs in vitro identifies new therapies for drug-resistant malaria. Importantly though, activity can be either growth-inhibitory (cytostatic) or parasite-kill (cytocidal), or both. The simple methods described here can allow for distinction between these activities, as well as definition of drug interactions between two or more compounds. The latter is important in the definition of novel drug combination therapy for malaria. These methods involve live malarial parasite red blood cell culture, routine pharmacology, high-throughput detection of parasite DNA with fluorescent reporters, and routine mathematical analysis of dose-response curves. The techniques and approaches are accessible to most laboratories and require minimal special equipment beyond a fluorescent plate reader and tissue culture facilities. PMID:25445179

  8. High-Throughput Assay for Modulators of Mitochondrial Membrane Potential Identifies a Novel Compound With Beneficial Effects on db/db Mice

    PubMed Central

    Qiu, Bei-Ying; Turner, Nigel; Li, Yuan-Yuan; Gu, Min; Huang, Meng-Wei; Wu, Fang; Pang, Tao; Nan, Fa-Jun; Ye, Ji-Ming; Li, Jing-Ya; Li, Jia

    2010-01-01

    OBJECTIVE Recently, several drugs have been shown to exert beneficial effects for metabolic syndrome through mild regulation of mitochondrial function. Hence, we explored a strategy of targeting mitochondrial function to improve glucose and lipid metabolism. RESEARCH DESIGN AND METHODS Mitochondrial membrane potential (??m) is a marker of mitochondrial function; therefore, we set up a high-throughput screening assay of ??m in L6 myotubes. The effects of a selected lead compound were investigated in vitro and in vivo in relation to metabolic syndrome. RESULTS A novel small-molecule compound, C1, was identified through this high-throughput screening. C1 depolarized ??m in L6 myotubes without cytotoxicity and led to increased cellular AMP-to-ATP ratio, activation of AMP-activated protein kinase (AMPK), and enhanced glucose uptake. It also stimulated the AMPK pathway in HepG2 cells, leading to decreased lipid content. Intriguingly, C1 inhibited respiration in L6 myotubes but did not affect respiration in isolated muscle mitochondria, suggesting that it may depolarize ??m indirectly by affecting the supply of electron donors. Acute administration of C1 in C57BL/6J mice markedly increased fat oxidation and the phosphorylation of AMPK and acetyl-CoA carboxylase in the liver. In diabetic db/db mice, chronic administration of C1 significantly reduced hyperglycemia, plasma fatty acids, glucose intolerance, and the mRNA levels of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in the liver. CONCLUSIONS Our results demonstrate a novel small molecule that mildly depolarizes ??m and is able to improve glucose and lipid metabolism to exert beneficial effects for metabolic syndrome. These findings suggest that compounds regulating mitochondrial function may have therapeutic potential for type 2 diabetes. PMID:19833880

  9. Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture

    PubMed Central

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

    2014-01-01

    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 [EC50s], 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

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

    PubMed

    Khan, Usman; Nicell, Jim

    2015-05-01

    In Canada, as many as 20 pharmaceutically active compounds (PhACs) have been detected in samples of treated drinking water. The presence of these PhACs in drinking water raises important questions as to the human health risk posed by their potential appearance in drinking water supplies and the extent to which they indicate that other PhACs are present but have not been detected using current analytical methods. Therefore, the goal of the current investigation was to conduct a screening-level assessment of the human health risks posed by the aquatic release of an evaluation set of 335 selected PhACs. Predicted and measured concentrations were used to estimate the exposure of Canadians to each PhAC in the evaluation set. Risk evaluations based on measurements could only be performed for 17 PhACs and, of these, all were found to pose a negligible risk to human health when considered individually. The same approach to risk evaluation, but based on predicted rather than measured environmental concentrations, suggested that 322 PhACs of the evaluation set, when considered individually, are expected to pose a negligible risk to human health due to their potential presence in drinking waters. However, the following 14 PhACs should beprioritized for further study: triiodothyronine, thyroxine, ramipril and its metabolite ramiprilat, candesartan, lisinopril, atorvastatin, lorazepam, fentanyl, atenolol, metformin, enalaprilat, morphine, and irbesartan. Finally, the currently available monitoring data for PhACs in Canadian surface and drinking waters was found to be lacking, irrespective of whether their suitability was assessed based on risk posed, predicted exposure concentrations, or potency. PMID:25739816

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  13. SYNTHESIZING ORGANIC COMPOUNDS USING LIGHT-ACTIVATED TIO2

    EPA Science Inventory

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

  14. Development of a QPatch Automated Electrophysiology Assay for Identifying KCa3.1 Inhibitors and Activators

    PubMed Central

    Jenkins, David Paul; Yu, Weifeng; Brown, Brandon M.; Ljkner, Lars Damgaard

    2013-01-01

    Abstract The intermediate-conductance Ca2+-activated K+ channel KCa3.1 (also known as KCNN4, IK1, or the Grdos channel) plays an important role in the activation of T and B cells, mast cells, macrophages, and microglia by regulating membrane potential, cellular volume, and calcium signaling. KCa3.1 is further involved in the proliferation of dedifferentiated vascular smooth muscle cells and fibroblast and endothelium-derived hyperpolarization responses in the vascular endothelium. Accordingly, KCa3.1 inhibitors are therapeutically interesting as immunosuppressants and for the treatment of a wide range of fibroproliferative disorders, whereas KCa3.1 activators constitute a potential new class of endothelial function preserving antihypertensives. Here, we report the development of QPatch assays for both KCa3.1 inhibitors and activators. During assay optimization, the Ca2+ sensitivity of KCa3.1 was studied using varying intracellular Ca2+ concentrations. A free Ca2+ concentration of 1??M was chosen to optimally test inhibitors. To identify activators, which generally act as positive gating modulators, a lower Ca2+ concentration (?200?nM) was used. The QPatch results were benchmarked against manual patch-clamp electrophysiology by determining the potency of several commonly used KCa3.1 inhibitors (TRAM-34, NS6180, ChTX) and activators (EBIO, riluzole, SKA-31). Collectively, our results demonstrate that the QPatch provides a comparable but much faster approach to study compound interactions with KCa3.1 channels in a robust and reliable assay. PMID:24351043

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

    PubMed

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

    2015-10-01

    New Zealand propolis is a "European" type propolis obtained by honey bees mainly from exudates of poplar. European type propolis is known to have anti-inflammatory and anti-cancer properties and this activity has been attributed to some of the main constituents such as chrysin and CAPE (caffeic acid phenethyl ester). As part of our studies on how New Zealand propolis might benefit gastro-intestinal health, we carried out in vitro bioactivity-guided fractionation of "Bio30" propolis using both anti-inflammatory (TNF-?, COX-1, COX-2) and anti-colon cancer (DLD-1 colon cancer cell viability) assays; and determined the phenolic compounds responsible for the activity. The New Zealand wax-free Bio30 propolis tincture solids had very high levels of the dihydroflavonoids pinocembrin and pinobanksin-3-O-acetate, and high levels of the dimethylallyl, benzyl and 3-methyl-3-butenyl caffeates relative to CAPE. The DLD-1 assays identified strong anti-proliferative activity associated with these components as well as chrysin, galangin and CAPE and a number of lesser known or lower concentration compounds including benzyl ferulate, benzyl isoferulate, pinostrobin, 5-phenylpenta-2,4-dienoic acid and tectochrysin. The phenolic compounds pinocembrin, pinobanksin-3-O-acetate, tectochrysin, dimethylallyl caffeate, 3-methyl-3-butenyl caffeate, benzyl ferulate and benzyl isoferulate also showed good broad spectrum activity in anti-proliferative assays against three other gastro-intestinal cancer cell lines; HCT-116 colon carcinoma, KYSE-30 oesophageal squamous cancer, and NCI-N87 gastric carcinoma. Activity is also observed in anti-inflammatory assays although it appears to be limited to one of the first cytokines in the inflammatory cascade, TNF-?. PMID:26347954

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

    SciTech Connect

    Xu, Feng; Sweeney, Matthew; Quinlan, Jason

    2015-06-16

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

  17. A Dual Read-Out Assay to Evaluate the Potency of Compounds Active against Mycobacterium tuberculosis

    PubMed Central

    Ollinger, Juliane; Bailey, Mai Ann; Moraski, Garrett C.; Casey, Allen; Florio, Stephanie; Alling, Torey; Miller, Marvin J.; Parish, Tanya

    2013-01-01

    Tuberculosis is a serious global health problem caused by the bacterium Mycobacterium tuberculosis. There is an urgent need for discovery and development of new treatments, but this can only be accomplished through rapid and reproducible M. tuberculosis assays designed to identify potent inhibitors. We developed an automated 96-well assay utilizing a recombinant strain of M. tuberculosis expressing a far-red fluorescent reporter to determine the activity of novel compounds; this allowed us to measure growth by monitoring both optical density and fluorescence. We determined that optical density and fluorescence were correlated with cell number during logarithmic phase growth. Fluorescence was stably maintained without antibiotic selection over 5 days, during which time cells remained actively growing. We optimized parameters for the assay, with the final format being 5 days growth in 96-well plates in the presence of 2% w/v DMSO. We confirmed reproducibility using rifampicin and other antibiotics. The dual detection method allows for a reproducible calculation of the minimum inhibitory concentration (MIC), at the same time detecting artefacts such as fluorescence quenching or compound precipitation. We used our assay to confirm anti-tubercular activity and establish the structure activity relationship (SAR) around the imidazo[1,2-a]pyridine-3-carboxamides, a promising series of M. tuberculosis inhibitors. PMID:23593234

  18. 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-β-d-glucopyranoside (5), isorhamentin-3-O-β-d-rutinoside (6), 8-O-methylretusin (7), 8-O-methylretusin-7-O-β-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 μg/mL, and median inhibitory concentration (IC50) values of 26.8–125.1 μg/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 μg/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 β-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

  19. Identification of Tetraazacyclic Compounds as Novel Potent Inhibitors Antagonizing RORγt Activity and Suppressing Th17 Cell Differentiation

    PubMed Central

    Ding, Qingfeng; Zhao, Mei; Yu, Bolan; Bai, Chuan; Huang, Zhaofeng

    2015-01-01

    CD4+ T-helper cells that produce interleukin-17 (Th17 cells) are characterized as pathological T-helper cells in autoimmune diseases. Differentiation of human and mouse Th17 cells requires a key transcription regulator, retinoic acid receptor-related orphan receptor γt (RORγt), which is a potential therapeutic target for autoimmune diseases. To develop a therapeutic agent for Th17-mediated autoimmune diseases, we have established a high-throughput screening (HTS) assay for candidate screening, in which the luciferase activity in RORγt-LBD positive and negative Jurkat cells were analyzed to evaluate induction of RORγt activity by compounds. This technique was applied to screen a commercially-available drug-like chemical compound library (Enamine) which contains 20155 compounds. The screening identified 17 compounds that can inhibit RORγt function in the HTS screen system. Of these, three tetraazacyclic compounds can potently inhibit RORγt activity, and suppress Th17 differentiation and IL-17 production. These three candidate compounds could significantly attenuate the expression of the Il17a by 65%- 90%, and inhibit IL-17A secretion by 47%, 63%, and 74%, respectively. These compounds also exhibited a potent anti-RORγt activity, with EC50 values of 0.25 μM, 0.67 μM and 2.6 μM, respectively. Our data demonstrated the feasibility of targeting the RORγt to inhibit Th17 cell differentiation and function with these tetraazacyclic compounds, and the potential to improve the structure of these compounds for autoimmune diseases therapeutics. PMID:26368822

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

    SciTech Connect

    Boehme, Kathleen; Simon, Stephanie

    2009-04-01

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

  1. Phenolic Compounds from the Flowers of Bombax malabaricum and Their Antioxidant and Antiviral Activities.

    PubMed

    Zhang, Yu-Bo; Wu, Peng; Zhang, Xiao-Li; Xia, Chao; Li, Guo-Qiang; Ye, Wen-Cai; Wang, Guo-Cai; Li, Yao-Lan

    2015-01-01

    Three new phenolic compounds 1-3 and twenty known ones 4-23 were isolated from the flowers of Bombax malabaricum. Their chemical structures were elucidated by spectroscopic analyses (IR, ESI-MS, HR-ESI-MS, 1D- and 2D-NMR) and chemical reactions. The antioxidant capacities of the isolated compounds were tested using FRAP and DPPH radical-scavenging assays, and compounds 4, 6, 8, 12, as well as the new compound 2, exhibited stronger antioxidant activities than ascorbic acid. Furthermore, all of compounds were tested for their antiviral activities against RSV by the CPE reduction assay and plaque reduction assay. Compounds 4, 10, 12 possess in vitro antiviral activities, and compound 10 exhibits potent anti-RSV effects, comparable to the positive control ribavirin. PMID:26556329

  2. Synthesis and antiplatelet activity of antithrombotic thiourea compounds: biological and structure-activity relationship studies.

    PubMed

    Loureno, Andr Luiz; Saito, Max Seidy; Dorneles, Lus Eduardo Gomes; Viana, Gil Mendes; Sathler, Plnio Cunha; Aguiar, Lcia Cruz de Sequeira; de Pdula, Marcelo; Domingos, Thaisa Francielle Souza; Fraga, Aline Guerra Manssour; Rodrigues, Carlos Rangel; de Sousa, Valeria Pereira; Castro, Helena Carla; Cabral, Lucio Mendes

    2015-01-01

    The incidence of hematological disorders has increased steadily in Western countries despite the advances in drug development. The high expression of the multi-resistance protein 4 in patients with transitory aspirin resistance, points to the importance of finding new molecules, including those that are not affected by these proteins. In this work, we describe the synthesis and biological evaluation of a series of N,N'-disubstituted thioureas derivatives using in vitro and in silico approaches. New designed compounds inhibit the arachidonic acid pathway in human platelets. The most active thioureas (compounds 3d, 3i, 3m and 3p) displayed IC50 values ranging from 29 to 84 M with direct influence over in vitro PGE2 and TXA2 formation. In silico evaluation of these compounds suggests that direct blockage of the tyrosyl-radical at the COX-1 active site is achieved by strong hydrophobic contacts as well as electrostatic interactions. A low toxicity profile of this series was observed through hemolytic, genotoxic and mutagenic assays. The most active thioureas were able to reduce both PGE2 and TXB2 production in human platelets, suggesting a direct inhibition of COX-1. These results reinforce their promising profile as lead antiplatelet agents for further in vivo experimental investigations. PMID:25903367

  3. Rapid identification of compounds with enhanced antimicrobial activity by using conformationally defined combinatorial libraries.

    PubMed Central

    Blondelle, S E; Takahashi, E; Houghten, R A; Prez-Pay, E

    1996-01-01

    We have combined the strength of our synthetic combinatorial library approach for the rapid identification of highly active compounds with prior knowledge of the relationship between the antimicrobial activities of individual peptides with specific induced conformations in order to identify new peptides with enhanced activity relative to a starting known antimicrobial sequence. In the current study, conformationally defined combinatorial libraries were generated based on an 18-mer antimicrobial peptide known to be induced into an alpha-helical conformation in a lipidic environment. Not only were novel sequences readily identified with 10-fold increases in activity, but detailed information about the structure-activity relationships of the peptides studied was also obtained during the deconvolution process. By using circular dichroism spectroscopy it was found that the individual 18-mer peptides could be induced into alpha-helical conformations on interaction with the cell lipid layer and/or sialic acids, which could result in bacterial cell lysis due to perturbation of the lipid packing of the cell wall. PMID:8546675

  4. 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.

  5. HPLC-Analysis of Polyphenolic Compounds in Gardenia jasminoides and Determination of Antioxidant Activity by Using Free Radical Scavenging Assays

    PubMed Central

    Uddin, Riaz; Saha, Moni Rani; Subhan, Nusrat; Hossain, Hemayet; Jahan, Ismet Ara; Akter, Raushanara; Alam, Ashraful

    2014-01-01

    Purpose: Gardenia jasminoides is a traditional medicinal plant rich in anti-inflammatory flavonoids and phenolic compounds and used for the treatment of inflammatory diseases and pain. In this present study, antioxidant potential of Gardenia jasminoides leaves extract was evaluated by using various antioxidant assays. Methods: Various antioxidant assays such as 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, reducing power and total antioxidant capacity expressed as equivalent to ascorbic acid were employed. Moreover, phenolic compounds were detected by high-performance liquid chromatography (HPLC) coupled with diode-array detection. Results: The methanol extract showed significant free radical scavenging activities in DPPH radical scavenging antioxidant assays compared to the reference antioxidant ascorbic acid. Total antioxidant activity was increased in a dose dependent manner. The extract also showed strong reducing power. The total phenolic content was determined as 190.97 mg/g of gallic acid equivalent. HPLC coupled with diode-array detection was used to identify and quantify the phenolic compounds in the extracts. Gallic acid, (+)-catechin, rutin hydrate and quercetin have been identified in the plant extracts. Among the phenolic compounds, catechin and rutin hydrate are present predominantly in the extract. The accuracy and precision of the presented method were corroborated by low intra- and inter-day variations in quantitative results in leaves extract. Conclusion: These results suggest that phenolic compounds and flavonoids might contribute to high antioxidant activities of Gardenia jasminoides leaves. PMID:24754012

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

    PubMed Central

    2012-01-01

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

  7. 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

  8. Correlation of nitroaromatic compounds with the mutagenic activity of coal fly ash

    SciTech Connect

    Harris, W.R.; Remsen, J.F.; Chess, E.K.; Later, D.W.

    1987-01-01

    Stack-collected fly-ash particles from a commercial pulverized-coal power plant were extracted with 60/40 w/w benzene-methanol to remove as much of the organic fraction as possible. The extract was sequentially fractionated on a series of high-performance liquid chromatography columns, and the Salmonella bacterial mutagenicity assay using both normal and nitroreductase-deficient strains was used to localize the most mutagenic fractions. Selected fractions were analyzed by a variety of techniques, including gas chromatography with dual-flame ionization and thermionic nitrogen-phosphorus detectors, gas chromatography-mass spectrometry, direct-probe low-resolution or low-voltage mass spectrometry, and high-resolution mass spectrometry. Mutagenicity data indicated that nitroorganic compounds were the primary mutagens in all samples submitted for chemical analysis. A series of homologous alkylated nitrophenanthrenes appear to be important mutagens in one major fraction, while alkylated nitrofluorenones appear to be the dominant mutagens in a second major fraction. No nitro compounds were identified in a third major fraction. In addition to the nitro compounds, substantial amounts of fluorenones were also found, although these are not believed to contribute to the direct-acting mutagenic activity of the samples.

  9. Volatile flavor compounds, total polyphenolic contents and antioxidant activities of a China gingko wine.

    PubMed

    Wang, Xu; Xie, Kelin; Zhuang, Haining; Ye, Ran; Fang, Zhongxiang; Feng, Tao

    2015-09-01

    The volatile compounds in gingko wine, a novel functional wine, were extracted by head-space solid phase micro-extraction (SPME) and analyzed by gas chromatography-mass spectrometry (GC-MS) coupled with odor activity value (OAV) and relative odor contribution (ROC) analyses. In addition, the total polyphenolic content of gingko wine was determined using the Folin-Ciocalteu reagent, and its antioxidant capacity was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. Fifty-eight compounds were tentatively identified, including 13 esters, 10 alcohols, 11 acids, 12 carbonyl compounds, 2 lactones, 2 phenols, and 8 hydrocarbons. Ethyl hexanoate, ethyl pentanoate, nonanal, ethyl butyrate and ethyl heptanoate were the major contributors to the gingko wine aroma based on the results of OAV and ROC. The total phenols content of the gingko wine was 456 mg/L gallic acid equivalents, and its antioxidant capacity was higher than those of typical Chinese liquors analyzed in this paper. PMID:25842306

  10. Evaluation of leishmanicidal and trypanocidal activities of phenolic compounds from Calea uniflora Less.

    PubMed

    Lima, Tamires C; Souza, Rafaela J; Santos, Alan D C; Moraes, Milene H; Biondo, Nicole E; Barison, Andersson; Steindel, Mário; Biavatti, Maique W

    2016-03-01

    The phytochemical study of Calea uniflora led to the isolation of nine phenolic compounds identified as noreugenin (1), ethyl caffeate (2), a mixture of butein (3) + orobol (4), α-hydroxy-butein (5), caffeic acid (6), butein 4'-O-glucopyranosyl (7), quercetin 3-O-glucopyranosyl (8) and 3,5-di-O-caffeoylquinic acid (9). The chemical identity of the isolates was established on the basis of NMR and physical data. The chemical shifts of 5 and 7 have been reassigned and all the isolates were tested against Leishmania amazonensis and Trypanosoma cruzi amastigotes. None of the metabolites showed promising leishmanicidal activity. However, 2 and the mixture of 3 and 4 demonstrated interesting trypanocidal effect with IC50 values of 18.27 and 26.53 μM, respectively. Besides, these compounds did not present cytotoxic effect towards THP-1 cells, and compound 2 was 3.5-fold more selective than the mixture of 3+4. PMID:25880257

  11. Anti-tumor activities of active ingredients in Compound Kushen Injection

    PubMed Central

    Wang, Wei; You, Rong-li; Qin, Wen-jie; Hai, Li-na; Fang, Ming-jing; Huang, Guo-hua; Kang, Rui-xia; Li, Ming-hua; Qiao, Yu-feng; Li, Jian-wei; Li, An-ping

    2015-01-01

    Kushen (Radix Sophorae Flavescentis) has a long history of use for the treatment of tumors, inflammation and other diseases in traditional Chinese medicine. Compound Kushen Injection (CKI) is a mixture of natural compounds extracted from Kushen and Baituling (Rhizoma Smilacis Glabrae). The main principles of CKI are matrine (MT) and oxymatrine (OMT) that exhibit a variety of pharmacological activities, including anti-inflammatory, anti-allergic, anti-viral, anti-fibrotic and cardiovascular protective effects. Recent evidence shows that these compounds also produce anti-cancer actions, such as inhibiting cancer cell proliferation, inducing cell cycle arrest, accelerating apoptosis, restraining angiogenesis, inducing cell differentiation, inhibiting cancer metastasis and invasion, reversing multidrug resistance, and preventing or reducing chemotherapy- and/or radiotherapy-induced toxicity when combined with chemotherapeutic drugs. In this review, we summarize recent progress in studying the anti-cancer activities of MT, OMT and CKI and their potential molecular targets, which provide clues and references for further study. PMID:25982630

  12. 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.

  13. Evaluation of antimicrobial activity of extracts of Tibouchina candolleana (melastomataceae), isolated compounds and semi-synthetic derivatives against endodontic bacteria

    PubMed Central

    dos Santos, Fernanda M.; de Souza, Maria Gorete; Crotti, Antnio E. Miller; Martins, Carlos H. G.; Ambrsio, Srgio R.; Veneziani, Rodrigo C. S.; e Silva, Mrcio L. Andrade; Cunha, Wilson R.

    2012-01-01

    This work describes the phytochemical study of the extracts from aerial parts of Tibouchina candolleana as well as the evaluation of the antimicrobial activity of extracts, isolated compounds, and semi-synthetic derivatives of ursolic acid against endodontic bacteria. HRGC analysis of the n-hexane extract of T. candolleana allowed identification of ?-amyrin, ?-amyrin, and ?-sitosterol as major constituents. The triterpenes ursolic acid and oleanolic acid were isolated from the methylene chloride extract and identified. In addition, the flavonoids luteolin and genistein were isolated from the ethanol extract and identified. The antimicrobial activity was investigated via determination of the minimum inhibitory concentration (MIC) using the broth microdilution method. Amongst the isolated compounds, ursolic acid was the most effective against the selected endodontic bacteria. As for the semi-synthetic ursolic acid derivatives, only the methyl ester derivative potentiated the activity against Bacteroides fragilis. PMID:24031892

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

    ERIC Educational Resources Information Center

    Finer, Kim R.

    1997-01-01

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

  15. A Survey of Marine Natural Compounds and Their Derivatives with Anti-cancer Activity Reported in 2012.

    PubMed

    Sawadogo, Wamtinga Richard; Boly, Rainatou; Cerella, Claudia; Teiten, Marie Hlne; Dicato, Mario; Diederich, Marc

    2015-01-01

    Although considerable effort and progress has been made in the search for new anticancer drugs and treatments in the last several decades, cancer remains a major public health problem and one of the major causes of death worldwide. Many sources, including plants, animals, and minerals, are of interest in cancer research because of the possibility of identifying novel molecular therapeutics. Moreover, structure-activity-relationship (SAR) investigations have become a common way to develop naturally derived or semi-synthetic molecular analogues with improved efficacy and decreased toxicity. In 2012, approximately 138 molecules from marine sources, including isolated compounds and their associated analogues, were shown to be promising anticancer drugs. Among these, 62% are novel compounds. In this report, we review the marine compounds identified in 2012 that may serve as novel anticancer drugs. PMID:25903364

  16. 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

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

    PubMed

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

    2015-04-01

    Five polyphenols were isolated and purified from a brown alga Ecklonia cava. These compounds showed diverse biological activities such as antioxidative, antiinflammatory, and enzyme inhibitory activities. This led us to investigate the potential of these compounds as Alzheimer's disease drugs. All of the compounds showed moderate acetylcholinesterase inhibitory activity in a micromolar range (IC50 from 16.0 to 96.3??M). For butyrylcholinesterase, a new target for the treatment of Alzheimer's disease, phlorofucofuroeckol-A (PFF-A), showed a particularly potent inhibitory activity (IC50 0.95??M), which is over 100-fold greater than for acetylcholinesterase. These compounds inhibited glycogen synthase kinase 3 beta, which is related to the formation of hyperphosphorylated tau and generation A?. Bieckol and PFF-A inhibited amyloid precursor protein biosynthesis. PFF-A also showed very strong ?-secretase inhibitory activity with IC50 of submicromole. These results render these compounds as interesting potential drug candidates for Alzheimer's disease. PMID:25640212

  18. Synthesis and quorum sensing inhibitory activity of key phenolic compounds of ginger and their derivatives.

    PubMed

    Kumar, N Vijendra; Murthy, Pushpa S; Manjunatha, J R; Bettadaiah, B K

    2014-09-15

    Phenolic components of ginger (Zingiber officinale Roscoe) viz. [6]-gingerol, [6]-shogaol and zingerone exhibited quorum sensing inhibitory activity (QSI) against Chromobacterium violaceum and Pseudomonas aeruginosa. The inhibitory activity of all the compounds was studied by zone inhibition, pyocyanin, and violacein assay. All the compounds displayed good inhibition at 500ppm. [6]-Azashogaol, a new derivative of [6]-shogaol has been synthesized by Beckmann rearrangement of its oxime in the presence of ZnCl2. The structure elucidation of this new derivative was carried out by 1D ((1)H NMR and (13)C NMR) and 2D-NMR (COSY, HSQC and NOESY) spectral studies. This compound showed good QSI activity against P. aeruginosa. An isoxazoline derivative of [6]-gingerol was prepared and it exhibited good QSI activity. Present study illustrated that, the phenolic compounds of ginger and their derivatives form a class of compounds with promising QSI activity. PMID:24767081

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

    PubMed

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

    1986-11-01

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

  20. Antibacterial activity of extracellular compounds produced by a Pseudomonas strain against methicillin-resistant Staphylococcus aureus (MRSA) strains

    PubMed Central

    2013-01-01

    Background The emergence of multidrug-resistant bacteria is a world health problem. Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) strains, is one of the most important human pathogens associated with hospital and community-acquired infections. The aim of this work was to evaluate the antibacterial activity of a Pseudomonas aeruginosa-derived compound against MRSA strains. Methods Thirty clinical MRSA strains were isolated, and three standard MRSA strains were evaluated. The extracellular compounds were purified by vacuum liquid chromatography. Evaluation of antibacterial activity was performed by agar diffusion technique, determination of the minimal inhibitory concentration, curve of growth and viability and scanning electron microscopy. Interaction of an extracellular compound with silver nanoparticle was studied to evaluate antibacterial effect. Results The F3 (ethyl acetate) and F3d (dichloromethane- ethyl acetate) fractions demonstrated antibacterial activity against the MRSA strains. Phenazine-1-carboxamide was identified and purified from the F3d fraction and demonstrated slight antibacterial activity against MRSA, and synergic effect when combined with silver nanoparticles produced by Fusarium oxysporum. Organohalogen compound was purified from this fraction showing high antibacterial effect. Using scanning electron microscopy, we show that the F3d fraction caused morphological changes to the cell wall of the MRSA strains. Conclusions These results suggest that P. aeruginosa-produced compounds such as phenazines have inhibitory effects against MRSA and may be a good alternative treatment to control infections caused by MRSA. PMID:23773484

  1. Cell-based screening assay for anti-inflammatory activity of bioactive compounds.

    PubMed

    Meijer, Kees; Vonk, Roel J; Priebe, Marion G; Roelofsen, Han

    2015-01-01

    Excess dietary intake may induce metabolic inflammation which is associated with insulin resistance and cardiovascular disease. Recent evidence indicates that dietary bioactive compounds may diminish metabolic inflammation. To identify anti-inflammatory bioactives, we developed a screening assay using the human H293-NF-?B-RE-luc2P reporter cell line. Under optimised conditions we determined the anti-inflammatory activity of vegetables and purified bioactives, by monitoring their potency to inhibit TNF-?-induced NF-?B activity, as assessed by sensitive chemiluminescence detection in a 96-well assay format. Minced broccoli seedlings reduced NF-?B activity by 16%, while sulphoraphane, the dominant bioactive in broccoli seedlings, inhibited NF-?B activity with an IC?? of 5.11 ?mol/l. Short-chain fatty acids also reduced NF-?B activity in the order butyrate>propionate?acetate with IC?? of 51, 223, and 1300 ?mol/l, respectively. The H293-NF-?B-RE-luc2P reporter cell line is a sensitive tool for rapid high-throughput screening for bioactives with anti-inflammatory activity. PMID:25053041

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

  3. 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

  4. High-throughput Screening and Sensitized Bacteria Identify an M. tuberculosis Dihydrofolate Reductase Inhibitor with Whole Cell Activity

    PubMed Central

    Zhu, Linyun; Liao, Reiling P.; Mutai, Charles; Hafsat, Shittu; Sherman, David R.; Wang, Ming-Wei

    2012-01-01

    Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is a bacterial pathogen that claims roughly 1.4 million lives every year. Current drug regimens are inefficient at clearing infection, requiring at least 6 months of chemotherapy, and resistance to existing agents is rising. There is an urgent need for new drugs that are more effective and faster acting. The folate pathway has been successfully targeted in other pathogens and diseases, but has not yielded a lead drug against tuberculosis. We developed a high-throughput screening assay against Mtb dihydrofolate reductase (DHFR), a critical enzyme in the folate pathway, and screened a library consisting of 32,000 synthetic and natural product-derived compounds. One potent inhibitor containing a quinazoline ring was identified. This compound was active against the wild-type laboratory strain H37Rv (MIC99?=?207 M). In addition, an Mtb strain with artificially lowered DHFR levels showed increased sensitivity to this compound (MIC99?=?70.7 M), supporting that the inhibition was target-specific. Our results demonstrate the potential to identify Mtb DHFR inhibitors with activity against whole cells, and indicate the power of using a recombinant strain of Mtb expressing lower levels of DHFR to facilitate the discovery of antimycobacterial agents. With these new tools, we highlight the folate pathway as a potential target for new drugs to combat the tuberculosis epidemic. PMID:22768185

  5. Antibacterial Activity of Rhizome of Curcuma aromatica and Partial Purification of Active Compounds

    PubMed Central

    Revathi, S.; Malathy, N. S.

    2013-01-01

    The hexane extract of Curcuma aromatica, a plant belonging to the family Zingiberaceae was tested on 10 bacterial strains (clinical isolates and standard strains). Agar diffusion method was adopted for determining the antibacterial activity of the extract. The hexane extract was found to be active against all Gram-positive strains tested, but inactive against Gram-negative strains. The minimum inhibitory concentration and minimum bactericidal concentration were determined and found to be 539 ?g/ml. The phytochemical analysis of hexane extract by gas chromatography mass spectrometry revealed the presence of 13 compounds. The crude hexane extract was partially purified by thin layer chromatography. The zone showing good antibacterial activity was analysed further by gas chromatography mass spectrometry, UV/Vis spectrophotometry and Fourier transform infrared spectroscopy, which indicated the probable presence of germacrone. PMID:24591751

  6. 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.

  7. A small organic compound enhances the religation reaction of human topoisomerase I and identifies crucial elements for the religation mechanism

    PubMed Central

    Arn, Barbara; Coletta, Andrea; Tesauro, Cinzia; Zuccaro, Laura; Fiorani, Paola; Lentini, Sara; Galloni, Pierluca; Conte, Valeria; Floris, Barbara; Desideri, Alessandro

    2013-01-01

    The different steps of the human Top1 (topoisomerase I) catalytic cycle have been analysed in the presence of a pentacyclic-diquinoid synthetic compound. The experiments indicate that it efficiently inhibits the cleavage step of the enzyme reaction, fitting well into the catalytic site. Surprisingly the compound, when incubated with the binary topoisomeraseDNA cleaved complex, helps the enzyme to remove itself from the cleaved DNA and close the DNA gap, increasing the religation rate. The compound also induces the religation of the stalled enzymeCPT (camptothecin)DNA ternary complex. Analysis of the molecule docked over the binary complex, together with its chemical properties, suggests that the religation enhancement is due to the presence on the compound of two oxygen atoms that act as hydrogen acceptors. This property facilitates the deprotonation of the 5? DNA end, suggesting that this is the limiting step in the topoisomerase religation mechanism. PMID:23368812

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

    NASA Astrophysics Data System (ADS)

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

    2004-09-01

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

  9. Larvicidal activity of medicinal plant extracts and lignan identified in Phryma leptostachya var. asiatica roots against housefly (Musca domestica L.).

    PubMed

    Seo, Seon-Mi; Park, Il-Kwon

    2012-05-01

    Medicinal plant extracts from 27 plant species in 20 families were tested for their larvicidal activity against housefly, Musca domestica (L.). Responses varied with plant material and concentration. Among plant species tested, Phryma leptostachya var. asiatica showed 100% larvicidal activity against M. domestica at 10 mg/g concentration. Larvicidal activities of Atractylodes japonica, Saussurea lappa, Asiasarum sieboldi, and Gleditsia japonica var. koraiensis were 89.3%, 85.3%, 93.3%, and 96.6% at 10 mg/g concentration, respectively. Extracts of Prunus persica, Curcuma longa, and Paeonia moutan produced moderate activity. Larvicidal activity of other plant extracts was less than 50%. Among test plant species, P. leptostachya var. asiatica showed the most potent larvicidal activity. The active constituent of P. leptostachya var. asiatica roots was identified as the leptostachyol acetate by spectroscopic analysis. The LC(50) values of leptostachyol acetate against M. domestica larvae were 0.039 mg/g. Naturally occurring medicinal plant extracts and P. leptostachya var. asiatica root-derived compounds merit further study as potential housefly larval control agents or lead compounds. PMID:22065063

  10. Antinociceptive and antitumor activity of novel synthetic mononuclear Ruthenium (II) compounds

    PubMed Central

    Sunder A, Shyam; Dhulipala, Satyavati; Thota, Sreekanth; Yerra, Rajeshwar; Balzarini, Jan; De Clercq, Erik

    2013-01-01

    Background: From the thousands of years, metal compounds have been used in medicine for treatment of various diseases including various types of cancers. Ruthenium was seen as a promising metal due to its similar kinetics to platinum and its lower toxicity. Therefore, we aimed to evaluate the newer mononuclear ruthenium (II) compounds for antinociceptive and antitumor activities. Materials and Methods: Ruthenium (II) compounds were evaluated for antinociceptive and antitumor activity using the various in vitro and in vivo models. The compounds were injected to mice at concentrations of 1 and 2 mg kg-1 intraperitoneally and were screened for antinociceptive activity, and the antiproliferative effect was evaluated against murine leukemia cells (L1210), human T-lymphocyte cells (CEM) and human cervix carcinoma cells (HeLa) using MTT assay. Results: The results for antitumor activity clearly indicated that compound R1 was potent cytotoxic agent than R2 with IC50 values ranging from 4-6 ?M for R1, whereas IC50 values for compound R2 ranging from 65-103 ?M. The compounds have shown a significant anti-inflammatory effect in carrageenan and dextran models but do not having the central analgesic activity, this indicating that the antinociceptive activity is related to the peripheral nervous system. The results for 5-Lipoxygenase (5-LOX) activity showed that both R1 and R2 compounds were found to be significant 5-LOX inhibitory activity with IC50 values of 14.35 ?g ml-1 and 29.24 ?g ml-1 respectively. Conclusion: These findings concluded that the new ruthenium compounds might be the promising antiproliferative agents as these compounds showing significant 5-LOX inhibitory activity and potential agents in the management of pain related disorders. PMID:23930118

  11. 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 M), 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

  12. A Rapid Screening Analysis of Antioxidant Compounds in Native Australian Food Plants Using Multiplexed Detection with Active Flow Technology Columns.

    PubMed

    Rupesinghe, Emmanuel Janaka Rochana; Jones, Andrew; Shalliker, Ross Andrew; Pravadali-Cekic, Sercan

    2016-01-01

    Conventional techniques for identifying antioxidant and phenolic compounds in native Australian food plants are laborious and time-consuming. Here, we present a multiplexed detection technique that reduces analysis time without compromising separation performance. This technique is achieved using Active Flow Technology-Parallel Segmented Flow (AFT-PSF) columns. Extracts from cinnamon myrtle (Backhousia myrtifolia) and lemon myrtle (Backhousia citriodora) leaves were analysed via multiplexed detection using an AFT-PSF column with underivatised UV-VIS, mass spectroscopy (MS), and the 2,2-diphenyl-1-picrylhydrazyl (DPPH()) derivatisation for antioxidants as detection methods. A number of antioxidant compounds were detected in the extracts of each leaf extract. PMID:26805792

  13. 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

  14. Asymmetric bioreduction of activated alkenes to industrially relevant optically active compounds

    PubMed Central

    Winkler, Christoph K.; Tasndi, Gbor; Clay, Dorina; Hall, Mlanie; Faber, Kurt

    2012-01-01

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

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

    SciTech Connect

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

    2003-06-01

    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 finish materials for RCs that have relatively low impacts with respect to their emissions of toxic and odorous VOCs. This task was part of a larger project to demonstrate the potential for simultaneous improvements in IEQ and energy efficiency in four new RCs equipped both with a continuously ventilating advanced heating, ventilating, and air conditioning system (HVAC) and a standard HVAC system. These HVACs were operated on alternate weeks. One RC per pair was constructed with standard interior finish materials, and the other included alternate interior materials identified in our prior laboratory study to have low VOC emissions. The RCs were sited in side-by-side pairs at two elementary schools in distinct northern California climate zones. Classroom VOC emission rates (mg hr{sup -1}) and concentrations were predicted based on VOC emission factors ({micro}g m{sup -2} hr{sup -1}) measured for individual materials in the laboratory, the quantities of installed materials and design ventilation rates. Predicted emission rates were compared to values derived from classroom measurements of VOC concentrations and ventilation rates made at pre-occupancy, eight weeks, and 27 weeks. Predicted concentrations were compared to measured integrated VOC indoor minus outdoor concentrations during school hours in the fall cooling season with the advanced HVAC operated. These measured concentrations also were compared between standard and material-modified RCs. Our combined laboratory and field process proved effective by correctly predicting that IEQ impacts of material VOC emissions would be minor when RCs were ventilated at or above code-minimum requirements. Assuming code-minimum ventilation rates are maintained, the benefits attributable to the use of alternate interior finish materials in RC's constructed by the manufacturer associated with this study are small, implying that it is not imperative to use such alternative finishing materials. However, it is essential to avoid materials that can degrade IEQ, and the results of this study demonstrate that laboratory-based material testing combined with modeling and field validation can help to achieve that aim.

  16. Volatile Organic Compounds Identified in Post-Flight Air Analysis of the Multipurpose Logistics Module from International Space Station

    NASA Astrophysics Data System (ADS)

    Peterson, B.; Wheeler, R.

    Bioregenerative systems involve storing and processing waste along with atmospheric management. The MPLM, Multipurpose Logistics Module, is a reusable logistics carrier and primary delivery system used to resupply the International Space Station (ISS) and return Station cargo that requires a pressurized environment. The cylindrical module is approximately 6.4 meters long, 4.6 meters in diameter, and weighs almost 4,082kg. The module provides storage and additional workspace for up to two astronauts when docked to the ISS. It can carry up to 9,072 kg of supplies, science experiments, spare parts and other logistical components for ISS. There is concern for a potentially hazardous condition caused by contamination of the atmosphere in the MPLM upon return from orbit. This would be largely due to unforeseen spills or container leakage. This has led to the need for special care in handling the returned module prior to processing the module for its next flight. Prior to opening the MPLM, atmospheric samples are analyzed for trace volatile organic compounds, VOC's. It is noted that our analyses also reflect the atmosphere in the ISS on that day of closure. With the re turn of STS-108, 12th ISS Flight (UF1), the analysis showed 24 PPM of methane. This corresponds to the high levels on space station during a time period when the air filtration system was shut off. Chemical characterization of atmospheres on the ISS and MPLM provide useful information for concerns with plant growth experiments on ISS. Work with closed plant growth chambers show potential for VOC's to accumulate to toxic levels for plants. The ethylene levels for 4 MPLM analyses over the course on one year were measured at, 0.070, 0.017, 0.012 and 0.007 PPM. Phytochemical such as ethylene are detected with natural plant physiological events such as flowering and as a result of plant damage or from decaying food. A build up of VOC's may contribute to phytotoxic effects for the plant growth experiments or health problems for humans. Other identified components from the MPLM are quite similar to those found from off gassing of construction material and laboratory reagents characterized in ground based studies with closed plant growth chambers.

  17. 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 30g/l sucrose showed highest accumulation of biomass (99.05g/l FW [fresh weight] and 10.95g/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 20days. Nearly 9.5-fold increment of biomass was evident in suspension cultures at 20days 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 30g/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

  18. 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

  19. 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

  20. Data mining the NCI cancer cell line compound GI(50) values: identifying quinone subtypes effective against melanoma and leukemia cell classes.

    PubMed

    Marx, Kenneth A; O'Neil, Philip; Hoffman, Patrick; Ujwal, M L

    2003-01-01

    Using data mining techniques, we have studied a subset (1400) of compounds from the large public National Cancer Institute (NCI) compounds data repository. We first carried out a functional class identity assignment for the 60 NCI cancer testing cell lines via hierarchical clustering of gene expression data. Comprised of nine clinical tissue types, the 60 cell lines were placed into six classes-melanoma, leukemia, renal, lung, and colorectal, and the sixth class was comprised of mixed tissue cell lines not found in any of the other five classes. We then carried out supervised machine learning, using the GI(50) values tested on a panel of 60 NCI cancer cell lines. For separate 3-class and 2-class problem clustering, we successfully carried out clear cell line class separation at high stringency, p < 0.01 (Bonferroni corrected t-statistic), using feature reduction clustering algorithms embedded in RadViz, an integrated high dimensional analytic and visualization tool. We started with the 1400 compound GI(50) values as input and selected only those compounds, or features, significant in carrying out the classification. With this approach, we identified two small sets of compounds that were most effective in carrying out complete class separation of the melanoma, non-melanoma classes and leukemia, non-leukemia classes. To validate these results, we showed that these two compound sets' GI(50) values were highly accurate classifiers using five standard analytical algorithms. One compound set was most effective against the melanoma class cell lines (14 compounds), and the other set was most effective against the leukemia class cell lines (30 compounds). The two compound classes were both significantly enriched in two different types of substituted p-quinones. The melanoma cell line class of 14 compounds was comprised of 11 compounds that were internal substituted p-quinones, and the leukemia cell line class of 30 compounds was comprised of 6 compounds that were external substituted p-quinones. Attempts to subclassify melanoma or leukemia cell lines based upon their clinical cancer subtype met with limited success. For example, using GI(50) values for the 30 compounds we identified as effective against all leukemia cell lines, we could subclassify acute lymphoblastic leukemia (ALL) origin cell lines from non-ALL leukemia origin cell lines without significant overlap from non-leukemia cell lines. Based upon clustering using GI(50) values for the 60 cancer cell lines laid out by the RadViz algorithm, these two compound subsets did not overlap with clusters containing any of the NCI's 92 compounds of known mechanism of action, a few of which are quinones. Given their structural patterns, the two p-quinone subtypes we identified would clearly be expected to possess different redox potentials/substrate specificities for enzymatic reduction in vivo. These two p-quinone subtypes represent valuable information that may be used in the elucidation of pharmacophores for the design of compounds to treat these two cancer tissue types in the clinic. PMID:14502500

  1. 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 200g of Spirulina powder at 40?C under 120bar pressure with CO2 flow rate of 1.2kgh(-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??0.01g/100g and 0.12??0.01g/100g respectively. The SCCO2 extract had antioxidant activity with IC50 value of 109.6??3.0?gmL(-1) for DPPH (2,2-Diphenyl-1-picryl hydrazyl radical), IC50 value of 81.66??2.5?gmL(-1) for reducing power and IC50 value of 112.70??0.8?gmL(-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?gmL(-1) and 307??2.0?gmL(-1) respectively. PMID:26028745

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

    PubMed

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

    2015-01-01

    6-(Benzo[d][1,3]dioxol-5-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile has been utilized for synthesis of the fused heterocyclic compounds namely thiazolopyrimidines, tetrazolopyrimidine, pyrimidoquinazoline, pyrimidothiazolopyrimidine, pyrimidothiazolotriazine and pyrrolothiazolopyrimidine derivatives. The newly synthesized compounds were characterized by IR, (1)H-NMR, (13)C-NMR, and mass spectral data. Antioxidant activities of all synthesized compounds were investigated. PMID:26521851

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

    SciTech Connect

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

    1982-04-01

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

  4. Antibacterial active compounds from Hypericum ascyron L. induce bacterial cell death through apoptosis pathway.

    PubMed

    Li, Xiu-Mei; Luo, Xue-Gang; Si, Chuan-Ling; Wang, Nan; Zhou, Hao; He, Jun-Fang; Zhang, Tong-Cun

    2015-01-01

    Hypericum ascyron L. has been used as a traditional medicine for the treatment of wounds, swelling, headache, nausea and abscesses in China for thousands of years. However, modern pharmacological studies are still necessary to provide a scientific basis to substantiate their traditional use. In this study, the mechanism underlying the antimicrobial effect of the antibacterial activity compounds from H. ascyron L. was investigated. Bioguided fractionation of the extract from H. ascyron L. afforded antibacterial activity fraction 8. The results of cup plate analysis and MTT assay showed that the MIC and MBC of fraction 8 is 5 mg/mL. Furthermore, using Annexin V-FITC/PI, TUNEL labeling and DNA gel electrophoresis, we found that cell death with apoptosis features similar to those in eucaryon could be induced in bacteria strains after exposure to the antibacterial activity compounds from H. ascyron L. at moderate concentration. In addition, we further found fraction 8 could disrupt the cell membrane potential indicate that fraction 8 exerts pro-apoptotic effects through a membrane-mediated apoptosis pathway. Finally, quercetin and kaempferol 3-O-?-(2?-acetyl)-galactopyranoside, were identified from fraction 8 by means of Mass spectrometry and Nuclear magnetic resonance. To our best knowledge, this study is the first to show that Kaempferol 3-O-?-(2?-acetyl)-galactopyranoside coupled with quercetin had significant antibacterial activity via apoptosis pathway, and it is also the first report that Kaempferol 3-O-?-(2?-acetyl)-galactopyranoside was found in clusiacea. Our data might provide a rational base for the use of H. ascyron L. in clinical, and throw light on the development of novel antibacterial drugs. PMID:25916905

  5. 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

  6. Eradication of Propionibacterium acnes biofilms by plant extracts and putative identification of icariin, resveratrol and salidroside as active compounds.

    PubMed

    Coenye, Tom; Brackman, Gilles; Rigole, Petra; De Witte, Evy; Honraet, Kris; Rossel, Bart; Nelis, Hans J

    2012-03-15

    Propionibacterium acnes is a Gram-positive bacterium that plays an important role in the pathogenesis of acne vulgaris. This organism is capable of biofilm formation and the decreased antimicrobial susceptibility of biofilm-associated cells may hamper efficient treatment. In addition, the prolonged use of systemic antibiotic therapy is likely to lead to the development and spread of antimicrobial resistance. In the present study we investigated whether P. acnes biofilms could be eradicated by plant extracts or their active compounds, and whether other mechanisms besides killing of biofilm cells could be involved. Out of 119 plant extracts investigated, we identified five with potent antibiofilm activity against P. acnes (extracts from Epimedium brevicornum, Malus pumila, Polygonum cuspidatum, Rhodiola crenulata and Dolichos lablab). We subsequently identified icariin, resveratrol and salidroside as active compounds in three of these extracts. Extracts from E. brevicornum and P. cuspidatum, as well as their active compounds (icariin and resveratrol, respectively) showed marked antibiofilm activity when used in subinhibitory concentrations, indicating that killing of microbial cells is not their only mode of action. PMID:22305279

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

    PubMed

    Zhang, Bijun; Vogt, Martin; Bajorath, Jrgen

    2014-09-01

    Activity landscapes (ALs) of compound data sets are rationalized as graphical representations that integrate similarity and potency relationships between active compounds. ALs enable the visualization of structure-activity relationship (SAR) information and are thus computational tools of interest for medicinal chemistry. For AL generation, similarity and potency relationships are typically evaluated in a pairwise manner and major AL features are assessed at the level of compound pairs. In this study, we add a conditional probability formalism to AL design that makes it possible to quantify the probability of individual compounds to contribute to characteristic AL features. Making this information graphically accessible in a molecular network-based AL representation is shown to further increase AL information content and helps to quickly focus on SAR-informative compound subsets. This feature probability-based AL variant extends the current spectrum of AL representations for medicinal chemistry applications. PMID:25001923

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

    PubMed

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

    2016-02-01

    The purpose of this study was to synthesize hydrophilic cinnamaldehyde Schiff base compounds and investigate those bioactivity. A total of 24 Schiff base compounds were synthesized using a simple approach with 3 cinnamaldehyde derivates and 8 amino acids as raw materials. The structures of synthesized compounds were confirmed using FTIR, (1)HNMR, HRMS purity and melting point. The antimicrobial activities of new compounds were evaluated with fluconazole and ciprofloxacin as the control against Aspergillus niger, Penicillium citrinum, Escherichia coli and Staphylococcus aureus. Findings show that major compounds exhibited significant bioactivity. Results from the structure-activity relationship suggest that both -p-Cl on benzene ring of cinnamaldehyde and the number of -COOK of amino acid salts significantly contributed to antimicrobial activity. PMID:26774583

  9. Active compounds from a diverse library of triazolothiadiazole and triazolothiadiazine scaffolds: synthesis, crystal structure determination, cytotoxicity, cholinesterase inhibitory activity, and binding mode analysis.

    PubMed

    Khan, Imtiaz; Ibrar, Aliya; Zaib, Sumera; Ahmad, Sarfraz; Furtmann, Norbert; Hameed, Shahid; Simpson, Jim; Bajorath, Jürgen; Iqbal, Jamshed

    2014-11-01

    In an effort to identify novel cholinesterase candidates for the treatment of Alzheimer's disease (AD), a diverse array of potentially bioactive compounds including triazolothiadiazoles (4a-h and 5a-f) and triazolothiadiazines (6a-h) was obtained in good yields through the cyclocondensation reaction of 4-amino-5-(pyridin-3-yl)-4H-1,2,4-triazole-3-thiol (3) with various substituted aryl/heteroaryl/aryloxy acids and phenacyl bromides, respectively. The structures of newly prepared compounds were confirmed by IR, (1)H and (13)C NMR spectroscopy and, in case of 4a, by single crystal X-ray diffraction analysis. The purity of the synthesized compounds was ascertained by elemental analysis. The newly synthesized conjugated heterocycles were screened for cholinesterase inhibitory activity against electric eel acetylcholinesterase (EeAChE) and horse serum butyrylcholinesterase (hBChE). Among the evaluated hybrids, several compounds were identified as potent inhibitors. Compounds 5b and 5d were most active with an IC50 value of 3.09 ± 0.154 and 11.3 ± 0.267 μM, respectively, against acetylcholinesterase, whereas 5b, 6a and 6g were most potent against butyrylcholinesterase, with an IC50 of 0.585 ± 0.154, 0.781 ± 0.213, and 1.09 ± 0.156 μM, respectively, compared to neostigmine and donepezil as standard drugs. The synthesized heteroaromatic compounds were also tested for their cytotoxic potential against lung carcinoma (H157) and vero cell lines. Among them, compound 6h exhibited highest antiproliferative activity against H157 cell lines, with IC50 value of 0.96 ± 0.43 μM at 1mM concentration as compared to vincristine (IC50=1.03 ± 0.04 μM), standard drug used in this study. PMID:25257911

  10. 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-β-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 μg/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 μg/ml). The 3 fractions and isolated compounds had LC50 values between 13.20 to > 100 μg/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

  11. Using Indices of Fidelity to Intervention Core Components to Identify Program Active Ingredients

    ERIC Educational Resources Information Center

    Abry, Tashia; Hulleman, Chris S.; Rimm-Kaufman, Sara E.

    2015-01-01

    Identifying the active ingredients of an intervention--intervention-specific components serving as key levers of change--is crucial for unpacking the intervention black box. Measures of intervention fidelity can be used to identify specific active ingredients, yet such applications are rare. We illustrate how fidelity measures can be used to

  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. Discovery and preliminary structure-activity relationship analysis of 1,14-sperminediphenylacetamides as potent and selective antimalarial lead compounds.

    PubMed

    Liew, Lydia P P; Kaiser, Marcel; Copp, Brent R

    2013-01-15

    Screening of synthesized and isolated marine natural products for in vitro activity against four parasitic protozoa has identified the ascidian metabolite 1,14-sperminedihomovanillamide (orthidine F, 1) as being a non-toxic, moderate growth inhibitor of Plasmodium falciparum (IC(50) 0.89 μM). Preliminary structure-activity relationship investigation identified essentiality of the spermine polyamine core and the requirement for 1,14-disubstitution for potent activity. One analogue, 1,14-spermine-di-(2-hydroxyphenylacetamide) (3), exhibited two orders of magnitude increased anti-P. f activity (IC(50) 8.6 nM) with no detectable in vitro toxicity. The ease of synthesis of phenylacetamido-polyamines, coupled with potent nM levels of activity towards dual drug resistant strains of P. falciparum makes this compound class of interest in the development of new antimalarial therapeutics. PMID:23265884

  14. Data on pigments and long-chain fatty compounds identified in Dietzia sp. A14101 grown on simple and complex hydrocarbons

    PubMed Central

    Hvidsten, Ina; Mjs, Svein Are; Bdtker, Gunhild; Barth, Tanja

    2015-01-01

    This data article provides: 1. An overview of tentatively identified long chain compounds in Dietzia sp. A14101 grown on simple and complex hydrocarbons; 2. Preliminary Identification of pigments in bacterial material obtained from incubation with a hydrocarbon (dodecane, n-C12) as the only carbon and energy source; 3. Some pictures to illustrate the cell surface charge test. PMID:26442286

  15. 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

  16. Update on project determining biologically active compounds in milk

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The added health value of raw and pasteurized milk from organic and grass-fed herds is strongly debated because of limited, and often conflicting, scientific data. The Dairy & Functional Foods Research Unit, USDA-ARS-NAA, Wyndmoor, PA has an ongoing project to identify and compare the levels of bio...

  17. Green alga Ulva pertusa--a new source of bioactive compounds with antialgal activity.

    PubMed

    Ying-ying, Sun; Hui, Wang; Gan-lin, Guo; Yin-fang, Pu; Bin-lun, Yan; Chang-hai, Wang

    2015-07-01

    We tested the effects of solvent fractions (FA, FB, FC, and FD), which partitioned by liquid-liquid extraction from the methanol extract of Ulva pertusa, on the growth of red tide microalgae (Karenia mikimitoi, Skeletonema costatum, Alexandrium tamarense, Heterosigma akashiwo, Prorocentrum donghaiense), and FA, FB, and FC exhibited significantly antialgal activity. The chemical constituent analysis showed the existence of bioactive compounds such as phenols and alkaloids. Further, four solvent fractions were applied to silica gel column and repeated preparative TLC to produce 13 samples and their purity qualified as thin-layer chromatographic grade. Among these purified samples, FA111, FB411, FC411, FD111, and FD211 exhibited stronger antialgal activity. Furthermore, their functional groups were analyzed by colorimetric methods and UV spectra data. FD111 and FD211 were temptatively identified as alkaloids; the others were initially identified as phenolic acids. This is a preliminary study and the structure identification of these purified samples requires further investigation. While concentration of these purified samples in this algae was very small, they showed excellent effects against red tide microalgae. PMID:25724801

  18. 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

  19. Phytotoxic activity in Flourensia campestris and isolation of (--)-hamanasic acid A as its active principle compound.

    PubMed

    Silva, Mariana P; Piazza, Leonardo A; López, Daniela; López Rivilli, Marisa J; Turco, Mauricio D; Cantero, Juan J; Tourn, Mónica G; Scopel, Ana L

    2012-05-01

    An aqueous extract from Flourensia campestris (Asteraceae) dry aerial parts showed strong inhibition on the germination and growth of Lactuca sativa. Based on bio-guided chromatographic fractionation of aq. extracts from dry and fresh leaves and spectroscopic means, (-)-hamanasic acid A (7-carboxy-8-hydroxy-1(2), 12(13)-dien-bisabolene (1)) was isolated as the most inhibitory active principle on germination (ECg(50)=2.9 mM) and on root (ECr(50)=1.5 mM)/shoot (ECs(50)=2.0 mM) growth. As measured by GC, and correlated with a simple designed 2D-TLC, compound 1 was distributed throughout the plant, with a remarkably high concentration (1.6%) in the leaves and the inflorescences. At least a quarter of the amount of 1 was found in aqueous extracts suggesting that leaching would be a key route for its release into the environment. By contrast, leaf essential oils (HD) between 0.5 and 1.5 μl ml(-1) did not show herbicidal effects and 1 was not found in them (TLC) nor among volatiles (HS-SPME). Volatile compositions were assessed by GC-FID and GC-MS and led to the identification of 23 compounds (4 monoterpenes and 19 sesquiterpenes) with a wide seasonal (spring-summer%) variation, represented principally by bicyclo-germacrene (37-6%), spathulenol (4-32%), globulol (20-0%), beta-caryophyllene (15-6%), caryophyllene oxide (1-13%) and bicycloelemene (10-1%), respectively. The high amount of 1 in F. campestris together with its feasibility of being extracted with water suggest that (-)-hamanasic acid A is an allelochemical in this species. Species-specific studies must be carried out to evaluate the potential of 1 as a natural herbicidal compound. PMID:22245633

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

    PubMed Central

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

    2013-01-01

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

  1. Reduction of toxicity of antimicrobial compounds by degradation processes using activated sludge, gamma radiation, and UV.

    PubMed

    Kim, Hyun Young; Jeon, Junho; Yu, Seungho; Lee, Myunjoo; Kim, Tae-Hun; Kim, Sang D

    2013-11-01

    The occurrence and persistence of pharmacologically active compounds in the environment has been an increasingly important issue. The objectives of this study were to investigate the decomposition of aqueous antimicrobial compounds using activated sludge, γ-irradiation, and UV treatment, and to evaluate the toxicity towards green algae, Pseudokirchneriella subcapitata, before and after treatment. Tetracycline (TCN), lincomycin (LMC) and sulfamethazine (SMZ) were used as target compounds. Gamma (γ)-irradiation showed the highest removal efficiency for all target compounds, while UV and activated sludge treatment showed compound-dependent removal efficiencies. TCN and SMZ were well degraded by all three treatment methods. However, LMC showed extremely low removal efficiency for UV and activated sludge treatments. Overall, the algal toxicity after degradation processes was significantly decreased, and was closely correlated to removal efficiency. However, in the case of γ-irradiated TCN, UV and activated sludge treated LMC as well as sludge treated SMZ, the observed toxicity was higher than expected, which indicates the substantial generation of byproducts or transformed compounds of a greater toxicity in the treated sample. Consequently, γ-radiation treatment could be an effective method for removal of recalcitrant compounds such as antibiotics. PMID:24083903

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

    PubMed Central

    Oh, Euna; Jeon, Byeonghwa

    2015-01-01

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

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

    PubMed

    Oh, Euna; Jeon, Byeonghwa

    2015-01-01

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

  4. Food Compounds Activating Thermosensitive TRP Channels in Asian Herbal and Medicinal Foods.

    PubMed

    Watanabe, Tatsuo; Terada, Yuko

    2015-01-01

    There are several thermosensitive transient receptor potential (TRP) ion channels including capsaicin receptor, TRPV1. Food components activating TRPV1 inhibit body fat deposition through sympathetic nerve stimulation. TRPA1 is another pungency sensor for pungent compounds and is mainly coexpressed with TRPV1 in sensory nerve endings. Therefore, TRPA1 activation is expected to have an anti-obesity effect similar to TRPV1 activation. We have searched for agonists for TRPV1 and TRPA1 in vitro from Asian spices by the use of TRPV1- and TRPA1-expressing cells. Further, we performed food component addition tests to high-fat and high-sucrose diets in mice. We found capsiate, capsiconiate, capsainol from hot and sweet peppers, several piperine analogs from black pepper, gingeriols and shogaols from ginger, and sanshools and hydroxysanshools from sansho (Japanese pepper) to be TRPV1 agonists. We also identified several sulfides from garlic and durian, hydroxy fatty acids from royal jelly, miogadial and miogatrial from mioga (Zingiber mioga), piperine analogs from black pepper, and acetoxychavicol acetate (ACA) from galangal (Alpinia galanga) as TRPA1 agonists. Piperine addition to diets diminished visceral fats and increased the uncoupling protein 1 (UCP1) in interscapular brown adipose tissue (IBAT), and black pepper extract showed stronger effects than piperine. Cinnamaldehyde and ACA as TRPA1 agonists inhibited fat deposition and increased UCP1. We found that several agonists of TRPV1 and TRPA1 and some agonists of TRPV1 and TRPA1 inhibit visceral fat deposition in mice. The effects of such compounds on humans remain to be clarified, but we expect that they will be helpful in the prevention of obesity. PMID:26598901

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

    PubMed

    Majcher, Małgorzata A; Klensporf-Pawlik, Dorota; Dziadas, Mariusz; Jeleń, 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

  6. Synthesis of androstanopyridine and pyrimidine compounds as novel activators of the tumor suppressor protein p53.

    PubMed

    Hussein, Mohamed M M; Amr, Abd El-Galil E; Abdalla, Mohamed M; Al-Omar, Mohamed A; Safwat, Hany M; Elgamal, Mohamed H

    2015-07-01

    A series of androstane derivatives 2-16 were synthesized from 3?-hydroxyandrostan-17-one derivatives (1a-e). Compounds (1a,b) were treated with ethyl cyanoacetate, cyanoacetamide, or malononitrile and gave the corresponding derivatives 2-7, respectively. Additionally, compounds (1a-e) were condensed with cyanothioacetamide, urea, or guanidine hydrochloride afforded the corresponding derivatives 8-12, which then by Moffat oxidation gave the oxidized derivatives 9, 11 and 13, respectively. Finally, compound (1) condensed with acetyl acetone or ethyl acetoacetate gave cyclohexene derivatives (14a-c) and (15a,b), respectively. Compound 15 was oxidized with a Moffat oxidizing agent and afforded the corresponding oxidized compound 16. The newly synthesized compounds activated the tumor suppressor p53 in cancer cells through inhibition of the p53-specific ubiquitin E3 ligase HDM2. PMID:26426889

  7. Bioactivity-guided fractionation and analysis of compounds with anti-influenza virus activity from Gardenia jasminoides Ellis.

    PubMed

    Yang, Quanjun; Wu, Bin; Shi, Yujing; Du, Xiaowei; Fan, Mingsong; Sun, Zhaolin; Cui, Xiaolan; Huang, Chenggang

    2012-01-01

    Bioassay-guided fractionation of extracts from Fructus Gardeniae led to analysis of its bioactive natural products. After infection by influenza virus strain A/FM/1/47-MA in vivo, antiviral activity of the extracts were investigated. The target fraction was orally administered to rats and blood was collected. High-performance liquid chromatography coupled with photo diode array detector and electrospray ion trap multiple-stage tandem mass spectrometry was applied to screen the compounds absorbed into the blood. A structural characterization based on the retention time, ultraviolet spectra, parent ions and fragmentation ions was performed. Thirteen compounds were confirmed or tentatively identified. This provides an accurate profile of the composition of bioactive compounds responsible for the anti-influenza properties. PMID:22297738

  8. 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

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

    PubMed

    Mokgotho, Matlou Phineas; Gololo, Stanley Sechene; Masoko, Peter; Mdee, Ladislaus Kakore; Mbazima, Vusi; Shai, Leshwene Jeremiah; Bagla, Victor Patrick; Eloff, Jacobus Nicolaas; Mampuru, Leseilane

    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

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

    PubMed

    Mulero, J; Martnez, G; Oliva, J; Cermeo, S; Cayuela, J M; Zafrilla, P; Martnez-Cach, 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

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

    PubMed

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

    2016-02-15

    The de novo purine biosynthesis pathway is an attractive target for antibacterial drug design, and PurE from this pathway has been identified to be crucial for Bacillus anthracis survival in serum. In this study we adopted a fragment-based hit discovery approach, using three screening methods-saturation transfer difference nucleus magnetic resonance (STD-NMR), water-ligand observed via gradient spectroscopy (WaterLOGSY) NMR, and surface plasmon resonance (SPR), against B. anthracis PurE (BaPurE) to identify active site binding fragments by initially testing 352 compounds in a Zenobia fragment library. Competition STD NMR with the BaPurE product effectively eliminated non-active site binding hits from the primary hits, selecting active site binders only. Binding affinities (dissociation constant, KD) of these compounds varied between 234 and 301?M. Based on test results from the Zenobia compounds, we subsequently developed and applied a streamlined fragment screening strategy to screen a much larger library consisting of 3000 computationally pre-selected fragments. Thirteen final fragment hits were confirmed to exhibit binding affinities varying from 14?M to 700?M, which were categorized into five different basic scaffolds. All thirteen fragment hits have ligand efficiencies higher than 0.30. We demonstrated that at least two fragments from two different scaffolds exhibit inhibitory activity against the BaPurE enzyme. PMID:26740153

  12. Synthesis, spectral studies and antibacterial activity of novel macrocyclic Co(II) compounds

    NASA Astrophysics Data System (ADS)

    Reddy, P. Muralidhar; Prasad, Adapa V. S. S.; Shanker, Kanne; Ravinder, Vadde

    2007-11-01

    Ten novel macrocyclic Co(II) compounds have been synthesized by treating four N 4 and six N 2O 2 donor macrocycles with cobalt chloride in methanol. These compounds were characterized by elemental, IR, 1H, 13C NMR, mass, electronic spectral analysis, molar conductance and magnetic susceptibility measurements. Thermal behavior of these compounds has been studied by the thermogravimetric analysis. An octahedral geometry has been proposed for all of these complexes. All the macrocycles and macrocyclic Co(II) compounds along with existing antibacterial drugs were screened for antibacterial activity against Gram +ve and Gram -ve bacteria. All these compounds were found to be more active when compared to streptomycin and ampicillin.

  13. Phenolic Compounds from the Roots of Rhodiola crenulata and Their Antioxidant and Inducing IFN-? Production Activities.

    PubMed

    Zhou, Jiang-Tao; Li, Chen-Yang; Wang, Chun-Hua; Wang, Yue-Fei; Wang, Xiao-Dong; Wang, Hong-Tao; Zhu, Yan; Jiang, Miao-Miao; Gao, Xiu-Mei

    2015-01-01

    In the present study, two new phenolic compounds 1 and 11, a pair of lignan isomers 12 and 13 with their absolute configurations established for the first time, were isolated from the ethanol extract of the roots of Rhodiola crenulata, together with 13 known phenolic compounds, and their structures were elucidated via NMR, HRESIMS, UV, IR and CD analyses. All the isolated compounds were evaluated for their in vitro antioxidant activities using the 2,2-diphenyl-1-picryhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays. Ten of them exhibited significant antioxidant activities compared to ascorbic acid. Furthermore, the inducibilities of the isolated compounds to IFN-? production were also assessed. Compounds 1, 8, 9, 12, 13, 14 and 15 could moderately stimulate IFN-? expression. PMID:26225952

  14. Synthetic mRNA Splicing Modulator Compounds with In Vivo Anti-tumor Activity

    PubMed Central

    Lagisetti, Chandraiah; Pourpak, Alan; Goronga, Tinopiwa; Jiang, Qin; Cui, Xiaoli; Hyle, Judith; Lahti, Jill; Morris, Stephan W.; Webb, Thomas R.

    2009-01-01

    We report our progress on the development of new synthetic anti-cancer lead compounds that modulate the splicing of mRNA. We also report the synthesis evaluation of new biologically active ester and carbamate analogs. Further, we describe initial animal studies demonstrating the antitumor efficacy of compound 5 in vivo. Additionally, we report the enantioselective and diastereospecific synthesis of a new 1,3-dioxane series of active analogs. We confirm that compound 5 inhibits the splicing of mRNA in both cell-free nuclear extracts and in a cell-based dual-reporter mRNA splicing assay. In summary, we have developed totally synthetic novel spliceosome modulators as therapeutic lead compounds for a number of highly aggressive cancers. Future efforts will be directed toward the more complete optimization of these compounds as potential human therapeutics. PMID:19877647

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

    PubMed

    Ares, Ana M; Nozal, Mara J; Bernal, Jos

    2013-10-25

    Broccoli (Brassica oleracea L. var. Italica) contains substantial amount of health-promoting compounds such as vitamins, glucosinolates, phenolic compounds, and dietary essential minerals; thus, it benefits health beyond providing just basic nutrition, and consumption of broccoli has been increasing over the years. This review gives an overview on the extraction and separation techniques, as well as the biological activity of some of the above mentioned compounds which have been published in the period January 2008 to January 2013. The work has been distributed according to the different families of health promoting compounds discussing the extraction procedures and the analytical techniques employed for their characterization. Finally, information about the different biological activities of these compounds has been also provided. PMID:23899380

  16. 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-Frdric 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 structureactivity 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

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

    SciTech Connect

    Cohen, G.M. )

    1990-04-01

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

  18. Structure-dependent binding and activation of perfluorinated compounds on human peroxisome proliferator-activated receptor ?

    SciTech Connect

    Zhang, Lianying; Ren, Xiao-Min; Wan, Bin; Guo, Liang-Hong

    2014-09-15

    Perfluorinated compounds (PFCs) have been shown to disrupt lipid metabolism and even induce cancer in rodents through activation of peroxisome proliferator-activated receptors (PPARs). Lines of evidence showed that PPAR? was activated by PFCs. However, the information on the binding interactions between PPAR? and PFCs and subsequent alteration of PPAR? activity is still limited and sometimes inconsistent. In the present study, in vitro binding of 16 PFCs to human PPAR? ligand binding domain (hPPAR?-LBD) and their activity on the receptor in cells were investigated. The results showed that the binding affinity was strongly dependent on their carbon number and functional group. For the eleven perfluorinated carboxylic acids (PFCAs), the binding affinity increased with their carbon number from 4 to 11, and then decreased slightly. The binding affinity of the three perfluorinated sulfonic acids (PFSAs) was stronger than their PFCA counterparts. No binding was detected for the two fluorotelomer alcohols (FTOHs). Circular dichroim spectroscopy showed that PFC binding induced distinctive structural change of the receptor. In dual luciferase reporter assays using transiently transfected Hep G2 cells, PFCs acted as hPPAR? agonists, and their potency correlated with their binding affinity with hPPAR?-LBD. Molecular docking showed that PFCs with different chain length bind with the receptor in different geometry, which may contribute to their differences in binding affinity and transcriptional activity. - Highlights: Binding affinity between PFCs and PPAR? was evaluated for the first time. The binding strength was dependent on fluorinated carbon chain and functional group. PFC binding induced distinctive structural change of the receptor. PFCs could act as hPPAR? agonists in Hep G2 cells.

  19. Anti depressant activity of Mamsyadi Kwatha: An Ayurvedic compound formulation.

    PubMed

    Shreevathsa, M; Ravishankar, B; Dwivedi, Rambabu

    2013-01-01

    Depression is a psychiatric condition in which there is loss of interest in all pleasurable outlets, viz. food, sex, work, friends, hobbies and entertainment. The prevalence rate of the disease is 6-8% in women and 3-5% in men. Ayurveda, the science of life, provides systematic management principles for depression. Mamsyadi Kwatha is one such formulation stated by Yadavji Trikamji Acharya in Siddha Yoga Sangraha and Bheshaja Samhita, which is said to be effective in psychiatric conditions. The ingredients are Jatamansi (Nardostachys jatamansi), Ashwagandh (Withania somnifera) and Parasika Yavani (Hyocymus niger) in an 8:4:1 ratio, respectively. The test drug was subjected for antidepressant activity in experimental models. The models selected for anti depressant activity were behavioral despair test, anti-reserpine test and Chronic Fatigue Syndrome (CFS) test in albino mice. The test formulation showed significant inhibition of behavioural despair (P < 0.05), weak to moderate anti-reserpine activity - ptosis (P < 0.001), catatonia (P < 0.01), sedation (P < 0.01) and moderate effect in CFS test (P < 0.050). These effects clearly show that Mamsyadi Kwatha has an anti-depressant activity. PMID:24049416

  20. Anti depressant activity of Mamsyadi Kwatha: An Ayurvedic compound formulation

    PubMed Central

    Shreevathsa, M.; Ravishankar, B.; Dwivedi, Rambabu

    2013-01-01

    Depression is a psychiatric condition in which there is loss of interest in all pleasurable outlets, viz. food, sex, work, friends, hobbies and entertainment. The prevalence rate of the disease is 6-8% in women and 3-5% in men. Ayurveda, the science of life, provides systematic management principles for depression. Mamsyadi Kwatha is one such formulation stated by Yadavji Trikamji Acharya in Siddha Yoga Sangraha and Bheshaja Samhita, which is said to be effective in psychiatric conditions. The ingredients are Jatamansi (Nardostachys jatamansi), Ashwagandh (Withania somnifera) and Parasika Yavani (Hyocymus niger) in an 8:4:1 ratio, respectively. The test drug was subjected for antidepressant activity in experimental models. The models selected for anti depressant activity were behavioral despair test, anti-reserpine test and Chronic Fatigue Syndrome (CFS) test in albino mice. The test formulation showed significant inhibition of behavioural despair (P < 0.05), weak to moderate anti-reserpine activity - ptosis (P < 0.001), catatonia (P < 0.01), sedation (P < 0.01) and moderate effect in CFS test (P < 0.050). These effects clearly show that Mamsyadi Kwatha has an anti-depressant activity. PMID:24049416

  1. Establishment and Validation of Whole-Cell Based Fluorescence Assays to Identify Anti-Mycobacterial Compounds Using the Acanthamoeba castellanii - Mycobacterium marinum Host-Pathogen System

    PubMed Central

    Kicka, Sébastien; Trofimov, Valentin; Harrison, Christopher; Ouertatani-Sakouhi, Hajer; McKinney, John; Scapozza, Leonardo; Hilbi, Hubert; Cosson, Pierre; Soldati, Thierry

    2014-01-01

    Tuberculosis is considered to be one of the world’s deadliest disease with 2 million deaths each year. The need for new antitubercular drugs is further exacerbated by the emergence of drug-resistance strains. Despite multiple recent efforts, the majority of the hits discovered by traditional target-based screening showed low efficiency in vivo. Therefore, there is heightened demand for whole-cell based approaches directly using host-pathogen systems. The phenotypic host-pathogen assay described here is based on the monitoring of GFP-expressing Mycobacterium marinum during infection of the amoeba Acanthamoeba castellanii. The assay showed straight-forward medium-throughput scalability, robustness and ease of manipulation, demonstrating its qualities as an efficient compound screening system. Validation with a series of known antitubercular compounds highlighted the advantages of the assay in comparison to previously published macrophage-Mycobacterium tuberculosis-based screening systems. Combination with secondary growth assays based on either GFP-expressing D. discoideum or M. marinum allowed us to further fine-tune compound characterization by distinguishing and quantifying growth inhibition, cytotoxic properties and antibiotic activities of the compounds. The simple and relatively low cost system described here is most suitable to detect anti-infective compounds, whether they present antibiotic activities or not, in which case they might exert anti-virulence or host defense boosting activities, both of which are largely overlooked by classical screening approaches. PMID:24498207

  2. A High-Content Biosensor Based Screen Identifies Cell Permeable Activators and Inhibitors of EGFR Function: Implications in Drug Discovery

    PubMed Central

    Antczak, Christophe; Mahida, Jeni P.; Bhinder, Bhavneet; Calder, Paul A.; Djaballah, Hakim

    2013-01-01

    Early success of kinase inhibitors has validated their use as drugs. However, discovery efforts have also suffered from high attrition rates; due to lack of cellular activity. We reasoned that screening for such candidates in live cells would identify novel cell permeable modulators for development. For this purpose, we have used our recently optimized EGFR biosensor (EGFRB) assay to screen for modulators of EGFR activity. Here, we report on its validation under HTS conditions displaying a S/N ratio of 21 and a Z’ value of 0.56; attributes of a robust cell based assay. We performed a pilot screen against a library of 6,912 compounds demonstrating good reproducibility and identifying 82 inhibitors and 66 activators with initial hit rates of 1.2% and 0.95 %, respectively. Follow up dose response studies revealed that 12 out of the 13 known EGFR inhibitors in the library confirmed as hits. ZM-306416, a VEGFR antagonist, was identified as a potent inhibitor of EGFR function. Flurandrenolide, beclomethasone and ebastine were confirmed as activators of EGFR function. Taken together, our results validate this novel approach and demonstrate its utility in the discovery of novel kinase modulators with potential use in the clinic. PMID:22573732

  3. High Throughput Screening for Compounds That Alter Muscle Cell Glycosylation Identifies New Role for N-Glycans in Regulating Sarcolemmal Protein Abundance and Laminin Binding*

    PubMed Central

    Cabrera, Paula V.; Pang, Mabel; Marshall, Jamie L.; Kung, Raymond; Nelson, Stanley F.; Stalnaker, Stephanie H.; Wells, Lance; Crosbie-Watson, Rachelle H.; Baum, Linda G.

    2012-01-01

    Duchenne muscular dystrophy is an X-linked disorder characterized by loss of dystrophin, a cytoskeletal protein that connects the actin cytoskeleton in skeletal muscle cells to extracellular matrix. Dystrophin binds to the cytoplasmic domain of the transmembrane glycoprotein ?-dystroglycan (?-DG), which associates with cell surface ?-dystroglycan (?-DG) that binds laminin in the extracellular matrix. ?-DG can also associate with utrophin, and this differential association correlates with specific glycosylation changes on ?-DG. Genetic modification of ?-DG glycosylation can promote utrophin binding and rescue dystrophic phenotypes in mouse dystrophy models. We used high throughput screening with the plant lectin Wisteria floribunda agglutinin (WFA) to identify compounds that altered muscle cell surface glycosylation, with the goal of finding compounds that increase abundance of ?-DG and associated sarcolemmal glycoproteins, increase utrophin usage, and increase laminin binding. We identified one compound, lobeline, from the Prestwick library of Food and Drug Administration-approved compounds that fulfilled these criteria, increasing WFA binding to C2C12 cells and to primary muscle cells from wild type and mdx mice. WFA binding and enhancement by lobeline required complex N-glycans but not O-mannose glycans that bind laminin. However, inhibiting complex N-glycan processing reduced laminin binding to muscle cell glycoproteins, although O-mannosylation was intact. Glycan analysis demonstrated a general increase in N-glycans on lobeline-treated cells rather than specific alterations in cell surface glycosylation, consistent with increased abundance of multiple sarcolemmal glycoproteins. This demonstrates the feasibility of high throughput screening with plant lectins to identify compounds that alter muscle cell glycosylation and identifies a novel role for N-glycans in regulating muscle cell function. PMID:22570487

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  5. Anti-inflammatory activity of Shirishavaleha: An Ayurvedic compound formulation.

    PubMed

    Yadav, Shyamlal Singh; Galib; Ravishankar, B; Prajapati, P K; Ashok, B K; Varun, B

    2010-10-01

    The purpose of the present study was to evaluate the anti-inflammatory activity of Shirishavaleha prepared from two different parts of Shirisha (Albizia lebbeck Benth.), viz. the bark (Twak) and the heartwood (Sara). The activity was screened in the carrageenan-induced rat paw edema model in albino rats. The raw materials were collected and authenticated in the university and the trial formulations were prepared by following standard classical guidelines. Randomly selected animals were divided into four groups of six animals each. The test drugs were administered orally at a dose of 1.8 g/kg for 5 days. Phenylbutazone was used as the standard anti-inflammatory drug for comparison. Between the two different test samples studied, the formulation made from heartwood showed a weak anti-inflammatory activity in this model while that made from the bark produced a considerable suppression of edema after 6 h. It appears that the bark sample would be preferable for clinical use. PMID:21455445

  6. Anti-inflammatory activity of Shirishavaleha: An Ayurvedic compound formulation

    PubMed Central

    Yadav, Shyamlal Singh; Galib; Ravishankar, B.; Prajapati, P.K.; Ashok, B.K.; Varun, B.

    2010-01-01

    The purpose of the present study was to evaluate the anti-inflammatory activity of Shirishavaleha prepared from two different parts of Shirisha (Albizia lebbeck Benth.), viz. the bark (Twak) and the heartwood (Sara). The activity was screened in the carrageenan-induced rat paw edema model in albino rats. The raw materials were collected and authenticated in the university and the trial formulations were prepared by following standard classical guidelines. Randomly selected animals were divided into four groups of six animals each. The test drugs were administered orally at a dose of 1.8 g/kg for 5 days. Phenylbutazone was used as the standard anti-inflammatory drug for comparison. Between the two different test samples studied, the formulation made from heartwood showed a weak anti-inflammatory activity in this model while that made from the bark produced a considerable suppression of edema after 6 h. It appears that the bark sample would be preferable for clinical use. PMID:21455445

  7. Global emissions and models of photochemically active compounds

    SciTech Connect

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

    1993-05-20

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

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

    PubMed

    Jimnez-Arellanes, Adelina; Len-Daz, Rosalba; Meckes, Mariana; Tapia, Amparo; Molina-Salinas, Gloria Mara; Luna-Herrera, Julieta; Ypez-Mulia, Lilin

    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 (IC(50) < 0.624??g?mL(-1)); in contrast, fargesin and (8R,8'R,9R)-cubebin were moderately active (IC(50) < 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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-01-01

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

  12. Total phenolic and phytosterol compounds and the radical scavenging activity of germinated Australian sweet lupin flour.

    PubMed

    Rumiyati; Jayasena, Vijay; James, Anthony P

    2013-12-01

    In addition to their favourable nutritional profile, legumes also contain a range of bioactive compounds such as phenolic compounds and phytosterols which may protect against chronic diseases including cancer and cardiovascular disease. Germination of some legume seeds has been previously reported to increase the concentration of the bioactive compounds. In this study, the effect of germination of Australian Sweet Lupin (ASL) seeds for 9 days on the concentration of some bioactive compounds and the radical scavenging activity in the resulting flour was determined. The concentration of total phenolic compounds in methanolic extracts of germinated ASL flour was determined using Folin Ciocalteu reagent and phytosterols in oil extracts were analyzed by gas-liquid chromatography. The methanolic and oil extracts were also used to determine radical scavenging activity toward 2,2-diphenyl-1-picrylhydrazyl. In the methanolic extracts of germinated ASL flour, phenolic contents and the antioxidant activity were significantly increased following germination (700 and 1400 %, respectively). Analysis of the oil extracts of germinated ASL flour revealed that the concentration of phytosterols and the antioxidant activity were also increased significantly compared to ungerminated ASL flour (300 and 800 %, respectively). The relative proportion of phytosterols in germinated ASL flour was: β-sitosterol (60 %), stigmasterol (30 %) and campesterol (10 %). Germination increases the concentration of bioactive compounds and the radical scavenging activity in the germinated ASL flour. PMID:23943234

  13. Differential in vitro activities of ionophore compounds against Plasmodium falciparum and mammalian cells.

    PubMed Central

    Gumila, C; Ancelin, M L; Jeminet, G; Delort, A M; Miquel, G; Vial, H J

    1996-01-01

    Twenty-two ionophore compounds were screened for their antimalarial activities. They consisted of true ionophores (mobile carriers) and channel-forming quasi-ionophores with different ionic specificities. Eleven of the compounds were found to be extremely efficient inhibitors of Plasmodium falciparum growth in vitro, with 50% inhibitory concentrations of less than 10 ng/ml. Gramicidin D was the most active compound tested, with 50% inhibitory concentration of 0.035 ng/ml. Compounds with identical ionic specificities generally had similar levels of antimalarial activity, and ionophores specific to monovalent cations were the most active. Compounds were further tested to determine their in vitro toxicities against mammalian lymphoblast and macrophage cell lines. Nine of the 22 compounds, i.e., alborixin, lonomycin, nigericin, narasin, monensin and its methylated derivative, lasalocid and its bromo derivative, and gramicidin D, most specific to monovalent cations, were at least 35-fold more active in vitro against P. falciparum than against the two other mammalian cell lines. The enhanced ability to penetrate the erythrocyte membrane after infection could be a factor that determines ionophore selectivity for infected erythrocytes. PMID:8851578

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

    PubMed

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

    2016-04-01

    Cell membrane chromatography is a useful tool for screening active compounds from natural products. As the reason of separation mechanism, traditional cell membrane chromatography could not be used for screening the active compounds absorbed through the cell membrane and influencing the cell signal transduction pathway. In this work, we establish a new method named cell extraction combined with off-line HPLC for screening the compounds penetrating the cell membrane. This is the first time 3 T3-L1 adipocyte culture has been combined with HPLC technology. Compared with other cell membrane chromatography methods, there is good resolution and no further analysis by other chromatographic steps is required. On co-incubating crude extracts of Coptis chinensis with cells and analyzing the compounds extracted by the cells, active compounds such as berberine were detected. Glucose consumption tests showed that berberine could increase glucose consumption by insulin-resistant 3 T3-L1 adipocytes. The levels of intracellular berberine correlated with its activity. The results indicate that the developed method could be an alternative method for screening active compounds from natural products. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26248814

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

    PubMed

    Nantitanon, W; Okonogi, S

    2012-02-01

    In the present study, quercetin (QT), morin (MR), and quercetin-3-O-glucopyranoside (QG) isolated from guava leaves were comparatively tested for antioxidant activity using DPPH, ABTS, and FRAP methods. QT was the most active among them. The free radical scavenging activity of QT was approximately four times higher than MR and two times higher than QG. The reducing power of QT was eight times higher than MR and two times higher than QG. A mixture of QT with MR or QG showed interesting combination effect. The synergistic antioxidant activity was obtained when QT was mixed with MR whereas the antagonistic effect was found when mixed with QG. The stability study of QT in liquid preparations indicated that the decomposition reaction rate of QT could be explained by a kinetic model assuming a first-order chemical reaction. The aqueous solution of QT was rapidly decomposed with t1/2 of approximately five days whereas QT entrapped in chitosan nanoparticles was five times longer. It was concluded that QT was the most active antioxidant from guava leaves. Entrapment of QT in chitosan nanoparticles could significantly enhance its stability. PMID:22460427

  16. Steroid-Derived Naphthoquinoline Asphaltene Model Compounds: Hydriodic Acid Is the Active Catalyst in I2-Promoted Multicomponent Cyclocondensation Reactions.

    PubMed

    Schulze, Matthias; Scott, David E; Scherer, Alexander; Hampel, Frank; Hamilton, Robin J; Gray, Murray R; Tykwinski, Rik R; Stryker, Jeffrey M

    2015-12-01

    A multicomponent cyclocondensation reaction between 2-aminoanthracene, aromatic aldehydes, and 5-α-cholestan-3-one has been used to synthesize model asphaltene compounds. The active catalyst for this reaction has been identified as hydriodic acid, which is formed in situ from the reaction of iodine with water, while iodine is not a catalyst under anhydrous conditions. The products, which contain a tetrahydro[4]helicene moiety, are optically active, and the stereochemical characteristics have been examined by VT-NMR and VT-CD spectroscopies, as well as X-ray crystallography. PMID:26584791

  17. Structure-function activity of dehydrozingerone and its derivatives as antioxidant and antimicrobial compounds.

    PubMed

    Kubra, Ismail Rahath; Bettadaiah, Bheemanakere Kempaiah; Murthy, Pushpa Srinivas; Rao, Lingamallu Jagan Mohan

    2014-02-01

    Dehydrozingerone, structural half analogue of curcumin, is a phenolic compound isolated from ginger (Zingiber officinale) rhizomes. Dehydrozingerone and several of its derivatives such as glucopyranosides and its tetra acetate derivative and 4-O-acetyl and methyl derivatives of dehydrozingerone were synthesized in the present study. Dehydrozingerone, synthesised with improved yield was used for the synthesis of Dehydrozingerone 4-O-?-D-glucopyranoside (first time report) by modified Koenigs-Knorr-Zempln method. Structures of all the compounds have been established using spectroscopic methods. These compounds were tested for radical scavenging activity by DPPH and FRAP method as well as for antibacterial and antifungal activities. The parent molecule exhibited better scavenging activity as compared to its derivatives indicating the significance of free phenolic hydroxyl group. Also, Dehydrozingerone and its derivatives exhibited antibacterial as well as antifungal activity due to the conjugation system present, which includes ?,?-unsaturated carbonyl (C = O) group. This study gave an insight into structural requirements for dehydrozingerone activity. PMID:24493881

  18. [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

  19. Active Compounds of Rhubarb Root and Rhizome in Animal Model Experiments of Focal Cerebral Ischemia

    PubMed Central

    Liu, Ai-ju; Song, Liang; Li, Yan; Zhang, Xiao-guang; Chen, Zi-xian; Huang, Li-bo; Zhang, Hong-feng; Zheng, Guo-qing

    2015-01-01

    Rhubarb root and rhizome (RRR) has been clinically used for stroke at least 2000 years and is still used in modern times in both China and elsewhere worldwide. The objective of present study was to evaluate the efficacy of active compounds of RRR (ACRRR) for experimental ischemic stroke. Studies of ACRRR in animal models of ischemic stroke were identified from 5 databases until April 2014. Study quality for each included article was evaluated according to the CAMARADES 10-item checklist. Outcome measures were neurological deficit score and infarct size. All the data were analyzed using RevMan 5.1 software. As a result, 20 studies were identified describing procedures involving 577 animals. The quality score of studies ranges from 2 to 6, and the median was 3.4. Six studies showed significant effects of ACRRR for improving infarct size compared with model group (P < 0.01). Six studies indicated significant effects of ACRRR for improving the neurological deficit scores according to Zea longa criterion or eight-point criterion (P < 0.01). In conclusion, these findings demonstrated a possible efficacy of ACRRR that have potential neuroprotective effect for experimental ischemic stroke. However, these apparently positive findings should be interpreted with caution because of the methodological flaws. PMID:26495006

  20. [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

  1. Anti-Prion Activity of a Panel of Aromatic Chemical Compounds: In Vitro and In Silico Approaches

    PubMed Central

    Ferreira, Natalia C.; Marques, Icaro A.; Conceio, Wesley A.; Macedo, Bruno; Machado, Clarice S.; Mascarello, Alessandra; Chiaradia-Delatorre, Louise Domeneghini; Yunes, Rosendo Augusto; Nunes, Ricardo Jos; Hughson, Andrew G.; Raymond, Lynne D.; Pascutti, Pedro G.; Caughey, Byron; Cordeiro, Yraima

    2014-01-01

    The prion protein (PrP) is implicated in the Transmissible Spongiform Encephalopathies (TSEs), which comprise a group of fatal neurodegenerative diseases affecting humans and other mammals. Conversion of cellular PrP (PrPC) into the scrapie form (PrPSc) is the hallmark of TSEs. Once formed, PrPSc aggregates and catalyzes PrPC misfolding into new PrPSc molecules. Although many compounds have been shown to inhibit the conversion process, so far there is no effective therapy for TSEs. Besides, most of the previously evaluated compounds failed in vivo due to poor pharmacokinetic profiles. In this work we propose a combined in vitro/in silico approach to screen for active anti-prion compounds presenting acceptable drugability and pharmacokinetic parameters. A diverse panel of aromatic compounds was screened in neuroblastoma cells persistently infected with PrPSc (ScN2a) for their ability to inhibit PK-resistant PrP (PrPRes) accumulation. From ?200 compounds, 47 were effective in decreasing the accumulation of PrPRes in ScN2a cells. Pharmacokinetic and physicochemical properties were predicted in silico, allowing us to obtain estimates of relative blood brain barrier permeation and mutagenicity. MTT reduction assays showed that most of the active compounds were non cytotoxic. Compounds that cleared PrPRes from ScN2a cells, were non-toxic in the MTT assay, and presented a good pharmacokinetic profile were investigated for their ability to inhibit aggregation of an amyloidogenic PrP peptide fragment (PrP109149). Molecular docking results provided structural models and binding affinities for the interaction between PrP and the most promising compounds. In summary, using this combined in vitro/in silico approach we have identified new small organic anti-scrapie compounds that decrease the accumulation of PrPRes in ScN2a cells, inhibit the aggregation of a PrP peptide, and possess pharmacokinetic characteristics that support their drugability. These compounds are attractive candidates for prion disease therapy. PMID:24400098

  2. Functional Brain Activation Differences in Stuttering Identified with a Rapid fMRI Sequence

    ERIC Educational Resources Information Center

    Loucks, Torrey; Kraft, Shelly Jo; Choo, Ai Leen; Sharma, Harish; Ambrose, Nicoline G.

    2011-01-01

    The purpose of this study was to investigate whether brain activity related to the presence of stuttering can be identified with rapid functional MRI (fMRI) sequences that involved overt and covert speech processing tasks. The long-term goal is to develop sensitive fMRI approaches with developmentally appropriate tasks to identify deviant speech…

  3. Functional Brain Activation Differences in Stuttering Identified with a Rapid fMRI Sequence

    ERIC Educational Resources Information Center

    Loucks, Torrey; Kraft, Shelly Jo; Choo, Ai Leen; Sharma, Harish; Ambrose, Nicoline G.

    2011-01-01

    The purpose of this study was to investigate whether brain activity related to the presence of stuttering can be identified with rapid functional MRI (fMRI) sequences that involved overt and covert speech processing tasks. The long-term goal is to develop sensitive fMRI approaches with developmentally appropriate tasks to identify deviant speech

  4. Strychnos pseudoquina and Its Purified Compounds Present an Effective In Vitro Antileishmanial Activity

    PubMed Central

    Lage, Paula Sousa; de Andrade, Pedro Henrique Rocha; Lopes, Amanda de Santana; Chvez Fumagalli, Miguel Angel; Valadares, Diogo Garcia; Duarte, Mariana Costa; Costa, Lourena Emanuele; Filho, Jos Dias de Souza; Tavares, Carlos Alberto Pereira; de Pdua, Rodrigo Maia; Leite, Joo Paulo Viana; Coelho, Eduardo Antonio Ferraz

    2013-01-01

    The development of new and cost-effective alternative therapeutic strategies to treat leishmaniasis has become a high priority. In the present study, the antileishmanial activity of Strychnos pseudoquina St. Hil. was investigated and pure compounds that presented this biological effect were isolated. An ethyl acetate extract was prepared, and it proved to be effective against Leishmania amazonensis. A bioactivity-guided fractionation was performed, and two flavonoids were identified, quercetin 3-O-methyl ether and strychnobiflavone, which presented an effective antileishmanial activity against L. amazonensis, and studies were extended to establish their minimum inhibitory concentrations (IC50), their leishmanicidal effects on the intra-macrophage Leishmania stage, as well as their cytotoxic effects on murine macrophages (CC50), and in O+ human red blood cells. The data presented in this study showed the potential of an ethyl acetate extract of S. pseudoquina, as well as two flavonoids purified from it, which can be used as a therapeutic alternative on its own, or in association with other drugs, to treat disease evoked by L. amazonensis. PMID:24194781

  5. Fate of alkylphenolic compounds during activated sludge treatment: impact of loading and organic composition.

    PubMed

    McAdam, Ewan J; Bagnall, John P; Soares, Ana; Koh, Yoong K K; Chiu, Tze Y; Scrimshaw, Mark D; Lester, John N; Cartmell, Elise

    2011-01-01

    The impact of loading and organic composition on the fate of alkylphenolic compounds in the activated sludge plant (ASP) has been studied. Three ASP designs comprising carbonaceous, carbonaceous/nitrification, and carbonaceous/nitrification/denitrification treatment were examined to demonstrate the impact of increasing levels of process complexity and to incorporate a spectrum of loading conditions. Based on mass balance, overall biodegradation efficiencies for nonylphenol ethoxylates (NPEOs), short chain carboxylates (NP(1-3)EC) and nonylphenol (NP) were 37%, 59%, and 27% for the carbonaceous, carbonaceous/nitrification, and carbonaceous/nitrification/denitrification ASP, respectively. The presence of a rich community of ammonia oxidizing bacteria does not necessarily facilitate effective alkylphenolic compound degradation. However, a clear correlation between alkylphenolic compound loading and long chain ethoxylate compound biodegradation was determined at the three ASPs, indicating that at higher initial alkylphenolic compound concentrations (or load), greater ethoxylate biotransformation can occur. In addition, the impact of settled sewage organic composition on alkylphenolic compound removal was evaluated. A correlation between the ratio of chemical oxygen demand (COD) to alkylphenolic compound concentration and biomass activity was determined, demonstrating the inhibiting effect of bulk organic matter on alkylphenol polyethoxylate transformation activity. At all three ASPs the biodegradation pathway proposed involves the preferential biodegradation of the amphiphilic ethoxylated compounds, after which the preferential attack of the lipophilic akylphenol moiety occurs. The extent of ethoxylate biodegradation is driven by the initial alkylphenolic compound concentration and the proportion of COD constituted by the alkylphenol polyethoxylates (APEOs) and their metabolites relative to the bulk organic concentration of the sewage composed of proteins, acids, fats, and polysaccharides. Secondary effluents from this study are characterized by low bulk organic concentrations and comparatively high micropollutant concentrations. Based on the biodegradation mechanism proposed in this study, application of high rate tertiary biological treatment processes to secondary effluents characterized by low bulk organic concentrations and comparatively high APEO concentrations is predicted to provide a sustainable solution to micropollutant removal. PMID:21128606

  6. 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.

  7. Synthesis, biological active molecular design, and molecular docking study of novel deazaflavin-cholestane hybrid compounds.

    PubMed

    Shrestha, Ajaya R; Shindo, Takashi; Ashida, Noriyuki; Nagamatsu, Tomohisa

    2008-09-15

    Novel deazaflavin-cholestane hybrid compounds, 3',8'-disubstituted-5'-deazacholest-2,4-dieno[2,3-g]pteridine-2',4'(3'H,8'H)-diones, have been synthesized by condensation reaction between 6-(monosubstituted amino)-pyrimidin-2,4(1H,3H)-diones and 2-hydroxymethylenecholest-4-en-3-one in presence of p-toluenesulfonic acid monohydrate and diphenyl ether. The antitumor activities against human tumor cell lines (CCRF-HSB-2 and KB cells) have been investigated in vitro, and many of these compounds showed promising antitumor activities. Furthermore, molecular docking study using LigandFit within the software package Discovery Studio 1.7 was done for lead optimization of these compounds as potential PTK inhibitors. In general, all of the synthesized steroid-hybrid compounds showed good binding affinities into PTK (PDB code: 1t46). PMID:18723355

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

    PubMed

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

    2015-12-01

    Multivariate analysis of thin-layer chromatography (TLC) images was modeled to predict antioxidant activity of Pereskia bleo leaves and to identify the contributing compounds of the activity. TLC was developed in optimized mobile phase using the 'PRISMA' optimization method and the image was then converted to wavelet signals and imported for multivariate analysis. An orthogonal partial least square (OPLS) model was developed consisting of a wavelet-converted TLC image and 2,2-diphynyl-picrylhydrazyl free radical scavenging activity of 24 different preparations of P. bleo as the x- and y-variables, respectively. The quality of the constructed OPLS model (1?+?1?+?0) with one predictive and one orthogonal component was evaluated by internal and external validity tests. The validated model was then used to identify the contributing spot from the TLC plate that was then analyzed by GC-MS after trimethylsilyl derivatization. Glycerol and amine compounds were mainly found to contribute to the antioxidant activity of the sample. An alternative method to predict the antioxidant activity of a new sample of P. bleo leaves has been developed. PMID:26033701

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-02-01

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

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

    PubMed

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

    2015-02-01

    Potent compounds do not necessarily make the best drugs in the market. Consequently, with the aim to describe tools that may be fundamental for refining the screening of candidates for animal and preclinical studies and further development, molecules of different structural classes synthesized within the frame of a broad screening platform were evaluated for their trypanocidal activities, cytotoxicities against murine macrophages J774.1 and selectivity indices, as well as for their ligand efficiencies and structural chemical properties. To advance into their modes of action, we also describe the morphological and ultrastructural changes exerted by selected members of each compound class on the parasite Trypanosoma brucei. Our data suggest that the potential organelles targeted are either the flagellar pocket (compound 77, N-Arylpyridinium salt; 15, amino acid derivative with piperazine moieties), the endoplasmic reticulum membrane systems (37, bisquaternary bisnaphthalimide; 77, N-Arylpyridinium salt; 68, piperidine derivative), or mitochondria and kinetoplasts (88, N-Arylpyridinium salt; 68, piperidine derivative). Amino acid derivatives with fumaric acid and piperazine moieties (4, 15) weakly inhibiting cysteine proteases seem to preferentially target acidic compartments. Our results suggest that ligand efficiency indices may be helpful to learn about the relationship between potency and chemical characteristics of the compounds. Interestingly, the correlations found between the physico-chemical parameters of the selected compounds and those of commercial molecules that target specific organelles indicate that our rationale might be helpful to drive compound design toward high activities and acceptable pharmacokinetic properties for all compound families. PMID:25416330

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

    SciTech Connect

    Jacobs, Miriam N. . E-mail: miriam.jacobs@jrc.it; Nolan, Gail T.; Hood, Steven R.

    2005-12-01

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

  13. Anti-Campylobacter Activities and Resistance Mechanisms of Natural Phenolic Compounds in Campylobacter

    PubMed Central

    Klančnik, Anja; Možina, Sonja Smole; Zhang, Qijing

    2012-01-01

    Background Campylobacter is a major foodborne pathogen and alternative antimicrobials are needed to prevent or decrease Campylobacter contamination in foods or food producing animals. The objectives of this study are to define the anti-Campylobacter activities of natural phenolic compounds of plant origin and to determine the roles of bacterial drug efflux systems in the resistance to these natural phenolics in Campylobacter jejuni. Methodology/Principal Findings Anti-Campylobacter activities were evaluated by an MIC assay using microdilution coupled with ATP measurement. Mutants of the cmeB and cmeF efflux genes and the cmeR transcriptional repressor gene were compared with the wild-type strain for their susceptibilities to phenolics in the absence and presence of efflux-pump inhibitors (EPIs). The phenolic compounds produced significant, but variable activities against both antibiotic-susceptible and antibiotic resistant Campylobacter. The highest anti-Campylobacter activity was seen with carnosic and rosmarinic acids in their pure forms or in enriched plant extracts. Inactivation of cmeB rendered C. jejuni significantly more susceptible to the phenolic compounds, while mutation of cmeF or cmeR only produced a moderate effect on the MICs. Consistent with the results from the efflux pump mutants, EPIs, especially phenylalanine-arginine β-naphthylamide and NMP, significantly reduced the MICs of the tested phenolic compounds. Further reduction of MICs by the EPIs was also observed in the cmeB and cmeF mutants, suggesting that other efflux systems are also involved in Campylobacter resistance to phenolic compounds. Conclusion/Significance Natural phenolic compounds of plant origin have good anti-Campylobacter activities and can be further developed for potential use in controlling Campylobacter. The drug efflux systems in Campylobacter contribute significantly to its resistance to the phenolics and EPIs potentiate the anti-Campylobacter activities of plant phenolic compounds. PMID:23284770

  14. RP-HPLC-DAD analysis of phenolic compounds in pomace extracts from five grape cultivars: Evaluation of their antioxidant, antiradical and antifungal activities in orange and apple juices.

    PubMed

    Sagdic, Osman; Ozturk, Ismet; Ozkan, Gulcan; Yetim, Hasan; Ekici, Lutfiye; Yilmaz, Mustafa Tahsin

    2011-06-15

    Phenolic compounds, related to antioxidative and antifungal properties of ethanolic extracts from five commercial grape cultivars (three red and two white) grown in Turkey were determined. A reversed-phase high performance liquid chromatography (RP-HPLC) procedure was developed, and a total 18 different phenolic compounds were identified. Total phenolic contents of the extracts were determined using Folin-Ciocalteau method. Antioxidant activities of the extracts were evaluated by using DPPH radical scavenging and phosphomolybdenum methods. All extracts exhibited strong antioxidant and antiradical activity. Phenolic compounds and antioxidant activities of the extracts were variety dependent. Antifungal activities of the pomaces and extracts were screened by both in vitro agar-well diffusion assay and antifungal activity in apple and orange juices in situ using Zygosaccharomyces rouxii and Z. bailii. Antifungal activities revealed that the pomaces and extracts of Gamay and Kalecik karasi could be more effective antifungal agents than those of Emir, Narince and Okuzgozu grape cultivars. PMID:25213954

  15. 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.

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

    DOEpatents

    Vo-Dinh, Tuan (Knoxville, TN)

    1994-01-01

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

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

    DOEpatents

    Vo-Dinh, T.

    1994-06-07

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

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

    DOEpatents

    Vo-Dinh, Tuan (Knoxville, TN)

    1993-01-01

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

  19. Screening structural-functional relationships of neuropharmacologically active organic compounds at the nicotinic acetylcholine receptor.

    PubMed

    Barrantes, G E; Ortells, M O; Barrantes, F J

    1997-03-01

    The mechanisms of action and pharmacological effects on the nicotinic cholinoceptor of a large database of organic compounds were analyzed using a new computational procedure. This procedure is a screening method based on comparison of the molecular structures (shape and charge) of the putative active organic compounds. The resulting predictions can be used as an exploratory tool in the design of experiments aimed at testing the effects of several compounds on a target macromolecule. Unlike a conventional database search for structural similarities, the present method is able to circumscribe objectively the results to the most statistically significant molecules. PMID:9175605

  20. Responses of mixtures of polyhalogenated aromatic compounds or single compounds in the CALUX-assay a novel species-specific bioassay for Ah-receptor active compounds

    SciTech Connect

    Murk, A.J.; Aarts, J.M.M.J.G.; Jonas, A.; Brouwer, A.; Denison, M.S.

    1995-12-31

    Polyhalogenated aromatic hydrocarbons (PHAHs) elicit a number of common toxic responses, including reproductive toxicity, teratogenicity, impairment of immune responses, alterations in vitamin A and thyroid hormone metabolism and carcinogenesis. The toxic effects however are highly dependent on the animal species used, The most toxic PHAHs are approximate isostereomeres of 2,3,7,8 tetrachlorinated dibenzo-p-dioxin (TCDD) and share a common mechanism of action mediated by the aryl hydrocarbon receptor (AhR). Based on the common receptor mediated mechanism, the toxic equivalency factor concept was developed, in which the potency of each individual congener is expressed relative to TCDD, thus allowing hazard and risk assessment for mixtures of PHAHs. A number of recombinant cell lines were developed, including hepalclc7 mouse and H4IIE rat hepatoma cell lines, with AhR-mediated firefly (Photinus pyralis) luciferase gene expression. The response in this so-called CALUX (chemical activated luciferase expression) assay is additive for polychlorinated dibenzofurans (PCDFs) and PCDDS, but for polychlorinated biphenyls (PCBs) both synergistic and antagonistic interactions have been demonstrated, which are partially species-dependent. Also some structurally related compounds, like polybrominated diphenyl ether, pentachlorinated phenol, benzo(a)pyrene, pyrene, tetrachlorobenzyltoluene (Ugilec 141) and mixtures of polychlorinated terphenyls have been tested in the CALUX assay. The responses of these compounds were sometimes agonistic, but also antagonistic and synergistic effects on the TCDO response were observed.

  1. 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,...

  2. Inhibition of guinea pig aldehyde oxidase activity by different flavonoid compounds: An in vitro study.

    PubMed

    Siah, Maryam; Farzaei, Mohammad Hosein; Ashrafi-Kooshk, Mohammad Reza; Adibi, Hadi; Arab, Seyed Shahriar; Rashidi, Mohammad Reza; Khodarahmi, Reza

    2016-02-01

    Aldehyde oxidase (AO), a cytosolic molybdenum-containing hydroxylase, is predominantly active in liver and other tissues of mammalian species and involved in the metabolism of extensive range of aldehydes and nitrogen-containing compounds. A wide range of natural components including polyphenols are able to interfere with AO-catalyzed reactions. Polyphenols and flavonoids are one of the extensive secondary plant metabolites ubiquitously present in plants considered an important part of the human diet. The aim of the present study was to investigate inhibitory effect of selected phenolic compounds from three subclasses of aurone, flavanone and phenolic lactone compounds on the activity of AO, spectrophotometrically. AO enzyme was partially purified from liver of guinea pig. Then, inhibitory effects of 10 flavonoid compounds including 8 derivatives of 2-benzylidenebenzofuran-3(2H)-ones, as well as naringenin and ellagic acid on the activity of aldehyde oxidase were assessed compared with the specific inhibitor of AO, menadione. Among the phenolic compounds with inhibitory effects on the enzyme, ellagic acid (IC50=14.47?M) was the most potent agent with higher inhibitory action than menadione (IC50=31.84?M). The mechanisms by which flavonoid compounds inhibit AO activity have been also determined. The inhibitory process of the assessed compounds occurs via either a non-competitive or mixed mode. Although flavonoid compounds extensively present in the nature, mainly in dietary regimen, aurones with promising biological properties are not widely distributed in nature, so synthesis of aurone derivatives is of great importance. Additionally, aurones seem to provide a promising scaffold in medicinal chemistry for the skeleton of new developing drugs, so the results of the current study can be valuable in order to better understanding drug-food as well as drug-drug interaction and also appears to be worthwhile in drug development strategies. PMID:26722818

  3. 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

  4. 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…

  5. 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

  6. Volatile compounds of Viola odorata absolutes: identification of odorant active markers to distinguish plants originating from France and Egypt.

    PubMed

    Saint-Lary, Laure; Roy, Cline; Paris, Jean-Philippe; Tournayre, Pascal; Berdagu, Jean-Louis; Thomas, Olivier P; Fernandez, Xavier

    2014-06-01

    Absolutes isolated from Viola odorata leaves, valuable materials for the flavor and fragrance industry, were studied. Violets are mainly cultivated in France and Egypt and extracted locally. The absolutes of the two origins showed different olfactory profiles both in top and heart notes, as evidenced by sensory analysis. The aims of this study were i) to characterize the volatile compounds, ii) to determine the odorant-active ones, and iii) to identify some markers of the plant origin. Two complementary analytical methods were used for these purposes, i.e., headspace solid-phase microextraction (HS-SPME) using different fiber coatings followed by GC/MS analysis and gas chromatography - olfactometry/mass spectrometry (GC-O/MS) applied to violet leaf extracts. From a total of 70 identified compounds, 61 have never been reported so far for this species, 17 compounds were characterized by both techniques (with seven among them known from the literature), 23 compounds were solely identified by HS-SPME GC/MS (among them only two being already mentioned as components of violet absolutes in the literature), and, finally, 30 compounds were only identified by GC-O/MS. According to the HS-SPME GC/MS analyses, ethyl hexanoate and (2E,6Z)-nona-2,6-dienol were specific volatile compounds of the sample with French origin, while (E,E)-hepta-2,4-dienal, hexanoic acid, limonene, tridecane, and eugenol were specific of the samples with Egyptian origin. Additional compounds that were not detected by HS-SPME GC/MS analysis were revealed by GC-O analyses, some of them being markers of origin. Pent-1-en-3-ol, 3-methylbut-2-enal, 2-methoxy-3-(1-methylethyl)pyrazine, 4-ethylbenzaldehyde, ?-phenethyl formate, and 2-methoxy-3-(2-methylpropyl)pyrazine revealed to be odorant markers of the French sample, whereas cis-rose oxide, trans-rose oxide, and 3,5,5-trimethylcyclohex-2-enone were odorant markers of the Egyptian samples. PMID:24934671

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

    PubMed

    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

  8. 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

  9. Identification and quantification of phenolic compounds in bambangan (Mangifera pajang Kort.) peels and their free radical scavenging activity.

    PubMed

    Hassan, Fouad Abdulrahman; Ismail, Amin; Abdulhamid, Azizah; Azlan, Azrina

    2011-09-14

    Phenolic compounds and antioxidant capacity of acidified methanolic extract prepared from fully ripe bambangan (Mangifera pajang K.) peel cultivated in Sarawak, Malaysia, were analyzed. The total phenolic content (98.3 mg GAE/g) of bambangan peel powder (BPP) was determined by the Folin-Ciocalteu method. BPP showed a strong potency of antioxidant activity and was consistent with that of BHT and vitamin C as confirmed by the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity and FRAP (ferric-reducing antioxidant power) assays. Gallic acid, p-coumaric acid, ellagic acid, protocatechuic acid, and mangiferin were the major compounds among the 16 phenolics that have been identified and quantified in M. pajang peels with 20.9, 12.7, 7.3, 5.4, and 4.8 mg/g BPP, respectively. Peak identities were confirmed by comparing their retention times, UV-vis absorption spectra, and mass spectra with authentic standards. The 16 phenolic compounds identified in M. pajang K. using HPLC-DAD and TSQ-ESI-MS are reported here for the first time. PMID:21800901

  10. Identification and antifungal activity of novel organic compounds found in cuticular and internal lipids of medically important flies.

    PubMed

    Go??biowski, Marek; Cerkowniak, Magdalena; Urbanek, Aleksandra; Dawgul, Ma?gorzata; Kamysz, Wojciech; Bogu?, Mieczys?awa I; Stepnowski, Piotr

    2015-01-01

    Novel organic compounds found in the cuticular and internal lipids of medically important flies were identified. Uracil, 9-tricosene, 1-oleoyl glycerol, dimethyl suberate and butyl stearate were tested for their potential antifungal activity. Minimal inhibitory concentrations of the compounds against reference strains of fungi were determined. Uracil and dimethyl suberate slightly inhibited the growth of entomopathogenic fungi. The cuticular and internal lipids of Calliphora vicina, Calliphora vomitoria, Sarcophaga carnaria and Musca domestica were studied by gas chromatography (GC) combined with mass spectrometry (GC/MS). A comparison of the lipid extracts between the preimaginal and mature stages showed adults flies contained a higher total content of the identified components. Furthermore, their amounts distinctly predominated in the internal lipids of all the species. The amount of 9-tricosene was the highest in adults of C. vicina, while the larvae and pupae had a definitively lower amount of this compound. Uracil was found to be the most abundant component in extracts obtained from C. vomitoria especially in the internal lipids of adults. 1-oleoyl glycerol was detected in all of the examined species of flies. It was most abundant in the internal extracts isolated from the larvae of C. vicina and the pupae of C. vomitoria. Suberic acid dimethyl ester was found in the larval and pupal internal lipids of C. vicina and S. carnaria in low amounts. Butyl stearate was identified only in the internal lipids of the larvae and adults of houseflies. PMID:25026883

  11. 6-shogaol, a major compound in ginger, induces aryl hydrocarbon receptor-mediated transcriptional activity and gene expression.

    PubMed

    Yoshida, Kazutaka; Satsu, Hideo; Mikubo, Ayano; Ogiwara, Haru; Yakabe, Takafumi; Inakuma, Takahiro; Shimizu, Makoto

    2014-06-18

    Xenobiotics are usually detoxified by drug-metabolizing enzymes and excreted from the body. The expression of many of drug-metabolizing enzymes is regulated by the aryl hydrocarbon receptor (AHR). Some substances in vegetables have the potential to be AHR ligands. To search for vegetable components that exhibit AHR-mediated transcriptional activity, we assessed the activity of vegetable extracts and identified the active compounds using the previously established stable AHR-responsive HepG2 cell line. Among the hot water extracts of vegetables, the highest activity was found in ginger. The ethyl acetate fraction of the ginger hot water extract remarkably induced AHR-mediated transcriptional activity, and the major active compound was found to be 6-shogaol. Subsequently, the mRNA levels of AHR-targeting drug-metabolizing enzymes (CYP1A1, UGT1A1, and ABCG 2) and the protein level of CYP1A1 in HepG2 cells were shown to be increased by 6-shogaol. This is the first report that 6-shogaol can regulate the expression of detoxification enzymes by AHR activation. PMID:24857157

  12. A high-content, multiplexed screen in human breast cancer cells identifies profilin-1 inducers with anti-migratory activities.

    PubMed

    Joy, Marion E; Vollmer, Laura L; Hulkower, Keren; Stern, Andrew M; Peterson, Cameron K; 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

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

    PubMed

    Fernndez, Mariana; Arce, Esteban Rodrguez; Sarniguet, Cynthia; Morais, Tnia S; Tomaz, Ana Isabel; Azar, Claudio Olea; Figueroa, Roberto; Diego Maya, J; Medeiros, Andrea; Comini, Marcelo; Helena Garcia, M; Otero, Luca; Gambino, Dinorah

    2015-12-01

    Searching for new prospective antitrypanosomal agents, three novel Ru(II)-cyclopentadienyl compounds, [Ru(?(5)-C5H5)(PPh3)L], with HL=bioactive 5-nitrofuryl containing thiosemicarbazones were synthesized and characterized in the solid state and in solution. The compounds were evaluated in vitro on the blood circulating trypomastigote form of Trypanosoma cruzi (Dm28c strain), the infective form of Trypanosoma brucei brucei (strain 427) and on J774 murine macrophages and human-derived EA.hy926 endothelial cells. The compounds were active against both parasites with IC50 values in the micromolar or submicromolar range. Interestingly, they are much more active on T. cruzi than previously developed Ru(II) classical and organometallic compounds with the same bioactive ligands. The new compounds showed moderate to very good selectivity towards the parasites in respect to mammalian cells. The global results point at [RuCp(PPh3)L2] (L2=N-methyl derivative of 5-nitrofuryl containing thiosemicarbazone and Cp=cyclopentadienyl) as the most promising compound for further developments (IC50T. cruzi=0.41?M; IC50T. brucei brucei=3.5?M). Moreover, this compound shows excellent selectivity towards T. cruzi (SI>49) and good selectivity towards T. brucei brucei (SI>6). In order to get insight into the mechanism of antiparasitic action, the intracellular free radical production capacity of the new compounds was assessed by ESR. DMPO (5,5-dimethyl-1-pirroline-N-oxide) spin adducts related to the bioreduction of the complexes and to redox cycling processes were characterized. In addition, DNA competitive binding studies with ethidium bromide by fluorescence measurements showed that the compounds interact with this biomolecule. PMID:26275470

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

    PubMed Central

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

    2013-01-01

    Objective To determine the repellent and pupicidal activities of Pogostemon cablin (P. cablin) chemical compositions were assayed for their toxicity against selected important vector mosquitoes, viz., Aedes aegypti (Ae. aegypti), Anopheles stephensi (An. stephensi) and Culex quinquefasciatus (Cx. quinquefasciatus) (Diptera: Culicidae). Methods The plants dry aerial parts were subjected to hydrodistillation using a modified Clevenger-type apparatus. The composition of the essential oil was analyzed by Gas Chromatography (GC) and GC mass spectrophotometry. Evaluation was carried out in a net cage (45 cm30 cm45 cm) containing 100 blood starved female mosquitoes and were assayed in the laboratory condition by using the protocol of WHO 2010. The repellent activity of P. cablin chemical compositions at concentration of 2mg/cm2were applied on skin of fore arm in man and exposed against adult female mosquitoes. The pupicidal activity was determined against selected important vector mosquitoes to concentration of 100 mg/L and mortality of each pupa was recorded after 24 h of exposure to the compounds. Results Chemical constituents of 15 compounds were identified in the oil of P.cablin compounds representing to 98.96%. The major components in essential oil were -patchoulene, -guaiene, -patchoulene, -bulnesene and patchouli alcohol. The repellent activity of patchouli alcohol compound was found to be most effective for repellent activity and 2 mg/cm2 concentration provided 100% protection up to 280 min against Ae. aegypti, An. stephensi and Cx. quinquefasciatus, respectively. Similarly, pupae exposed to 100 mg/L concentrations of P. cablin chemical compositions. Among five compounds tested patchouli alcoholwas found to be most effective for pupicidal activity provided 28.44, 26.28 and 25.36 against Ae.aegypti, An.stephensi and Cx. quinquefasciatus, respectively. The percent adult emergence was inversely proportional to the concentration of compounds and directly proportional to the pupal mortality. Conclusion These results suggest that the P. cablin chemical compositions have the potential to be used as an ideal eco-friendly approach for the control of mosquitoes. This is the first report on the mosquito repellent and pupicidal activities of the reported P. cablin chemical compositions.

  15. Structural activity of bovidic acid and related compounds as feeding deterrents against Aedes aegypti.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    5-(1-hydroxynonyl)-2-tetrahydrofuranpentanoic acid (18-Bovidic acid), a compound recently identified as a mosquito deterrent from the hair of gaur, has been evaluated for its efficacy compared to known synthetic repellents. In the present study we have evaluated analogs of Bovidic acid, related hydr...

  16. STRUCTURAL ACTIVITY OF BOVIDIC ACID AND RELATED COMPOUNDS AS FEEDING DETERRENTS AGAINST AEDES AEGYPTI.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    5-(1-hydroxynonyl)-2-tetrahydrofuranpentanoic acid (18-Bovidic acid), a compound recently identified as a mosquito deterrent from the hair of gaur, has been evaluated for its efficacy compared to known synthetic repellents. In the present study we have evaluated analogs of Bovidic acid, related hydr...

  17. Inhibition of tumor growth by a newly-identified activator for epidermal fatty acid binding protein

    PubMed Central

    Rao, Enyu; Singh, Puja; Zhai, Xiuhong; Li, Yan; Zhu, Ganqian; Zhang, Yuwen; Hao, Jiaqing; Chi, Young-In; Brown, Rhoderick E.; Cleary, Margot P.; Li, Bing

    2015-01-01

    Our previous studies have demonstrated that expression of epidermal fatty acid binding protein (E-FABP) in tumor associated macrophages (TAMs) promotes macrophage anti-tumor activity by enhancing IFN? responses in tumor models. Thus, E-FABP represents a new protective factor in enhancing tumor immune surveillance against tumor development. Herein, we report the compound 5-(benzylamino)-2-(3-methylphenyl)-1,3-oxazole-4-carbonitrile (designated EI-05) as a novel E-FABP activator for inhibition of mammary tumor growth. EI-05 was selected from the ZINC compound library using molecular docking analysis based on the crystal structure of E-FABP. Although EI-05 is unable to bind E-FABP directly, it significantly increases E-FABP expression in macrophages during inflammation. Stimulation of macrophages with EI-05 remarkably enhances lipid droplet formation and IFN? production, which further promotes the anti-tumor activity of macrophages. Importantly, administering EI-05 in vivo significantly inhibits mammary tumor growth in a syngeneic mouse model. Altogether, these results suggest that EI-05 may represent a promising drug candidate for anti-tumor treatment through enhancing E-FABP activity and IFN? responses in macrophages. PMID:25796556

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

    PubMed

    Moraes, rica Aguiar; Marineli, Rafaela da Silva; Lenquiste, Sabrina Alves; Steel, Caroline Joy; de Menezes, Ccero Beserra; Queiroz, Valria Aparecida Vieira; Marstica Jnior, Mrio Roberto

    2015-08-01

    Nutrients composition, phenolic compounds, antioxidant activity and estimated glycemic index (EGI) were evaluated in sorghum bran (SB) and decorticated sorghum flour (DSF), obtained by a rice-polisher, as well as whole sorghum flour (WSF). Correlation between EGI and the studied parameters were determined. SB presented the highest protein, lipid, ash, ?-glucan, total and insoluble dietary fiber contents; and the lowest non-resistant and total starch contents. The highest carbohydrate and resistant starch contents were in DSF and WSF, respectively. Phenolic compounds and antioxidant activities were concentrated in SB. The EGI values were: DSF 84.5 0.41; WSF 77.2 0.33; and SB 60.3 0.78. Phenolic compounds, specific flavonoids and antioxidant activities, as well as total, insoluble and soluble dietary fiber and ?-glucans of sorghum flour samples were all negatively correlated to EGI. RS content was not correlated to EGI. PMID:25766808

  19. Antibacterial activity of coffee extracts and selected coffee chemical compounds against enterobacteria.

    PubMed

    Almeida, Ana Amlia P; Farah, Adriana; Silva, Daniela A M; Nunan, Elzria A; Glria, M Beatriz A

    2006-11-15

    The in vitro antimicrobial activity of commercial coffee extracts and chemical compounds was investigated on nine strains of enterobacteria. The antimicrobial activity investigated by the disc diffusion method was observed in both the extracts and tested chemical compounds. Even though pH, color, and the contents of trigonelline, caffeine, and chlorogenic acids differed significantly among the coffee extracts, no significant differences were observed in their antimicrobial activity. Caffeic acid and trigonelline showed similar inhibitory effect against the growth of the microorganisms. Caffeine, chlorogenic acid, and protocatechuic acid showed particularly strong effect against Serratia marcescens and Enterobacter cloacae. The IC(50) and IC(90) for the compounds determined by the microtiter plate method indicated that trigonelline, caffeine, and protocatechuic acids are potential natural antimicrobial agents against Salmonella enterica. The concentrations of caffeine found in coffee extracts are enough to warrant 50% of the antimicrobial effect against S. enterica, which is relevant to human safety. PMID:17090115

  20. Identification of a compound in Chamaecyparis taiwanensis inhibiting the ice-nucleating activity of Pseudomonas fluorescens KUIN-1.

    PubMed

    Kawahara, H; Masuda, K; Obata, H

    2000-12-01

    Inactivation of the ice-nucleating activity of Pseudomonas fluorescens KUIN-1 by compounds in the leaves from coniferous trees were investigated, and the inactivated material was identified. Intact cells of the strain KUIN-1 and the acetone or methanol extracts of leaves of various coniferous trees were allowed to react for 30 min at 18 degrees C. Antinucleation compounds were obtained from Chamaecyparis taiwanensis. When the acetone extract from the leaves of coniferous trees was added to the cell suspension (about 10(6) cells/ml) in 50 mM potassium phosphate buffer (pH 7.0), the ice nucleating temperature, T50, was significantly decreased (T50 < -5 degrees C). This inhibitor was isolated by using TLC, then identified as hinokitiol based on UV-VIS, IR, and mass spectral data. When intact cells of the strain KUIN-1 were incubated with hinokitiol, limonene, and alpha-pinene of the principal constituent of the leaves of coniferous trees in 50 mM potassium phosphate buffer (pH 7.0), the ice-nucleating activity decreased, but not in alpha-terpinene. Furthermore, the ice-nucleating activities from other ice-nucleating bacteria also decreased in the presence of hinokitiol. This inhibition was proportional to the concentration of hinokitinol. The pH and thermal stabilities of the ice-nucleating activity of the cells were changed by the addition of hinokitiol (10 mM). PMID:11210129

  1. Drug Discovery for Schistosomiasis: Hit and Lead Compounds Identified in a Library of Known Drugs by Medium-Throughput Phenotypic Screening

    PubMed Central

    Wolff, Brian; Snedecor, June; Lim, Kee-Chong; Xu, Fengyun; Renslo, Adam R.; Williams, Janice; McKerrow, James H.; Caffrey, Conor R.

    2009-01-01

    Background Praziquantel (PZQ) is the only widely available drug to treat schistosomiasis. Given the potential for drug resistance, it is prudent to search for novel therapeutics. Identification of anti-schistosomal chemicals has traditionally relied on phenotypic (whole organism) screening with adult worms in vitro and/or animal models of diseasetools that limit automation and throughput with modern microtiter plate-formatted compound libraries. Methods A partially automated, three-component phenotypic screen workflow is presented that utilizes at its apex the schistosomular stage of the parasite adapted to a 96-well plate format with a throughput of 640 compounds per month. Hits that arise are subsequently screened in vitro against adult parasites and finally for efficacy in a murine model of disease. Two GO/NO GO criteria filters in the workflow prioritize hit compounds for tests in the animal disease model in accordance with a target drug profile that demands short-course oral therapy. The screen workflow was inaugurated with 2,160 chemically diverse natural and synthetic compounds, of which 821 are drugs already approved for human use. This affords a unique starting point to reposition (re-profile) drugs as anti-schistosomals with potential savings in development timelines and costs. Findings Multiple and dynamic phenotypes could be categorized for schistosomula and adults in vitro, and a diverse set of hit drugs and chemistries were identified, including anti-schistosomals, anthelmintics, antibiotics, and neuromodulators. Of those hits prioritized for tests in the animal disease model, a number of leads were identified, one of which compares reasonably well with PZQ in significantly decreasing worm and egg burdens, and disease-associated pathology. Data arising from the three components of the screen are posted online as a community resource. Conclusions To accelerate the identification of novel anti-schistosomals, we have developed a partially automated screen workflow that interfaces schistosomula with microtiter plate-formatted compound libraries. The workflow has identified various compounds and drugs as hits in vitro and leads, with the prescribed oral efficacy, in vivo. Efforts to improve throughput, automation, and rigor of the screening workflow are ongoing. PMID:19597541

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

    PubMed

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

    2014-01-01

    Zebrafish embryos were exposed to concentration ranges of selected thyroid-active model compounds in order to assess the applicability of zebrafish-based developmental scoring systems withinan alternative testing strategy to detect the developmental toxicity ofthyroid-active compounds. Model compounds tested included triiodothyronine (T3), propylthiouracil (PTU), methimazole (MMI), sodium perchlorate (NaClO4) and amiodarone hydrochloride (AMI), selected to represent different modes of action affecting thyroid activity. Tested time windows included 48-120 hours post fertilization (hpf), 0-72 hpf and 0-120 hpf. All tested compounds resulted in developmental changes, with T3 being the most potent. The developmental parameters affected included reflective iridophores, beat and glide swimming, inflated swim bladders, as well as resorbed yolk sacs. These effects are only evident by 120 hpf and therefore an existing General Morphology Score (GMS) system was extended to create a General Developmental Score(GDS) that extends beyond the 72 hpfscoring limit of GMS and includes additional parameters that are affected by exposure to model thyroid-active compounds. Moreover, the GDS is cumulative as it includes not only the scoring of developmental morphologies but also integrates developmental dysmorphologies. Exposures from 48-120 hpf did not provide additional information to exposures from 0-120 hpf. The results indicate that the zebrafish GDS can detect the developmental toxicity of thyroid toxicants and may be of use in an integrated testing strategy to reduce, refine and in certain cases replace animal testing. PMID:24793664

  3. Antioxidant, ?-glucosidase and xanthine oxidase inhibitory activity of bioactive compounds from maize (Zea mays L.).

    PubMed

    Nile, Shivraj H; Park, Se W

    2014-01-01

    Chemical investigations into maize (Zea mays L.) kernels yielded phenolic compounds, which were structurally established using chromatographic and spectroscopic methods. The isolated phenolic compounds from maize kernel were examined in vitro for their antioxidant abilities by DPPH (2,2-diphenyl-1-picryl hydrazine) radical, OH radical scavenging activity, and reducing ability, along with ?-glucosidase and xanthine oxidase (XO) inhibition. The isolated maize phenolics revealed significant xanthine oxidase and ?-glucosidase inhibitory activity to that of allopurinol and acarbose in vitro and in vivo, respectively. The kinetics study with xanthine oxidase revealed competitive type of inhibition by isolated maize vanillic acid (M2), ferulic acid (M5), 3'-methoxyhirsutrin (M7), and peonidin-3-glucoside (M10) as compared to control allopurinol. Overall, with few exceptions, all the phenolic compounds from maize kernel revealed significant biological activities with all parameters examined. Also, the phenolic compounds from maize were found to be more reactive toward DPPH radical and had considerable reducing ability and OH radical scavenging activity. These findings suggest that maize kernel phenolic compounds can be considered as potential antioxidant, ?-glucosidase, and XO inhibitory agents those might be further explored for the design of lead antioxidant, antidiabetic and antigout drug candidates using in vivo trials. PMID:23957301

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

    PubMed

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

  5. A High-content screen identifies compounds promoting the neuronal differentiation and the midbrain dopamine neuron specification of human neural progenitor cells

    PubMed Central

    Rhim, Ji heon; Luo, Xiangjian; Xu, Xiaoyun; Gao, Dongbing; Zhou, Tieling; Li, Fuhai; Qin, Lidong; Wang, Ping; Xia, Xiaofeng; Wong, Stephen T. C.

    2015-01-01

    Small molecule compounds promoting the neuronal differentiation of stem/progenitor cells are of pivotal importance to regenerative medicine. We carried out a high-content screen to systematically characterize known bioactive compounds, on their effects on the neuronal differentiation and the midbrain dopamine (mDA) neuron specification of neural progenitor cells (NPCs) derived from the ventral mesencephalon of human fetal brain. Among the promoting compounds three major pharmacological classes were identified including the statins, TGF-βRI inhibitors, and GSK-3 inhibitors. The function of each class was also shown to be distinct, either to promote both the neuronal differentiation and mDA neuron specification, or selectively the latter, or promote the former but suppress the latter. We then carried out initial investigation on the possible mechanisms underlying, and demonstrated their applications on NPCs derived from human pluripotent stem cells (PSCs). Our study revealed the potential of several small molecule compounds for use in the directed differentiation of human NPCs. The screening result also provided insight into the signaling network regulating the differentiation of human NPCs. PMID:26542303

  6. Identifying vacancy complexes in compound semiconductors with positron annihilation spectroscopy: A case study of InN

    NASA Astrophysics Data System (ADS)

    Rauch, Christian; Makkonen, Ilja; Tuomisto, Filip

    2011-09-01

    We present a comprehensive study of vacancy and vacancy-impurity complexes in InN combining positron annihilation spectroscopy and ab initio calculations. Positron densities and annihilation characteristics of common vacancy-type defects are calculated using density functional theory, and the feasibility of their experimental detection and distinction with positron annihilation methods is discussed. The computational results are compared to positron lifetime and conventional as well as coincidence Doppler broadening measurements of several representative InN samples. The particular dominant vacancy-type positron traps are identified and their characteristic positron lifetimes, Doppler ratio curves, and line-shape parameters determined. We find that indium vacancies (VIn) and their complexes with nitrogen vacancies (VN) or impurities act as efficient positron traps, inducing distinct changes in the annihilation parameters compared to the InN lattice. Neutral or positively charged VN and pure VN complexes, on the other hand, do not trap positrons. The predominantly introduced positron trap in irradiated InN is identified as the isolated VIn, while in as-grown InN layers VIn do not occur isolated but complexed with one or more VN. The number of VN per VIn in these complexes is found to increase from the near-surface region toward the layer-substrate interface.

  7. Activity-enhancing mutations in an E3 ubiquitin ligase identified by high-throughput mutagenesis

    PubMed Central

    Starita, Lea M.; Pruneda, Jonathan N.; Lo, Russell S.; Fowler, Douglas M.; Kim, Helen J.; Hiatt, Joseph B.; Shendure, Jay; Brzovic, Peter S.; Fields, Stanley; Klevit, Rachel E.

    2013-01-01

    Although ubiquitination plays a critical role in virtually all cellular processes, mechanistic details of ubiquitin (Ub) transfer are still being defined. To identify the molecular determinants within E3 ligases that modulate activity, we scored each member of a library of nearly 100,000 protein variants of the murine ubiquitination factor E4B (Ube4b) U-box domain for auto-ubiquitination activity in the presence of the E2 UbcH5c. This assay identified mutations that enhance activity both in vitro and in cellular p53 degradation assays. The activity-enhancing mutations fall into two distinct mechanistic classes: One increases the U-box:E2-binding affinity, and the other allosterically stimulates the formation of catalytically active conformations of the E2∼Ub conjugate. The same mutations enhance E3 activity in the presence of another E2, Ube2w, implying a common allosteric mechanism, and therefore the general applicability of our observations to other E3s. A comparison of the E3 activity with the two different E2s identified an additional variant that exhibits E3:E2 specificity. Our results highlight the general utility of high-throughput mutagenesis in delineating the molecular basis of enzyme activity. PMID:23509263

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

    NASA Astrophysics Data System (ADS)

    Cukurovali, Alaaddin; Yilmaz, Engin

    2014-10-01

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

  9. Synthesis and evaluation of diaryl sulfides and diaryl selenide compounds for antitubulin and cytotoxic activity

    PubMed Central

    dos Santos, Edson dos A.; Hamel, Ernest; Bai, Ruoli; Burnett, James C.; Tozatti, Camila Santos Suniga; Bogo, Danielle; Perdomo, Renata T.; Antunes, Alexandra M. M.; Marques, M. Matilde; Matos, Maria de F. C.; de Lima, Dnis P.

    2013-01-01

    We have devised a procedure for the synthesis of analogs of combretastatin A-4 (CA-4) containing sulfur and selenium atoms as spacer groups between the aromatic rings. CA-4 is well known for its potent activity as an inhibitor of tubulin polymerization, and its prodrugs combretastatin A-4 phosphate (CA-4P) and combretastatin A-1 phosphate (CA-1P) are being investigated as antitumor agents that cause tumor vascular collapse in addition to their activity as cytotoxic compounds. Here we report the preparation of two sulfur analogs and one selenium analog of CA-4. All synthesized compounds, as well as several synthetic intermediates, were evaluated for inhibition of tubulin polymerization and for cytotoxic activity in human cancer cells. Compounds 3 and 4 were active at nM concentration against MCF-7 breast cancer cells. As inhibitors of tubulin polymerization, both 3 and 4 were more active than CA-4 itself. In addition, 4 was the most active of these agents against 786, HT-29 and PC-3 cancer cells. Molecular modeling binding studies are also reported for compounds 1, 3, 4 and CA-4 to tubulin within the colchicine site. PMID:23810282

  10. Antioxidant activity of various solvent fractions from edible brown alga, Eisenia bicyclis and its active compounds.

    PubMed

    Kwon, Tae-Hyung; Kim, Tae-Wan; Kim, Choong-Gon; Park, Nyun-Ho

    2013-05-01

    In this study, we aimed to elucidate the antioxidant capacity of Eisenia bicyclis and evaluated its antioxidant activity using various assay systems such as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, 2,2-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging, reducing power ability, and content of total polyphenol. Among all the performed experiments, the ethyl acetate fraction of E. bicyclis exhibited higher antioxidant activities. From this finding, isolation and purification were performed on the ethyl acetate fraction and identified dieckol and phlorofucofureoeckol-A by spectroscopic analyses including FAB-mass in the negative mode, (1) H NMR, (13) C NMR, (1) H-(1) H COSY, HMQC, and HMBC spectra. Interestingly, ABTS radical scavenging activities of dieckol and phlorofucofuroeckol showed strong effects of 65.36% and 70.38% at a concentration of 50 ?g/mL, respectively. DPPH radical scavenging and reducing power abilities were increased in a dose-dependent manner at various concentrations. These results suggest that dieckol and phlorofucofuroeckol-A of E. bicyclis may play an important role in protection from oxidative stress involving reactive oxygen species and may contribute to the development of new bio products, for example, a useful preservative to improve food quality and a drug for various oxidative damage-associated diseases. Practical Application: The results suggest that dieckol and phlorofucofuroeckol-A can be utilized as a natural source for potential application of antioxidant in food industry and drug for oxidative damage-associated diseases. PMID:23557350

  11. Novel anti-Cryptosporidium activity of known drugs identified by high-throughput screening against parasite fatty acyl-CoA binding protein (ACBP)

    PubMed Central

    Fritzler, Jason M.; Zhu, Guan

    2012-01-01

    Background Cryptosporidium parvum causes an opportunistic infection in AIDS patients, and no effective treatments are yet available. This parasite possesses a single fatty acyl-CoA binding protein (CpACBP1) that is localized to the unique parasitophorous vacuole membrane (PVM). The major goal of this study was to identify inhibitors from known drugs against CpACBP1 as potential new anti-Cryptosporidium agents. Methods A fluorescence assay was developed to detect CpACBP1 activity and to identify inhibitors by screening known drugs. Efficacies of top CpACBP1 inhibitors against Cryptosporidium growth in vitro were evaluated using a quantitative RT–PCR assay. Results Nitrobenzoxadiazole-labelled palmitoyl-CoA significantly increased the fluorescent emission upon binding to CpACBP1 (excitation/emission 460/538 nm), which was quantified to determine the CpACBP1 activity and binding kinetics. The fluorescence assay was used to screen a collection of 1040 compounds containing mostly known drugs, and identified the 28 most active compounds that could inhibit CpACBP1 activity with sub-micromolar IC50 values. Among them, four compounds displayed efficacies against parasite growth in vitro with low micromolar IC50 values. The effective compounds were broxyquinoline (IC50 64.9 μM), cloxyquin (IC50 25.1 μM), cloxacillin sodium (IC50 36.2 μM) and sodium dehydrocholate (IC50 53.2 μM). Conclusions The fluorescence ACBP assay can be effectively used to screen known drugs or other compound libraries. Novel anti-Cryptosporidium activity was observed in four top CpACBP1 inhibitors, which may be further investigated for their potential to be repurposed to treat cryptosporidiosis and to serve as leads for drug development. PMID:22167242

  12. 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

  13. Inhibition by toxic compounds in the hemicellulosic hydrolysates on the activity of xylose reductase from Candida tropicalis.

    PubMed

    Rafiqul, I S M; Sakinah, A M M; Zularisam, A W

    2015-01-01

    Xylose reductase (XR) is an oxidoreductase having potential applications in the production of various specialty products, mainly xylitol. It is important to screen for compounds that can decrease XR activity and consequently can decrease xylitol production. We have identified the byproducts in the hemicellulosic hydrolysate that inhibit XR from Candida tropicalis and measured their effects. XR inhibitory activities of byproducts, glucose, acetic acid, arabinose, lignin-degradation products (LDPs), furfural and hydroxymethylfurfural (HMF), were evaluated by measuring the MIC and IC50 values. XR activity was 11.2 U/ml. Acetic acid, LDPs, furfural and HMF significantly inhibited XR with IC50 values of 11, 6.4, 2.3 and 0.4 g/l, respectively. This is the first report on the inhibitory activities of several byproducts for XR. PMID:25214231

  14. 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 M and 3,3',5-trihydroxy-2'-methoxybibenzyl showed the highest inhibition with an IC50 value of 8.8 M. This study is a first to reveal the pancreatic lipase inhibitory activity by both D. opposita and its isolated compounds. PMID:23327640

  15. Design, Synthesis, and Biological Characterization of Novel Mitochondria Targeted Dichloroacetate-Loaded Compounds with Antileukemic Activity.

    PubMed

    Trapella, Claudio; Voltan, Rebecca; Melloni, Elisabetta; Tisato, Veronica; Celeghini, Claudio; Bianco, Sara; Fantinati, Anna; Salvadori, Severo; Guerrini, Remo; Secchiero, Paola; Zauli, Giorgio

    2016-01-14

    The mitochondrial kinase inhibitor dichloroacetate (DCA) has recently received attention in oncology due to its ability to target glycolysis. However, DCA molecule exhibits poor bioavailability and cellular uptake with limited ability to reach its target mitochondria. To overcome these biases, we have synthesized novel DCA-loaded compounds. The selection of the most promising therapeutic molecule was evaluated by combining in vitro assays, to test the antitumoral potential on leukemic cells, and a preliminary characterization of the molecule stability in vivo, in mice. Among the newly synthesized compounds, we have selected the multiple DCA-loaded compound 10, characterized by a tertiary amine scaffold, because it exhibited enhanced (>30-fold) in vitro antitumor activity with respect to DCA and increased in vivo stability. On the basis of these results, we believe that compound 10 should be considered for further preclinical evaluations for the treatment of cancers and/or other diseases characterized by altered metabolic origin. PMID:26653539

  16. Custom active RFId solution for children tracking and identifying in a resuscitation ward.

    PubMed

    Iadanza, Ernesto; Dori, Fabrizio

    2009-01-01

    In this work is discussed an active RFId system to track and identify patients in a children's critical care ward. The technical solutions may be very different according to the patients type, age and cognitive conditions and according to the hospital shapes. The proposed system to track and identify patients has been developed taking into account all the constraints induced by the particular environment. The system is composed of five different hardware devices and a tracking software, purposely designed and realized. PMID:19964116

  17. Seasonal variation of pharmaceutically active compounds in surface (Tagus River) and tap water (Central Spain).

    PubMed

    Valcrcel, Y; Alonso, S Gonzlez; Rodrguez-Gil, J L; Castao, A; Montero, J C; Criado-Alvarez, J J; Mirn, I J; Catal, M

    2013-03-01

    Numerous studies have shown the presence of pharmaceutically active compounds (PhACs) in different environmental compartments, for example, in surface water or wastewater ranging from nanograms per litre to micrograms per litre. Likewise, some recent studies have pointed to seasonal variability, thus indicating that PhAcs concentrations in the aquatic environment may depend on the time of year. This work intended to find out (1) whether Tagus fluvial and drinking water were polluted with different groups of PhACs and (2) if their concentrations differed between winter and summer seasons. From the 58 substances analysed, 41 were found belonging to the main therapeutic groups. Statistical differences were seen for antibacterials, antidepressants, anxiolytics, antiepileptics, and cardiovascular drugs, with higher concentrations being detected in winter than in summer. These results might indicate that the PhACs analysed in this study undergo lower environmental degradation in winter than in summer. In order to confirm these initial results, a continuous monitoring should be performed especially on those PhACs that either because of an elevated consumption or an intrinsic chemical persistence are poorly degraded during winter months due to low temperatures and solar irradiation. It is especially important to identify which of these specific PhACs are in order to recommend their substitution by equally effective and safe substances but also environmentally friendly. PMID:22847337

  18. 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.

  19. Antimicrobial activities of the methanol extract and compounds from the twigs of Dorstenia mannii (Moraceae)

    PubMed Central

    2012-01-01

    Background Dorstenia mannii (Moraceae) is a medicinal herb used traditionally for the treatment of many diseases. In the present study, the methanol extract of D. mannii and nine of its isolated compounds, namely dorsmanin A (1), B (2), C (3), D (4), E (6), F (7), G (8) dorsmanin I (9) and 6,8-diprenyleriodictyol (5), were tested for their antimicrobial activities against yeast, Mycobacteria and Gram-negative bacteria. Methods The microplate alamar blue assay (MABA) and the broth microdilution method were used to determine the minimal inhibitory concentration (MIC) and minimal microbicidal concentration (MMC) of the above extract and compounds on a panel of bacterial species. Results The results of the MIC determinations demonstrated that the methanol extract as well as compounds 3 and 8 were able to prevent the growth of all the fourteen studied microorganisms within the concentration range of 4 to 1024 μg/ml. The lowest MIC value for the methanol extract (64 μg/ml) was obtained on Candida albicans. The lowest value for individual compounds (4 μg/ml) was recorded with compounds 3 on Pseudomonas aeruginosa PA01 and 7 on Eschericia coli ATCC strain. The MIC values recorded with compounds 3 on P. aeruginosa PA01, 6 on C. albicans,7 on P. aeruginosa PA01 and K. pneumoniae ATCC strain and C. albicans,and 8 on P. aeruginosa PA01, PA124, P. stuartii, M. tuberculosis MTCS1 were lower than or equal to those of the reference drugs. MMC values not greater than 1024 μg/ml were recorded on all studied microorganisms with compounds 3 and 8. Conclusion The overall results of the present investigation provided evidence that the crude extract of D. mannii as well as some of its compounds such compounds 3 and 8 could be a potential source of natural antimicrobial products. PMID:22747736

  20. Active Compounds Against Anopheles minimus Carboxypeptidase B for Malaria Transmission-Blocking Strategy.

    PubMed

    Mongkol, Watcharakorn; Arunyawat, Uraiwan; Surat, Wunrada; Kubera, Anchanee

    2015-11-01

    Malaria transmission-blocking compounds have been studied to block the transmission of malaria parasites, especially the drug-resistant Plasmodium. Carboxypeptidase B (CPB) in the midgut of Anopheline mosquitoes has been demonstrated to be essential for the sexual development of Plasmodium in the mosquito. Thus, the CPB is a potential target for blocking compounds. The aim of this research was to screen compounds from the National Cancer Institute (NCI) diversity dataset and U.S. Food and Drug Administration (FDA)-approved drugs that could reduce the Anopheles CPB activity. The cDNA fragment of cpb gene from An. minimus (cpbAmi) was amplified and sequenced. The three-dimensional structure of CPB was predicted from the deduced amino acid sequence. The virtual screening of the compounds from NCI diversity set IV and FDA-approved drugs was performed against CPBAmi. The inhibition activity against CPBAmi of the top-scoring molecules was characterized in vitro. Three compounds-NSC-1014, NSC-332670, and aminopterin with IC50 at 0.99 mM, 1.55 mM, and 0.062 mM, respectively-were found to significantly reduce the CPBAmi activity. PMID:26352934

  1. Performance of phenol-acclimated activated sludge in the presence of various phenolic compounds

    NASA Astrophysics Data System (ADS)

    Lim, Jun-Wei; Tan, Je-Zhen; Seng, Chye-Eng

    2013-06-01

    The objective of this study was to evaluate the performance of phenol-acclimated activated sludge in the presence of various phenolic compounds in the separated batch reactors. The phenol-acclimated activated sludge was observed to be capable of completely removing phenol, o-cresol, m-cresol, and 4-chlorophenol. Nevertheless, in the presence of 2-chlorophenol and 3-chlorophenol merely at 50 mg/L, incomplete removal of these phenolic compounds were noticed. The specific oxygen uptake rate patterns obtained for phenol, o-cresol, m-cresol, and 4-chlorophenol could be used to approximate the end point of these phenolic compounds removal as well as to monitor the growth of biomass. As the 2-chlorophenol and 3-chlorophenol were only partially removed in the mixed liquor, the patterns of specific oxygen uptake rate attained for these phenolic compounds were not feasible for the similar estimation. The calculated toxicity percentages show the toxicity effects of phenolic compounds on the phenol-acclimated activated sludge followed the order of 2-chlorophenol ? 3-chlorophenol > 4-chlorophenol > o-cresol ? m-cresol > phenol.

  2. Neuroprotective and free radical scavenging activities of phenolic compounds from Hovenia dulcis.

    PubMed

    Li, Gao; Min, Byung-Sun; Zheng, Changji; Lee, Joongku; Oh, Sei-Ryang; Ahn, Kyung-Seop; Lee, Hyeong-Kyu

    2005-07-01

    The EtOAc-soluble fraction from a methanolic extract of Hovenia dulcis Thunb. exhibited neuroprotective activity against glutamate-induced neurotoxicity in mouse hippocampal HT22 cells. The neuroprotective activity-guided isolation resulted in 8 phenolic compounds (1-8), such as vanillic acid (1), ferulic acid (2), 3,5-dihydroxystilbene (3), (+)-aromadendrin (4), methyl vanillate (5), (-)-catechin (6), 2,3,4-trihydrobenzoic acid (7), and (+)-afzelechin (8). Among these, compounds 6 and 8 had a neuroprotective effect on the glutamate-induced neurotoxicity in HT22 cells. Furthermore, compound 6 had a DPPH free radical scavenging effect with an IC50 value of 57.7 microM, and a superoxide anion radical scavenging effect with an IC50 value of 8.0 microM. Both compounds 6 and 8 had ABTS cation radical scavenging effects with IC50 values of 7.8 microM and 23.7 microM, respectively. These results suggest that compounds 6 and 8 could be neuroprotectants owing to their free radical scavenging activities. PMID:16114495

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

    PubMed

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

    2014-12-01

    The antifungal activity of twenty-two common spices was evaluated against plant pathogens using direct-bioautography coupled Colletotrichum bioassays. Turmeric, nutmeg, ginger, clove, oregano, cinnamon, anise, fennel, basil, black cumin, and black pepper showed antifungal activity against the plant pathogens Colletotrichum acutatum, Colletotrichum fragariae, and Colletotrichum gloeosporioides. Among the active extracts, turmeric and nutmeg were the most active and were chosen for further investigation. The bioassay-guided fractionation led to the isolation of three compounds from turmeric (1-3) and three compounds from nutmeg (4-6). Their chemical structures were elucidated by spectroscopic analysis including HR-MS, 1D, and 2D NMR as curcumin (1), demethoxycurcumin (2) and bisdemethoxy-curcumin (3), erythro-(7R,8R)-Δ(8')-4,7-dihydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan (4), erythro-(7R,8R)-Δ8'-7-acetoxy-3,4,3',5'-tetra-methoxy-8-O-4'-neolignan (5), and 5-hydroxy-eugenol (6). The isolated compounds were subsequently evaluated using a 96-well microbioassay against plant pathogens. At 30 μM, compounds 2 and 3 possessed the most antifungal activity against Phomopsis obscurans and Phomopsis viticola, respectively. PMID:25173461

  4. Synthesis and biological activity of amino acid derivatives of avarone and its model compound.

    PubMed

    Vilipi?, Jovana; Novakovi?, Irena; Stanojkovi?, Tatjana; Mati?, Ivana; egan, Dejan; Kljaji?, Zoran; Sladi?, Duan

    2015-11-01

    A series of eighteen derivatives of marine sesquiterpene quinone avarone and its model system tert-butylquinone with amino acids has been synthesized by nucleophilic addition of amino acids to the quinones. In vitro cytotoxic activity toward human cancer cell lines (HeLa, A549, Fem-X, K562, MDA-MB-453) and normal MRC-5 cell line was determined. Several compounds showed very strong inhibitory activity with IC50 values less than 10?M. Avarone derivatives were more active than the corresponding tert-butylquinone derivatives. The results of the cytofluorimetric analysis of cell cycle of HeLa cells showed that apoptosis might be one of possible mechanism of action of these compounds in cancer cells. In order to examine the influence of caspases on cell death, the apoptotic mechanisms induced by the tested compounds were determined using specific caspases 3, 8 and 9 inhibitors. For all compounds antibacterial activities against six strains of Gram-positive and four strains of Gram-negative bacteria were determined, as well as antifungal activity against three fungal species. PMID:26476666

  5. Monitoring of pharmaceutically active compounds on the Guadalquivir River basin (Spain): occurrence and risk assessment.

    PubMed

    Martn, J; Camacho-Muoz, D; Santos, J L; Aparicio, I; Alonso, E

    2011-07-01

    Guadalquivir River (South of Spain) is among the major freshwater sources of the European Atlantic basin. Until now scientific efforts have been focused on contamination by heavy metals and some priority pollutants in Guadalquivir River. However, the presence of "emerging contaminants", such as pharmaceutically active compounds, has not yet been studied. In this work the occurrence and risk assessment of sixteen pharmaceutically active compounds, belonging to different therapeutic groups, in Guadalquivir River during its course through Seville city are reported. Wastewater effluents from four wastewater treatment plants discharging into Guadalquivir River and river water samples were analyzed. All studied pharmaceutically active compounds, except sulfamethoxazole, trimethoprim, estrone and clofibric acid, were detected in effluent wastewaters at concentration levels up to 28.9 ?g L(-1). Among the pharmaceutically active compounds found in effluent wastewater, seven were present in Guadalquivir River samples at concentration levels up to 0.75 ?g L(-1), which indicated an important dilution from effluent discharge. Environmental risk assessment reveals that potential ecotoxicological risk cannot be expected on Guadalquivir River at measured concentration levels. Only, the lipid regulator gemfibrozil showed a medium risk for the environment. The risk for acute toxic effects in the environment with the current use of active pharmaceutical ingredients is unlikely. However, the results do not rule out the potential for chronic environmental effects. PMID:21666922

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

    PubMed

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

    2005-04-01

    The screening of 50 sorghum varieties showed that, on average, germination did not affect the content in total phenolic compounds but decreased the content of proanthocyanidins, 3-deoxyanthocyanidins, and flavan-4-ols. Independent of germination, there are intervarietal differences in antioxidant activities among sorghum varieties. Phenolic compounds and antioxidant activities were more positively correlated in ungerminated varieties than in germinated ones. Sorghum grains with pigmented testa layer, chestnut color glumes, and red plants had higher contents, larger diversity of phenolic compounds, and higher antioxidant activities than other sorghums. Some red sorghum varieties had higher antioxidant activities (30-80 mumol of Trolox equiv/g) than several sources of natural antioxidants from plant foods. Among varieties used for "to", "dolo", couscous, and porridge preparation, the "dolo"(local beer) varieties had the highest average content and diversity in phenolic compounds as well as the highest antioxidant activities. The biochemical markers determined are useful indicators for the selection of sorghum varieties for food and agronomic properties. PMID:15796598

  7. 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

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

    PubMed Central

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

    2003-01-01

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

  9. Rethinking molecular similarity: comparing compounds on the basis of biological activity.

    PubMed

    Petrone, Paula M; Simms, Benjamin; Nigsch, Florian; Lounkine, Eugen; Kutchukian, Peter; Cornett, Allen; Deng, Zhan; Davies, John W; Jenkins, Jeremy L; Glick, Meir

    2012-08-17

    Since the advent of high-throughput screening (HTS), there has been an urgent need for methods that facilitate the interrogation of large-scale chemical biology data to build a mode of action (MoA) hypothesis. This can be done either prior to the HTS by subset design of compounds with known MoA or post HTS by data annotation and mining. To enable this process, we developed a tool that compares compounds solely on the basis of their bioactivity: the chemical biological descriptor "high-throughput screening fingerprint" (HTS-FP). In the current embodiment, data are aggregated from 195 biochemical and cell-based assays developed at Novartis and can be used to identify bioactivity relationships among the in-house collection comprising ~1.5 million compounds. We demonstrate the value of the HTS-FP for virtual screening and in particular scaffold hopping. HTS-FP outperforms state of the art methods in several aspects, retrieving bioactive compounds with remarkable chemical dissimilarity to a probe structure. We also apply HTS-FP for the design of screening subsets in HTS. Using retrospective data, we show that a biodiverse selection of plates performs significantly better than a chemically diverse selection of plates, both in terms of number of hits and diversity of chemotypes retrieved. This is also true in the case of hit expansion predictions using HTS-FP similarity. Sets of compounds clustered with HTS-FP are biologically meaningful, in the sense that these clusters enrich for genes and gene ontology (GO) terms, showing that compounds that are bioactively similar also tend to target proteins that operate together in the cell. HTS-FP are valuable not only because of their predictive power but mainly because they relate compounds solely on the basis of bioactivity, harnessing the accumulated knowledge of a high-throughput screening facility toward the understanding of how compounds interact with the proteome. PMID:22594495

  10. An artificial neural network to estimate physical activity energy expenditure and identify physical activity type from an accelerometer

    PubMed Central

    Pober, David; Crouter, Scott; Bassett, David; Freedson, Patty

    2009-01-01

    The aim of this investigation was to develop and test two artificial neural networks (ANN) to apply to physical activity data collected with a commonly used uniaxial accelerometer. The first ANN model estimated physical activity metabolic equivalents (METs), and the second ANN identified activity type. Subjects (n = 24 men and 24 women, mean age = 35 yr) completed a menu of activities that included sedentary, light, moderate, and vigorous intensities, and each activity was performed for 10 min. There were three different activity menus, and 20 participants completed each menu. Oxygen consumption (in mlkg?1min?1) was measured continuously, and the average of minutes 49 was used to represent the oxygen cost of each activity. To calculate METs, activity oxygen consumption was divided by 3.5 mlkg?1min?1 (1 MET). Accelerometer data were collected second by second using the Actigraph model 7164. For the analysis, we used the distribution of counts (10th, 25th, 50th, 75th, and 90th percentiles of a minute's second-by-second counts) and temporal dynamics of counts (lag, one autocorrelation) as the accelerometer feature inputs to the ANN. To examine model performance, we used the leave-one-out cross-validation technique. The ANN prediction of METs root-mean-squared error was 1.22 METs (confidence interval: 1.141.30). For the prediction of activity type, the ANN correctly classified activity type 88.8% of the time (confidence interval: 86.491.2%). Activity types were low-level activities, locomotion, vigorous sports, and household activities/other activities. This novel approach of applying ANNs for processing Actigraph accelerometer data is promising and shows that we can successfully estimate activity METs and identify activity type using ANN analytic procedures. PMID:19644028

  11. Genome-wide quantitative enhancer activity maps identified by STARR-seq.

    PubMed

    Arnold, Cosmas D; Gerlach, Daniel; Stelzer, Christoph; Bory?, ?ukasz M; Rath, Martina; Stark, Alexander

    2013-03-01

    Genomic enhancers are important regulators of gene expression, but their identification is a challenge, and methods depend on indirect measures of activity. We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes. When applied to the Drosophila genome, STARR-seq identifies thousands of cell type-specific enhancers across a broad continuum of strengths, links differential gene expression to differences in enhancer activity, and creates a genome-wide quantitative enhancer map. This map reveals the highly complex regulation of transcription, with several independent enhancers for both developmental regulators and ubiquitously expressed genes. STARR-seq can be used to identify and quantify enhancer activity in other eukaryotes, including humans. PMID:23328393

  12. Stress responses. Mutations in a translation initiation factor identify the target of a memory-enhancing compound.

    PubMed

    Sekine, Yusuke; Zyryanova, Alisa; Crespillo-Casado, Ana; Fischer, Peter M; Harding, Heather P; Ron, David

    2015-05-29

    The integrated stress response (ISR) modulates messenger RNA translation to regulate the mammalian unfolded protein response (UPR), immunity, and memory formation. A chemical ISR inhibitor, ISRIB, enhances cognitive function and modulates the UPR in vivo. To explore mechanisms involved in ISRIB action, we screened cultured mammalian cells for somatic mutations that reversed its effect on the ISR. Clustered missense mutations were found at the amino-terminal portion of the delta subunit of guanine nucleotide exchange factor (GEF) eIF2B. When reintroduced by CRISPR-Cas9 gene editing of wild-type cells, these mutations reversed both ISRIB-mediated inhibition of the ISR and its stimulatory effect on eIF2B GEF activity toward its substrate, the translation initiation factor eIF2, in vitro. Thus, ISRIB targets an interaction between eIF2 and eIF2B that lies at the core of the ISR. PMID:25858979

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

    PubMed Central

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

    2015-01-01

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

  14. Quantitative assessment of bioactive compounds and the antioxidant activity of 15 jujube cultivars.

    PubMed

    Kou, Xiaohong; Chen, Qiong; Li, Xianhua; Li, Mianfang; Kan, Cong; Chen, Boru; Zhang, Ying; Xue, Zhaohui

    2015-04-15

    Fifteen jujube cultivars late in their maturation were analysed in the red stage for bioactive compounds; including total phenolics (bound/free), total flavonoids, total polysaccharides, ascorbic acid, total triterpenes, proanthocyanidins and cyclic adenosine monophosphate (cAMP). The antioxidant activity was evaluated using the 2,2-diphenyl-1-picrylhydracyl (DPPH) and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonicacid) (ABTS(+)) scavenging methods and the ferric reducing antioxidant power (FRAP) assay. The Order Performance by Similarity to Ideal Solution method (TOPSIS) was employed to evaluate the nutrition of different jujube cultivars based on their bioactive compounds. The results indicated that the contents of bioactive compounds and antioxidant capacities vary between different jujube cultivars. Correlation analysis revealed that ascorbic acid, polyphenols and proanthocyanidins were the 3 main components responsible for the antioxidant activity of jujubes. TOPSIS analysis indicated that Zyzyphus jujube cv. Nanjingyazao ranks the highest of the 15 jujube fruits with regards to nutritional value. PMID:25466122

  15. 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

  16. Identifying clustering at high redshift through actively star-forming galaxies

    NASA Astrophysics Data System (ADS)

    Davies, L. J. M.; Bremer, M. N.; Stanway, E. R.; Husband, K.; Lehnert, M. D.; Mannering, E. J. A.

    2014-03-01

    Identifying galaxy clustering at high redshift (i.e. z > 1) is essential to our understanding of the current cosmological model. However, at increasing redshift, clusters evolve considerably in star formation activity and so are less likely to be identified using the widely used red-sequence method. Here we assess the viability of instead identifying high-redshift clustering using actively star-forming galaxies (submillimetre galaxies, SMGs, associated with overdensities of BzKs/LBGs). We perform both a 2D and 3D clustering analysis to determine whether or not true (3D) clustering can be identified where only 2D data are available. As expected, we find that 2D clustering signals are weak at best and inferred results are method dependent. In our 3D analysis, we identify 12 SMGs associated with an overdensity of galaxies coincident both spatially and in redshift - just 8 per cent of SMGs with known redshifts in our sample. Where an SMG in our target fields lacks a known redshift, their sight line is no more likely to display clustering than blank sky fields; prior redshift information for the SMG is required to identify a true clustering signal. We find that the strength of clustering in the volume around typical SMGs, while identifiable, is not exceptional. However, we identify a small number of highly clustered regions, all associated with an SMG. The most notable of these, surrounding LESS J033336.8-274401, potentially contains an SMG, a quasi stellar object (QSO) and 36 star-forming galaxies (a >20σ overdensity) all at z ˜ 1.8. This region is highly likely to represent an actively star-forming cluster and illustrates the success of using star-forming galaxies to select sites of early clustering. Given the increasing number of deep fields with large volumes of spectroscopy, or high quality and reliable photometric redshifts, this opens a new avenue for cluster identification in the young Universe.

  17. SABER: a computational method for identifying active sites for new reactions.

    PubMed

    Nosrati, Geoffrey R; Houk, K N

    2012-05-01

    A software suite, SABER (Selection of Active/Binding sites for Enzyme Redesign), has been developed for the analysis of atomic geometries in protein structures, using a geometric hashing algorithm (Barker and Thornton, Bioinformatics 2003;19:1644-1649). SABER is used to explore the Protein Data Bank (PDB) to locate proteins with a specific 3D arrangement of catalytic groups to identify active sites that might be redesigned to catalyze new reactions. As a proof-of-principle test, SABER was used to identify enzymes that have the same catalytic group arrangement present in o-succinyl benzoate synthase (OSBS). Among the highest-scoring scaffolds identified by the SABER search for enzymes with the same catalytic group arrangement as OSBS were L-Ala D/L-Glu epimerase (AEE) and muconate lactonizing enzyme II (MLE), both of which have been redesigned to become effective OSBS catalysts, demonstrated by experiments. Next, we used SABER to search for naturally existing active sites in the PDB with catalytic groups similar to those present in the designed Kemp elimination enzyme KE07. From over 2000 geometric matches to the KE07 active site, SABER identified 23 matches that corresponded to residues from known active sites. The best of these matches, with a 0.28 catalytic atom RMSD to KE07, was then redesigned to be compatible with the Kemp elimination using RosettaDesign. We also used SABER to search for potential Kemp eliminases using a theozyme predicted to provide a greater rate acceleration than the active site of KE07, and used Rosetta to create a design based on the proteins identified. PMID:22492397

  18. 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

  19. A simplified method to assess structurally identifiable parameters in Monod-based activated sludge models.

    PubMed

    Petersen, Britta; Gernaey, Krist; Devisscher, Martijn; Dochain, Denis; Vanrolleghem, Peter A

    2003-07-01

    The first step in the estimation of parameters of models applied for data interpretation should always be an investigation of the identifiability of the model parameters. In this study the structural identifiability of the model parameters of Monod-based activated sludge models (ASM) was studied. In an illustrative example it was assumed that respirometric (dissolved oxygen or oxygen uptake rates) and titrimetric (cumulative proton production) measurements were available for the characterisation of nitrification. Two model structures, including the presence and absence of significant growth for description of long- and short-term experiments, respectively, were considered. The structural identifiability was studied via the series expansion methods. It was proven that the autotrophic yield becomes uniquely identifiable when combined respirometric and titrimetric data are assumed for the characterisation of nitrification. The most remarkable result of the study was, however, that the identifiability results could be generalised by applying a set of ASM1 matrix based generalisation rules. It appeared that the identifiable parameter combinations could be predicted directly based on the knowledge of the process model under study (in ASM1-like matrix representation), the measured variables and the biodegradable substrate considered. This generalisation reduces the time-consuming task of deriving the structurally identifiable model parameters significantly and helps the user to obtain these directly without the necessity to go too deeply into the mathematical background of structural identifiability. PMID:12767292

  20. Synthesis, pharmacological activity evaluation and molecular modeling of new polynuclear heterocyclic compounds containing benzimidazole derivatives.

    PubMed

    Bassyouni, Fatma A; Saleh, Tamer S; ElHefnawi, Mahmoud M; Abd El-Moez, Sherein I; El-Senousy, Waled M; Abdel-Rehim, Mohamed E

    2012-12-01

    Novel heterocyclic compounds containing benzimidazole derivatives were synthesized from 2-(1H-benzimidazol-2-yl) acetonitrile (1) and arylhydrazononitrile derivative 2 was obtained via coupling of 1 with 4-methyl phenyldiazonium salt, which was then reacted with hydroxylamine hydrochloride to give amidooxime derivative 3. This product was cyclized into the corresponding oxadiazole derivative 4 upon reflux in acetic anhydride. Compound 4 was refluxed in DMF in the presence of triethylamine to give the corresponding 5-(1H-benzimidazol-2-yl)-2-p-tolyl-2H-1,2,3-triazol-4-amine 6. Treatment of compound 6 with ethyl chloroformate afforded 2,6-dihydro-2-(4-methylphenyl)-1,2,3-triazolo[4",5"-4',5']pyrimido[1,6-a]benzimidazole-5(4H)-one (8). 1,2-bis(2-cyanomethyl-1H-benzimidazol-1-yl)ethane-1,2-dione (10) was synthesized via the condensation reaction of 2-(1H-benzimidazol-2-yl) acetonitrile (1) and diethyloxalate. The reactivity of compound 10 towards some diamine reagents was studied. The in vitro antimicrobial activity of the synthesized compounds was investigated against several pathogenic bacterial strains such as Escherichia coli O157, Salmonella typhimurium, E. coli O119, S. paratyphi, Pseudomonas aeruginosa, Staphylococcus aureus, Listeria monocytogenes and Bacillus cereus. The results of MIC revealed that compounds 12a-c showed the most effective antimicrobial activity against tested strains. On the other hand, compounds 12a, b exhibited high activity against rotavirus Wa strain while compounds 12b, c exhibited high activity against adenovirus type 7. In silico target prediction, docking and validation of the compounds 12a-c were performed. The dialkylglycine decarboxylase bacterial enzyme was predicted as a potential bacterial target receptor using pharmacophore-based correspondence with previous leads; giving the highest normalized scores and a high correlation docking score with mean inhibition concentrations. A novel binding mechanism was predicted after docking using the MOE software and its validation. PMID:23263801

  1. 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

  2. Optimization of the culture condition for an antitumor bacterium Serratia proteamacula 657 and identification of the active compounds.

    PubMed

    Miao, Li; Wang, Xueling; Jiang, Wei; Yang, Shengping; Zhou, Huiru; Zhai, Youpeng; Zhou, Xiaojian; Dong, Kunming

    2013-05-01

    Exploration of novel active anti-tumor compounds from marine microbes for pharmaceutical applications has been a continuously hot spot in natural product research. Bacterial growth and metabolites may greatly vary under different culture conditions. In this study, the effects of different culture conditions and medium components on the growth and bioactive metabolites of Serratia proteamacula 657, an anti-tumor bacterium found in our previous study, were investigated. The results showed that lower temperature, weak acidic condition and solid fermentation favored the bacterial growth and the production of active compounds. Four components in the culture medium, NaCl, peptone, yeast extract and MgSO4, were found important to the bacterial growth and active compounds production in medium optimization. Under the optimized condition of solid state fermentation at pH 6.0-7.0, 23-25 C, with the MgSO4-free medium containing 10.0 g/L peptone, 1.0 g/L yeast extract and 19.45 g/L NaCl, the antitumor activity of S. proteamacula 657 and the yield of crude extracts increased about 15 times and 6 times than the sample obtained in the original liquid fermentation, respectively. The active components in the metabolites of S. proteamacula 657 were identified as a homolog of prodigiosin, a red bacterial pigment, based on the analysis of the NMR and GC-MS. The bacterium S. proteamacula 657, which is adapted to lower temperature, produced prodigiosin-like pigments with highly antitumor activity, suggesting the bacterium is a potential new source for prodigiosin production. PMID:23271461

  3. Synthesis, spectroscopy and antibacterial activity of supermolecular compounds of organotitanium substituted heteropolytungstates containing 8-quinolinol.

    PubMed

    Feng, Chang-gen; Xiong, Yu-di; Liu, Xia

    2011-05-01

    Parent compounds of cyclopentadienyltitanium substituted heteropolytungstates with Keggin structure, An[(CpTi)XW11O39] xH2O (A=Me4N, K; X=P, Si, Co; Cp=eta5-C5H5) were synthesized in aqueous phase. By allowing parent heteropoly compounds to react with protonated 8-quinolinol, the title supermolecular compounds (C9H8NO)mAn[(CpTi)XW11O39] xH2O (A=Me4N, H; X=P, Si, Co) were synthesized. The title compounds were characterized by means of elementary analysis, IR, UV, 1H NMR, XRD and TG-DSC. The results indicate that the title compounds are new heteropoly compounds, and there is a charge transfer interaction between the organic cation and heteropoly anion. The results obtained from thermal analysis show that QCpTiPW, QCpTiSiW and QCpTiCoW begin to decompose at 212.4, 194.2 and 171.2 degrees C, respectively. The results obtained from antibacterial test reveal that QCpTiSiW has the best antibacterial activity, and the MIC values of QCpTiSiW against Escherichia coli and Staphylococcus aurous are 64.0 and 0.500 microg mL(-1), respectively. PMID:21800553

  4. 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

  5. Identifying Predictors of Activity Based Anorexia Susceptibility in Diverse Genetic Rodent Populations

    PubMed Central

    Pjetri, Eneda; de Haas, Ria; de Jong, Simone; Gelegen, Cigdem; Oppelaar, Hugo; Verhagen, Linda A. W.; Eijkemans, Marinus J. C.; Adan, Roger A.; Olivier, Berend; Kas, Martien J.

    2012-01-01

    Animal studies are very useful in detection of early disease indicators and in unravelling the pathophysiological processes underlying core psychiatric disorder phenotypes. Early indicators are critical for preventive and efficient treatment of progressive psychiatric disorders like anorexia nervosa. Comparable to physical hyperactivity observed in anorexia nervosa patients, in the activity-based anorexia rodent model, mice and rats express paradoxical high voluntary wheel running activity levels when food restricted. Eleven inbred mouse strains and outbred Wistar WU rats were exposed to the activity-based anorexia model in search of identifying susceptibility predictors. Body weight, food intake and wheel running activity levels of each individual mouse and rat were measured. Mouse strains and rats with high wheel running activity levels during food restriction exhibited accelerated body weight loss. Linear mixed models for repeated measures analysis showed that baseline wheel running activity levels preceding the scheduled food restriction phase strongly predicted activity-based anorexia susceptibility (mice: Beta ?=? ?0.0158 (0.003 SE), P<0.0001; rats: Beta ?=? ?0.0242 (0.004 SE), P<0.0001) compared to other baseline parameters. These results suggest that physical activity levels play an important role in activity-based anorexia susceptibility in different rodent species with genetically diverse background. These findings support previous retrospective studies on physical activity levels in anorexia nervosa patients and indicate that pre-morbid physical activity levels could reflect an early indicator for disease severity. PMID:23226287

  6. Identifying predictors of activity based anorexia susceptibility in diverse genetic rodent populations.

    PubMed

    Pjetri, Eneda; de Haas, Ria; de Jong, Simone; Gelegen, Cigdem; Oppelaar, Hugo; Verhagen, Linda A W; Eijkemans, Marinus J C; Adan, Roger A; Olivier, Berend; Kas, Martien J

    2012-01-01

    Animal studies are very useful in detection of early disease indicators and in unravelling the pathophysiological processes underlying core psychiatric disorder phenotypes. Early indicators are critical for preventive and efficient treatment of progressive psychiatric disorders like anorexia nervosa. Comparable to physical hyperactivity observed in anorexia nervosa patients, in the activity-based anorexia rodent model, mice and rats express paradoxical high voluntary wheel running activity levels when food restricted. Eleven inbred mouse strains and outbred Wistar WU rats were exposed to the activity-based anorexia model in search of identifying susceptibility predictors. Body weight, food intake and wheel running activity levels of each individual mouse and rat were measured. Mouse strains and rats with high wheel running activity levels during food restriction exhibited accelerated body weight loss. Linear mixed models for repeated measures analysis showed that baseline wheel running activity levels preceding the scheduled food restriction phase strongly predicted activity-based anorexia susceptibility (mice: Beta ?=? -0.0158 (0.003 SE), P<0.0001; rats: Beta ?=? -0.0242 (0.004 SE), P<0.0001) compared to other baseline parameters. These results suggest that physical activity levels play an important role in activity-based anorexia susceptibility in different rodent species with genetically diverse background. These findings support previous retrospective studies on physical activity levels in anorexia nervosa patients and indicate that pre-morbid physical activity levels could reflect an early indicator for disease severity. PMID:23226287

  7. 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...

  8. 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...

  9. 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...

  10. COST ANALYSIS OF ACTIVATED CARBON VERSUS PHOTOCATALYTIC OXIDATION FOR REMOVING ORGANIC COMPOUNDS FROM INDOOR AIR

    EPA Science Inventory

    A cost comparison has been conducted of 1 m3/s indoor air cleaners using granular activated carbon (GAC) vs. photocatalytic oxidation (PCO) for treating a steady-state inlet volatile organic compound (VOC) concentration of 0.3 mg/m3. The commercial GAC unit was costed assuming t...

  11. Intercalation and controlled release of pharmaceutically active compounds from a layered double hydroxide.

    PubMed

    Khan, A I; Lei, L; Norquist, A J; O'Hare, D

    2001-11-21

    A series of pharmaceutically active compounds including diclofenac, gemfibrozil, ibuprofen, naproxen, 2-propylpentanoic acid, 4-biphenylacetic acid and tolfenamic acid can be reversibly intercalated into a layered double hydroxide, initial studies suggest that these materials may have application as the basis of a novel tuneable drug delivery system. PMID:12240066

  12. EFFECTIVENESS OF ACTIVATED CARBON FOR REMOVAL OF TOXIC AND/OR CARCINOGENIC COMPOUNDS FROM WATER SUPPLIES

    EPA Science Inventory

    This research addressed quantification of the performance of fixed-bed granular activated carbon processes for treatment of public water supplies. It included evaluation of the adsorption of selected toxic and/or carcinogenic trace compounds of man-related origin, including carbo...

  13. 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.

  14. Antibacterial Activities of Naturally occurring Compounds against Mycobacterium avium subspecies paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibacterial activities of 19 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 subspecies paratuberculosis (Map), a bovine isolate NCTC 8578, a raw ...

  15. 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...

  16. Identifying the Common Characteristics of Comprehensive School Physical Activity Programs in Louisiana

    ERIC Educational Resources Information Center

    Deslatte, Kyrie'; Carson, Russell L.

    2014-01-01

    The purpose of this project was to (a) determine the common characteristics of current comprehensive school physical activity programs (CSPAP) in Louisiana and (b) identify strategies for implementing a CSPAP. Four individuals (i.e., one physical education teacher, one principal, and two classroom teachers) were recruited from three public schools

  17. Secoiridoid glucosides and related compounds from Syringa reticulata and their antioxidant activities.

    PubMed

    Bi, Xueyan; Li, Wei; Sasaki, Tatsunori; Li, Qin; Mitsuhata, Naoko; Asada, Yoshihisa; Zhang, Qingbo; Koike, Kazuo

    2011-11-01

    A 70% EtOH extract from the bark of Syringareticulata has shown significant antioxidant activity. Chemical study on the extract resulted in the isolation of seventeen compounds (1-17), including a novel oleoside-type secoiridoid glucoside, reticuloside (1), and the structures were elucidated on the basis of extensive spectroscopic analyses. Among the isolated compounds, jaspolyoside (2), oleuropein (4) and 2-(3,4-dihydroxy)-phenylethyl-?-d-glucopyranoside (17), showed the most potent superoxide anion scavenging activity with the EC(50) values of 4.97, 2.57 and 4.97?M, respectively. The structure-activity relationship indicated that the presence of 2-(3,4-dihydroxyphenyl)-ethoxy group is important for exhibiting the activity. PMID:21955940

  18. [Correlation between antioxidant activity and bioactive compounds of aa (Euterpe oleracea Mart) comercial pulps].

    PubMed

    Santos, Gerusa Matias dos; Maia, Geraldo Arraes; Sousa, Paulo Henrique Machado de; Costa, Jos Maria Correia da; Figueiredo, Raimundo Wilane de; Prado, Giovana Matias do

    2008-06-01

    The purpose of this work was to analyze commercial aa pulp and to correlate the contribution of vitamin C, total carotenoids and phenolic compounds with the antioxidant activity of there products besides the examination of the standard related to the quality of the obtained products. Analysis were made with regard to pH, acidity total, soluble solids, sugars, color, water activity, vitamin C, total anthocyanins, total carotenoids, antioxidant activity and phenolic compounds. All parameters analyzed showed significative difference among the marks not added with preservatives and sucrose. The aa fruit can be considered a fair source of vitamin C and good source of natural antioxidants. In regard to the correlation with the antioxidant activity only the total anthocyanins and the total carotenoids presented positive and significative correlation. PMID:18833997

  19. In Silico Analysis and Experimental Validation of Active Compounds from Cichorium intybus L. Ameliorating Liver Injury.

    PubMed

    Li, Guo-Yu; Zheng, Ya-Xin; Sun, Fu-Zhou; Huang, Jian; Lou, Meng-Meng; Gu, Jing-Kai; Wang, Jin-Hui

    2015-01-01

    This study aimed at investigating the possible mechanisms of hepatic protective activity of Cichorium intybus L. (chicory) in acute liver injury. Pathological observation, reactive oxygen species (ROS) detection and measurements of biochemical indexes on mouse models proved hepatic protective effect of Cichorium intybus L. Identification of active compounds in Cichorium intybus L. was executed through several methods including ultra performance liquid chromatography/time of flight mass spectrometry (UPLC-TOF-MS). Similarity ensemble approach (SEA) docking, molecular modeling, molecular docking, and molecular dynamics (MD) simulation were applied in this study to explore possible mechanisms of the hepato-protective potential of Cichorium intybus L. We then analyzed the chemical composition of Cichorium intybus L., and found their key targets. Furthermore, in vitro cytological examination and western blot were used for validating the efficacy of the selected compounds. In silico analysis and western blot together demonstrated that selected compound 10 in Cichorium intybus L. targeted Akt-1 in hepatocytes. Besides, compound 13 targeted both caspase-1 and Akt-1. These small compounds may ameliorate liver injury by acting on their targets, which are related to apoptosis or autophagy. The conclusions above may shed light on the complex molecular mechanisms of Cichorium intybus L. acting on hepatocytes and ameliorating liver injury. PMID:26389883

  20. In Silico Analysis and Experimental Validation of Active Compounds from Cichorium intybus L. Ameliorating Liver Injury

    PubMed Central

    Li, Guo-Yu; Zheng, Ya-Xin; Sun, Fu-Zhou; Huang, Jian; Lou, Meng-Meng; Gu, Jing-Kai; Wang, Jin-Hui

    2015-01-01

    This study aimed at investigating the possible mechanisms of hepatic protective activity of Cichorium intybus L. (chicory) in acute liver injury. Pathological observation, reactive oxygen species (ROS) detection and measurements of biochemical indexes on mouse models proved hepatic protective effect of Cichorium intybus L. Identification of active compounds in Cichorium intybus L. was executed through several methods including ultra performance liquid chromatography/time of flight mass spectrometry (UPLC-TOF-MS). Similarity ensemble approach (SEA) docking, molecular modeling, molecular docking, and molecular dynamics (MD) simulation were applied in this study to explore possible mechanisms of the hepato-protective potential of Cichorium intybus L. We then analyzed the chemical composition of Cichorium intybus L., and found their key targets. Furthermore, in vitro cytological examination and western blot were used for validating the efficacy of the selected compounds. In silico analysis and western blot together demonstrated that selected compound 10 in Cichorium intybus L. targeted Akt-1 in hepatocytes. Besides, compound 13 targeted both caspase-1 and Akt-1. These small compounds may ameliorate liver injury by acting on their targets, which are related to apoptosis or autophagy. The conclusions above may shed light on the complex molecular mechanisms of Cichorium intybus L. acting on hepatocytes and ameliorating liver injury. PMID:26389883

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

    PubMed Central

    2011-01-01

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

  2. 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