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Sample records for identify active compounds

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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

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

    PubMed

    Dean, Scott N; van Hoek, Monique L

    2015-01-01

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

  7. Microfluidic in vivo screen identifies compounds enhancing neuronal

    E-print Network

    Haggarty, Stephen J.

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

  8. 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...

  9. 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...

  10. 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 ...

  11. 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

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

    PubMed Central

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  14. 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

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

    PubMed

    Herrmann, Uli S; Schütz, Anne K; Shirani, Hamid; Huang, Danzhi; Saban, Dino; Nuvolone, Mario; Li, Bei; Ballmer, Boris; Åslund, Andreas K O; Mason, Jeffrey J; Rushing, Elisabeth; Budka, Herbert; Nyström, Sofie; Hammarström, Per; Böckmann, 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

  16. Strategies and future trends to identify the mode of action of phytotoxic compounds.

    PubMed

    Tresch, Stefan

    2013-11-01

    Small molecules affecting plant processes have been widely used as probes to study basic physiology. In agricultural practices some of these molecules have served as herbicides or plant growth regulators. Historically, most of the compounds were identified in large screens by the agrochemical industry, but also as phytoactive natural products. More recently, novel phytoactive compounds originated from academic research by chemical screens performed to induce specific phenotypes of interest. In the present review different approaches were evaluated for the identification of the mode of action (MoA) of phytoactive compounds. Based on the methodologies used for MoA identification, three approaches are differentiated: a phenotyping approach, an approach based on a genetic screen and a biochemical screening approach. Target sites of compounds targeting primary or secondary metabolism were identified most successfully with a phenotyping approach. Target sites for compounds that influence cell structure, such as cell wall biosynthesis or the cytoskeleton, or compounds that interact with the hormone system, were in most cases discovered by using a genetic approach. Examples showing the strengths and weaknesses of the different approaches are discussed in detail. Additionally, new techniques that could contribute to future MoA identification projects are reviewed. In particular, next-generation sequencing techniques may be used for the fast-forward mapping of mutants identified in genetic screens. Finally, a revised three-tiered approach for the MoA identification of phytoactive compounds is proposed. The approach consists of a 1st tier, which addresses compound stability, uniformity of effects in different species, general cytotoxicity and the effect on common processes such as transcription and translation. Advanced studies based on these findings initiate the 2nd tier MoA characterization, either with further phenotypic characterization, starting a genetic screen or establishing a biochemical screen. At the 3rd tier, enzyme assays or protein affinity studies should show the activity of the compound on the hypothesized target and should associate the in vitro effects with the in vivo profile of the compound. PMID:24094055

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

    PubMed Central

    2014-01-01

    Background In Chinese traditional medicine, Agrimonia pilosa Ledeb (APL) exhibits great effect on treatment of type 2 diabetes mellitus (T2DM), however its mechanism is still unknown. Considering that T2DM are correlated with postprandial hyperglycemia and oxidative stress, we investigated the ?-glucosidase inhibitory activity and the antioxidant activity of flavonoid compound (FC) and triterpenoid compound (TC) from APL. Methods Entire plants of APL were extracted using 95% ethanol and 50% ethanol successively. The resulting extracts were partitioned and isolated by applying liquid chromatography using silica gel column and Sephadex LH 20 column to give FC and TC. The content of total flavonoids in FC and the content of total triterpenoids in TC were determined by using UV spectrophotometry. HPLC analysis was used to identify and quantify the monomeric compound in FC and TC. The ?-glucosidase inhibitory activities were determined using the chromogenic method with p-nitrophenyl-?-D-glucopyranoside as substrate. Antioxidant activities were assessed through three kinds of radical scavenging assays (DPPH radical, ABTS radical and hydroxyl radical) & ?-carotene-linoleic acid assay. Results The results indicate FC is abundant of quercitrin, and hyperoside, and TC is abundant of 1?, 2?, 3?, 19?-tetrahydroxy-12-en-28-oic acid (265.2 mg/g) and corosolic acid (100.9 mg/g). The FC & the TC have strong ?-glucosidase inhibitory activities with IC50 of 8.72 ?g/mL and 3.67 ?g/mL, respectively. We find that FC show competitive inhibition against ?-glucosidase, while the TC exhibits noncompetitive inhibition. Furthermore, The FC exhibits significant radical scavenging activity with the EC50 values of 7.73 ?g/mL, 3.64 ?g/mL and 5.90 ?g/mL on DPPH radical, hydroxyl radical and ABTS radical, respectively. The FC also shows moderate anti-lipid peroxidation activity with the IC50 values of 41.77 ?g/mL on inhibiting ?-carotene bleaching. Conclusion These results imply that the FC and the TC could be responsible for the good clinical effects of APL on T2MD through targeting oxidative stress and postprandial hyperglycaemia. So APL may be good sources of natural antioxidants and ?-glucosidase inhibitors exhibiting remarkable potential value for the therapy of T2DM. PMID:24410924

  18. Sensitive markers used to identify compounds that trigger apoptosis in cultured hepatocytes.

    PubMed

    Gómez-Lechón, María José; O'Connor, Enrique; Castell, José Vicente; Jover, Ramiro

    2002-02-01

    Apoptosis may be a major event in chemical-induced injury, and therefore the detection of apoptotic effects when developing new drugs is highly relevant in screening for pharmacotoxicological risk assessment. However, as apoptosis in vitro normally degenerates to secondary necrosis, it is possible that it is underestimated, unless sensitive and specific parameters are used. In this present study we have evaluated the usefulness of a set of markers associated with the pivotal steps in the execution phase of apoptosis, in order to detect apoptotic compounds in hepatocytes before significant necrosis takes place. The markers selected include several biochemical parameters (downregulation of the antiapoptotic bclX(L) gene, caspase-3 activation, and cytochrome C release from mitochondria), and flow cytometry determinations (analysis of the size of the nuclei, chromatin complexity, and DNA integrity). The effects of several well-known model apoptotic toxicants (galactosamine, tertiary-butyl-hydroperoxide, etoposide, campothecine, and curcumin) were analyzed in hepatocytes. The aim was to identify early markers of apoptosis using known inducers of apoptosis in hepatocytes, as this battery of markers is designed to identify compounds triggering apoptosis in hepatocytes prior to necrosis. Concentrations of the compounds, as low as possible in order to keep 90% of hepatocyte viability, were selected according to their intracellular lactate dehydrogenase (LDH) leakage, which is well known as an indicator of cell membrane integrity and cell viability. The results demonstrated that (1) the apoptotic effect of 4 out of 5 compounds could be detected in low concentrations of the drugs long before cell necrosis (tertiary-butyl-hydroperoxide-induced apoptosis was only detected at concentrations causing concomitant necrosis) and (2) among the markers evaluated, caspase 3 activation and nucleus and DNA analysis by flow cytometry were used to fulfil the compromise between reliability, sensitivity, and ease of performance, which are critical issues when screening for an apoptotic effect of newly developed drugs. PMID:11812934

  19. 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 ? = 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

  20. 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

  1. 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

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

    NASA Astrophysics Data System (ADS)

    Hilchenbach, M.; Fischer, H.; Krüger, H.; Thirkell, L.; Rynö, 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.

  3. 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.

  4. 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...

  5. 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...

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

    PubMed

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

    2008-06-01

    Nature is a rich source of taste-active compounds, in particular of plant origin, many of which have unusual tastes. Many of these are found in traditional food, where spontaneous plants are used as ingredients. Some taste-active compounds were identified in the bulbs of Muscari comosum, a spontaneous plant belonging to the family of the Liliaceae, very common in the Mediterranean area, and used in traditional gastronomy (called 'lampascioni' in South Italy). The bulbs were extracted with a series of solvents of different polarity. The different fractions were submitted to a preliminary sensory evaluation, and the most interesting ones, characterized by a strong bitter taste and some chemestetic properties, were submitted to further purification and structural analysis. From the ethereal extract, several 3-benzyl-4-chromanones and one stilbene derivative were isolated. Pure compounds were examined for their taste activity by means of sensory evaluation, and proved to be responsible for the characteristic taste of this food. Some of these compounds have been synthesized de novo to confirm their structure. PMID:18618404

  7. 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 ?g/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, ?-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 ?g/mL and was not cytotoxic to mouse macrophage cells (CC50 > 100 ?g/mL). PMID:26411017

  8. Development of an electronic nose to identify and quantify volatile hazardous compounds.

    PubMed

    Fernandes, Daniel L A; Gomes, M Teresa S R

    2008-10-19

    A new electronic nose was developed to identify the chemical compound released when a 2.5-L flask was broken inside a 3 m x 3 m x 2.5 m store-room. Flasks of 10 different hazardous compounds were initially present in the room: ammonia, propanone, hexane, acetic acid, toluene, methanol, tetrachloromethane, chloroform, ethanol and dichloromethane. Besides identification, quantification of the compound present in the air was also performed by the electronic nose, in order to evaluate the risk level for room cleaning. An array of six sensors based on coated piezoelectric quartz crystals was used. Although none of the individual sensors was specific for a single compound, an artificial neural network made it possible to identify and quantify the released vapour, among a series of 10 compounds, with six sensors. The neural network could be simplified, and the number of neurons reduced, provided it was used just for the identification task. Quantification could be performed later using the individual calibration of the sensor most sensitive to the identified compound. PMID:18804602

  9. 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

  10. 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

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

    PubMed

    Stumpfe, Dagmar; Dimova, Dilyana; Bajorath, Jürgen

    2014-02-24

    The assessment of activity cliffs has thus far mostly focused on compound pairs, although the majority of activity cliffs are not formed in isolation but in a coordinated manner involving multiple active compounds and cliffs. However, the composition of coordinated activity cliff configurations and their topologies are unknown. Therefore, we have identified all activity cliff configurations formed by currently available bioactive compounds and analyzed them in network representations where activity cliff configurations occur as clusters. The composition, topology, frequency of occurrence, and target distribution of activity cliff clusters have been determined. A limited number of large cliff clusters with unique topologies were identified that were centers of activity cliff formation. These clusters originated from a small number of target sets. However, most clusters were of small to moderate size. Three basic topologies were sufficient to describe recurrent activity cliff cluster motifs/topologies. For example, frequently occurring clusters with star topology determined the scale-free character of the global activity cliff network and represented a characteristic activity cliff configuration. Large clusters with complex topology were often found to contain different combinations of basic topologies. Our study provides a first view of activity cliff configurations formed by currently available bioactive compounds and of the recurrent topologies of activity cliff clusters. Activity cliff clusters of defined topology can be selected, and from compounds forming the clusters, SAR information can be obtained. The SAR information of activity cliff clusters sharing a/one specific activity and topology can be compared. PMID:24437577

  12. 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

  13. 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...

  14. 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...

  15. 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...

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

    PubMed Central

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

    2015-01-01

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

  17. 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

  18. 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, Agnès; Eon, Mélissa; 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 14 days 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

  19. 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...

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

    PubMed Central

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

    2013-01-01

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

  1. 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

  2. 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

  3. Biologically active compounds of semi-metals.

    PubMed

    Rezanka, Tomás; Sigler, Karel

    2008-02-01

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

  4. 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…

  5. 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…

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

    PubMed

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

    2013-04-01

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

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

    PubMed Central

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

    2012-01-01

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

  8. Histone markers identify the mode of action for compounds positive in the TK6 micronucleus assay.

    PubMed

    Cheung, Jennifer R; Dickinson, Donna A; Moss, Jocelyn; Schuler, Maik J; Spellman, Richard A; Heard, Pamela L

    2015-01-01

    The in vitro micronucleus assay with TK6 cells is frequently used as part of the genotoxicity testing battery for pharmaceuticals. Consequently, follow-up testing strategies are needed for positive compounds to determine their mode of action, which would then allow for deployment of appropriate in vivo follow-up strategies. We have chosen 3 micronucleus positive compounds, the clastogen etoposide, the aneugen noscapine and the cytotoxicant tunicamycin to evaluate different approaches to determine their aneugenic or clastogenic properties. Each of the three compounds were evaluated following 4 and 24h of continuous treatment by flow cytometry for micronucleus induction, the aneugenicity markers phosphorylated-histone 3 (p-H3) and polyploidy, the clastogenicity marker ?H2AX and the apoptosis marker cleaved caspase 3. They were further evaluated by Western blot for mono-ubiquitinated and ?H2AX. Results show that the clastogen etoposide produced a dose related increase in ?H2AX and mono-ubiquitinated H2AX and a dose related decrease in p-H3 positive mitotic cells. Conversely, the aneugen produced increases in p-H3 and polyploidy with no significant increases seen in mono-ubiquitinated H2AX or ?H2AX. Lastly, the cytotoxicant tunicamycin induced neither an increase in p-H3 nor ?H2AX. All three compounds produced dose-related increases in cleaved caspase 3. The results from this study provide evidence that adding clastogenicity and aneugenicity markers to the in vitro micronucleus assay in TK6 cells could help to identify the mode of action of positive compounds. The combination of endpoints suggested here needs to be further evaluated by a broader set of test compounds. PMID:25726170

  9. Antioxidant activity and effective compounds of immature calamondin peel.

    PubMed

    Yu, Ming-Wen; Lou, Shyi-Neng; Chiu, E-Mean; Ho, Chi-Tang

    2013-02-15

    The antioxidant activity and the flavonoids of mature and immature calamondin (Citrus mitis Blanco) peel were investigated. The hot water extract of immature calamondin peel exhibited the highest oxygen radical absorbance capacity (ORAC), reducing power, and superoxide scavenging effect. 3',5'-Di-C-?-glucopyranosylphloretin, naringin, hesperidin, nobiletin, and tangeretin are the five major flavonoids found in hot water extract with the levels of 6888±522, 2333±157, 1350±94, 165±13, and 8±4 mg/100 g dry basis, respectively. The contents of nobiletin and tangeretin increased after ripening. The hot water extract of immature calamondin peel was fractionated using a semi-preparative HPLC. Fraction VI showed the highest ORAC value (28.02±2.73 mmol Trolox equivalents (TE)/g fraction) and two compounds, naringin and hesperidin, were identified as the major active components attributed to the antioxidant activity. Fraction V contained 3',5'-di-C-?-glucopyranosylphloretin, which revealed low ORAC value with 7.43 mmol TE/g fraction. However, it might also contribute to antioxidant activity in immature calamondin peel due to its greatest quantity. PMID:23194504

  10. 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

  11. 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

  12. 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.

  13. Identifying Well-Evaluated Activities in Career Education.

    ERIC Educational Resources Information Center

    Hamilton, Jack A.; And Others

    1979-01-01

    Identifies information about evaluated outcomes of local school career education activities representing the best of current career education programs and practices. Seven activities were ultimately approved by the HEW Education Division's Joint Dissemination Review Panel for nationwide distribution. (Author)

  14. Identification of Orthologous Target Pairs with Shared Active Compounds and Comparison of Organism-specific Activity Patterns.

    PubMed

    Dimova, Dilyana; Stumpfe, Dagmar; Bajorath, Jürgen

    2015-11-01

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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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, ...

  1. 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...

  2. 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

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

    PubMed

    Hole, Magnus; Underhaug, Jarl; Diez, Hector; Ying, Ming; Røhr, Åsmund Kjendseth; Jorge-Finnigan, Ana; Fernàndez-Castillo, Noèlia; García-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

  4. Prediction of Antifungal Activity of Gemini Imidazolium Compounds

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Stumpfe, Dagmar; Dimova, Dilyana; Bajorath, Jürgen

    2015-07-01

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

  6. 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

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

    PubMed

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

    2012-01-01

    Procaspase-Activating Compound 1 (PAC-1) is an ortho-hydroxy N-acyl hydrazone that enhances the enzymatic activity of procaspase-3 in vitro and induces apoptosis in cancer cells. An analogue of PAC-1, called S-PAC-1, was evaluated in a veterinary clinical trial in pet dogs with lymphoma and found to have considerable potential as an anticancer agent. With the goal of identifying more potent compounds in this promising class of experimental therapeutics, a combinatorial library based on PAC-1 was created, and the compounds were evaluated for their ability to induce death of cancer cells in culture. For library construction, 31 hydrazides were condensed in parallel with 27 aldehydes to create 837 PAC-1 analogues, with an average purity of 91%. The compounds were evaluated for their ability to induce apoptosis in cancer cells, and through this work, six compounds were discovered to be substantially more potent than PAC-1 and S-PAC-1. These six hits were further evaluated for their ability to relieve zinc-mediated inhibition of procaspase-3 in vitro. In general, the newly identified hit compounds are two- to four-fold more potent than PAC-1 and S-PAC-1 in cell culture, and thus have promise as experimental therapeutics for treatment of the many cancers that have elevated expression levels of procaspase-3. PMID:22007686

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

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

    PubMed

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

    2015-12-01

    Strain HSY05 was isolated from sea sediment collected from the South China Sea and was later identified as Penicillium oxalicum by 16S rDNA sequence analysis. Various chromatographic processes led to the isolation and purification of two metabolites from the fermentation culture of HSY05, including one new compound, 2,2',4,4'-tetrahyoxy-8'-methyl-6-methoxy-acyl-ethyl-diphenylmethanone (1), and a known compound secalonic acid D (SAD, 2), as characterised by UV, IR, 1D, 2D-NMR and MS data. The inhibitory activities against topoisomerase I of these two compounds were evaluated. The result showed that in addition to the known topo I inhibitor SAD (2), compound 1 also exhibited a moderate inhibitory effect. PMID:25966868

  18. 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.

  19. 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; Spänkuch, 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

  20. High-Throughput Screening Identifies a Bisphenol Inhibitor of SV40 Large T Antigen ATPase Activity

    PubMed Central

    Seguin, Sandlin P.; Evans, Carrie W.; Nebane-Akah, Miranda; Mckellip, Sara; Ananthan, Subramaniam; Tower, Nichole A.; Sosa, Melinda; Rasmussen, Lynn; White, E. Lucile; Maki, Brooks E.; Matharu, Daljit S.; Golden, Jennifer E.; Aubé, Jeffrey; Brodsky, Jeffrey L.; Noah, James W.

    2013-01-01

    The authors conducted a high-throughput screening campaign for inhibitors of SV40 large T antigen ATPase activity to identify candidate antivirals that target the replication of polyomaviruses. The primary assay was adapted to 1536-well microplates and used to screen the National Institutes of Health Molecular Libraries Probe Centers Network library of 306 015 compounds. The primary screen had an Z value of ~0.68, signal/background = 3, and a high (5%) DMSO tolerance. Two counterscreens and two secondary assays were used to prioritize hits by EC50, cytotoxicity, target specificity, and off-target effects. Hits that inhibited ATPase activity by >44% in the primary screen were tested in dose–response efficacy and eukaryotic cytotoxicity assays. After evaluation of hit cytotoxicity, drug likeness, promiscuity, and target specificity, three compounds were chosen for chemical optimization. Chemical optimization identified a class of bisphenols as the most effective biochemical inhibitors. Bisphenol A inhibited SV40 large T antigen ATPase activity with an IC50 of 41 ?M in the primary assay and 6.2 ?M in a cytoprotection assay. This compound class is suitable as probes for biochemical investigation of large T antigen ATPase activity, but because of their cytotoxicity, further optimization is necessary for their use in studying polyomavirus replication in vivo. PMID:21948801

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

    PubMed Central

    Tiwari, Vishvanath; Roy, Ranita; Tiwari, Monalisa

    2015-01-01

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

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

    PubMed

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

    2015-04-01

    Activity-guided isolation of compounds from the fruits of Amomum xanthioides resulted in the purification of fourteen phenolic compounds, 4-hydroxy-benzaldehyde (1), 3,4-dihydroxybenzaldehyde (2), 3,5-dimethoxy-4-methylbenzaldehyde (3), syringic aldehyde (4), benzoic acid (5), 3,4-dihydroxy benzoic acid (6), vanillic acid (7), 3-hydroxy-2-methoxybenzoic acid (8), o-vanillic acid (9), phenylacetic acid (10), tyrosol (11), pyrocatechol (12), 1,2,4,5-tetramethoxybenzene (13), and 3,3',5,5'-tetramethoxybiphenyl-4,4'-diol (14). To evaluate the anti-allergic inflammatory activities of these compounds, we examined the inhibitory effects of the isolates (1-14) on histamine release and on the expressions of tumor necrosis factor (TNF)-ca and interleukin (IL)-6 genes by using human mast cells. Of the tested compounds, 9, 11, and 13 suppressed histamine release from mast cells, and all isolates attenuated the expressions of the pro-inflammatory cytokines, TNF-? and IL-6 genes in human mast cells. PMID:25973495

  3. 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

  4. 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

  5. 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??g?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??g?ml(-1) and 7.8??g?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??g?ml(-1), and compound 2, known as myriocin, with MIC values of 0.5??g?ml(-1) against C. neoformans and C. gattii. These compounds are reported for the first time in the Mycosphaerella genus. PMID:25712396

  6. Identification of compounds with potential antibacterial activity against Mycobacterium through structure-based drug screening.

    PubMed

    Kinjo, Tomohiro; Koseki, Yuji; Kobayashi, Maiko; Yamada, Atsumi; Morita, Koji; Yamaguchi, Kento; Tsurusawa, Ryoya; Gulten, Gulcin; Komatsu, Hideyuki; Sakamoto, Hiroshi; Sacchettini, James C; Kitamura, Mitsuru; Aoki, Shunsuke

    2013-05-24

    To identify novel antibiotics against Mycobacterium tuberculosis, we performed a hierarchical structure-based drug screening (SBDS) targeting the enoyl-acyl carrier protein reductase (InhA) with a compound library of 154,118 chemicals. We then evaluated whether the candidate hit compounds exhibited inhibitory effects on the growth of two model mycobacterial strains: Mycobacterium smegmatis and Mycobacterium vanbaalenii. Two compounds (KE3 and KE4) showed potent inhibitory effects against both model mycobacterial strains. In addition, we rescreened KE4 analogs, which were identified from a compound library of 461,383 chemicals through fingerprint analysis and genetic algorithm-based docking simulations. All of the KE4 analogs (KES1-KES5) exhibited inhibitory effects on the growth of M. smegmatis and/or M. vanbaalenii. Based on the predicted binding modes, we probed the structure-activity relationships of KE4 and its analogs and found a correlative relationship between the IC50 values and the interaction residues/LogP values. The most potent inhibitor, compound KES4, strongly and stably inhibited the long-term growth of the model bacteria and showed higher inhibitory effects (IC50 = 4.8 ?M) than isoniazid (IC50 = 5.4 ?M), which is a first-line drug for tuberculosis therapy. Moreover, compound KES4 did not exhibit any toxic effects that impede cell growth in several mammalian cell lines and enterobacteria. The structural and experimental information of these novel chemical compounds will likely be useful for the development of new anti-TB drugs. Furthermore, the methodology that was used for the identification of the effective chemical compound is also likely to be effective in the SBDS of other candidate medicinal drugs. PMID:23600706

  7. 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

  8. Evaluation of compounds for insecticidal activity on adult mosquitos*

    PubMed Central

    Hadaway, A. B.; Barlow, F.; Grose, J. E. H.; Turner, C. R.; Flower, L. S.

    1970-01-01

    Responses shown by female mosquitos to topical applications of solutions, to deposits from water-dispersible-powder formulations, or to exposure to the vapour from such deposits, are described for a number of compounds that have shown promise as residual contact insecticides. The behaviour of Anopheles stephensi females in laboratory tests indicates that departures of mosquitos from treated buildings, and their survival rates, are likely to be increased as a result of irritation and consequent activity after only a brief period of contact with phthalthrin (OMS-1011) and other synthetic pyrethroids but not with dieldrin (OMS-18) and lindane (OMS-17) or the carbamates and organophosphorus compounds tested. Mosquitos were not disturbed by exposure to the vapour from deposits of any of the compounds. The rates of action of the different compounds following their application in solution directly to the insect cuticle or contact of the mosquitos with deposits on plywood and plaster emphasize the importance of the lipid-solubility and partitioning properties of an insecticide in determining its passage from a surface deposit into, and through, the cuticle to the site of action. PMID:4392935

  9. 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

  10. 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

  11. 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.

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

    PubMed

    Bézivin, Carine; Tomasi, Sophie; Rouaud, Isabelle; Delcros, Jean-Guy; Boustie, Joël

    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

  13. 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

  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. 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

  16. Phenolic compounds and antimicrobial activity of olive (Olea europaea L. Cv. Cobrançosa) leaves.

    PubMed

    Pereira, Ana Paula; Ferreira, Isabel C F R; Marcelino, Filipa; Valentão, Patricia; Andrade, Paula B; Seabra, Rosa; Estevinho, Leticia; Bento, Albino; Pereira, José Alberto

    2007-01-01

    We report the determination of phenolic compounds in olive leaves by reversed-phase HPLC/DAD, and the evaluation of their in vitro activity against several microorganisms that may be causal agents of human intestinal and respiratory tract infections, namely gram positive (Bacillus cereus, B. subtilis and Staphylococcus aureus), gram negative bacteria (Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae) and fungi (Candida albicans and Cryptococcus neoformans). Seven phenolic compounds were identified and quantified: caffeic acid, verbascoside, oleuropein, luteolin 7-O-glucoside, rutin, apigenin 7-O-glucoside and luteolin 4'-O-glucoside. At low concentrations olive leaves extracts showed an unusual combined antibacterial and antifungal action, which suggest their great potential as nutraceuticals, particularly as a source of phenolic compounds. PMID:17873849

  17. Applications of Artificial Neural Networks and Fuzzy Models in High Throughput Screening: Classifying the activities of various compounds towards Cobalt

    E-print Network

    Kansas, University of

    : Classifying the activities of various compounds towards Cobalt Mithun Hebbar, Stan R. Svojanovsky, Qi with >40% inhibition activities towards Cobalt are selected as active. Each compound is characterized

  18. 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 Köhler 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.

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

    DOE PAGESBeta

    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 Köhler theory with semi-empirical group contribution methods to estimate molar volumes, activity coefficients and liquid-liquid phase boundaries tomore »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.« less

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

    PubMed

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

    2015-06-01

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

  1. 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

  2. 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-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

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

    PubMed

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

    2014-04-01

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

  4. Phenolic compounds from Halimodendron halodendron (Pall.) voss and their antimicrobial and antioxidant activities.

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  6. 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

  7. 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

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

    PubMed

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

    2014-05-01

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

  9. Table olives from Portugal: phenolic compounds, antioxidant potential, and antimicrobial activity.

    PubMed

    Pereira, José Alberto; Pereira, Ana P G; Ferreira, Isabel C F R; Valentão, Patrícia; Andrade, Paula B; Seabra, Rosa; Estevinho, Letícia; Bento, Albino

    2006-11-01

    The phenolic compounds composition, antioxidant potential, and antimicrobial activity of different table olives from Portugal, namely, natural black olives "Galega", black ripe olive "Negrinha de Freixo", Protected Designation of Origin (PDO) "Azeitona de Conserva Negrinha de Freixo" olives, and "Azeitona de Conserva de Elvas e Campo Maior" Designation of Origin (DO) olives, were investigated. The analysis of phenolic compounds was performed by reversed-phase HPLC/DAD, and seven compounds were identified and quantified: hydroxytyrosol, tyrosol, 5-O-caffeoilquinic acid, verbascoside, luteolin 7-O-glucoside, rutin, and luteolin. The antioxidant activity was assessed by the reducing power assay, the scavenging effect on DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals, and the beta-carotene linoleate model system. The antioxidant activity was correlated with the amount of phenolics found in each sample. The antimicrobial activity was screened using Gram-positive (Bacillus cereus, Bacillus subtilis, Staphylococcus aureus) and Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae) and fungi (Candida albicans, Cryptococcus neoformans). PDO and DO table olives revealed a wide range of antimicrobial activity. C. albicans was resistant to all the analyzed extracts. PMID:17061816

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

    PubMed

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

    2013-12-01

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

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

    PubMed Central

    Weidner, Stanis?aw; Powa?ka, Anna; Karama?, Magdalena; Amarowicz, Ryszard

    2012-01-01

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

  12. 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 ?M. 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

  13. 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.

  14. 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

  15. Antifungal Activity of Bacillus amyloliquefaciens NJN-6 Volatile Compounds against Fusarium oxysporum f. sp. cubense

    PubMed Central

    Yuan, Jun; Raza, Waseem

    2012-01-01

    Bacillus amyloliquefaciens NJN-6 produces volatile compounds (VOCs) that inhibit the growth and spore germination of Fusarium oxysporum f. sp. cubense. Among the total of 36 volatile compounds detected, 11 compounds completely inhibited fungal growth. The antifungal activity of these compounds suggested that VOCs can play important roles over short and long distances in the suppression of Fusarium oxysporum. PMID:22685147

  16. 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

  17. 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

  18. 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

  19. 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

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

    PubMed Central

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

    2014-01-01

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

  1. Implementation of a High-Throughput Screen for Identifying Small Molecules to Activate the Keap1-Nrf2-ARE Pathway

    PubMed Central

    Liu, Jie Jerry; Chaguturu, Rathnam; Klaassen, Curtis D.

    2012-01-01

    Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that induces a battery of cytoprotective genes involved in antioxidant defense through binding to Antioxidant Response Elements (ARE) located in the promoter regions of these genes. To identify Nrf2 activators for the treatment of oxidative/electrophilic stress-induced diseases, the present study developed a high-throughput assay to evaluate Nrf2 activation using AREc32 cells that contain a luciferase gene under the control of ARE promoters. Of the 47,000 compounds screened, 238 (top 0.5% hits) of the chemicals increased the luminescent signal more than 14.4-fold and were re-tested at eleven concentrations in a range of 0.01–30 µM. Of these 238 compounds, 231 (96%) increased the luminescence signal in a concentration-dependent manner. Chemical structure relationship analysis of these 231 compounds indicated enrichment of four chemical scaffolds (diaryl amides and diaryl ureas, oxazoles and thiazoles, pyranones and thiapyranones, and pyridinones and pyridazinones). In addition, 30 of these 231 compounds were highly effective and/or potent in activating Nrf2, with a greater than 80-fold increase in luminescence, or an EC50 lower than 1.6 µM. These top 30 compounds were also screened in Hepa1c1c7 cells for an increase in Nqo1 mRNA, the prototypical Nrf2-target gene. Of these 30 compounds, 17 increased Nqo1 mRNA in a concentration-dependent manner. In conclusion, the present study documents the development, implementation, and validation of a high-throughput screen to identify activators of the Keap1-Nrf2-ARE pathway. Results from this screening identified Nrf2 activators, and provide novel insights into chemical scaffolds that might prevent oxidative/electrophilic stress-induced toxicity and carcinogenesis. PMID:23056183

  2. 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.

  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. 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

  5. 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

  6. 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

  7. Parallel RNAi and compound screens identify the PDK1 pathway as a target for tamoxifen sensitization.

    PubMed

    Iorns, Elizabeth; Lord, Christopher J; Ashworth, Alan

    2009-01-01

    Tamoxifen is the most commonly used drug to treat breast cancer and acts by blocking ERalpha (oestrogen receptor alpha) signalling. Although highly effective, its usefulness is limited by the development of resistance. Given this, strategies that limit resistance by sensitizing cells to tamoxifen may be of use in the clinic. To gain insight into how this might be achieved, we used chemical and genetic screens to identify targets and small-molecule inhibitors that cause tamoxifen sensitization. A high-throughput genetic screen, using an RNA interference library targeting 779 kinases and related proteins, identified the PDK1 (phosphoinositide-dependent kinase 1) signalling pathway as a strong determinant of sensitivity to multiple ERalpha antagonists, including tamoxifen. A chemical screen using existing drugs and known kinase inhibitors also identified inhibitors of the PDK1 pathway, including triciribine and tetrandrine. Aside from identifying novel agents and targets for tamoxifen sensitization, this approach also provides evidence that performing chemical and genetic screens in parallel may be useful. PMID:18976239

  8. 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.

  9. 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

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

    NASA Astrophysics Data System (ADS)

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

    2009-12-01

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

  11. 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 ?-amylase and ?-glucosidase enzymes. Leccino, among all analysed cultivars, and luteolin, among identified phenolic compounds, were found to be the best inhibitors of ?-amylase and ?-glucosidase enzymes. Results demonstrated that Olea europaea fruit extracts can represent an important natural source with high antioxidant potential and significant ?-amylase and ?-glucosidase inhibitory effects. PMID:26557862

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

    PubMed

    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

  13. 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

  14. 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??g/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 17?-estradiol. We had further assessed the protective role of PME on skeletal system, using MC3T3-E1 cells. The results indicated that PME (80??g/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

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

    PubMed Central

    Berthier, Alexandre; Oger, Frédérik; Gheeraert, Céline; Boulahtouf, Abdel; Le Guével, Rémy; Balaguer, Patrick; Staels, Bart; Salbert, Gilles; Lefebvre, Philippe

    2012-01-01

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

  16. 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.

  17. 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 ?m 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 ?m) powders of six different silicates and measured their VNIR (0.35-2.5 ?m) reflectance spectra under ambient air, and mid-IR (1.2-20 ?m) 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.

  18. 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...

  19. Acaricidal Activity of Eugenol Based Compounds against Scabies Mites

    PubMed Central

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

    2010-01-01

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

  20. 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

  1. Identification of Tetraazacyclic Compounds as Novel Potent Inhibitors Antagonizing ROR?t 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 ?t (ROR?t), 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 ROR?t-LBD positive and negative Jurkat cells were analyzed to evaluate induction of ROR?t 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 ROR?t function in the HTS screen system. Of these, three tetraazacyclic compounds can potently inhibit ROR?t 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-ROR?t activity, with EC50 values of 0.25 ?M, 0.67 ?M and 2.6 ?M, respectively. Our data demonstrated the feasibility of targeting the ROR?t 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

  2. Compound

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

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

  3. Inhibitors of VIM-2 by screening pharmacologically active and click-chemistry compound libraries.

    PubMed

    Minond, Dmitriy; Saldanha, S Adrian; Subramaniam, Prem; Spaargaren, Michael; Spicer, Timothy; Fotsing, Joseph R; Weide, Timo; Fokin, Valery V; Sharpless, K Barry; Galleni, Moreno; Bebrone, Carine; Lassaux, Patricia; Hodder, Peter

    2009-07-15

    VIM-2 is an Ambler class B metallo-beta-lactamase (MBL) capable of hydrolyzing a broad-spectrum of beta-lactam antibiotics. Although the discovery and development of MBL inhibitors continue to be an area of active research, an array of potent, small molecule inhibitors is yet to be fully characterized for VIM-2. In the presented research, a compound library screening approach was used to identify and characterize VIM-2 inhibitors from a library of pharmacologically active compounds as well as a focused 'click' chemistry library. The four most potent VIM-2 inhibitors resulting from a VIM-2 screen were characterized by kinetic studies in order to determine K(i) and mechanism of enzyme inhibition. As a result, two previously described pharmacologic agents, mitoxantrone (1,4-dihydroxy-5,8-bis([2-([2-hydroxyethyl]amino)ethyl]amino)-9,10-anthracenedione) and 4-chloromercuribenzoic acid (pCMB) were found to be active, the former as a non-competitive inhibitor (K(i)=K(i)(')=1.5+/-0.2microM) and the latter as a slowly reversible or irreversible inhibitor. Additionally, two novel sulfonyl-triazole analogs from the click library were identified as potent, competitive VIM-2 inhibitors: N-((4-((but-3-ynyloxy)methyl)-1H-1,2,3-triazol-5-yl)methyl)-4-iodobenzenesulfonamide (1, K(i)=0.41+/-0.03microM) and 4-iodo-N-((4-(methoxymethyl)-1H-1,2,3-triazol-5-yl)methyl)benzenesulfonamide (2, K(i)=1.4+/-0.10microM). Mitoxantrone and pCMB were also found to potentiate imipenem efficacy in MIC and synergy assays employing Escherichia coli. Taken together, all four compounds represent useful chemical probes to further investigate mechanisms of VIM-2 inhibition in biochemical and microbiology-based assays. PMID:19553129

  4. 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

  5. Synthesis, biological profiling and mechanistic studies of 4-aminoquinoline-based heterodimeric compounds with dual trypanocidal-antiplasmodial activity.

    PubMed

    Sola, Irene; Castellà, Sílvia; Viayna, Elisabet; Galdeano, Carles; Taylor, Martin C; Gbedema, Stephen Y; Pérez, Belén; Clos, M Victòria; Jones, Deuan C; Fairlamb, Alan H; Wright, Colin W; Kelly, John M; Muñoz-Torrero, Diego

    2015-08-15

    Dual submicromolar trypanocidal-antiplasmodial compounds have been identified by screening and chemical synthesis of 4-aminoquinoline-based heterodimeric compounds of three different structural classes. In Trypanosoma brucei, inhibition of the enzyme trypanothione reductase seems to be involved in the potent trypanocidal activity of these heterodimers, although it is probably not the main biological target. Regarding antiplasmodial activity, the heterodimers seem to share the mode of action of the antimalarial drug chloroquine, which involves inhibition of the haem detoxification process. Interestingly, all of these heterodimers display good brain permeabilities, thereby being potentially useful for late stage human African trypanosomiasis. Future optimization of these compounds should focus mainly on decreasing cytotoxicity and acetylcholinesterase inhibitory activity. PMID:25678015

  6. 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

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

    PubMed

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

    2014-05-01

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

  8. 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.

  9. 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

  10. 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

  11. 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

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

    PubMed Central

    Blondelle, S E; Takahashi, E; Houghten, R A; Pérez-Payá, 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

  13. Low cost whole-organism screening of compounds for anthelmintic activity.

    PubMed

    Preston, Sarah; Jabbar, Abdul; Nowell, Cameron; Joachim, Anja; Ruttkowski, Bärbel; Baell, Jonathan; Cardno, Tony; Korhonen, Pasi K; Piedrafita, David; Ansell, Brendan R E; Jex, Aaron R; Hofmann, Andreas; Gasser, Robin B

    2015-04-01

    Due to major problems with drug resistance in parasitic nematodes of animals, there is a substantial need and excellent opportunities to develop new anthelmintics via genomic-guided and/or repurposing approaches. In the present study, we established a practical and cost-effective whole-organism assay for the in vitro-screening of compounds for activity against parasitic stages of the nematode Haemonchus contortus (barber's pole worm). The assay is based on the use of exsheathed L3 (xL3) and L4 stages of H. contortus of small ruminants (sheep and goats). Using this assay, we screened a panel of 522 well-curated kinase inhibitors (GlaxoSmithKline, USA; code: PKIS2) for activity against H. contortus by measuring the inhibition of larval motility using an automated image analysis system. We identified two chemicals within the compound classes biphenyl amides and pyrazolo[1,5-?]pyridines, which reproducibly inhibit both xL3 and L4 motility and development, with IC50s of 14-47 ?M. Given that these inhibitors were designed as anti-inflammatory drugs for use in humans and fit the Lipinski rule-of-five (including bioavailability), they show promise for hit-to-lead optimisation and repurposing for use against parasitic nematodes. The screening assay established here has significant advantages over conventional methods, particularly in terms of ease of use, throughput, time and cost. Although not yet fully automated, the current assay is readily suited to the screening of hundreds to thousands of compounds for subsequent hit-to-lead optimisation. The current assay is highly adaptable to many parasites of socioeconomic importance, including those causing neglected tropical diseases. This aspect is of major relevance, given the urgent need to deliver the goals of the London Declaration (http://unitingtocombatntds.org/resource/london-declaration) through the rapid and efficient repurposing of compounds in public-private partnerships. PMID:25746136

  14. 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

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

    PubMed

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

    2015-01-13

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

  16. 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 Hélène; 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

  17. 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

  18. 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

  19. 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...

  20. Enrichment of surface-active compounds in coalescing cloud drops Ilya Taraniuk,1

    E-print Network

    Kostinski, Alex

    Enrichment of surface-active compounds in coalescing cloud drops Ilya Taraniuk,1 Alex B. Kostinski the combined volume of all cloud droplets, it reduces the combined surface area. This could lead to enrichment (2008), Enrichment of surface-active compounds in coalescing cloud drops, Geophys. Res. Lett., 35, L

  1. 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.

  2. Target Prediction for an Open Access Set of Compounds Active against Mycobacterium tuberculosis

    E-print Network

    Sali, Andrej

    Target Prediction for an Open Access Set of Compounds Active against Mycobacterium tuberculosis tuberculosis, the causative agent of tuberculosis (TB), infects an estimated two billion people worldwide. The screen revealed 776 compounds with significant activity against the M. tuberculosis H37Rv strain

  3. 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)

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

    PubMed

    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

  5. 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

  6. 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

  7. 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

  8. Zebrafish promoter microarrays identify actively transcribed embryonic genes

    E-print Network

    Wardle, Fiona C.; Odom, Duncan T.; Bell, George W.; Yuan, Bingbing; Danford, Timothy W.; Wiellette, Elizabeth L.; Herbolsheimer, Elizabeth; Sive, Hazel L.; Young, Richard A.; Smith, James C.

    2006-08-04

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

  9. Zebrafish promoter microarrays identify actively transcribed embryonic genes

    E-print Network

    Wardle, Fiona C

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

  10. Isolation of pure compound R/J/3 from Pluchea indica (L.) Less. and its anti-amoebic activities against Entamoeba histolytica.

    PubMed

    Biswas, Ria; Dutta, P K; Achari, B; Bandyopadhyay, Durba; Mishra, Moumita; Pramanik, K C; Chatterjee, T K

    2007-08-01

    The plant Pluchea indica is known for its anti-inflammatory, anti-ulcer, anti-pyretic, hypoglycemic, diuretic and anti-microbial activities besides many other pharmacological activities. We have isolated and purified seven compounds from the methanolic root extract of this plant by column chromatography. The compounds were identified by spectroscopic analyses. The anti-amoebic activities of the pure compound R/J/3 was investigated against the HM1 strain of Entamoeba histolytica. The compound, R/J/3 showed the most pronounced anti-proliferative activity at a dose of 50 microg/ml. It also showed a marked activity on cell lysis of trophozoites, 4h after administration. The cell lytic activity was compared with metronidazole (5 microg/ml) as positive control. PMID:17174538

  11. Activity artifacts in drug discovery and different facets of compound promiscuity

    PubMed Central

    Bajorath, Jürgen

    2014-01-01

    Compounds with apparent activity in a variety of assays might disable target proteins or produce false assay signals in the absence of specific interactions. In some instances, such effects are easy to detect, in others they are not. Observed promiscuity of compounds might be due to such non-specific assay artifacts. By contrast, promiscuity might also result from specific interactions with multiple targets. In the latter case, promiscuous compounds can be attractive candidates for certain therapeutic applications. However, compounds with artificial activity readouts are often not recognized and are further progressed, which presents a substantial problem for drug discovery. In this context, the concept of PAINS (pan-assay interference compounds) should be seriously considered, which makes it possible to eliminate flawed compounds from the discovery pipeline, even if their activities appear to be sound at a first glance. PMID:25339989

  12. 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

  13. Frameworks for Compound Documents 1/15 Frameworks for Compound Active Documents (Draft)

    E-print Network

    Wegner, Peter

    of interaction. CORBA/OpenDoc, COM/OLE/ ActiveX, and Java/JavaBeans concretely illustrate emerging principles and simple com­ pound document model on top of CORBA's interoperable distributed objects. ActiveX providesDoc, ActiveX, and JavaBeans document models yields principles for the design and implementation of frameworks

  14. Selective and direct inhibition of TRPC3 channels underlies biological activities of a pyrazole compound

    PubMed Central

    Kiyonaka, Shigeki; Kato, Kenta; Nishida, Motohiro; Mio, Kazuhiro; Numaga, Takuro; Sawaguchi, Yuichi; Yoshida, Takashi; Wakamori, Minoru; Mori, Emiko; Numata, Tomohiro; Ishii, Masakazu; Takemoto, Hiroki; Ojida, Akio; Watanabe, Kenta; Uemura, Aya; Kurose, Hitoshi; Morii, Takashi; Kobayashi, Tsutomu; Sato, Yoji; Sato, Chikara; Hamachi, Itaru; Mori, Yasuo

    2009-01-01

    Canonical transient receptor potential (TRPC) channels control influxes of Ca2+ and other cations that induce diverse cellular processes upon stimulation of plasma membrane receptors coupled to phospholipase C (PLC). Invention of subtype-specific inhibitors for TRPCs is crucial for distinction of respective TRPC channels that play particular physiological roles in native systems. Here, we identify a pyrazole compound (Pyr3), which selectively inhibits TRPC3 channels. Structure-function relationship studies of pyrazole compounds showed that the trichloroacrylic amide group is important for the TRPC3 selectivity of Pyr3. Electrophysiological and photoaffinity labeling experiments reveal a direct action of Pyr3 on the TRPC3 protein. In DT40 B lymphocytes, Pyr3 potently eliminated the Ca2+ influx-dependent PLC translocation to the plasma membrane and late oscillatory phase of B cell receptor-induced Ca2+ response. Moreover, Pyr3 attenuated activation of nuclear factor of activated T cells, a Ca2+-dependent transcription factor, and hypertrophic growth in rat neonatal cardiomyocytes, and in vivo pressure overload-induced cardiac hypertrophy in mice. These findings on important roles of native TRPC3 channels are strikingly consistent with previous genetic studies. Thus, the TRPC3-selective inhibitor Pyr3 is a powerful tool to study in vivo function of TRPC3, suggesting a pharmaceutical potential of Pyr3 in treatments of TRPC3-related diseases such as cardiac hypertrophy. PMID:19289841

  15. 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

  16. Walnut (Juglans regia L.) leaves: phenolic compounds, antibacterial activity and antioxidant potential of different cultivars.

    PubMed

    Pereira, José Alberto; Oliveira, Ivo; Sousa, Anabela; Valentão, Patrícia; Andrade, Paula B; Ferreira, Isabel C F R; Ferreres, Federico; Bento, Albino; Seabra, Rosa; Estevinho, Letícia

    2007-11-01

    Different cultivars of walnut (Juglans regia L.) leaves (Cv. Lara, Franquette, Mayette, Marbot, Mellanaise and Parisienne) grown in Portugal, were investigated in what concerns phenolic compounds and antimicrobial and antioxidant properties. Phenolics analysis was performed by reversed-phase HPLC/DAD and 10 compounds were identified and quantified: 3- and 5-caffeoylquinic acids, 3- and 4-p-coumaroylquinic acids, p-coumaric acid, quercetin 3-galactoside, quercetin 3-pentoside derivative, quercetin 3-arabinoside, quercetin 3-xyloside and quercetin 3-rhamnoside. The antimicrobial capacity was screened against Gram positive (Bacillus cereus, B. subtilis, Staphylococcus aureus) and Gram negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae) and fungi (Candida albicans, Cryptococcus neoformans). Walnut leaves selectively inhibited the growth of Gram positive bacteria, being B. cereus the most susceptible one (MIC 0.1mg/mL). Gram negative bacteria and fungi were resistant to the extracts at 100mg/mL. Lara walnut leaves were also submitted to antibacterial assays using 18 clinical isolates of Staphylococcus sp. Antioxidant activity was accessed by the reducing power assay, the scavenging effect on DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals and beta-carotene linoleate model system. In a general way, all of the studied walnut leaves cultivars presented high antioxidant activity (EC(50) values lower than 1mg/mL), being Cv. Lara the most effective one. PMID:17637491

  17. 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

  18. 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.

  19. 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.

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

    PubMed

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

    2008-08-27

    A study was conducted to determine the content of phenolic compounds and the antioxidative activity of five edible and five medicinal mushrooms commonly cultivated in Korea. Phenolic compounds were analyzed using high performance liquid chromatography, and antioxidant activity was evaluated by 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and superoxide dismutase activity. A total of 28 phenolic compounds were detected in the mushrooms studied. The average total concentration of phenolic compounds was 326 microg/g, the average being of 174 microg/g in edible mushrooms and 477 microg/g in medicinal mushrooms. The average total flavonoids concentration was 49 microg/g, with averages of 22 and 76 microg/g in edible and medicinal mushrooms, respectively. The DPPH radical scavenging activities ranged between 15 (Pleurotus eryngii) and 70% (Ganoderma lucidum) when reaction time was for 1 min. When reaction time was 30 min, the values ranged between 5 (Pleurotus eryngii) and 78% (Agaricus bisporus). The SOD activity averaged 28% among the 10 mushroom species, averages for edible and medicinal mushrooms being comparable. DPPH activities was significantly correlated (p < 0.01) with total content of phenolic compounds in edible mushrooms, while in medicinal mushrooms there was a significant correlation (p < 0.01) between SOD activity and total concentration of phenolic compounds. Numerous significant positive correlations were observed between phenolic compounds detected and antioxidative potential. PMID:18616260

  1. 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.

  2. 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

  3. 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

  4. 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 ?M, 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 ?M, 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 ?M at 1mM concentration as compared to vincristine (IC50=1.03 ± 0.04 ?M), standard drug used in this study. PMID:25257911

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

    PubMed Central

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

    2013-01-01

    Abstract The intermediate-conductance Ca2+-activated K+ channel KCa3.1 (also known as KCNN4, IK1, or the Gárdos 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

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

    E-print Network

    Kang, Mijeong

    2007-04-25

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

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

    PubMed Central

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  9. 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

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

    PubMed

    Revathi, S; Malathy, N S

    2013-11-01

    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

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

    PubMed

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

    2015-06-01

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

  12. 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 ...

  13. 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

  14. 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

  15. 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

  16. 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).

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

    PubMed Central

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

    2012-01-01

    Ene-reductases from the ‘Old Yellow Enzyme’ family of flavoproteins catalyze the asymmetric reduction of various ?,?-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

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

    PubMed

    Zhang, Bijun; Vogt, Martin; Bajorath, Jürgen

    2014-09-01

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

  19. 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.

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

    PubMed

    Raki?, Vesna; Rac, Vladislav; Krmar, Marija; Otman, Otman; Auroux, Aline

    2015-01-23

    In this study, the adsorption of pharmaceutically active compounds - salicylic acid, acetylsalicylic acid, atenolol and diclofenac-Na onto activated carbons has been studied. Three different commercial activated carbons, possessing ?650, 900 or 1500m(2)g(-1) surface areas were used as solid adsorbents. These materials were fully characterized - their textural, surface features and points of zero charge have been determined. The adsorption was studied from aqueous solutions at 303K using batch adsorption experiments and titration microcalorimetry, which was employed in order to obtain the heats evolved as a result of adsorption. The maximal adsorption capacities of investigated solids for all target pharmaceuticals are in the range of 10(-4)molg(-1). The obtained maximal retention capacities are correlated with the textural properties of applied activated carbon. The roles of acid/base features of activated carbons and of molecular structures of adsorbate molecules have been discussed. The obtained results enabled to estimate the possibility to use the activated carbons in the removal of pharmaceuticals by adsorption. PMID:24857621

  1. 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

  2. Femtosecond IR Studies of Alkane C-H Bond Activation by Organometallic Compounds: Direct

    E-print Network

    Harris, Charles B.

    Femtosecond IR Studies of Alkane C-H Bond Activation by Organometallic Compounds: Direct and its solvated forms in the liquefied rare gases Kr and Xe6 detected by microsecond time-resolved IR quantum yield (1%) for loss of CO in the well-studied model compounds Cp*M(CO)2 (M ) Rh, Ir)7 has hindered

  3. Modulation of Activity of Known Cytotoxic Ruthenium(III) Compound (KP418) with Hampered Transmembrane Transport

    E-print Network

    Ljubljana, University of

    Modulation of Activity of Known Cytotoxic Ruthenium(III) Compound (KP418) with Hampered on the cytotoxic and antitumor effect of a ruthenium(III) com- pound with hampered transmembrane transport, (im after ECT with KP418 in vitro. In addition, platinum compound cisplatin (CDDP) and ruthenium

  4. 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

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

    PubMed Central

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

    2013-01-01

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

  6. Antimicrobial activities against periodontopathic bacteria of Pittosporum tobira and its active compound.

    PubMed

    Oh, Jung-Hyun; Jeong, Yong Joon; Koo, Hyun Jung; Park, Dae Won; Kang, Se Chan; Khoa, Hoang Viet Bach; Le, Le Ba; Cho, Joon Hyeong; Lee, Jin-Yong

    2014-01-01

    The study of medicinal plants for treatment of periodontitis is of great value to establish their efficacy as sources of new antimicrobial drugs. Five hundred and fifty eight Korean local plant extracts were screened for antibacterial activity against representative periodontopathic bacteria such as Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum. Among the various medicinal plants, the alcohol extract of Pittosporum tobira, which significantly exhibited antibacterial effect for all tested strains, showed the highest activity in the antimicrobial assays. NMR analyses revealed that R1-barrigenol, a triterpene sapogenin, was the most effective compound in P. tobira. These results demonstrated that P. tobira possesses antimicrobial properties and would be beneficial for the prevention and treatment of periodontitis. PMID:24662076

  7. 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

  8. 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

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

    PubMed

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

    2013-03-20

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

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

    PubMed

    Civilini, Marcello

    2006-07-01

    In the northeast of Italy, high volatile organic carbon (VOC) emissions originate from small-medium companies producing furniture. In these conditions it is difficult to propose a single, efficient, and economic system to reduce pollution. Among the various choices, the biofiltration method could be a good solution, because microbial populations possess multiple VOC degradation potentials used to oxidize these compounds to CO2. Starting from the air emissions of a typical industrial wood-painting plant, a series of experiments studied in vitro microbial degradation of each individual VOC. Isolated strains were then added to a laboratory-scale biofiltration apparatus filled with an organic matrix, and the different VOC behavior demonstrated the potential of single and/or synergic microbial removal actions. When a single substrate was fed, the removal efficiency of a Pseudomonas aeruginosa inoculated reactor was 1.1, 1.17, and 0.33 g m(-3) hr(-1), respectively, for xylene, toluene, and ethoxy propyl acetate. A VOC mixture composed of butyl acetate, ethyl acetate, diacetin alcohol, ethoxy propanol acetate, methyl ethyl ketone, methyl isobutyl ketone, toluene, and xylene was then fed into a 2-m(3) reactor treating 100 m3 hr(-1) of contaminated air. The reactor was filled with the same mixture of organic matrix, enriched with all of the isolated strains together. During reactor study, different VOC loading rates were used, and the behavior was evaluated continuously. After a short acclimation period, the removal efficiency was > 65% at VOC load of 150-200 g m(-3) hr(-1). Quantification of removal efficiencies and VOC speciation confirmed the relationship among removal efficiencies, compound biodegradability, and the dynamic transport of each mixture component within the organic matrix. Samples of the fixed bed were withdrawn at different intervals and the heterogeneous microbial community evaluated for both total and differential compound counts. PMID:16878585

  11. 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

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

    PubMed

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

    2015-08-01

    The effect of treating grapes with six fungicides, applied under critical agricultural practices (CAP) on levels of phenolic compounds and antioxidant activity of red wines of Monastrell variety was studied. Vinifications were performed through addition of active dry yeast (ADY). Measurement of phenolic compounds was made with HPLC-DAD. Determination of antioxidant activity was through reaction of the wine sample with the DPPH radical. The wine prepared from grapes treated with quinoxyfen shows a greater increase of phenolic compounds than the control wine. In contrast, the wine obtained from grapes treated with trifloxystrobin showed lower total concentration of phenolic compounds, including stilbenes, whilst treatments with kresoxim-methyl, fluquinconazole, and famoxadone slightly reduced their content. Hence, the use of these last four fungicides could cause a decrease in possible health benefits to consumers. Antioxidant activity hardly varied in the assays with quinoxyfen, fluquinconazole and famoxadone, and decreased in the other wines. PMID:25766797

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

    E-print Network

    Aguirre-Flores, Jessica Dafhne

    2011-02-22

    The molecular characteristics that affect the activity of various dirhodium complexes are reported. The importance of the axial position in the action of dirhodium compounds was studied. Three dirhodium complexes with ...

  14. 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 e?ux 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 e?ux. PMID:26528273

  15. 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

  16. [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

  17. 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

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

    PubMed

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

    2013-10-25

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

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

    PubMed Central

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

    2015-01-01

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

  20. 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-?-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

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

    PubMed

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

    2014-05-27

    Active compounds can participate in different local structure-activity relationship (SAR) environments and introduce different degrees of local SAR discontinuity, depending on their structural and potency relationships in data sets. Such SAR features have thus far mostly been analyzed using descriptive approaches, in particular, on the basis of activity landscape modeling. However, compounds in different local SAR environments have not yet been predicted. Herein, we adapt the emerging chemical patterns (ECP) method, a machine learning approach for compound classification, to systematically predict compounds with different local SAR characteristics. ECP analysis is shown to accurately assign many compounds to different local SAR environments across a variety of activity classes covering the entire range of observed local SARs. Control calculations using random forests and multiclass support vector machines were carried out and a variety of statistical performance measures were applied. In all instances, ECP calculations yielded comparable or better performance than controls. The approach presented herein can be applied to predict compounds that complement local SARs or prioritize compounds with different SAR characteristics. PMID:24803014

  2. Olfactometric determination of the most potent odor-active compounds in salmon muscle (Salmo salar) smoked by using four smoke generation techniques.

    PubMed

    Varlet, Vincent; Serot, Thierry; Cardinal, Mireille; Knockaert, Camille; Prost, Carole

    2007-05-30

    The volatile compounds of salmon fillets smoked according to four smoked generation techniques (smoldering, thermostated plates, friction, and liquid smoke) were investigated. The main odor-active compounds were identified by gas chromatography coupled with olfactometry and mass spectrometry. Only the odorant volatile compounds detected by at least six judges (out of eight) were identified as potent odorants. Phenolic compounds and guaiacol derivatives were the most detected compounds in the olfactometric profile whatever the smoking process and could constitute the smoky odorant skeleton of these products. They were recovered in the aromatic extracts of salmon smoked by smoldering and by friction, which were characterized by 18 and 25 odor-active compounds, respectively. Furannic compounds were more detected in products smoked with thermostated plates characterized by 26 odorants compounds. Finally, the 27 odorants of products treated with liquid smoke were significantly different from the three others techniques applying wood pyrolysis because pyridine derivatives and lipid oxidation products were perceived in the aroma profile. PMID:17488025

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

    PubMed Central

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

    2012-01-01

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

  4. 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

  5. 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

  6. 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...

  7. 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

  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. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26033701

  9. 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-Zemplén 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

  10. [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

  11. 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

  12. Comparison of odor-active volatile compounds of fresh and smoked salmon.

    PubMed

    Varlet, Vincent; Knockaert, Camille; Prost, Carole; Serot, Thierry

    2006-05-01

    The odorant volatile compounds of raw salmon and smoked salmon have been investigated by two gas chromatography-olfactometry methods (frequency detection and odorant intensity) and gas chromatography-mass spectrometry. After simultaneous steam distillation-solvent extraction with diethyl ether and the recovery of the aromatic extract in ethanol, qualitative olfactometric characterization and identification followed by a quantitative assessment of the odorant volatile compounds were carried out. The origin of many odorant compounds of smoked salmon can be attributed to wood smoke. Another part of smoked salmon aroma is due either to the odorant compounds of the raw fish flesh or to an evolution of fish flesh aroma thanks to the smoking process conditions. Forty-nine odorant compounds have been identified in fresh salmon and 74 in smoked salmon. Carbonyl compounds, such as heptanal or (E,Z)-2,6-nonadienal, show a high detection frequency and odorant intensity in unsmoked fish, giving the flesh its typical fishy odor. For smoked salmon, phenolic compounds, such as cresol or guaiacol, and furanic compounds seem to be responsible for the smoked odor. PMID:16637700

  13. Removal of Metabolic Liabilities Enables Development of Derivatives of Procaspase-Activating Compound 1 (PAC-1) with Improved Pharmacokinetics.

    PubMed

    Roth, Howard S; Botham, Rachel C; Schmid, Steven C; Fan, Timothy M; Dirikolu, Levent; Hergenrother, Paul J

    2015-05-14

    Procaspase-activating compound 1 (PAC-1) is an o-hydroxy-N-acylhydrazone that induces apoptosis in cancer cells by chelation of labile inhibitory zinc from procaspase-3. PAC-1 has been assessed in a wide variety of cell culture experiments and in vivo models of cancer, with promising results, and a phase 1 clinical trial in cancer patients has been initiated (NCT02355535). For certain applications, however, the in vivo half-life of PAC-1 could be limiting. Thus, with the goal of developing a compound with enhanced metabolic stability, a series of PAC-1 analogues were designed containing modifications that systematically block sites of metabolic vulnerability. Evaluation of the library of compounds identified four potentially superior candidates with comparable anticancer activity in cell culture, enhanced metabolic stability in liver microsomes, and improved tolerability in mice. In head-to-head experiments with PAC-1, pharmacokinetic evaluation in mice demonstrated extended elimination half-lives and greater area under the curve values for each of the four compounds, suggesting them as promising candidates for further development. PMID:25856364

  14. 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.

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

    PubMed

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

    2002-01-01

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

  16. 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

  17. Apple peels, from seven cultivars, have lipase-inhibitory activity and contain numerous ursenoic acids as identified by LC-ESI-QTOF-HRMS.

    PubMed

    McGhie, Tony K; Hudault, Sébastien; Lunken, Rona C M; Christeller, John T

    2012-01-11

    Apple peel contains numerous phytochemicals, many of which show bioactivity. This study investigated the identity of triterpenoid compounds contained in ethanolic extracts of peel from seven apple cultivars. Using HPLC-ESI-QTOF-HRMS, accurate mass information was obtained for 43 compounds, and chemical identity was inferred from the calculated elemental composition, fragment masses, ms/ms, and a limited set of authentic standards. Compounds were identified as triterpene acids and tentatively identified as ursenoic (or oleanoic) acid derivatives containing hydroxyl, oxo, and coumaroyloxy groups. These apple skin extracts exhibited lipase-inhibitory activity, which may be linked to the ursenoic acid content. Furthermore, both triterpene content and lipase-inhibitory activity varied by cultivar. PMID:22148752

  18. 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

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

    PubMed

    Zhu, Xianfeng; Zhang, Hongxun; Lo, Raymond

    2004-12-01

    A preliminary antimicrobial disk assay of chloroform, ethyl acetate, and n-butanol extracts of artichoke (Cynara scolymus L.) leaf extracts showed that the n-butanol fraction exhibited the most significant antimicrobial activities against seven bacteria species, four yeasts, and four molds. Eight phenolic compounds were isolated from the n-butanol soluble fraction of artichoke leaf extracts. On the basis of high-performance liquid chromatography/electrospray ionization mass spectrometry, tandem mass spectrometry, and nuclear magnetic resonance techniques, the structures of the isolated compounds were determined as the four caffeoylquinic acid derivatives, chlorogenic acid (1), cynarin (2), 3,5-di-O-caffeoylquinic acid (3), and 4,5-di-O-caffeoylquinic acid (4), and the four flavonoids, luteolin-7-rutinoside (5), cynaroside (6), apigenin-7-rutinoside (7), and apigenin-7-O-beta-D-glucopyranoside (8), respectively. The isolated compounds were examined for their antimicrobial activities on the above microorganisms, indicating that all eight phenolic compounds showed activity against most of the tested organisms. Among them, chlorogenic acid, cynarin, luteolin-7-rutinoside, and cynaroside exhibited a relatively higher activity than other compounds; in addition, they were more effective against fungi than bacteria. The minimum inhibitory concentrations of these compounds were between 50 and 200 microg/mL. PMID:15563206

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

    PubMed Central

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

    2015-01-01

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

  2. 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

  3. Volatile compounds of Viola odorata absolutes: identification of odorant active markers to distinguish plants originating from France and Egypt.

    PubMed

    Saint-Lary, Laure; Roy, Céline; Paris, Jean-Philippe; Tournayre, Pascal; Berdagué, 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

  4. 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.

  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. Phenolic compounds and antioxidant activity of olive leaf extracts.

    PubMed

    Kontogianni, Vassiliki G; Gerothanassis, Ioannis P

    2012-01-01

    The total phenolic content and antioxidant activities of olive leaf extracts were determined. Plant material was extracted with methanol and fractionated with solvents of increasing polarity, giving certain extracts. The qualitative changes in the composition of the extracts were determined after the storage of leaves for 22?h at 37°C, before the extraction. Total polyphenol contents in extracts were determined by the Folin-Ciocalteu procedure. They were also analysed by liquid chromatography-mass spectrometry. Their antioxidant activities were evaluated using the diphenyl picrylhydrazyl method and the ?-carotene linoleate model assay. Moreover, the effects of different crude olive leaf extracts on the oxidative stability of sunflower oil at 40°C and sunflower oil-in-water emulsions (10% o/w) at 37°C, at a final concentration of crude extract 200?mg?kg(-1) oil, were tested and compared with butylated hydroxyl toluene. PMID:22060136

  7. 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…

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

    PubMed Central

    Hvidsten, Ina; Mjøs, Svein Are; Bødtker, 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

  9. 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

  10. 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.

  11. 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,...

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

    PubMed

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

    2015-02-01

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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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

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

    E-print Network

    Bae, Hae Jin

    2012-02-14

    preparation and the impact of pre-harvest factors affecting bioactive compounds and antioxidant activity. Optimal extraction procedures were developed, and HPLC methods were validated for bioactive compounds in peppers. The highest flavonoids were extracted...

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

    NASA Astrophysics Data System (ADS)

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

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

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

    PubMed

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

    2015-12-01

    Searching for new prospective antitrypanosomal agents, three novel Ru(II)-cyclopentadienyl compounds, [Ru(?(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

  2. 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.

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

    PubMed

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

    2013-01-01

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

  4. 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...

  5. Antibacterial activity of coffee extracts and selected coffee chemical compounds against enterobacteria.

    PubMed

    Almeida, Ana Amélia P; Farah, Adriana; Silva, Daniela A M; Nunan, Elzíria A; Glória, 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

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

    PubMed

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

    2015-08-01

    Nutrients composition, phenolic compounds, antioxidant activity and estimated glycemic index (EGI) were evaluated in sorghum bran (SB) and decorticated sorghum flour (DSF), obtained by a rice-polisher, as well as whole sorghum flour (WSF). Correlation between EGI and the studied parameters were determined. SB presented the highest protein, lipid, ash, ?-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

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

    PubMed

    K?rm?z?bekmez, Hasan; Uysal, Görkem Berk; Masullo, Milena; Demirci, Fatih; Ba?c?, Yavuz; Kan, Yüksel; Piacente, Sonia

    2015-06-01

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

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

    PubMed

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

    2005-02-01

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

  10. 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

  11. Identifiers Identifiers

    E-print Network

    Brass, Stefan

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

  12. Identifiers Identifiers

    E-print Network

    Brass, Stefan

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

  13. Seasonal variation of pharmaceutically active compounds in surface (Tagus River) and tap water (Central Spain).

    PubMed

    Valcárcel, Y; Alonso, S González; Rodríguez-Gil, J L; Castaño, A; Montero, J C; Criado-Alvarez, J J; Mirón, I J; Catalá, 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

  14. 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.

  15. Synthesis, anticancer, and cytotoxic activities of some mononuclear Ru(II) compounds.

    PubMed

    Karki, Subhas S; Thota, Sreekanth; Darj, Satyanarayana Y; Balzarini, Jan; De Clercq, Erik

    2007-11-01

    The synthesis and characterization of ruthenium compounds (Ru1-Ru12) of the type [Ru(S)(2)(K)], (where S=1,10-phenanthroline/2,2'-bipyridine and K=itsz, MeO-btsz, 4-Cl-btsz, 2-Cl-btsz, 2-F-btsz, hfc and itsz=isatin-3-thiosemicarbazone, MeO-btsz=1-(4'-methoxy-benzyl)-thiosemicarbazone, hfc=2-{[3-chloro-4-fluoro-phenylimino]methyl}phenol, 4-Cl-btsz=1-(4'-chlorobenzyl)-thiosemicarbazone, 2-Cl-btsz=1-(2'-chloro benzyl)-thiosemicarbazone, 2-F-btsz=1-(2'-fluorobenzyl)-thiosemicarbazone) are described. These ligands form bidentate octahedral ruthenium compounds. The title compounds were subjected to in vivo anticancer activity against a transplantable murine tumor cell line Ehrlich's Ascites Carcinoma (EAC) and in vitro cytotoxic activity against human cancer cell line Molt 4/C8, CEM and murine tumor cell line L1210. Ruthenium compounds (Ru1-Ru12) showed promising biological activity especially in decreasing tumor volume and viable ascites cell counts. Treatment with these compounds prolonged the life span of mice bearing EAC tumor by 10-43%. In vitro evaluation of these ruthenium compounds revealed cytotoxic activity from 0.24 to 27 microM against Molt 4/C8, 0.27 to 48 microM against CEM, and 0.94 to 248 microM against L1210. Their ligands alone failed to show cytotoxic activity at the concentrations tested (68-405 microM). PMID:17765549

  16. 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

  17. 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.

  18. Biological activity of saponins and saponin-like compounds from starfish and brittle-stars.

    PubMed

    Andersson, L; Bohlin, L; Iorizzi, M; Riccio, R; Minale, L; Moreno-López, W

    1989-01-01

    Twenty-four saponins and saponin-like compounds, isolated from starfish and brittle-stars, have been tested in four in vitro tests, based upon bacterial and cell tissue cultures. Saponin-like compounds from brittle-stars have previously not been tested for biological activity. In an antibacterial test based on an agar diffusion test, the Gram positive bacterium S. aureus was affected by the polyhydroxylated steroidal glycosides, polyhydroxylated sterols and disulfated sterols. However, none of the 21 compounds tested were active against the Gram negative bacterium E. coli. In a cytotoxicity test all 21 compounds tested influenced the cells at a concentration of 100 micrograms/ml, while the cells were unaffected at 1 microgram/ml. In an antitumor test, 16 compounds were tested on two lymphoma cell lines. Inhibition of cell growth, at a concentration of 5 ng/ml, was seen for three polyhydroxylated sterols, in one cell line. Weak activity was seen in an antiviral test at a concentration of 10 micrograms/ml. PMID:2718189

  19. 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

  20. Synthesis and biological activity of amino acid derivatives of avarone and its model compound.

    PubMed

    Vilipi?, Jovana; Novakovi?, Irena; Stanojkovi?, Tatjana; Mati?, Ivana; Šegan, Dejan; Kljaji?, Zoran; Sladi?, Dušan

    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

  1. 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)-?(8')-4,7-dihydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan (4), erythro-(7R,8R)-?8'-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 ?M, compounds 2 and 3 possessed the most antifungal activity against Phomopsis obscurans and Phomopsis viticola, respectively. PMID:25173461

  2. 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

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

    PubMed

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

    2015-12-01

    Extracts of Styrax ramirezii Greenm., a fruit traditionally valued for health and wellness in Mexico, were analyzed phytochemically and evaluated for antioxidant and anti-inflammatory activity. Six norneolignans were identified by HPLC-TOF-MS, and the two major compounds were isolated for further evaluation. The effects of the isolated norneolignans, egonol and homoegonol, on lipopolysaccharide (LPS)-induced nitric oxide (NO) production, reactive oxygen species (ROS) production, and biomarkers of inflammation were evaluated. Of the tested compounds, egonol potently inhibited the production of NO and also significantly reduced the release of ROS. Consistent with these observations, the mRNA expression levels of inducible nitric oxide synthase (iNOS) (0.668 ± 0.108), cyclooxygenase-2 (COX-2) (0.553 ± 0.007), interleukin-1? (IL-1?) (0.093 ± 0.005), and interleukin-6 (IL-6) (0.298 ± 0.076) were reduced by egonol. The activity for both egonol and homoegonol increased in a concentration-dependent manner. These results suggest the potential of S. ramirezii Greenm. fruit to contribute to a healthy diet, rich in antioxidant and anti-inflammatory compounds. PMID:26575200

  4. Cytotoxic activity of C-geranyl compounds from Paulownia tomentosa fruits.

    PubMed

    Smejkal, Karel; Babula, Petr; Slapetová, Tereza; Brognara, Eleonora; Dall'acqua, Stefano; Zemlicka, Milan; Innocenti, Gabbriella; Cvacka, Josef

    2008-10-01

    The newly discovered 5,7-dihydroxy-6-geranylchromone ( 1) was isolated from PAULOWNIA TOMENTOSA fruit and subsequently characterized. The structure of the isolated compound was elucidated on the basis of extensive NMR experiments including HMQC, HMBC, COSY, and NOESY, as well as HR-MS, IR, and UV. The cytotoxicity of 1 was evaluated using a plant cell model represented by tobacco BY-2 cells. The other phytoconstituents ( 2 - 8) previously isolated from P. TOMENTOSA were similarly evaluated together with the known flavanones 10 and 11. The cytotoxicity (human erythro-leukaemia cell line K562) and activity on erythroid differentiation of compounds 2 - 9 and 12 and 13 have also been evaluated. Acteoside ( 2) was determined to be the most toxic of the compounds tested on BY-2 cells, diplacone ( 6) on the K562 cell line. Some aspects of the relationship between the flavanone skeleton substitution and the metabolic activation necessary for a toxic effect are discussed. PMID:18729043

  5. 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

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

    PubMed Central

    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

  7. 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 ?M), cloxyquin (IC50 25.1 ?M), cloxacillin sodium (IC50 36.2 ?M) and sodium dehydrocholate (IC50 53.2 ?M). 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

  8. Novel Indole-2-Carboxamide Compounds Are Potent Broad-Spectrum Antivirals Active against Western Equine Encephalitis Virus In Vivo

    PubMed Central

    Delekta, Phillip C.; Dobry, Craig J.; Sindac, Janice A.; Barraza, Scott J.; Blakely, Pennelope K.; Xiang, Jianming; Kirchhoff, Paul D.; Keep, Richard F.; Irani, David N.; Larsen, Scott D.

    2014-01-01

    ABSTRACT Neurotropic alphaviruses, including western, eastern, and Venezuelan equine encephalitis viruses, cause serious and potentially fatal central nervous system infections in humans for which no currently approved therapies exist. We previously identified a series of thieno[3,2-b]pyrrole derivatives as novel inhibitors of neurotropic alphavirus replication, using a cell-based phenotypic assay (W. Peng et al., J. Infect. Dis. 199:950–957, 2009, doi:http://dx.doi.org/10.1086/597275), and subsequently developed second- and third-generation indole-2-carboxamide derivatives with improved potency, solubility, and metabolic stability (J. A. Sindac et al., J. Med. Chem. 55:3535–3545, 2012, doi:http://dx.doi.org/10.1021/jm300214e; J. A. Sindac et al., J. Med. Chem. 56:9222–9241, 2013, http://dx.doi.org/10.1021/jm401330r). In this report, we describe the antiviral activity of the most promising third-generation lead compound, CCG205432, and closely related analogs CCG206381 and CCG209023. These compounds have half-maximal inhibitory concentrations of ?1 ?M and selectivity indices of >100 in cell-based assays using western equine encephalitis virus replicons. Furthermore, CCG205432 retains similar potency against fully infectious virus in cultured human neuronal cells. These compounds show broad inhibitory activity against a range of RNA viruses in culture, including members of the Togaviridae, Bunyaviridae, Picornaviridae, and Paramyxoviridae families. Although their exact molecular target remains unknown, mechanism-of-action studies reveal that these novel indole-based compounds target a host factor that modulates cap-dependent translation. Finally, we demonstrate that both CCG205432 and CCG209023 dampen clinical disease severity and enhance survival of mice given a lethal western equine encephalitis virus challenge. These studies demonstrate that indole-2-carboxamide compounds are viable candidates for continued preclinical development as inhibitors of neurotropic alphaviruses and, potentially, of other RNA viruses. IMPORTANCE There are currently no approved drugs to treat infections with alphaviruses. We previously identified a novel series of compounds with activity against these potentially devastating pathogens (J. A. Sindac et al., J. Med. Chem. 55:3535–3545, 2012, doi:http://dx.doi.org/10.1021/jm300214e; W. Peng et al., J. Infect. Dis. 199:950–957, 2009, doi:http://dx.doi.org/10.1086/597275; J. A. Sindac et al., J. Med. Chem. 56:9222–9241, 2013, http://dx.doi.org/10.1021/jm401330r). We have now produced third-generation compounds with enhanced potency, and this manuscript provides detailed information on the antiviral activity of these advanced-generation compounds, including activity in an animal model. The results of this study represent a notable achievement in the continued development of this novel class of antiviral inhibitors. PMID:25031353

  9. Antileishmanial activity of compounds produced by endophytic fungi derived from medicinal plant Vernonia polyanthes and their potential as source of bioactive substances.

    PubMed

    do Nascimento, Adriana M; Soares, Mateus Gonçalves; da Silva Torchelsen, Fernanda K V; de Araujo, Jorge A Viana; Lage, Paula S; Duarte, Mariana C; Andrade, Pedro H R; Ribeiro, Tatiana G; Coelho, Eduardo A F; do Nascimento, Andréa M

    2015-11-01

    The purpose of this work was to evaluate the antileishmanial activity of endophytic fungi isolated from leaves of Vernonia polyanthes plant and their prospective use in the discovery of bioactive compounds. Sixteen endophytes were isolated by using potato dextrose agar medium and submitted to cultivation in rice medium. The fungal cultures were extracted with ethanol and used as crude extracts for testing their antileishmanial activity. The most active ethanol extract was obtained from P2-F3 strain, which was identified as Cochliobolus sativus by ITS rRNA gene sequence data. Followed by a bioassay-guided fractionation, the cochlioquinone A, isocochlioquinone A and anhydrocochlioquinone A compounds were isolated from the crude extracts and demonstrated to inhibit the parasites. From the present work, it is possible to conclude that endophytic fungi derived from medicinal plant V. polyanthes may be considered promising source for the discovery of bioactive compounds. PMID:26318306

  10. 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…

  11. 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 ...

  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. 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...

  14. 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...

  15. Fractionation of phenolic compounds from a purple corn extract and evaluation of antioxidant and antimutagenic activities 

    E-print Network

    Pedreschi, Romina Paola

    2005-08-29

    of antimutagenic action by the phenolic compounds present either in the anthocyanin-rich fraction or the ethyl acetate fraction and sub-fraction EAFIV seems to be a contribution of a direct action on the enzymes involved in the activation of the mutagen...

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

    E-print Network

    Hergenrother, Paul J.

    Differential Effects of Procaspase-3 Activating Compounds in the Induction of Cancer Cell Death ions in vitro, induce apoptotic death of cancer cells in culture, and reduce tumor burden in vivo. Ip discovery. As cancer cells characteristically evade apoptosis through inactivating muta- tions and aberrant

  17. 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...

  18. 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...

  19. 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

  20. 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

  1. 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

  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

  3. 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

  4. 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

  5. Inhibition of polyphenoloxidase activity by mixtures of heated cysteine derivatives with carbonyl compounds.

    PubMed

    Chériot, Sophie; Billaud, Catherine; Maillard, Marie-Noëlle; Nicolas, Jacques

    2007-04-01

    It had previously been shown that soluble Maillard reaction products (MRP) made from thiol compounds and glucose or fructose contained powerful inhibitors of various fruit and vegetable polyphenoloxidase (PPO) activity. In MRP from cysteine and glucose, the amount of hydroxymethylfurfural (HMF) formed increased with the increase in glucose concentration (0-1 M), particularly under acidic (pH 2) conditions. Using model mixtures containing a preheated cysteine-derived compound and a carbonyl component, especially HMF, furfural and benzaldehyde, we showed that the neoformed compounds produced exhibited a stronger inhibitory potency toward PPO activity of eggplant, apple, and mushroom than former MRP. Optimal reaction conditions for the formation of inhibitory compounds when HMF reacted with preheated cysteine were investigated. It was found that a reactants molar ratio of 1:1 and a reaction time exceeding 1 h were the most efficient reaction conditions to generate inhibitory compounds. The stability of the newly formed products, evaluated during storage, showed that their inhibitory potency was globally kept at 4, 21, and 37 degrees C for 72 h but was unstable when stored at -20 degrees C and lost when exposed to UV radiations for 24 h. PMID:17357978

  6. Novel arylalkylamine compounds exhibits potent selective antiparasitic activity against Leishmania major

    PubMed Central

    Iniguez, Eva A.; Perez, Andrea; Maldonado, Rosa A.; Skouta, Rachid

    2015-01-01

    Leishmania major (L. major) is a protozoan parasite causal agent of Leishmaniasis. It is estimated that 12 million people are currently infected and around 2 million infections occur each year. Current treatments suffer of high toxicity for the patient, low efficacy toward the parasite, high cost, and are losing effectiveness due to parasite resistance. Discovering novel small molecule with high specificity/selectivity and drug-like properties for anti-leishmanial activity remains a significant challenge. The purpose of this study is to communicate the design and synthesis strategies of novel chemical compounds based of the arylalkylamine scaffold with selective toxicity towards L. major and less toxicity to human cells in vitro. Here, we have developed a structure activity relationship (SAR) study of arylalkylamine AA1 in order to study their anti-parasitic effect in L. major. Overall, 27 arylalkylamine compounds derived from AA1 were synthesized and purified by silica gel column chromatography. The purity of each analog was confirmed by spectroscopic methods (1H, 13C NMR and LC/MS). Among these analogs, the compound AA9 showed the best toxic activity on L. major (LD50 = 3.34 ?M), which represents a 9 fold higher lethality as compared with its parental AA1 (Fer-1) compound (LD50 = 28.75 ?M). In addition, AA9 showed no significant toxicity at 80 ?M on U20S Human Osteoblasts, Raw 264.7 Macrophages or intraperitoneal macrophages. In summary, our combined SAR study and biological evaluation data of AA1-AA27 compounds allow the identification of novel arylalkylamine compound AA9 that exhibits potent cytotoxicity against L. major promastigote with minimum toxic effect on human cells. PMID:26410073

  7. Pharmaceutically active compounds in sludge stabilization treatments: anaerobic and aerobic digestion, wastewater stabilization ponds and composting.

    PubMed

    Martín, Julia; Santos, Juan Luis; Aparicio, Irene; Alonso, Esteban

    2015-01-15

    Sewage sludge disposal onto lands has been stabilized previously but still many pollutants are not efficiently removed. Special interest has been focused on pharmaceutical compounds due to their potential ecotoxicological effects. Nowadays, there is scarce information about their occurrence in different sludge stabilization treatments. In this work, the occurrence of twenty-two pharmaceutically active compounds has been studied in sludge from four sludge stabilization treatments: anaerobic digestion, aerobic digestion, composting and lagooning. The types of sludge evaluated were primary, secondary, anaerobically-digested and dehydrated, composted, mixed, aerobically-digested and dehydrated and lagoon sludge. Nineteen of the twenty-two pharmaceutically active compounds monitored were detected in sewage sludge. The most contaminated samples were primary sludge, secondary sludge and mixed sludge (the average concentrations of studied compounds in these sludges were 179, 310 and 142 ?g/kg dm, respectively) while the mean concentrations found in the other types of sewage sludge were 70 ?g/kg dm (aerobically-digested sludge), 63 ?g/kg dm (lagoon sludge), 12 ?g/kg dm (composted sludge) and 8 ?g/kg dm (anaerobically-digested sludge). The antibiotics ciprofloxacin and norfloxacin were found at the highest concentration levels in most of the analyzed sludge samples (up to 2660 and 4328 ?g/kg dm, respectively). Anaerobic-digestion treatment reduced more considerably the concentration of most of the studied compounds than aerobic-digestion (especially in the case of bezafibrate and fluoroquinolones) and more than anaerobic stabilization ponds (in the case of acetaminophen, atenolol, bezafibrate, carbamazepine, 17?-ethinylestradiol, naproxen and salicylic acid). Ecotoxicological risk assessment, of sludge application onto soils, has also been evaluated. Risk quotients, expressed as the ratio between the predicted environmental concentration and the predicted non-effect concentration, were lower than 1 for all the pharmaceutically active compounds so no significant risks are expected to occur due to the application of sewage sludge onto soils, except for 17?-ethinylestradiol when chronic toxicity was considered. PMID:24909712

  8. Novel arylalkylamine compounds exhibits potent selective antiparasitic activity against Leishmania major.

    PubMed

    Iniguez, Eva A; Perez, Andrea; Maldonado, Rosa A; Skouta, Rachid

    2015-11-15

    Leishmania major (L. major) is a protozoan parasite causal agent of Leishmaniasis. It is estimated that 12 million people are currently infected and around 2 million infections occur each year. Current treatments suffer of high toxicity for the patient, low efficacy toward the parasite, high cost, and are losing effectiveness due to parasite resistance. Discovering novel small molecule with high specificity/selectivity and drug-like properties for anti-leishmanial activity remains a significant challenge. The purpose of this study is to communicate the design and synthesis strategies of novel chemical compounds based of the arylalkylamine scaffold with selective toxicity towards L. major and less toxicity to human cells in vitro. Here, we have developed a structure activity relationship (SAR) study of arylalkylamine AA1 in order to study their anti-parasitic effect in L. major. Overall, 27 arylalkylamine compounds derived from AA1 were synthesized and purified by silica gel column chromatography. The purity of each analog was confirmed by spectroscopic methods ((1)H, (13)C NMR and LC/MS). Among these analogs, the compound AA9 showed the best toxic activity on L. major (LD50=3.34?M), which represents a 9 fold higher lethality as compared with its parental AA1 (Fer-1) compound (LD50=28.75?M). In addition, AA9 showed no significant toxicity at 80?M on U20S Human Osteoblasts, Raw 264.7 Macrophages or intraperitoneal macrophages. In summary, our combined SAR study and biological evaluation data of AA1-AA27 compounds allow the identification of novel arylalkylamine compound AA9 that exhibits potent cytotoxicity against L. major promastigote with minimum toxic effect on human cells. PMID:26410073

  9. 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…

  10. ORIGINAL ARTICLE Assessing a signal model and identifying brain activity from fMRI

    E-print Network

    Gao, Jianbo

    ORIGINAL ARTICLE Assessing a signal model and identifying brain activity from fMRI data is to develop simple and reliable methods to correlate brain regions with functionality. In this paper, we brain activity from fMRI data. We perform three tasks: (a) Estimating noise level from experimental f

  11. Synthesis, reactions and biological activity of some new bis-heterocyclic ring compounds containing sulphur atom

    PubMed Central

    2013-01-01

    Background The derivatives of thieno[2,3-b]thiophene belong to a significant category of heterocyclic compounds, which have shown a wide spectrum of medical and industrial application. Results A new building block with two electrophilic center of thieno[2,3-b]thiophene derivatives 2 has been reported by one-pot reaction of diketone derivative 1 with Br2/AcOH in excellent yield. A variety of heteroaromatics having bis(1H-imidazo[1,2a] benzimidazole), bis(1H-imidazo[1,2-b][1,2,4]triazole)-3-methyl-4-phenylthieno[2,3-b]thiophene derivatives, dioxazolo-, dithiazolo-, and 1H-imidazolo-3-methyl-4-phenylthieno[2,3-b]thiophene derivatives as well pyrrolo, thiazolo -3-methyl-4-phenylthieno[2,3-b]thiophene derivatives have been designed, synthesized, characterized, and evaluated for their biological activity. Compounds 3–9 showed good bioassay result. These new derivatives were evaluated for anti-cancer activity against PC-3 cell lines, in vitro antioxidant potential and ?-glucuronidase and ?-glucosidase inhibitory activities. Compound 3 (IC50?=?56.26?±?3.18??M) showed a potent DPPH radical scavenging antioxidant activity and found to be more active than standard N-acetylcystein (IC50?=?105.9?±?1.1??M). Compounds 8a (IC50?=?13.2?±?0.34??M) and 8b (IC50?=?14.1?±?0.28??M) found as potent inhibitor of ?-glucusidase several fold more active than the standard acarbose (IC50?=?841?±?1.73??M). Most promising results were obtained in ?-glucuronidase enzyme inhibition assay. Compounds 5 (IC50?=?0.13?±?0.019??M), 6 (IC50?=?19.9?±?0.285??M), 8a (IC50?=?1.2?±?0.0785??M) and 9 (IC50?=?0.003?±?0.09??M) showed a potent inhibition of ?-glucuronidase. Compound 9 was found to be several hundred fold more active than standard D-Saccharic acid 1,4-lactone (IC50?=?45.75?±?2.16??M). Conclusions Synthesis, characterization, and in vitro biological activity of a series of thieno[2,3-b]thiophene have been investigated. PMID:23829861

  12. Application of the rough sets theory in structure activity relationship of antielectrostatic ammonium compounds.

    PubMed

    Krysi?ski, Jerzy; Skrzypczak, Andrzej; Demski, Grzegorz

    2003-01-01

    The relationships between the chemical structure and the antielectrostatic effect of 112 ammonium compounds were analysed using the method of rough sets. The antielectrostatic activity was determined by measurements of the maximum voltage induced. Using the rough sets approach the smallest set of condition attributes significant for high quality of classification has been found. The resulting decision rules describe relations between the structure and the antielectrostatic properties of ammonium chlorides in terms of significant condition attributes. This may be helpful in predicting the structures of the new antielectrostatic compounds to be synthesized. PMID:13678321

  13. Adsorption of selected pharmaceuticals and an endocrine disrupting compound by granular activated carbon. 2. Model prediction

    SciTech Connect

    Yu, Z.; Peldszus, S.; Huck, P.M.

    2009-03-01

    The adsorption of two representative pharmaceutically active compounds (PhACs) naproxen and carbamazepine and one endocrine disrupting compound (EDC) nonylphenol was studied in pilot-scale granular activated carbon (GAC) adsorbers using post-sedimentation (PS) water from a full-scale drinking water treatment plant. The GAC adsorbents were coal-based Calgon Filtrasorb 400 and coconut shell-based PICA CTIF TE. Acidic naproxen broke through fastest while nonylphenol was removed best, which was consistent with the degree to which fouling affected compound removals. Model predictions and experimental data were generally in good agreement for all three compounds, which demonstrated the effectiveness and robustness of the pore and surface diffusion model (PSDM) used in combination with the time-variable parameter approach for predicting removals at environmentally relevant concentrations (i.e., ng/L range). Sensitivity analyses suggested that accurate determination of film diffusion coefficients was critical for predicting breakthrough for naproxen and carbamazepine, in particular when high removals are targeted. Model simulations demonstrated that GAC carbon usage rates (CURs) for naproxen were substantially influenced by the empty bed contact time (EBCT) at the investigated conditions. Model-based comparisons between GAC CURs and minimum CURs for powdered activated carbon (PAC) applications suggested that PAC would be most appropriate for achieving 90% removal of naproxen, whereas GAC would be more suitable for nonylphenol. 25 refs., 4 figs., 1 tab.

  14. Biological activity of Pinus nigra terpenes--evaluation of FtsZ inhibition by selected compounds as contribution to their antimicrobial activity.

    PubMed

    Sarac, Zorica; Mateji?, Jelena S; Stojanovi?-Radi?, Zorica Z; Veselinovi?, Jovana B; Džami?, Ana M; Bojovi?, Srdjan; Marin, Petar D

    2014-11-01

    In the current work, in vitro antioxidant, antibacterial, and antifungal activites of the needle terpenes of three taxa of Pinus nigra from Serbia (ssp. nigra, ssp. pallasiana, and var. banatica) were analyzed. The black pine essential oils showed generally weak antioxidative properties tested by two methods (DPPH and ABTS scavenging assays), where the highest activity was identified in P. nigra var. banatica (IC50=25.08 mg/mL and VitC=0.67 mg (vitamin C)/g when tested with the DPPH and ABTS reagents, respectively). In the antimicrobial assays, one fungal (Aspergilus niger) and two bacterial strains (Staphylococcus aureus and Bacillus cereus) showed sensitivity against essential oils of all three P. nigra taxa. The tested oils have been shown to possess inhibitory action in the range from 20.00 to 0.62 mg/mL, where var. banatica exhibited the highest and ssp. nigra the lowest antimicrobial action. In order to determine potential compounds that are responsible for alternative mode of action, molecular docking simulations inside FtsZ (a prokaryotic homolog of tubulin) were performed. Tested compounds were the most abundant terpenoid (germacrene D-4-ol) and its structurally similar terpene (germacrene D), both present in all three essential oils. It was determined that the oxygenated form of the molecule creates stable bonds with investigated enzyme FtsZ, and that this compound, through this mechanism of action participates in the antimicrobial activity. PMID:25217763

  15. Phenolic Compounds from the Leaves of Stewartia pseudocamellia Maxim. and their Whitening Activities.

    PubMed

    Roh, Hyun Jung; Noh, Hye-Ji; Na, Chun Su; Kim, Chung Sub; Kim, Ki Hyun; Hong, Cheol Yi; Lee, Kang Ro

    2015-05-01

    The half-dried leaves of Stewartia. pseudocamellia were extracted with hot water (SPE) and partitioned with n-hexane (SPEH), dichloromethane (SPED), and ethyl acetate (SPEE) successively. SPE and SPEE showed significant inhibitory effects against melanogenesis and tyrosinase activities. By bioassay-guided isolation, ten phenolic compounds were isolated by column chromatography from SPEE. The whitening effect of the isolated compounds from SPEE were tested for the inhibitory activities against melanogenesis using B16 melanoma cells, in vitro inhibition of tyrosinase, and L-3,4-dihydorxy-indole-2-carboxylic acid (L-DOPA) auto-oxidation assay. A cytotoxic activity assay was done to examine the cellular toxicity in Raw 264.7 macrophage cells. Of the compounds isolated, gallic acid and quercetin revealed significant inhibitory activities against melanogenesis compared to arbutin. In particular, quercetin exhibited similar inhibitory activities against tyrosinase and L-DOPA oxidation without cytotoxicity. These results suggested that SPE could be used as a potential source of natural skin-whitening material in cosmetics as well as in food products. PMID:25995828

  16. Phenolic Compounds from the Leaves of Stewartia pseudocamellia Maxim. and their Whitening Activities

    PubMed Central

    Roh, Hyun Jung; Noh, Hye-Ji; Na, Chun Su; Kim, Chung Sub; Kim, Ki Hyun; Hong, Cheol Yi; Lee, Kang Ro

    2015-01-01

    The half-dried leaves of Stewartia. pseudocamellia were extracted with hot water (SPE) and partitioned with n-hexane (SPEH), dichloromethane (SPED), and ethyl acetate (SPEE) successively. SPE and SPEE showed significant inhibitory effects against melanogenesis and tyrosinase activities. By bioassay-guided isolation, ten phenolic compounds were isolated by column chromatography from SPEE. The whitening effect of the isolated compounds from SPEE were tested for the inhibitory activities against melanogenesis using B16 melanoma cells, in vitro inhibition of tyrosinase, and L-3,4-dihydorxy-indole-2-carboxylic acid (L-DOPA) auto-oxidation assay. A cytotoxic activity assay was done to examine the cellular toxicity in Raw 264.7 macrophage cells. Of the compounds isolated, gallic acid and quercetin revealed significant inhibitory activities against melanogenesis compared to arbutin. In particular, quercetin exhibited similar inhibitory activities against tyrosinase and L-DOPA oxidation without cytotoxicity. These results suggested that SPE could be used as a potential source of natural skin-whitening material in cosmetics as well as in food products. PMID:25995828

  17. Cytotoxic Activity and Chemical Composition of the Root Extract from the Mexican Species Linum scabrellum: Mechanism of Action of the Active Compound 6-Methoxypodophyllotoxin

    PubMed Central

    Alejandre-García, Ivonne; Álvarez, Laura; Cardoso-Taketa, Alexandre; González-Maya, Leticia; Antúnez, Mayra; Salas-Vidal, Enrique; Díaz, J. Fernando; Marquina-Bahena, Silvia; Villarreal, María Luisa

    2015-01-01

    The cytotoxic activity and the chemical composition of the dichloromethane/methanol root extract of Linum scabrellum Planchon (Linaceae) were analyzed. Using NMR spectra and mass spectrometry analyses of the extract we identified eight main constituents: oleic acid (1), octadecenoic acid (2), stigmasterol (3), ?-amyrin (4), pinoresinol (5), 6 methoxypodophyllotoxin (6), coniferin (7), and 6-methoxypodophyllotoxin-7-O-?-D-glucopyranoside (8). By using the sulforhodamine B assay, an important cytotoxic activity against four human cancer cell lines, HF6 colon (IC50 = 0.57??g/mL), MCF7 breast (IC50 = 0.56??g/mL), PC3 prostate (IC50 = 1.60??g/mL), and SiHa cervical (IC50 = 1.54??g/mL), as well as toward the normal fibroblasts line HFS-30 IC50 = 1.02??g/mL was demonstrated. Compound 6 (6-methoxypodophyllotoxin) was responsible for the cytotoxic activity exhibiting an IC50 value range of 0.0632 to 2.7433?µg/mL against the tested cell lines. Cell cycle studies with compound 6 exhibited a cell arrest in G2/M of the prostate PC3 cancer cell line. Microtubule disruption studies demonstrated that compound 6 inhibited the polymerization of tubulin through its binding to the colchicine site (binding constant Kb = 7.6 × 106?M?1). A dose-response apoptotic effect was also observed. This work constitutes the first investigation reporting the chemical composition of L. scabrellum and the first study determining the mechanism of action of compound 6. PMID:26246833

  18. Synthesis and antioxidant activities of some new triheterocyclic compounds containing benzimidazole, thiophene, and 1,2,4-triazole rings.

    PubMed

    Mente?e, Emre; Y?lmaz, Fatih; Balta?, Nimet; Bekircan, Olcay; Kahveci, Bahittin

    2015-06-01

    Various triheterocyclic compounds containing benzimidazole, thiophene, and 1,2,4-triazole rings (3-6) were synthesized and screened for their antioxidant activities. The structures of the synthesized compounds (2-6) were judged by (1)H NMR, (13)C NMR, elemental analysis, and LC-MS spectral data. Antioxidant activities of the synthesized compounds (2-6) were determined with CUPric Reducing Antioxidant Capacity (CUPRAC), ABTS (2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)/persulfate, and DPPH (1,1-diphenyl-2-picrylhydrazyl) assays. Most of the compounds showed a significant antioxidant activity and especially, compound 5c showed very good SC50 value for DPPH method and compound 5h exhibited very high scavenging activity to ABTS method. PMID:25198894

  19. [Discovery of Novel Biologically Active Compounds of Natural Origin, with a Focus on Anti-tumor Activity].

    PubMed

    Yokosuka, Akihito

    2015-01-01

    Numerous clinically valuable medicines, including anticancer drugs, have been developed from biologically active natural compounds and their structurally related derivatives. This review discusses novel natural compounds with promising biological activities and those with novel chemical structures. Glaziovianin A, an isoflavone isolated from the leaves of Ateleia glazioviana (Legminosae), inhibited cell cycle progression at the M-phase with an abnormal spindle structure. AU-1 and YG-1, 5?-steroidal glycosides isolated from the whole plants of Agave utahensis and the underground parts of Yucca glauca (Agavaceae), induced apoptosis of HL-60 cells via caspase-3 activation. Lycolicidinol, an alkaloid isolated from the bulbs of Lycoris albiflora (Amaryllidaceae), induced transient autophagy and morphological changes in mitochondria in the early stage of the apoptotic cell death process in HSC-2 cells. Taccasterosides isolated from the rhizomes of Tacca chantrieri (Taccaceae) and stryphnosides isolated from the pericarps of Stryphnodendron fissuratum (Legminosae) are steroidal and triterpene glycosides with unique chemical structures having novel sugar sequences. PMID:26423865

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

    PubMed

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

    2008-02-01

    An endophytic Xylaria sp., having broad antimicrobial activity, was isolated and characterized from Ginkgo biloba L. From the culture extracts of this fungus, a bioactive compound P3 was isolated by bioactivity-guided fractionation and identified as 7-amino-4-methylcoumarin by nuclear magnetic resonance, infrared, and mass spectrometry spectral data. The compound showed strong antibacterial and antifungal activities in vitro against Staphylococcus aureus [minimal inhibitory concentrations (MIC) 16 microg.ml(-1)], Escherichia coli (MIC, 10 microg.ml(-1)), Salmonella typhia (MIC, 20 microg.ml(-1)), Salmonella typhimurium (MIC, 15 microg.ml(-1)), Salmonella enteritidis (MIC, 8.5 microg.ml(-1)), Aeromonas hydrophila (MIC, 4 microg.ml(-1)), Yersinia sp. (MIC, 12.5 microg.ml(-1)), Vibrio anguillarum (MIC, 25 microg.ml(-1)), Shigella sp. (MIC, 6.3 microg.ml(-1)), Vibrio parahaemolyticus (MIC, 12.5 microg.ml(-1)), Candida albicans (MIC, 15 microg.ml(-1)), Penicillium expansum (MIC, 40 microg.ml(-1)), and Aspergillus niger (MIC, 25 microg.ml(-1)). This is the first report of 7-amino-4-methylcoumarin in fungus and of the antimicrobial activity of this metabolite. The obtained results provide promising baseline information for the potential use of this unusual endophytic fungus and its components in the control of food spoilage and food-borne diseases. PMID:18092158

  1. Assessment of flavonoids and volatile compounds in tea infusions of water lily flowers and their antioxidant activities.

    PubMed

    Yin, Dan-Dan; Yuan, Ru-Yu; Wu, Qian; Li, Shan-Shan; Shao, Shuai; Xu, Yan-Jun; Hao, Xiang-Hong; Wang, Liang-Sheng

    2015-11-15

    Water lily, a member of the Nymphaeaceae family, can be made into tea on the basis of outstanding fragrance characteristics and health care functions. In this study, 16 flavonoids were identified and quantified in tea infusions prepared from the petals of 33 water lily cultivars using HPLC-DAD and HPLC-ESI-MS/MS. The infusions were analyzed with HS-SPME coupled with GC-MS; 29 volatile compounds were detected, of which nine were found to be scent components. The cultivars were clustered into three clusters characterized according to scent components. The 'Conqueror' and 'Virginia' cultivars had the highest antioxidant activities. The concentrations of polyphenols and flavonoids showed significant positive correlations with antioxidant activity as measured by DPPH, ABTS(+), and FRAP assays. This study is valuable for a fuller understanding of this important tea and can also be used for the development of water lily. PMID:25976993

  2. 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 disease—tools 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

  3. Effect of cultivar and variety on phenolic compounds and antioxidant activity of cherry wine.

    PubMed

    Xiao, Zuobing; Fang, Lingling; Niu, Yunwei; Yu, Haiyan

    2015-11-01

    To compare the influence of cultivar and variety on the phenolic compounds and antioxidant activity (AA) of cherry wines, total phenolic (TP), total flavonoid (TF), total anthocyanin (TA), total tannin (TT), five individual phenolic acids, and AA were determined. An ultra-performance liquid chromatography tandem mass spectrometry (HPLC-DAD/ESI-MS) method was developed for the determination of gallic acid (GAE), p-hydroxybenzoic acid (PHB), chlorogenic acid (CHL), vanillic acid (VAN), and caffeic acid (CAF). A principal component analysis (PCA) and a cluster analysis (CA) were used to analyze differences related to cultivar and variety. The TP, TF, TA, TT, and AA of samples sourced from the Shandong province of China were higher than those from the Jiangsu province. The PCA and CA results showed that phenolic compounds in cherry wines were closely related to cultivar and variety and that cultivar had more influence on the phenolic compounds of cherry wines than variety. PMID:25976793

  4. 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-?RI 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

  5. Synthesis, structural characterization, and anticancer activity of a monobenzyltin compound against MCF-7 breast cancer cells

    PubMed Central

    Fani, Somayeh; Kamalidehghan, Behnam; Lo, Kong Mun; Hashim, Najihah Mohd; Chow, Kit May; Ahmadipour, Fatemeh

    2015-01-01

    A new monoorganotin Schiff base compound, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, (compound C1), was synthesized, and its structural features were investigated by spectroscopic techniques and single-crystal X-ray diffractometry. Compound C1 was exposed to several human cancer cell lines, including breast adenocarcinoma cell lines MCF-7 and MDA-MB-231, ovarian adenocarcinoma cell lines Skov3 and Caov3, and prostate cancer cell line PC3, in order to examine its cytotoxic effect for different forms of cancer. Human hepatic cell line WRL-68 was used as a normal cell line. We concentrated on the MCF-7 cell line to detect possible underlying mechanism involvement of compound C1. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed the strongest cytotoxicity of compound C1 against MCF-7 cells, with a half maximal inhibitory concentration (IC50) value of 2.5±0.50 ?g/mL after 48 hours treatment. The IC50 value was >30 ?g/mL in WRL-68 cells. Induced antiproliferative activity of compound C1 for MCF-7 cells was further confirmed by lactate dehydrogenase, reactive oxygen species, acridine orange/propidium iodide staining, and DNA fragmentation assays. A significant increase of lactate dehydrogenase release in treated cells was observed via fluorescence analysis. Luminescent analysis showed significant growth in intracellular reactive oxygen species production after treatment. Morphological changes of necrosis and early and late apoptosis stages were observed in treated cells after staining with acridine orange/propidium iodide. DNA fragmentation was observed as a characteristic of apoptosis in treated cells. Results of the present study obviously reveal potential cytotoxic effects of compound C1 against human breast cancer MCF-7 cells. PMID:26648695

  6. High-Throughput Screening Using iPSC-Derived Neuronal Progenitors to Identify Compounds Counteracting Epigenetic Gene Silencing in Fragile X Syndrome.

    PubMed

    Kaufmann, Markus; Schuffenhauer, Ansgar; Fruh, Isabelle; Klein, Jessica; Thiemeyer, Anke; Rigo, Pierre; Gomez-Mancilla, Baltazar; Heidinger-Millot, Valerie; Bouwmeester, Tewis; Schopfer, Ulrich; Mueller, Matthias; Fodor, Barna D; Cobos-Correa, Amanda

    2015-10-01

    Fragile X syndrome (FXS) is the most common form of inherited mental retardation, and it is caused in most of cases by epigenetic silencing of the Fmr1 gene. Today, no specific therapy exists for FXS, and current treatments are only directed to improve behavioral symptoms. Neuronal progenitors derived from FXS patient induced pluripotent stem cells (iPSCs) represent a unique model to study the disease and develop assays for large-scale drug discovery screens since they conserve the Fmr1 gene silenced within the disease context. We have established a high-content imaging assay to run a large-scale phenotypic screen aimed to identify compounds that reactivate the silenced Fmr1 gene. A set of 50,000 compounds was tested, including modulators of several epigenetic targets. We describe an integrated drug discovery model comprising iPSC generation, culture scale-up, and quality control and screening with a very sensitive high-content imaging assay assisted by single-cell image analysis and multiparametric data analysis based on machine learning algorithms. The screening identified several compounds that induced a weak expression of fragile X mental retardation protein (FMRP) and thus sets the basis for further large-scale screens to find candidate drugs or targets tackling the underlying mechanism of FXS with potential for therapeutic intervention. PMID:26024946

  7. Photo-activated luminescence sensor and method of detecting trichloroethylene and related volatile organochloride compounds

    DOEpatents

    Dinh, Tuan V. (Knoxville, TN)

    1996-01-01

    A sensor for detecting trichloroethylene and related volatile organochloride compounds uses a photo-activator that produces a photo-product complex with the contaminant. Characteristics of the light emitted from the complex will indicate the presence of the contaminant. A probe containing the photo-activator has an excitation light interface and a contaminant interface. One particular embodiment uses a porous membrane as the contaminant interface, so that the contaminant can migrate therethrough to the photo-activator and thereby form the complex.

  8. Photo-activated luminescence sensor and method of detecting trichloroethylene and related volatile organochloride compounds

    DOEpatents

    Dinh, T.V.

    1996-06-11

    A sensor for detecting trichloroethylene and related volatile organochloride compounds uses a photo-activator that produces a photo-product complex with the contaminant. Characteristics of the light emitted from the complex will indicate the presence of the contaminant. A probe containing the photo-activator has an excitation light interface and a contaminant interface. One particular embodiment uses a porous membrane as the contaminant interface, so that the contaminant can migrate there through to the photo-activator and thereby form the complex. 23 figs.

  9. A concise synthesis and antimicrobial activity of a novel series of naphthylpyridine-3-carbonitrile compounds.

    PubMed

    Kotb, Eman R; Anwar, Manal M; Abbas, Hebat-Allah S; Abd El-Moez, Sherein I

    2013-01-01

    A novel series of acyclic nucleosides 2-5 and 13a-c were synthesized by utilizing 4-phenyl-6(naphthalen-2-yl)-2-oxo-1,2-dihydropridine-3-carbonitrile (1) as a key starting material. Chlorination of 1 yielded the chloro analogue 6 that was allowed to react with urea, thiourea, thiosemicarbazide and alicyclic secondary amines to produce the corresponding derivatives 7a-c and 11a-c. Further condensation of 6 with various amino acids provided the compounds 8-10, whereas hydrazinolysis of 6 yielded the hydrazinyl analogue 12 which was condensed with different isothiocyanates and acid anhydrides to afford derivatives 18-20, respectively. Upon treatment of 12 with sodium nitrite, the azide derivative 14 was obtained which was subjected to reaction with various active methylene compounds to obtain the corresponding triazolo derivatives 15-17. The structure assignment of the new compounds is based on chemicaland spectroscopic evidence. Antimicrobial evaluation of the newly synthesized derivatives was performed using ciprofloxacin and fluconazole as reference antibacterial and antifungal drugs. The most effective compounds against the tested bacterial and fungal isolates were the benzothiohydrazide compound 18b followed by the hydrazone and the phthalic anhydride derivatives 13c and 20, respectively. PMID:23923391

  10. 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

  11. Antioxidant and Anti-Inflammatory Activity Determination of One Hundred Kinds of Pure Chemical Compounds Using Offline and Online Screening HPLC Assay

    PubMed Central

    Lee, Kwang Jin; Oh, You Chang; Cho, Won Kyung; Ma, Jin Yeul

    2015-01-01

    This study investigated the antioxidant activity of one hundred kinds of pure chemical compounds found within a number of natural substances and oriental medicinal herbs (OMH). Three different methods were used to evaluate the antioxidant activity of DPPH radical-scavenging activity, ABTS radical-scavenging activity, and online screening HPLC-ABTS assays. The results indicated that 17 compounds exhibited better inhibitory activity against ABTS radical than DPPH radical. The IC50 rate of a more practical substance is determined, and the ABTS assay IC50 values of gallic acid hydrate, (+)-catechin hydrate, caffeic acid, rutin hydrate, hyperoside, quercetin, and kaempferol compounds were 1.03 ± 0.25, 3.12 ± 0.51, 1.59 ± 0.06, 4.68 ± 1.24, 3.54 ± 0.39, 1.89 ± 0.33, and 3.70 ± 0.15??g/mL, respectively. The ABTS assay is more sensitive to identifying the antioxidant activity since it has faster reaction kinetics and a heightened response to antioxidants. In addition, there was a very small margin of error between the results of the offline-ABTS assay and those of the online screening HPLC-ABTS assay. We also evaluated the effects of 17 compounds on the NO secretion in LPS-stimulated RAW 264.7 cells and also investigated the cytotoxicity of 17 compounds using a cell counting kit (CCK) in order to determine the optimal concentration that would provide an effective anti-inflammatory action with minimum toxicity. These results will be compiled into a database, and this method can be a powerful preselection tool for compounds intended to be studied for their potential bioactivity and antioxidant activity related to their radical-scavenging capacity. PMID:26504472

  12. Antibacterial activities of the extracts, fractions and compounds from Dioscorea bulbifera

    PubMed Central

    2012-01-01

    Background Dioscorea bulbifera is an African medicinal plant used to treat microbial infections. In the present study, the methanol extract, fractions (DBB1 and DBB2) and six compounds isolated from the bulbils of D. bulbifera, namely bafoudiosbulbins A (1), B (2), C (3), F (4), G (5) and 2,7-dihydroxy-4-methoxyphenanthrene (6), were tested for their antimicrobial activities against Mycobacteria and Gram-negative bacteria involving multidrug resistant (MDR) phenotypes expressing active efflux pumps. Methods The microplate alamar blue assay (MABA) and the broth microdilution methods were used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the above samples. Results The results of the MIC determinations indicated that when tested alone, the crude extract, fractions DBB1 and DBB2 as well as compounds 2 to 5 were able to prevent the growth of all the fifteen studied microorganisms, within the concentration range of 8 to 256 ?g/mL. The lowest MIC value for the methanol extract and fractions (16 ?g/mL) was obtained with DBB1 and DBB2 on E, coli AG100A and DBB2 on Mycobacterium tuberculosis MTCS2. The lowest value for individual compounds (8 ?g/mL) was recorded with compound 3 on M. smegmatis and M. tuberculosis ATCC and MTCS2 strains respectively. The activity of the samples on many MDR bacteria such as Enterobacter aerogenes EA289, CM64, Klebsiella pneumoniae KP63 and Pseudomonas aeruginosa PA124 was better than that of chloramphenicol. When tested in the presence of the efflux pump inhibitor against MDR Gram-negative bacteria, the activity of most of the samples increased. MBC values not greater than 512 ?g/mL were recorded on all studied microorganisms with fraction DBB2 and compounds 2 to 5. Conclusions The overall results of the present investigation provided evidence that the crude extract D. bulbifera as well as some of the compounds and mostly compounds 3 could be considered as potential antimicrobial drugs to fight against MDR bacteria. PMID:23176193

  13. Phenolic compounds with in vitro activity against respiratory syncytial virus from the Nigerian lichen Ramalina farinacea.

    PubMed

    Lai, Daowan; Odimegwu, Damian C; Esimone, Charles; Grunwald, Thomas; Proksch, Peter

    2013-10-01

    The extract of the Nigerian lichen Ramalina farinacea showed inhibitory activity against the respiratory syncytial virus in a preliminary assay. A follow-up chemical investigation of this lichen led to the isolation of thirteen phenolic compounds (1-13), including one new hydroquinone depside, designated 5-hydroxysekikaic acid (1), and one new orsellinic acid derivative, 2,3-dihydroxy-4-methoxy-6-pentylbenzoic acid (8). Their structures were unambiguously determined by analysis of 1D and 2D NMR and mass spectroscopic data, as well as by comparison with literature data. Compound 1 was found to partially convert to a 1,4-benzoquinone derivative (1a) during storage. The antiviral activities of the isolated compounds were evaluated against the respiratory syncytial virus. Among them, sekikaic acid (2) showed potent inhibition towards a recombinant strain rg respiratory syncytial virus (IC50 5.69 µg/mL) and respiratory syncytial virus A2 strain (IC50 7.73 µg/mL). The effect of sekikaic acid on the cell viability of HEp2 and Vero cell lines was investigated, and the time of addition assay revealed that sekikaic acid clearly interferes with viral replication at a viral post-entry step, which is over 1.3-fold more active than the control ribavirin at 4 hours postinfection addition. Furthermore, sekikaic acid did not display virucidal activity at concentrations below the TC50, whereas the parental extract did. PMID:23970423

  14. Synthesis, algal inhibition activities and QSAR studies of novel gramine compounds containing ester functional groups

    NASA Astrophysics Data System (ADS)

    Li, Xia; Yu, Liangmin; Jiang, Xiaohui; Xia, Shuwei; Zhao, Haizhou

    2009-05-01

    2,5,6-Tribromo-1-methylgramine (TBG), isolated from bryozoan Zoobotryon pellucidum was shown to be very efficient in preventing recruitment of larval settlement. In order to improve the compatibility of TBG and its analogues with other ingredients in antifouling paints, structural modification of TBG was focused mainly on halogen substitution and N-substitution. Two halogen-substitute gramines and their derivatives which contain ester functional groups at N-position of gramines were synthesized. Algal inhibition activities of the synthesized compounds against algae Nitzschia closterium were evaluated and the Median Effective Concentration (EC50) range was 1.06-6.74 ?g ml-1. Compounds that had a long chain ester group exhibited extremely high antifouling activity. Quantitive Structure Activity Relationship (QSAR) studies with multiple linear regression analysis were applied to find correlation between different calculated molecular descriptors and biological activity of the synthesized compounds. The results show that the toxicity (log (1/EC50)) is correlated well with the partition coefficient log P. Thus, these products have potential function as antifouling agents.

  15. Relationships between antioxidant compounds and antioxidant activities of tartary buckwheat during germination.

    PubMed

    Zhou, Xiaoli; Hao, Tingfeng; Zhou, Yiming; Tang, Wen; Xiao, Ying; Meng, Xiaoxiao; Fang, Xiang

    2015-04-01

    Relationships of changes between major non-enzymatic antioxidant compounds and antioxidant capacities of tartary buckwheat during germination were evaluated by means of correlation analysis and principal component analysis in this paper. The changes of antioxidant compounds, including vitamin C, vitamin E, flavonoids, carotenoids, and chlorophyll, and antioxidant activities were detected. A good accumulation in the content of vitamin C (0.71 mg/g), total flavonoids (19.53 mg rutin/g), and rutin (11.34 mg/g) was found after 7-day germination, but germination decreased the vitamin E activity. Germination improved the activities of buckwheat extracts to scavenge DPPH, ABTS, and superoxide free radicals by 107, 144, and 88 %, respectively. Furthermore, the correlation and principal component analysis showed that the vitamin C, total flavonoids, and rutin contents were closely related positively with free radicals scavenging properties, indicating that the compounds which play a key role in the elevated antioxidant activities during germination consisted of vitamin C, total flavonoids, and rutin, but not vitamin E and quercetin. PMID:25829633

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

    PubMed Central

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

    2014-01-01

    Organocatalysts, low-molecular mass organic compounds composed of nonmetallic elements, are often used in organic synthesis, but there have been no reports of organocatalysts of biological origin that function in vivo. Here, we report that actinorhodin (ACT), a natural product derived from Streptomyces coelicolor A3(2), acts as a biocatalyst. We purified ACT and assayed its catalytic activity in the oxidation of l-ascorbic acid and l-cysteine as substrates by analytical methods for enzymes. Our findings were as follows: (i) oxidation reactions producing H2O2 proceeded upon addition of ACT to the reaction mixture; (ii) ACT was not consumed during the reactions; and (iii) a small amount (catalytic amount) of ACT consumed an excess amount of the substrates. Even at room temperature, atmospheric pressure, and neutral pH, ACT showed catalytic activity in aqueous solution, and ACT exhibited substrate specificity in the oxidation reactions. These findings reveal ACT to be an organocatalyst. ACT is known to show antibiotic activity, but its mechanism of action remains unknown. On the basis of our results, we propose that ACT kills bacteria by catalyzing the production of toxic levels of H2O2. We also screened various other natural products of bacterial, plant, and animal origins and found that several of the compounds exhibited catalytic activity, suggesting that living organisms produce and use these compounds as biocatalysts in nature. PMID:25411318

  17. 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 ml·kg?1·min?1) was measured continuously, and the average of minutes 4–9 was used to represent the oxygen cost of each activity. To calculate METs, activity oxygen consumption was divided by 3.5 ml·kg?1·min?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: 1.14–1.30). For the prediction of activity type, the ANN correctly classified activity type 88.8% of the time (confidence interval: 86.4–91.2%). 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

  18. Cyclooctadepsipeptides--an anthelmintically active class of compounds exhibiting a novel mode of action.

    PubMed

    Harder, Achim; Schmitt-Wrede, Hans-Peter; Krücken, Jürgen; Marinovski, Predrag; Wunderlich, Frank; Willson, James; Amliwala, Kiran; Holden-Dye, Lindy; Walker, Robert

    2003-09-01

    There are three major classes of anthelmintics for veterinary use: the benzimidazoles/prebenzimidazoles, the tetrahydropyrimidines/imidazothiazoles, and the macrocyclic lactones. In nematodes, there are five targets for the existing anthelmintics: the nicotinergic acetylcholine receptor which is the target of tetrahydropyrimidines/imidazothiazoles and indirectly that of the acetylcholineesterase inhibitors; the GABA receptor which is the target of piperazine, the glutamate-gated chloride channel as the target of the macrocyclic lactones, and beta-tubulin as the target of prebenzimidazoles/benzimidazoles. All these anthelmintics are now in serious danger because of the worldwide spread of resistant nematodes in sheep, cattle, horses and pigs. The class of cyclooctadepsipeptides has entered the scene of anthelmintic research in the early 1990s. PF1022A, the first anthelmintically active member, is a natural compound from the fungus Mycelia sterilia that belongs to the microflora of the leaves of the Camellia japonica. PF1022A contains 4 N-Methyl-L-leucines, 2 D-lactic acids and 2-D-phenyllactic acids arranged as a cyclic octadepsipeptide with an alternating L-D-L-configuration. Emodepside is a semisynthetic derivative of PF1022A with a morpholine ring at each of the two D-phenyllactic acids in para position. The anthelmintic activity is directed against gastrointestinal nematodes in chicken, mice, rats, meriones, dogs, cats, sheep, cattle and horses. Moreover, emodepside is active against Trichinella spiralis larvae in muscles, microfilariae and preadult filariae and Dictyocaulus viviparus. PF1022A and emodepside are fully effective against benzimidazole-, levamisole or ivermectin-resistant nematodes in sheep and cattle. In Ascaris suum both cyclooctadepsipeptides lead to paralysis indicating a neuropharmacological action of these compounds. Using a PF1022A-ligand immunoscreening of a cDNA library from Haemonchus contortus a cDNA clone of 3569 base pairs could be identified. This clone codes for a novel 110 kDa heptahelical transmembrane receptor, named HC110R. Database- and phylogenetic analysis reveals that this receptor is a homolog to B0457.1 from Caenorhabditis elegans and has significant similarity to latrophilins from human, cattle and rat. HC110R is located in the plasma membrane and in lysosomes and endosomes. Alpha-latrotoxin, the poison of the black widow spider, binds at a 54 kDa aminoterminal fragment of HC110R. After binding a Ca2+-influx into HEK293 cells is induced which can be blocked by EGTA, Cd2+ or nifedipin. PF1022A or emodepside also bind to this 54 kDa aminoterminal region of HC110R and interact with the functional responses of alpha-latrotoxin. In C. elegans antibodies against the C-or N-terminus of HC110R bind to the B0457.1 protein located in the pharynx. Electrophysiological studies reveal that emodepside inhibits pharyngeal pumping of the nematodes in a concentration dependent way with an IC(50) value of about 4 nM. Thus, it is tempting to speculate that emodepside exerts its action on nematodes via a latrophilin-like receptor which might have an important regulatory function on pharyngeal pumping. PMID:13678839

  19. 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

  20. Use of high-resolution mass spectrometry to identify precursors and biodegradation products of perfluorinated and polyfluorinated compounds in end-user products.

    PubMed

    Yamamoto, Atsushi; Hisatomi, Hirotaka; Ando, Tomoshige; Takemine, Shusuke; Terao, Tomoko; Tojo, Toshiki; Yagi, Masahiro; Ono, Daisuke; Kawasaki, Hideya; Arakawa, Ryuichi

    2014-07-01

    Structural identification of perfluoroalkyl and polyfluoroalkyl substances found in end-user products and their biodegradation products was performed using ultra-high resolution mass spectrometry. Little attention has so far been paid to the environmental burden of perfluorooctane sulfonate and perfluorooctanoic acid from compounds with a molar mass of ~2,000. Analysis of end-user waterproofing and stain repellent products revealed the presence of numerous ions with molar masses ranging from 1,000 to 2,000 and complex mass spectra. Ultra-high resolution mass spectrometry determined the accurate mass of the observed ions, allowing the cleavage position and fragment structure to be determined. The precursor structures were determined based on reconstitution of the retrieved fragments. Products of fluorochemical manufacturers before voluntary regulation comprised compounds with plural perfluorooctyl chains. In the current product lines, compounds comprising perfluorobutyl chains were detected. Biodegradation tests using activated sludge revealed that biodegradation products consistent with those reported previously were generated even from complex end-user products. For example, the biodegradation test revealed the formation of N-ethyl perfluorooctane sulfonamido acetic acid and various fluorotelomer acids in the samples. The results of the present study suggest that the environmental burden of these compounds should be reevaluated. PMID:24828983

  1. Quantitative structure activity relationship modeling for predicting radiosensitization effectiveness of nitroimidazole compounds.

    PubMed

    Long, Wei; Liu, Peixun

    2010-01-01

    This paper provides quantitative structure activity relationship (QSAR) models for predicting the radiosensitization effectiveness of nitroimidazole compounds. A new method, combining a heuristic method and projection pursuit regression, was used to build an advanced QSAR model. Compared to the conventional multi-linear regression model, this model showed better predictive ability and reliability, with the values of regression coefficient (R(2)) and root mean square error (RMSE) 0.92 and 0.18 for the training set and 0.90 and 0.17 for the test set, respectively. The provided models were useful tools to predict the radiosensitization effectiveness of nitroimidazole compounds. Also, the new finding descriptors derived from this study will help us to facilitate the design of new radiation sensitizers with better activities. PMID:20921823

  2. In Silico Repositioning-Chemogenomics Strategy Identifies New Drugs with Potential Activity against Multiple Life Stages of Schistosoma mansoni

    PubMed Central

    Neves, Bruno J.; Braga, Rodolpho C.; Bezerra, José C. B.; Cravo, Pedro V. L.; Andrade, Carolina H.

    2015-01-01

    Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD), DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes. PMID:25569258

  3. Activity-Aware Map: Identifying human daily activity pattern using mobile phone data [book chapter

    E-print Network

    Phithakkitnukoon, Santi

    2010-01-01

    Being able to understand dynamics of human mobility is essential for urban planning and transportation management. Besides geographic space, in this paper, we characterize mobility in a profile-based space (activity-aware ...

  4. Patient-Specific Pathway Analysis Using PARADIGM Identifies Key Activities in Multiple Cancers - Josh Stuart, TCGA Scientific Symposium 2011

    Cancer.gov

    Home News and Events Multimedia Library Videos Patient-Specific Pathway Analysis Using PARADIGM Identifies Key Activities in Cancers - Josh Stuart Patient-Specific Pathway Analysis Using PARADIGM Identifies Key Activities in Multiple Cancers - Josh

  5. Synthesis and Anti-influenza A Virus Activity of 2,2-Dialkylamantadines and Related Compounds

    PubMed Central

    2012-01-01

    The synthesis of several 2,2-dialkyladamantyl-1-amines through the combination of a Ritter reaction with a Wagner–Meerwein rearrangement from noradamantane alcohols is reported. Several of the novel amines displayed low micromolar activities against several H1N1 influenza virus strains, including the amantadine-resistant A/PuertoRico/8/34 strain. Most of the compounds did not show cytotoxicity for MDCK cells. PMID:24900429

  6. Synthesis and Anti-influenza A Virus Activity of 2,2-Dialkylamantadines and Related Compounds.

    PubMed

    Torres, Eva; Fernández, Roser; Miquet, Stéphanie; Font-Bardia, Mercè; Vanderlinden, Evelien; Naesens, Lieve; Vázquez, Santiago

    2012-12-13

    The synthesis of several 2,2-dialkyladamantyl-1-amines through the combination of a Ritter reaction with a Wagner-Meerwein rearrangement from noradamantane alcohols is reported. Several of the novel amines displayed low micromolar activities against several H1N1 influenza virus strains, including the amantadine-resistant A/PuertoRico/8/34 strain. Most of the compounds did not show cytotoxicity for MDCK cells. PMID:24900429

  7. Hepatoprotective activity of polyphenolic compounds from Cynara scolymus against CCl4 toxicity in isolated rat hepatocytes.

    PubMed

    Adzet, T; Camarasa, J; Laguna, J C

    1987-01-01

    The hepatoprotective activity against CCl4 toxicity in isolated rat hepatocytes of some polyphenolic compounds, such as cynarin, isochlorogenic acid, chlorogenic acid, luteolin-7-glucoside, and two organic acids, caffeic and quinic, from Cynara scolymus, is tested. Only cynarine and, to a lesser extent, caffeic acid showed cytoprotective action. The possible relationship between the molecular structure and the protective effect found is discussed. PMID:3430163

  8. Isolation and characterisation of new bio-active compounds from Euphorbia cornigera: cytotoxic ingenol esters.

    PubMed

    Baloch, Imam Bakhsh; Baloch, Musa Kaleem

    2012-01-01

    The aerial parts of Euphorbia cornigera Boiss., on extraction with MeOH, yielded new bio-active constituents (1, 2) and known compounds (3 and 4) after MTT cytotoxicity assay-guided fractionation and chromatographic separation were conducted. From the aerial parts of E. cornigera Boiss., new bio-active constituents were extracted in methanol. The extract was partitioned in different organic solvents and the ethylacetate-soluble portion was subjected to Craig's distribution. The MTT cytotoxicity assay-guided chromatographic separation yielded four (1-4), out of which two (1, 2) were new and two known (3, 4) bio-active compounds, and they are reported for the first time from this source. Their structure and relative stereochemistry were established by analysing spectroscopic and mass measurement data. The isolates were named as: 13-O-[(2Z ,4 E ,6 Z)]-deca-2,4,6-trienoylingenol (1), 13-O-( 2 Z ,4 E ,6 Z)-deca-2,4,6-trienoyl-20-O-angeloylingenol (2), 13-O-dodecanoyl-20-O-hexanoylingenol (3) and 3-O-(2,3-dimethylbutanoyl)-13-O-dodecanoyl-20-O-hexadecanoylingenol (4). Literature revealed that compounds 1 and 2 are new metabolites, while 3 and 4 are known, and are reported for the first time from this source. Cytotoxicities of isolates were evaluated in terms of IC(50) against RAW and HT-29 cell lines through MTT assay using ambrucin hydrochloride as a control. Compound 3 showed more activity than control, while 1, 2 and 4 were moderate. PMID:22007629

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

    SciTech Connect

    Aziz, Gulzeb; Akselsen, Oyvind W.; Hansen, Trond V.; Paulsen, Ragnhild E.

    2010-09-15

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

  10. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin.

    PubMed

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

    2004-03-25

    Six members of the mammalian transient receptor potential (TRP) ion channels respond to varied temperature thresholds. The natural compounds capsaicin and menthol activate noxious heat-sensitive TRPV1 and cold-sensitive TRPM8, respectively. The burning and cooling perception of capsaicin and menthol demonstrate that these ion channels mediate thermosensation. We show that, in addition to noxious cold, pungent natural compounds present in cinnamon oil, wintergreen oil, clove oil, mustard oil, and ginger all activate TRPA1 (ANKTM1). Bradykinin, an inflammatory peptide acting through its G protein-coupled receptor, also activates TRPA1. We further show that phospholipase C is an important signaling component for TRPA1 activation. Cinnamaldehyde, the most specific TRPA1 activator, excites a subset of sensory neurons highly enriched in cold-sensitive neurons and elicits nociceptive behavior in mice. Collectively, these data demonstrate that TRPA1 activation elicits a painful sensation and provide a potential molecular model for why noxious cold can paradoxically be perceived as burning pain. PMID:15046718

  11. CE can identify small molecules that selectively target soluble oligomers of amyloid beta protein and display antifibrillogenic activity.

    PubMed

    Colombo, Raffaella; Carotti, Angelo; Catto, Marco; Racchi, Marco; Lanni, Cristina; Verga, Laura; Caccialanza, Gabriele; De Lorenzi, Ersilia

    2009-04-01

    Soluble and toxic oligomers of amyloid beta (A beta) protein have been identified as the true neurotoxic species involved in Alzheimer's disease and considering them as targets to inhibit A beta aggregation might have a therapeutic value. We previously set up a CE method that enables the separation and quantification of transient oligomers of A beta protein-containing 42 amino acids (A beta(1-42)) along the pathway leading to fibrils and we now demonstrate how this method can be successfully applied to examine the in vitro inhibitory effects of small molecules on A beta oligomerization. To this end, we investigated mitoxantrone and pixantrone, two well-known anticancer drugs, as well as suramin and a suramin-like compound. By using CE, it is here shown how mitoxantrone and pixantrone either reduce or block A beta(1-42) oligomerization, while Thioflavin T spectrofluorimetric assay and transmission electron microscopy demonstrate how these two compounds also display antifibrillogenic activity. Interestingly, in vitro cell viability experiments indicated that pixantrone significantly reduces A beta(1-42) neurotoxicity. PMID:19306269

  12. An Antifungal Combination Matrix Identifies a Rich Pool of Adjuvant Molecules that Enhance Drug Activity against Diverse Fungal Pathogens.

    PubMed

    Robbins, Nicole; Spitzer, Michaela; Yu, Tennison; Cerone, Robert P; Averette, Anna K; Bahn, Yong-Sun; Heitman, Joseph; Sheppard, Donald C; Tyers, Mike; Wright, Gerard D

    2015-11-17

    There is an urgent need to identify new treatments for fungal infections. By combining sub-lethal concentrations of the known antifungals fluconazole, caspofungin, amphotericin B, terbinafine, benomyl, and cyprodinil with ?3,600 compounds in diverse fungal species, we generated a deep reservoir of chemical-chemical interactions termed the Antifungal Combinations Matrix (ACM). Follow-up susceptibility testing against a fluconazole-resistant isolate of C. albicans unveiled ACM combinations capable of potentiating fluconazole in this clinical strain. We used chemical genetics to elucidate the mode of action of the antimycobacterial drug clofazimine, a compound with unreported antifungal activity that synergized with several antifungals. Clofazimine induces a cell membrane stress for which the Pkc1 signaling pathway is required for tolerance. Additional tests against additional fungal pathogens, including Aspergillus fumigatus, highlighted that clofazimine exhibits efficacy as a combination agent against multiple fungi. Thus, the ACM is a rich reservoir of chemical combinations with therapeutic potential against diverse fungal pathogens. PMID:26549450

  13. Antioxidant and antiacetylcholinesterase activities of some commercial essential oils and their major compounds.

    PubMed

    Aazza, Smail; Lyoussi, Badiâ; Miguel, Maria G

    2011-01-01

    The commercial essential oils of Citrus aurantium L., Cupressus sempervirens L., Eucalyptus globulus Labill., Foeniculum vulgare Mill. and Thymus vulgaris L., isolated by steam distillation by a company of Morocco were evaluated in terms of in vitro antioxidant activity through several methods. In vitro acetylcholinesterase inhibitory activity was also determined. Citrus limon (L.) Burm. f. oil was also studied, but it was obtained by peel expression. The best antioxidant was T. vulgaris oil, independent of the method used, mainly due to the presence of the phenolic monoterpenes thymol and carvacrol, which when studied as single compounds also presented the best activities. Concerning the acetylcholinesterase inhibition activity, E. globulus was the most effective. Nevertheless its main components 1,8-cineole and limonene were not the most active, a feature that corresponded to d-3-carene. PMID:21900869

  14. Bioactive compounds, antioxidant and binding activities and spear yield of Asparagus officinalis L.

    PubMed

    Lee, Jong Won; Lee, Jeong Hyun; Yu, In Ho; Gorinstein, Shela; Bae, Jong Hyang; Ku, Yang Gyu

    2014-06-01

    The aim of this investigation was to find a proper harvesting period and establishing fern number, which effects the spear yield, bioactive compounds and antioxidant activities of Asparagus officinalis L. Spears were harvested at 2, 4, and 6 weeks after sprouting. Control for comparison was used without harvest. Spears and total yield increased with prolonged spear harvest period. In harvest of 6 weeks long optimum spear yield was the highest and fern numbers were 5?~?8. Bioactive compounds (polyphenols, flavonoids, flavanols, tannins and ascorbic acid) and the levels of antioxidant activities by ferric-reducing/antioxidant power (FRAP) and cupric reducing antioxidant capacity (CUPRAC) assays in asparagus ethanol extracts significantly differed in the investigated samples and were the highest at 6 weeks harvest period (P?compounds, binding and antioxidant activities) improved with the harvesting period and the first segment from spear tip. Appropriate harvesting is effective for higher asparagus yield and its bioactivity. PMID:24793354

  15. Hydraphiles: A Rigorously Studied Class of Synthetic Channel Compounds with In Vivo Activity

    PubMed Central

    Negin, Saeedeh; Smith, Bryan A.; Unger, Alexandra; Leevy, W. Matthew; Gokel, George W.

    2013-01-01

    Hydraphiles are a class of synthetic ion channels that now have a twenty-year history of analysis and success. In early studies, these compounds were rigorously validated in a wide range of in vitro assays including liposomal ion flow detected by NMR or ion-selective electrodes, as well as biophysical experiments in planar bilayers. During the past decade, biological activity was observed for these compounds including toxicity to bacteria, yeast, and mammalian cells due to stress caused by the disruption of ion homeostasis. The channel mechanism was verified in cells using membrane polarity sensitive dyes, as well as patch clamping studies. This body of work has provided a solid foundation with which hydraphiles have recently demonstrated acute biological toxicity in the muscle tissue of living mice, as measured by whole animal fluorescence imaging and histological studies. Here we review the critical structure-activity relationships in the hydraphile family of compounds and the in vitro and in cellulo experiments that have validated their channel behavior. This report culminates with a description of recently reported efforts in which these molecules have demonstrated activity in living mice. PMID:23401675

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

    PubMed Central

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

    2011-01-01

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

  17. Chemical composition and biological activity of four salvia essential oils and individual compounds against two species of mosquitoes.

    PubMed

    Ali, Abbas; Tabanca, Nurhayat; Demirci, Betul; Blythe, Eugene K; Ali, Zulfiqar; Baser, K Husnu Can; Khan, Ikhlas A

    2015-01-21

    The chemical compositions of essential oils obtained from four species of genus Salvia were analyzed by gas chromatography with a flame ionization detector (GC-FID) and gas chromatography-mass spectrometry (GC-MS). The main compounds identified from Salvia species essential oils were as follows: 1,8-cineole (71.7%), ?-pinene (5.1%), camphor (4.4%), and ?-pinene (3.8%) in Salvia apiana; borneol (17.4%), ?-eudesmol (10.4%), bornyl acetate (5%), and guaiol (4.8%) in Salvia elegans; bornyl acetate (11.4%), ?-caryophyllene (6.5%), caryophyllene oxide (13.5%), and spathulenol (7.0%) in Salvia leucantha; ?-thujene (25.8%), viridiflorol (20.4%), ?-thujene (5.7%), and camphor (6.4%) in Salvia officinalis. In biting-deterrent bioassays, essential oils of S. leucantha and S. elegans at 10 ?g/cm(2) showed activity similar to that of DEET (97%, N, N-diethyl-m-toluamide) in two species of mosquitoes, whereas the activities of S. officinalis and S. apiana essential oils were lower than those of the other oils or DEET. Pure compounds ?-eudesmol and guaiol showed biting-deterrent activity similar to DEET at 25 nmol/cm(2), whereas the activity of 13-epi-manool, caryophyllene oxide, borneol, bornyl acetate, and ?-caryophyllene was significantly lower than that of ?-eudesmol, guaiol, or DEET. All essential oils showed larvicidal activity except that of S. apiana, which was inactive at the highest dose of 125 ppm against both mosquito species. On the basis of 95% CIs, all of the essential oils showed higher toxicity in Anopheles quadrimaculatus than in Aedes aegypti. The essential oil of S. leucantha with an LC50 value of 6.2 ppm showed highest toxicity in An. quadrimaculatus. PMID:25531412

  18. ACTIVATION OF APOPTOSIS BY 1-HYDROXY-5, 7-DIMETHOXY-2-NAPHTHALENE-CARBOXALDEHYDE (HDNC), A NOVEL COMPOUND FROM AEGLE MARMELOS

    PubMed Central

    Subramaniam, Dharmalingam; Giridharan, Periyasamy; Murmu, Nabendu; Shankarnarayanan, N.P.; May, Randal; Houchen, Courtney W.; Ramanujam, Rama P.; Balakrishnan, Arun; Vishwakarma, Ram A.; Anant, Shrikant

    2009-01-01

    We have identified a natural compound that activates apoptosis of epithelial cancer cells through activation of TNF-?, TRADD and caspases. The molecule, 1-hydroxy-5, 7-dimethoxy-2-naphthalene-carboxaldehyde (HDNC, marmelin) was isolated and characterized from ethyl acetate fraction of extracts of Aegle marmelos. HDNC treatment inhibited the growth of HCT-116 colon cancer tumor xenografts in vivo. Immunostaining for CD31 showed that there was a significant reduction in microvessels in the HDNC-treated animals, coupled with decreased cyclooxygenase-2, interleukin-8 and vascular endothelial growth factor mRNA. Using hexoseaminidase assay, we determined that HDNC inhibits proliferation of HCT-116 colon and HEp-2 alveolar epithelial carcinoma cells. Furthermore, the cancer cells showed increased levels of activated caspase-3 and induced G1 cell cycle arrest, which was suppressed by caspase-3 inhibitors. HDNC induced TNF-?, TNFR1, and TRADD mRNA and protein expression. Moreover, caspase-8 and Bid activation, and cytochrome C release was observed suggesting the existence of a crosstalk between death receptor and the mitochondrial pathways. HDNC inhibited AKT and ERK phosphorylation, both in cells in culture and in tumor xenografts. In addition, EMSA and luciferase reporter assays demonstrated that HDNC significantly suppressed TNF-?-mediated activation and translocation of NF-?B. This was further confirmed by western blot analysis of nuclear extracts wherein levels of RelA, the p65 component of NF-?B was significantly less in cells treated with HDNC. Together, the data suggest that the novel compound HDNC (marmelin) is a potent anti-cancer agent that induces apoptosis during G1 phase of cell cycle and could be a potential chemotherapeutic candidate. PMID:18922933

  19. Occurrence and removal of pharmaceutically active compounds in sewage treatment plants with different technologies

    USGS Publications Warehouse

    Ying, Guang-Guo; Kookana, Rai S.; Kolpin, Dana W.

    2009-01-01

    Occurrence of eight selected pharmaceutically active compounds (PhACs; caffeine, carbamazepine, triclosan, gemfibrozil, diclofenac, ibuprofen, ketoprofen and naproxen) were investigated in effluents from fifteen sewage treatment plants (STPs) across South Australia. In addition, a detailed investigation into the removal of these compounds was also carried out in four STPs with different technologies (Plant A: conventional activated sludge; plant B: two oxidation ditches; plant C: three bioreactors; and plant D: ten lagoons in series). The concentrations of these compounds in the effluents from the fifteen STPs showed substantial variations among the STPs, with their median concentrations ranging from 26 ng/L for caffeine to 710 ng/L for carbamazepine. Risk assessment based on the "worst case scenario" of the monitoring data from the present study suggested potential toxic risks to aquatic organisms posed by carbamazepine, triclosan and diclofenac associated with such effluent discharge. With the exception of carbamazepine and gemfibrozil, significant concentration decreases between influent and effluent were observed in the four STPs studied in more detail. Biodegradation was found to be the main mechanism for removing concentrations from the liquid waste stream for the PhACs within the four STPs, while adsorption onto sludge appeared to be a minor process for all target PhACs except for triclosan. Some compounds (e.g. gemfibrozil) exhibited variable removal efficiencies within the four STPs. Plant D (10 lagoons in series) was least efficient in the removal of the target PhACs; significant biodegradation of these compounds only occurred from the sixth or seventh lagoon.

  20. A Novel High-Content Immunofluorescence Assay as a Tool to Identify at the Single Cell Level ?-Globin Inducing Compounds

    PubMed Central

    Durlak, Marta; Fugazza, Cristina; Elangovan, Sudharshan; Marini, Maria Giuseppina; Marongiu, Maria Franca; Moi, Paolo; Fraietta, Ivan; Cappella, Paolo; Barbarani, Gloria; Font-Monclus, Isaura; Mauri, Mario; Ottolenghi, Sergio; Gasparri, Fabio; Ronchi, Antonella

    2015-01-01

    The identification of drugs capable of reactivating ?-globin to ameliorate ?-thalassemia and Sickle Cell anemia is still a challenge, as available ?-globin inducers still have limited clinical indications. High-throughput screenings (HTS) aimed to identify new potentially therapeutic drugs require suitable first-step-screening methods combining the possibility to detect variation in the ?/? globin ratio with the robustness of a cell line. We took advantage of a K562 cell line variant expressing ?-globin (?-K562) to set up a new multiplexed high-content immunofluorescence assay for the quantification of ?- and ?-globin content at single-cell level. The assay was validated by using the known globin inducers hemin, hydroxyurea and butyric acid and further tested in a pilot screening that confirmed HDACs as targets for ?-globin induction (as proved by siRNA-mediated HDAC3 knockdown and by treatment with HDACs inhibitors entinostat and dacinostat) and identified Heme-oxygenases as novel candidate targets for ?-globin induction. Indeed, Heme-oxygenase2 siRNA knockdown as well as its inhibition by Tin protoporphyrin-IX (TinPPIX) greatly increased ?-globin expression. This result is particularly interesting as several metalloporphyrins have already been developed for clinical uses and could be tested (alone or in combination with other drugs) to improve pharmacological ?-globin reactivation for the treatment of ?-hemoglobinopathies. PMID:26509275

  1. Structure-antioxidant efficiency relationships of phenolic compounds and their contribution to the antioxidant activity of sea buckthorn juice.

    PubMed

    Rösch, Daniel; Bergmann, Meike; Knorr, Dietrich; Kroh, Lothar W

    2003-07-16

    The phenolic composition of juice derived from fruits of sea buckthorn (Hippophae rhamnoides) was investigated by high-performance liquid chromatography (HPLC) with diode array and electrochemical detection. Flavonols were found to be the predominating polyphenols while phenolic acids and catechins represent minor components. Of the seven flavonols identified, isorhamnetin 3-O-glycosides were the most important representatives quantitatively. However, because of their structural properties, they were poor radical scavengers as shown by electron spin resonance spectroscopy. Phenolic compounds such as quercetin 3-O-glycosides, catechins, and hydroxybenzoic acids with a catechol structure exhibited good antioxidant capacities, but their concentration in sea buckthorn juice was small. These phenolic compounds, determined by HPLC, accounted for less than 5% of the total antioxidant activity of the filtered juice. Ascorbic acid was shown to be the major antioxidant in sea buckthorn juice. Because of its high concentration of 1.22 g/L, it contributes approximately 75% to total antioxidant activity. The remaining difference can be attributed to higher molecular weight flavan-3-ols (proanthocyanidins), which were determined photometrically after acid depolymerization to colored anthocyanidins. PMID:12848490

  2. Isolation and identification of colourless caffeoyl compounds in purple sweet potato by HPLC-DAD-ESI/MS and their antioxidant activities.

    PubMed

    Zhao, Jin-Ge; Yan, Qian-Qian; Xue, Ren-Yu; Zhang, Jian; Zhang, Yu-Qing

    2014-10-15

    More than 10 red anthocyanins and related glucosides have been isolated and identified from purple sweet potato (Ipomoea batatas, Ayamurasaki) in the recent decades. This paper reports the isolation of colourless caffeoyl compounds from purple sweet potato using AB-8 macroresin absorption and semi-preparative HPLC-DAD. The structures of the five isolated monomers were identified as: 5-caffeoylquinic acid (1), 6-O-caffeoyl-?-d-fructofuranosyl-(2-1)-?-d-glucopyranoside (2) and trans-4,5-dicaffeoylquinic acid (3), 3,5-dicaffeoylquinic acid (4), 4,5-dicaffeoylquinic acid (5), and by ESI/MS and NMR. Compounds 1, 4 and 5 were reported previously in combination with anthocyanins in purple sweet potato, whereas 2 and 3 were found for the first time. In vitro antioxidant assay showed trans-4,5-dicaffeoylquinic acid has significant antioxidant activities. These results should lay the groundwork for further work identifying purple sweet potato as a healthy food. PMID:24837917

  3. 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 Å 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

  4. Identifying vacancy complexes in compound semiconductors with positron annihilation spectroscopy: a case study of InN

    E-print Network

    Rauch, Christian; Tuomisto, Filip

    2011-01-01

    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 lineshape parameters determined. We find that In vacancies and their complexes with N vacancies or impurities act as efficient positron traps, inducing distinct changes in the annihilation parameters compared to the InN lattice. Neutral or positively charged N vacancies and pure N vacancy complexes on the other h...

  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. The surface-active properties of biomass burning aerosol: the importance of water soluble organic compounds.

    NASA Astrophysics Data System (ADS)

    Decesari, S.; Facchini, M. C.; Mircea, M.; Cavalli, F.; Fuzzi, S.; Mayol-Bracero, O. L.

    2003-04-01

    Organic films on humid aerosols lower the surface tension of water and inhibit the exchange of water vapor between the gas phase and the condensed phase, with important implications for the cloud condensation nuclei activity. The present study reports an investigation of the film-forming compounds in biomass burning aerosols collected in the Amazon Basin as part of the European contribution to the Large-Scale Biosphere-Atmosphere Experiment in Amazonia (LBA-EUSTACH). The chemical characterization of fine aerosol samples showed that water-soluble organic compounds (WSOC) accounted for a substantial fraction of OC (45-75%). WSOC could be separated into three main classes by liquid chromatography: neutral compounds, mono- and di-carboxylic acids, and polycarboxylic acids. The sum of these three groups accounted for about 70% of the WSOC, with the acidic classes being most abundant. Water extracts of fine aerosol samples collected during the peak of the dry season were subjected to surface tension measurement by a drop shape tensiometer. The results demonstrate that the carbonaceous aerosols produced by biomass burning contain substantial amounts of surface-active compounds. Furthermore, the rheological properties of the films on the water extracts were studied by dynamic measurements of surface tension. The calculated dilatational elasticity and viscosity of organic films followed the Gibbs theory of adsorption layer formation, suggesting that the surfactants are mainly water-soluble. These findings show that WSOC represent an important reservoir of film-forming agents, and that the bulk WSOC concentration is the most important parameter controlling the surface excess of organic compounds on humid aerosols and droplets. A quantitative relationship between surface tension lowering and WSOC concentration could be established, however the observed variability within samples indicates that the chemical composition of the WSOC mixture affects extension and structure of the Gibbs layers. In particular, polyacidic compounds carrying both polar and extended hydrophobic groups were found to be the most effective film-forming compounds. These organic substances are expected to play an important role in determining the overall cloud nucleating properties of biomass burning aerosols.

  8. A new flavonol glycoside and activity of compounds from the flower of Nymphaea candida.

    PubMed

    Liu, R-N; Wang, W; Ding, Y; Xie, W-D; Ma, C; Du, L-J

    2007-01-01

    A new compound, kaempferol 3-O-(2''-O-galloylrutinoside) (1), was isolated from the white flower of Nymphaea candida, together with nine known flavonol glycosides, kaempferol (2), kaempferol 3-O-beta-D-glucopyranoside (3), kaempferol 3-O-alpha-l-rhamnopyranoside (4), kaempferol 3-O-alpha-l-rhamnopyranosylglucopyranoside (5), kaempferol 7-O-beta-D-glucopyranoside 3-(O-alpha-l-rhamnopyranosylglucopyranoside) (6), quercetin (7), quercetin 3-O-beta-D-xylopyranoside (8), myricetin (9), myricetin 3'-O-beta-D-xylopyranoside (10). The structure of 1 was established on the basis of the analysis of its 1D and 2D NMR spectral data. Compounds 1-7 and 9 exhibited moderate to significant antioxidant activities, which were evaluated by measurement of low-density lipoprotein (LDL) and malondialdehyde (MDA) levels in vitro. Compounds 1, 3, 4, 6 and 9 exhibited promising neuroprotective effects on ischemic injury model of cultured rat cortical neurons treated with sodium dithionite in glucose-free medium. Furthermore, compounds 1, 5, and 9 had distinct cytotoxicity to adrenal gland pheochromocytoma, PC12 cells, being treated by the same way. PMID:17613618

  9. Pyridoxine-derived organoselenium compounds with glutathione peroxidase-like and chain-breaking antioxidant activity.

    PubMed

    Singh, Vijay P; Poon, Jia-Fei; Butcher, Ray J; Engman, Lars

    2014-09-22

    One of the vitamin B6 vitamers, pyridoxine, was modified to incorporate selenium in various oxidation states in place of the methyl group in position 2. Such compounds were conveniently accessed by treatment of bis-4,5-(carboethoxy)-2-iodo-3-pyridinol with disodium diselenide and LiAlH4 -reduction. After work-up, selone 7 was isolated in good yield as an air-stable crystalline material. Hydrogen bonding to the neighboring hydroxyl group, as revealed by the short intramolecular Se???H distance in the crystal structure is likely to provide extra stabilization to the compound. Computational studies showed that selone 7 is more stable than the corresponding selenol tautomer by 12.2?kcal?mol(-1) . Hydrogen peroxide oxidation of the selone 7 afforded diselenide 12, and, on further oxidation, seleninic acid 13. Treatment of the seleninic acid with thiophenol provided an isolable selenosulfide 14. The glutathione peroxidase-like properties of the pyridoxine-derived compounds were assessed by using the coupled reductase method. Seleninic acid 13 was found to be twofold more active than ebselen. The chain-breaking capacity of the pyridoxine compounds were studied in a water/chlorobenzene membrane model containing linoleic acid as an oxidizable substrate and N-acetylcysteine as a thiol reducing agent. Diselenide 15 could match ?-tocopherol when it comes to reactivity towards peroxyl radicals and inhibition time. PMID:25123932

  10. Screening Libraries To Identify Proteins with Desired Binding Activities Using a Split-GFP

    E-print Network

    Regan, Lynne

    of automation of the screen. Here, we describe both the construction of a na¨ive protein library, and screeningScreening Libraries To Identify Proteins with Desired Binding Activities Using a Split is to construct and screen libraries. Here we present a detailed description of us- ing a split-GFP reassembly

  11. Model-Eliciting Activities as a Tool to Develop and Identify Creatively Gifted Mathematicians

    ERIC Educational Resources Information Center

    Chamberlin, Scott A.; Moon, Sidney M.

    2005-01-01

    This article addresses the use of Model-Eliciting Activities (MEAs) as a (curricular) tool to develop mathematical creativity and identify students who are creatively gifted in mathematics. The thesis of this article is that by using MEAs, gifted educators can: (a) provide students with opportunities to develop creative and applied mathematical…

  12. Cooking techniques improve the levels of bioactive compounds and antioxidant activity in kale and red cabbage.

    PubMed

    Murador, Daniella Carisa; Mercadante, Adriana Zerlotti; de Rosso, Veridiana Vera

    2016-04-01

    The aim of this study is to investigate the effects of different home cooking techniques (boiling, steaming, and stir-frying) in kale and red cabbage, on the levels of bioactive compounds (carotenoids, anthocyanins and phenolic compounds) determined by high-performance liquid chromatography coupled with photodiode array and mass spectrometry detectors (HPLC-DAD-MS(n)), and on the antioxidant activity evaluated by ABTS, ORAC and cellular antioxidant activity (CAA) assays. The steaming technique resulted in a significant increase in phenolic content in kale (86.1%; p<0.001) whereas in red cabbage it was significantly reduced (34.6%; p<0.001). In the kale, steaming resulted in significant increases in antioxidant activity levels in all of the evaluation methods. In the red cabbage, boiling resulted in a significant increase in antioxidant activity using the ABTS assay but resulted in a significant decrease using the ORAC assay. According to the CAA assay, the stir-fried sample displayed the highest levels of antioxidant activity. PMID:26593594

  13. Determination of some physicochemical characteristics, bioactive compounds and antioxidant activity of tropical fruits from Yucatan, Mexico.

    PubMed

    Moo-Huchin, Víctor M; Estrada-Mota, Iván; Estrada-León, Raciel; Cuevas-Glory, Luis; Ortiz-Vázquez, Elizabeth; Vargas y Vargas, María de Lourdes; Betancur-Ancona, David; Sauri-Duch, Enrique

    2014-01-01

    The aim to the study was to determine the physicochemical composition, bioactive compounds and antioxidant activity of fruits from Yucatan, Mexico such as star apple, cashew, mombin, mamey sapote, white sapote, sugar apple, sapodilla, dragon fruit, nance, ilama, custard apple, mamoncillo and black sapote. The physicochemical characteristics were different between fruits and were good sources of bioactive compounds. The edible part with the highest values of antioxidant activity were mamoncillo, star apple, mombin, cashew, white sapote, ilama, custard apple, sugar apple, and nance. Total soluble phenols content showed a correlation with antioxidant activity by ABTS (R=0.52, P?0.05) and DPPH (R=0.43, P?0.05). A high correlation was obtained between the two assays (ABTS and DPPH) used to measure antioxidant activity in the tropical fruit species under study (R=0.82, P?0.05). The results show promising perspectives for the exploitation and use of tropical fruits studied with significant levels of nutrients and antioxidant activity. PMID:24444968

  14. Your Mission: (1) Identify 20 active faults in California (2) Identify the direction of fault motion and the slip rate for each fault

    E-print Network

    Smith-Konter, Bridget

    Your Mission: (1) Identify 20 active faults in California (2) Identify the direction of fault motion and the slip rate for each fault (3) Investigate recent earthquakes near your hometown (4) Use Microsoft Excel to plot a small set of earthquake data Your Supplies: California Faults map handout

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

    PubMed

    Boulinguiez, B; Le Cloirec, P

    2009-01-01

    The study assesses the adsorption onto activated carbon materials of selected volatile organic compounds -VOCs- (dichloromethane, 2-propanol, toluene, siloxane D4) in a biogas matrix composed of methane and carbon dioxide (55:45 v/v). Three different adsorbents are tested, two of them are granular activated carbon (GAC), and the last is an activated carbon fiber-cloth (ACFC). The adsorption isotherm data are fitted by different models by nonlinear regression. The Langmuir-Freundlich model appears to be the adequate one to describe the adsorption phenomena independently of the VOC considered or the adsorbent. The adsorbents present attractive adsorption capacity of the undesirable compounds in biogas atmosphere though the maximum adsorption capacities for a VOC are quite different from each other. The adsorption kinetics are characterized through three coefficients: the initial adsorption coefficient, the external film mass transfer coefficient and the internal diffusion coefficient of Weber. The ACFC demonstrates advanced kinetic yields compared to the granular activated carbon materials whatever VOC is considered. Therefore, pre-upgrading of biogas produced from wastewater sludge or co-digestion system by adsorption onto activated carbon appears worth investigating. Especially with ACFC material that presents correct adsorption capacities toward VOCs and concrete regeneration process opportunity to realize such process. PMID:19273892

  16. The effect of phase partitioning of semivolatile compounds on the measured CCN activity of aerosol particles

    NASA Astrophysics Data System (ADS)

    Romakkaniemi, S.; Jaatinen, A.; Laaksonen, A.; Nenes, A.; Raatikainen, T.

    2013-09-01

    The effect of inorganic semivolatile aerosol compounds on the CCN activity of aerosol particles was studied by using a computational model for a DMT-CCN counter, a cloud parcel model for condensation kinetics and experiments to quantify the modelled results. Concentrations of water vapour and semivolatiles as well as aerosol trajectories in the CCN column were calculated by a computational fluid dynamics model. These trajectories and vapour concentrations were then used as an input for the cloud parcel model to simulate mass transfer kinetics of water and semivolatiles between aerosol particles and the gas phase. Two different questions were studied: (1) how big fraction of semivolatiles is evaporated from particles before activation in the CCN counter? (2) How much the CCN activity can be increased due to condensation of semivolatiles prior to the maximum water supersaturation in the case of high semivolatile concentration in the gas phase? The results show that, to increase the CCN activity of aerosol particles, a very high gas phase concentration (as compared to typical ambient conditions) is needed. We used nitric acid as a test compound. A concentration of several ppb or higher is needed for measurable effect. In the case of particle evaporation, we used ammonium nitrate as a test compound and found that it partially evaporates before maximum supersaturation is reached in the CCN counter, thus causing an underestimation of CCN activity. The effect of evaporation is clearly visible in all supersaturations, leading to an underestimation of the critical dry diameter by 10 to 15 nanometres in the case of ammonium nitrate particles in different supersaturations. This result was also confirmed by measurements in supersaturations between 0.1 and 0.7%.

  17. Concept for a Compound Analysis in Active Learning for Remote Sensing

    NASA Astrophysics Data System (ADS)

    Wuttke, S.; Middelmann, W.; Stilla, U.

    2015-03-01

    Active learning reduces training costs for supervised classification by acquiring ground truth data only for the most useful samples. We present a new concept for the analysis of active learning techniques. Our framework is split into an outer and an inner view to facilitate the assignment of different influences. The main contribution of this paper is a concept of a new compound analysis in the active learning loop. It comprises three sub-analyses: structural, oracle, prediction. They are combined to form a hypothesis of the usefulness for each unlabeled training sample. Though the analysis is in an early stage, different extensions are highlighted. Further we show how variations inside the framework lead to many techniques from the active learning literature. In this work we focus on remote sensing, but the proposed method can be applied to other fields as well.

  18. Preparation of activated carbons from raw and biotreated agricultural residues for removal of volatile organic compounds.

    PubMed

    Hsi, Hsing-Cheng; Horng, Richard S; Pan, Tai-An; Lee, Shin-Ku

    2011-05-01

    Activated carbons with diverse physical and chemical properties were produced from four agriculture residues, including raw barley husk, biotreated barley husk, rice husk, and pistachio shell. Results showed that with adequate steam activation (30-90 min, 50% H2O(g),/50% N2), activated carbons with surface areas between 360 and 950 m2 g(-1) were developed. Further increases in the activation time destroyed the pore structure of activated carbons, which resulted in a decrease in the surface area and pore volume. Biotreated agricultural residues were found to be suitable precursors for producing mesoporous activated carbons. The oxygen content of activated carbons increased with increasing activation time. Results from X-ray photoelectron spectroscopy examination further suggested that H2O molecules react with the carbon surface, enhancing the deconvoluted peak area of carbonyl and carboxyl groups. Equilibrium adsorption of toluene indicated that the adsorption capacities increased with an increase in the inlet toluene concentration and a decrease in temperature. The adsorption isotherms were successfully fitted with Freundlich, Langmuir, and Dubinin-Radushkevich equations. Activated carbons derived from agricultural residues appear to be more applicable to adsorb volatile organic compounds at a low concentration and high-temperature environment. PMID:21608494

  19. Facile Synthesis and Antimicrobial Evaluation of Some New Heterocyclic Compounds Incorporating a Biologically Active Sulfamoyl Moiety

    PubMed Central

    Darwish, Elham S.

    2014-01-01

    A facile and convenient synthesis of new heterocyclic compounds containing a sulfamoyl moiety suitable for use as antimicrobial agents was reported. The precursor 3-oxo-3-phenyl-N-(4-sulfamoylphenyl)propionamide was coupled smoothly with arenediazonium salt producing hydrazones which reacted with malononitrile or triethylorthoformate affording pyridazine and triazine derivatives, respectively. Also, the reactivity of the same precursor with DMF-DMA was followed by aminotriazole; aromatic aldehydes was followed by hydrazine hydrate, triethylorthoformate, or thiourea affording triazolo[1,5-a]pyrimidine, pyrazole, acrylamide, and dihydropyrimidine derivatives, respectively. On the other hand, treatment of the precursor propionamide with phenyl isothiocyanate and KOH in DMF afforded the intermediate salt which was treated with dilute HCl followed by 2-bromo-1-phenylethanone affording carboxamide derivative. While the same intermediate salt reacted in situ with chloroacetone, ethyl 2-chloroacetate, 3-(2-bromoacetyl)-2H-chromen-2-one, methyl iodide, or 2-oxo-N-phenylpropane hydrazonoyl chloride afforded the thiophene, ketene N,S-acetal, and thiadiazole derivatives, respectively. The structure of the new products was established based on elemental and spectral analysis. Antimicrobial evaluation of some selected examples from the synthesized products was carried out whereby four compounds were found to have moderate activities and one compound showed the highest activity. PMID:25215312

  20. Ligand substitutions between ruthenium–cymene compounds can control protein versus DNA targeting and anticancer activity

    PubMed Central

    Adhireksan, Zenita; Davey, Gabriela E.; Campomanes, Pablo; Groessl, Michael; Clavel, Catherine M.; Yu, Haojie; Nazarov, Alexey A.; Yeo, Charmian Hui Fang; Ang, Wee Han; Dröge, Peter; Rothlisberger, Ursula; Dyson, Paul J.; Davey, Curt A.

    2014-01-01

    Ruthenium compounds have become promising alternatives to platinum drugs by displaying specific activities against different cancers and favourable toxicity and clearance properties. Nonetheless, their molecular targeting and mechanism of action are poorly understood. Here we study two prototypical ruthenium-arene agents—the cytotoxic antiprimary tumour compound [(?6-p-cymene)Ru(ethylene-diamine)Cl]PF6 and the relatively non-cytotoxic antimetastasis compound [(?6-p-cymene)Ru(1,3,5-triaza-7-phosphaadamantane)Cl2]—and discover that the former targets the DNA of chromatin, while the latter preferentially forms adducts on the histone proteins. Using a novel ‘atom-to-cell’ approach, we establish the basis for the surprisingly site-selective adduct formation behaviour and distinct cellular impact of these two chemically similar anticancer agents, which suggests that the cytotoxic effects arise largely from DNA lesions, whereas the protein adducts may be linked to the other therapeutic activities. Our study shows promise for developing new ruthenium drugs, via ligand-based modulation of DNA versus protein binding and thus cytotoxic potential, to target distinguishing epigenetic features of cancer cells. PMID:24637564

  1. Plant Natural Compounds with Antibacterial Activity towards Common Pathogens of Pond-Cultured Channel Catfish (Ictalurus punctatus)

    PubMed Central

    Schrader, Kevin K.

    2010-01-01

    The bacteria Edwardsiella ictaluri and Flavobacterium columnare cause enteric septicemia and columnaris disease, respectively, in channel catfish (Ictalurus punctatus). Natural therapeutants may provide an alternative to current management approaches used by producers. In this study, a rapid bioassay identified plant compounds as potential therapeutants. Chelerythrine chloride and ellagic acid were the most toxic toward E. ictaluri, with 24-h IC50 of 7.3 mg/L and 15.1 mg/L, respectively, and MIC of 2.1 mg/L and 6.5 mg/L, respectively. Chelerythrine chloride, ellagic acid, ?-glycyrrhetinic acid, sorgoleone, and wogonin were the most toxic towards two genomovars of F. columnare, and wogonin had the strongest antibacterial activity (MIC = 0.3 mg/L). PMID:22069655

  2. Synthesis of Polyheteroaromatic Compounds via Rhodium-Catalyzed Multiple C-H Bond Activation and Oxidative Annulation.

    PubMed

    Peng, Shiyong; Liu, Suna; Zhang, Sai; Cao, Shengyu; Sun, Jiangtao

    2015-10-16

    Polyheteroaromatic compounds are potential optoelectronic conjugated materials due to their electro- and photochemical properties. Transition-metal-catalyzed multiple C-H activation and sequential oxidative annulation allows rapidly assembling of those compounds from readily available starting materials. A rhodium-catalyzed cascade oxidative annulation of ?-enamino esters or 4-aminocoumarins with internal alkynes is described to access those compounds, featuring multiple C-H/N-H bond cleavages and sequential C-C/C-N bond formations in one pot. PMID:26439472

  3. Structural Characterization and Evaluation of the Antioxidant Activity of Phenolic Compounds from Astragalus taipaishanensis and Their Structure-Activity Relationship

    NASA Astrophysics Data System (ADS)

    Pu, Wenjun; Wang, Dongmei; Zhou, Dan

    2015-09-01

    Eight phenolic compounds were isolated using bio-guided isolation and purified from the roots of Astragalus taipaishanensis Y. C. Ho et S. B. Ho (A. taipaishanensis) for the first time. Their structures were elucidated by ESI-MS, HR-ESI-MS, 1D-NMR and 2D-NMR as 7,2?-dihydroxy-3?,4?-dimethoxy isoflavan (1), formononetin (2), isoliquiritigenin (3), quercetin (4), kaempferol (5), ononin (6), p-hydroxybenzoic acid (7) and vanillic acid (8). Six flavonoids (compounds 1-6) exhibited stronger antioxidant activities (determined by DPPH, ABTS, FRAP and lipid peroxidation inhibition assays) than those of BHA and TBHQ and also demonstrated noticeable protective effects (particularly quercetin and kaempferol) on Escherichia coli under oxidative stress. Additionally, the chemical constituents compared with those of Astragalus membranaceus and the structure-activity relationship of the isolated compounds were both analyzed. The results clearly demonstrated that A. taipaishanensis has the potential to be selected as an alternative medicinal and food plant that can be utilized in health food products, functional tea and pharmaceutical products.

  4. Structural Characterization and Evaluation of the Antioxidant Activity of Phenolic Compounds from Astragalus taipaishanensis and Their Structure-Activity Relationship

    PubMed Central

    Pu, Wenjun; Wang, Dongmei; Zhou, Dan

    2015-01-01

    Eight phenolic compounds were isolated using bio-guided isolation and purified from the roots of Astragalus taipaishanensis Y. C. Ho et S. B. Ho (A. taipaishanensis) for the first time. Their structures were elucidated by ESI-MS, HR-ESI-MS, 1D-NMR and 2D-NMR as 7,2?-dihydroxy-3?,4?-dimethoxy isoflavan (1), formononetin (2), isoliquiritigenin (3), quercetin (4), kaempferol (5), ononin (6), p-hydroxybenzoic acid (7) and vanillic acid (8). Six flavonoids (compounds 1-6) exhibited stronger antioxidant activities (determined by DPPH, ABTS, FRAP and lipid peroxidation inhibition assays) than those of BHA and TBHQ and also demonstrated noticeable protective effects (particularly quercetin and kaempferol) on Escherichia coli under oxidative stress. Additionally, the chemical constituents compared with those of Astragalus membranaceus and the structure-activity relationship of the isolated compounds were both analyzed. The results clearly demonstrated that A. taipaishanensis has the potential to be selected as an alternative medicinal and food plant that can be utilized in health food products, functional tea and pharmaceutical products. PMID:26350974

  5. DRUG-REPOSITIONING SCREENING IDENTIFIED PIPERLONGUMINE AS A DIRECT STAT3 INHIBITOR WITH POTENT ACTIVITY AGAINST BREAST CANCER

    PubMed Central

    Bharadwaj, Uddalak; Eckols, T. Kris; Kolosov, Mikhail; Kasembeli, Moses M.; Adam, Abel; Torres, David; Zhang, Xiaomei; Dobrolecki, Lacey E.; Wei, Wei; Lewis, Michael T.; Dave, Bhuvanesh; Chang, Jenny C.; Landis, Melissa D.; Creighton, Chad J.; Mancini, Michael A.; Tweardy, David J.

    2014-01-01

    Signal transducer and activator of transcription (STAT) 3 regulates many cardinal features of cancer including cancer cell growth, apoptosis resistance, DNA damage response, metastasis, immune escape, tumor angiogenesis, the Warburg effect, and oncogene addiction and has been validated as a drug target for cancer therapy. Several strategies have been employed to identify agents that target Stat3 in breast cancer but none has yet entered into clinical use. We used a high-throughput fluorescence microscopy search strategy to identify compounds in a drug-repositioning library (Prestwick library) that block ligand-induced nuclear translocation of Stat3 and identified piperlongumine (PL), a natural product isolated from the fruit of the pepper Piper longum. Piperlongumine inhibited Stat3 nuclear translocation, inhibited ligand-induced and constitutive Stat3 phosphorylation, and modulated expression of multiple Stat3-regulated genes. Surface plasmon resonance assay revealed that piperlongumine directly inhibited binding of Stat3 to its phosphotyrosyl (pY) peptide ligand. Phosphoprotein antibody array analysis revealed that PL does not modulate kinases known to activate Stat3 such as JAKs, Src kinase family members, or RTKs. PL inhibited anchorage-independent and anchorage-dependent growth of multiple breast cancer cell lines having increased pStat3 or total Stat3, and induced apoptosis. PL also inhibited mammosphere formation by tumor cells from patient derived xenografts (PDX). PL’s anti-tumorigenic function was causally linked to its Stat3-inhibitory effect. PL was non-toxic in mice up to a dose of 30 mg/Kg/day for 14 days and caused regression of breast cancer cell line xenografts in nude mice. Thus, PL represents a promising new agent for rapid entry into the clinic for use in treating breast cancer, as well as other cancers in which Stat3 plays a role. PMID:24681959

  6. Drug-repositioning screening identified piperlongumine as a direct STAT3 inhibitor with potent activity against breast cancer.

    PubMed

    Bharadwaj, U; Eckols, T K; Kolosov, M; Kasembeli, M M; Adam, A; Torres, D; Zhang, X; Dobrolecki, L E; Wei, W; Lewis, M T; Dave, B; Chang, J C; Landis, M D; Creighton, C J; Mancini, M A; Tweardy, D J

    2015-03-12

    Signal transducer and activator of transcription (STAT) 3 regulates many cardinal features of cancer including cancer cell growth, apoptosis resistance, DNA damage response, metastasis, immune escape, tumor angiogenesis, the Warburg effect and oncogene addiction and has been validated as a drug target for cancer therapy. Several strategies have been used to identify agents that target Stat3 in breast cancer but none has yet entered into clinical use. We used a high-throughput fluorescence microscopy search strategy to identify compounds in a drug-repositioning library (Prestwick library) that block ligand-induced nuclear translocation of Stat3 and identified piperlongumine (PL), a natural product isolated from the fruit of the pepper Piper longum. PL inhibited Stat3 nuclear translocation, inhibited ligand-induced and constitutive Stat3 phosphorylation, and modulated expression of multiple Stat3-regulated genes. Surface plasmon resonance assay revealed that PL directly inhibited binding of Stat3 to its phosphotyrosyl peptide ligand. Phosphoprotein antibody array analysis revealed that PL does not modulate kinases known to activate Stat3 such as Janus kinases, Src kinase family members or receptor tyrosine kinases. PL inhibited anchorage-independent and anchorage-dependent growth of multiple breast cancer cell lines having increased pStat3 or total Stat3, and induced apoptosis. PL also inhibited mammosphere formation by tumor cells from patient-derived xenografts. PL's antitumorigenic function was causally linked to its Stat3-inhibitory effect. PL was non-toxic in mice up to a dose of 30?mg/kg/day for 14 days and caused regression of breast cancer cell line xenografts in nude mice. Thus, PL represents a promising new agent for rapid entry into the clinic for use in treating breast cancer, as well as other cancers in which Stat3 has a role. PMID:24681959

  7. Antioxidant activity and bioactive compounds of lettuce improved by espresso coffee residues.

    PubMed

    Cruz, Rebeca; Gomes, Teresa; Ferreira, Anabela; Mendes, Eulália; Baptista, Paula; Cunha, Sara; Pereira, José Alberto; Ramalhosa, Elsa; Casal, Susana

    2014-02-15

    The antioxidant activity and individual bioactive compounds of lettuce, cultivated with 2.5-30% (v/v) of fresh or composted espresso spent coffee grounds, were assessed. A progressive enhancement of lettuce's antioxidant capacity, evaluated by radical scavenging effect and reducing power, was exhibited with the increment of fresh spent coffee amounts, while this pattern was not so clear with composted treatments. Total reducing capacity also improved, particularly for low spent coffee concentrations. Additionally, very significant positive correlations were observed for all carotenoids in plants from fresh spent coffee treatments, particularly for violaxanthin, evaluated by HPLC. Furthermore, chlorophyll a was a good discriminating factor between control group and all spent coffee treated samples, while vitamin E was not significantly affected. Espresso spent coffee grounds are a recognised and valuable source of bioactive compounds, proving herein, for the first time, to potentiate the antioxidant pool and quality of the vegetables produced. PMID:24128454

  8. E–H Bond Activation of Ammonia and Water by a Geometrically Constrained Phosphorus(III) Compound

    PubMed Central

    Robinson, Thomas P; De Rosa, Daniel M; Aldridge, Simon; Goicoechea, Jose M

    2015-01-01

    The synthesis of a phosphorus(III) compound bearing a N,N-bis(3,5-di-tert-butyl-2-phenoxy)amide ligand is reported. This species has been found to react with ammonia and water, activating the E–H bonds in both substrates by formal oxidative addition to afford the corresponding phosphorus(V) compounds. In the case of water, both O–H bonds can be activated, splitting the molecule into its constituent elements. To our knowledge, this is the first example of a compound based on main group elements that sequentially activates water in this manner. PMID:26404498

  9. Cysticidal activity of extracts and isolated compounds from Teloxys graveolens: In vitro and in vivo studies.

    PubMed

    Palomares-Alonso, Francisca; Rojas-Tomé, Irma Susana; Juárez Rocha, Victorino; Palencia Hernández, Guadalupe; González-Maciel, Angélica; Ramos-Morales, Andrea; Santiago-Reyes, Rosalba; González-Hernández, Iliana Elvira; Jung-Cook, Helgi

    2015-09-01

    In the search of new alternatives for neurocysticercosis treatment, the cysticidal activity of organic extracts of Teloxys graveolens was evaluated. The in vitro activity of hexane, ethyl acetate and methanol extracts against Taenia crassiceps cysts was tested and the selectivity index relative to human fibroblasts was determined. Subsequently, the in vivo efficacy of the methanolic extract at doses of 200 and 500?mg/kg in the murine cysticercosis model was evaluated. The ultrastructural effects in vitro and in vivo of the methanolic extract were also investigated using scanning electron microscopy. Additionally, a bioassay-guided fractionation for the isolation of the cysticidal components was performed. Our in vitro findings revealed that all extracts exhibited good cysticidal activity with EC50 values from 44.8 to 67.1?µg/mL. Although the ethyl acetate and methanolic extracts displayed low cytotoxicity, the methanolic extract was the most selective. The methanolic extract also showed in vivo efficacy which was similar to that obtained with ABZ. Significant alterations were found on the germinal layer of the cysts, with a high accumulation of granules of glycogen and vacuoles. The bioguided fractionation of methanolic extract led to the isolation of three flavonoids: chrysin, pinocembrin and pinostrobin; among them, pinocembrin was the compound that displayed cysticidal activity. This is the first study which reveals that T. graveolens could be a potential source for cysticidal and non-toxic compounds. PMID:26072200

  10. Structure-activity relationship study of novel anticancer aspirin-based compounds

    PubMed Central

    JOSEPH, STANCY; NIE, TING; HUANG, LIQUN; ZHOU, HUI; ATMAKUR, KRISHNAIAH; GUPTA, RAMESH C.; JOHNSON, FRANCIS; RIGAS, BASIL

    2013-01-01

    We performed a structure-activity relationship (SAR) study of a novel aspirin (ASA) derivative, which shows strong anticancer activity in vitro and in vivo. A series of ASA-based benzyl esters (ABEs) were synthesized and their inhibitory activity against human colon (HT-29 and SW480) and pancreatic (BxPC-3 and MIA PaCa-2) cancer cell lines was evaluated. The ABEs that we studied largely comprise organic benzyl esters bearing an ASA or acyloxy group (X) at the meta or para position of the benzyl ring and one of four different leaving groups. The nature of the salicyloyl/acyloxy function, the leaving group, and the additional substituents affecting the electron density of the benzyl ring, all were influential determinants of the inhibitory activity on cancer cell growth for each ABE. Positional isomerism also played a significant role in this effect. The mechanism of action of these compounds appears consistent with the notion that they generate either a quinone methide or an m-oxybenzyl zwitterion (or an m-hydroxybenzyl cation), which then reacts with a nucleophile, mediating their biological effect. Our SAR study provides an insight into the biological properties of this novel class of compounds and underscores their potential as anticancer agents. PMID:21805049

  11. Characteristic Chemical Components and Aroma-active Compounds of the Essential Oils from Ranunculus nipponicus var. submersus Used in Japanese Traditional Food.

    PubMed

    Nakaya, Satoshi; Usami, Atsushi; Yorimoto, Tomohito; Miyazawa, Mitsuo

    2015-01-01

    Ranunculus nipponicus var. submersus is an aquatic macrophyte; it is known as a wild edible plant in Japan for a long time. In this study, the essential oils from the fresh and dried aerial parts of R. nipponicus var. submersus were extracted by hydrodistillation and analyzed by gas chromatography (GC) and GC-mass spectrometry (GC-MS). Moreover, important aroma-active compounds were also detected in the oil using GC-olfactometry (GC-O) and aroma extract dilution analysis (AEDA). Thus, 98 compounds (accounting for 93.86%) of the oil were identified. The major compounds in fresh plant oil were phytol (41.94%), heptadecane (5.92%), and geranyl propionate (5.76%), while those of. Dried plant oil were ?-ionone (23.54%), 2-hexenal (8.75%), and dihydrobovolide (4.81%). The fresh and dried oils had the green-floral and citrus-floral odor, respectively. The GC-O and AEDA results show that phenylacetaldehyde (green, floral odor, FD-factor = 8) and ?-ionone (violet-floral odor, FD-factor = 8) were the most characteristic odor compounds of the fresh oils. ?-Cyclocitral (citrus odor, FD-factor = 64) and ?-ionone (violet-floral odor, FD-factor = 64) were the most characteristic odor compounds of the dried oil. These compounds are thought to contribute to the flavor of R. nipponicus var. submersus. PMID:25891110

  12. Recent advances on antimony(III/V) compounds with potential activity against tumor cells.

    PubMed

    Hadjikakou, S K; Ozturk, I I; Banti, C N; Kourkoumelis, N; Hadjiliadis, N

    2015-12-01

    Antimony one of the heavier pnictogens, has been in medical use against microbes and parasites as well. Antimony-based drugs have been prescribed against leishmaniasis since the parasitic transmission of the tropical disease was understood in the beginning of the 20th century. The activity of arsenic against visceral leishmaniasis led to the synthesis of an array of arsenic-containing parasitic agents, among them the less toxic pentavalent antimonials: Stibosan, Neostibosan, and Ureastibamine. Other antimony drugs followed: sodium stibogluconate (Pentostam) and melglumine antimoniate (Glucantim or Glucantime); both continue to be in use today despite their toxic side effects and increasing loss in potency due to the growing resistance of the parasite against antimony. Antimony compounds and their therapeutic potentials are under consideration from many research groups, while a number of early reviews recording advances of antimony biomedical applications are also available. However, there are only few reports on the screening for antitumor potential of antimony compounds. This review focuses upon results obtained on the anti-proliferative activity of antimony compounds in the past years. This survey shows that antimony(III/V) complexes containing various types of ligands such as thiones, thiosemicarbazones, dithiocarbamates, carboxylic acids, or ketones, nitrogen donor ligands, exhibit selectivity against a variety of cancer cells. The role of the ligand type of the complex is elucidated within this review. The complexes and their biological activity are already reported elsewhere. However quantitative structure-activity relationship (QSAR) modeling studies have been carried out and they are reported for the first time here. PMID:26092367

  13. Simultaneous determination of thirteen major active compounds in Guanjiekang preparation by UHPLC-QQQ-MS/MS.

    PubMed

    Wang, Canjian; Xie, Ying; Xiang, Zheng; Zhou, Hua; Liu, Liang

    2016-01-25

    An ultra high performance liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS) method has been developed to evaluate the quality of a pharmaceutical herbal preparation, Guanjiekang (GJK), through a simultaneous determination of 13 major active compounds with a huge difference in level of content. Chromatographic separation was achieved on a Waters Acquilty UPLC C18 column (2.1×100mm, 1.7?m) with a mobile phase consisting of acetonitrile and buffer solution (10mM ammonium acetate containing 0.1% acetic acid) under a gradient elution manner. A triple quadrupole mass spectrometer was operated in positive ionization mode with multiple reaction monitoring for the detection of the 13 compounds. All calibration curves showed excellent linear regressions (R(2)>0.999) within the test range. The precision, repeatability and stability of the 13 compounds were below 5.0% in terms of RSD. The recoveries were 99.2-103.9% with RSD of 0.23-3.30% for GJK samples. The method was successfully used for the analysis of samples of GJK preparation and showed that the lowest level was in aconitine (0.582±0.143ng/g) and the highest was in paeoniflorin (16.80±0.886mg/g), with a 41800 folds of difference. In conclusion, a rapid, sensitive, precise, accurate, and reliable UHPLC-QQQ-MS/MS method has been developed for the simultaneous detection of 13 active compounds with massive difference in level of content in the pharmaceutical samples of GJK preparation, which can be applied for the quality control of GJK product. PMID:26588049

  14. Antimicrobial activities of the methanol extract, fractions and compounds from Ficus polita Vahl. (Moraceae)

    PubMed Central

    2011-01-01

    Background Many plants of the family Moraceae are used in the treatment of infectious diseases. Ficus polita Vahl., an edible plant belonging to this family is used traditionally in case of dyspepsia, infectious diseases, abdominal pains and diarrhea. The present work was designed to assess the antimicrobial activity of the methanol extract from the roots of F. polita (FPR), as well as that of its fractions (FPR1-5) and two of the eight isolated compounds, namely euphol-3-O-cinnamate (1) and (E)-3,5,4'-trihydroxy-stilbene-3,5-O-?-D-diglucopyranoside (8). Methods The liquid microdilution assay was used in the determination of the minimal inhibitory concentration (MIC) and the minimal microbicidal concentration (MMC), against seven bacterial and one fungal species. Results The results of the MIC determination showed that the crude extract, fractions FPR1, FPR2 and compound 8 were able to prevent the growth of the eight tested microorganisms. Other samples showed selective activity. The lowest MIC value of 64 ?g/ml for the crude extract was recorded on 50% of the studied microbial species. The corresponding value for fractions of 32 ?g/ml was obtained on Salmonella typhi, Escherichia coli and Candida albicans ATCC strains. The MIC values recorded with compound 8 on the resistant Pseudomonas aeruginosa PA01 strain was equal to that of chloramphenicol used as reference antibiotic. Conclusion The obtained results highlighted the interesting antimicrobial potency of F. polita as well as that of compound 8, and provided scientific basis for the traditional use of this taxon in the treatment of microbial infections. PMID:21269424

  15. Macrocarpal-like Compounds from Eugenia umbelliflora Fruits and Their Antibacterial Activity.

    PubMed

    Faqueti, Larissa Gabriela; Farias, Ingrid Vicente; Sabedot, Elem Cristina; Delle Monache, Franco; San Feliciano, Arturo; Schuquel, Ivânia Teresinha Albrecht; Cechinel-Filho, Valdir; Cruz, Alexandre Bella; Meyre-Silva, Christiane

    2015-09-23

    Certain members of the genus Eugenia are used as foods. One of these species is Eugenia umbelliflora, which is used for its fruits. The aim of the study was to isolate the constituents of the CH2Cl2 fraction obtained from E. umbelliflora O. Berg (Myrtaceae) and also to evaluate its antimicrobial properties. Two new meroterpenoids, eugenial C (3) and eugenial D (4) were isolated from the unripe fruits of E. umbelliflora and their structures established mainly by extensive NMR spectroscopy. In previous studies, the CH2Cl2 extract showed significant antibacterial activity, which can be attributed to meroterpenoids isolated in this study. The compounds eugenials C and D exhibited potent activity against Bacillus subtilis and Staphylococcus aureus and different strains of MRSA and activity similar to those of the antibiotics used in antimicrobial therapies. PMID:26308768

  16. Pharmaceutical screen identifies novel target processes for activation of autophagy with a broad translational potential

    PubMed Central

    Chauhan, Santosh; Ahmed, Zahra; Bradfute, Steven B.; Arko-Mensah, John; Mandell, Michael A.; Won Choi, Seong; Kimura, Tomonori; Blanchet, Fabien; Waller, Anna; Mudd, Michal H.; Jiang, Shanya; Sklar, Larry; Timmins, Graham S.; Maphis, Nicole; Bhaskar, Kiran; Piguet, Vincent; Deretic, Vojo

    2015-01-01

    Autophagy is a conserved homeostatic process active in all human cells and affecting a spectrum of diseases. Here we use a pharmaceutical screen to discover new mechanisms for activation of autophagy. We identify a subset of pharmaceuticals inducing autophagic flux with effects in diverse cellular systems modelling specific stages of several human diseases such as HIV transmission and hyperphosphorylated tau accumulation in Alzheimer's disease. One drug, flubendazole, is a potent inducer of autophagy initiation and flux by affecting acetylated and dynamic microtubules in a reciprocal way. Disruption of dynamic microtubules by flubendazole results in mTOR deactivation and dissociation from lysosomes leading to TFEB (transcription factor EB) nuclear translocation and activation of autophagy. By inducing microtubule acetylation, flubendazole activates JNK1 leading to Bcl-2 phosphorylation, causing release of Beclin1 from Bcl-2-Beclin1 complexes for autophagy induction, thus uncovering a new approach to inducing autophagic flux that may be applicable in disease treatment. PMID:26503418

  17. Electrochemical versus spectrophotometric assessment of antioxidant activity of hop (Humulus lupulus L.) products and individual compounds.

    PubMed

    Gorjanovi?, Stanislava; Pastor, Ferenc T; Vasi?, Radica; Novakovi?, Miroslav; Simonovi?, Mladen; Mili?, Sonja; Sužnjevi?, Desanka

    2013-09-25

    Antioxidant (AO) activity of extracts of hop cones (Serbian domestic varieties) and commercial hop products (Saaz, Spalter, Spalter select, and Magnum pellets) was determined by parallel application of recently developed direct current (DC) polarographic and widely used DPPH assay. Correlations between 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging and total phenolics (TPC) determined by the Folin-Ciocalteu assay (FC) (0.99), and between H2O2 scavenging (HPS) and humulone content (H) determined by conductometric method (0.94), total resins (TR) (0.85), and hop storage index (HIS) (-0.90), were found statistically significant at p < 0.05 level while complete lack of HPS correlation with TPC and DPPH was observed. To obtain an insight into differences between results of AO assays applied, activity of individual compounds, prevalent hop phenolics, and bitter acids was determined. By far superior HPS activity of humulone was followed by catechin, quercetin, xanthohumol, lupulone, and rutin. In contrast, DPPH scavenging activity of phenolics (quercetin > catechin > rutin > xantohumol) was found substantially higher than activity of bitter acids. According to ferric reducing antioxidant power (FRAP) and scavenging of 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), higher AO activity was ascribed to phenolics, while almost neglecting humulone. Besides reliability, low cost, and an easy-to-handle procedure, an ability to recognize humulone as the major contributor of hop AO activity could allow DC polarographic assay to be applied in analysis of various hop-derived products. PMID:23971792

  18. Single, competitive, and dynamic adsorption on activated carbon of compounds used as plasticizers and herbicides.

    PubMed

    Abdel daiem, Mahmoud M; Rivera-Utrilla, José; Sánchez-Polo, Manuel; Ocampo-Pérez, Raúl

    2015-12-15

    The main aim of this study was to investigate the single, competitive, and dynamic adsorption of phthalic acid (PA), bisphenol A (BPA), diphenolic acid (DPA), 2,4-dichlorophenoxy-acetic acid (2,4-D), and 4-chloro-2-methylphenoxyacetic acid (MCPA) on two activated carbons with different chemical natures and similar textural characteristics. The adsorption mechanism was also elucidated by analyzing the influence of solution pH and ionic strength. The activated carbons demonstrated high adsorption capacity to remove all micropollutants due to the presence of active sites on their surfaces, which increase dispersive interactions between the activated carbon graphene layers and the aromatic ring of pollutants. The adsorption capacity of the activated carbons increased in the order: DPAactivated carbon decreased by around 50% and 70% in the presence of DPA and BPA, respectively, indicating that both compounds are adsorbed on the same adsorption sites of the activated carbon. PMID:26282767

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

    PubMed

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

    2015-08-15

    The chalcone compound isosalipurposide (ISPP) has been successfully isolated from the native Korean plant species Corylopsis coreana Uyeki (Korean winter hazel). However, the therapeutic efficacy of ISPP remains poorly understood. This study investigated whether ISPP has the capacity to activate NF-E2-related factor (Nrf2)-antioxidant response element (ARE) signaling and induce its target gene expression, and to determined the protective role of ISPP against oxidative injury of hepatocytes. In HepG2 cells, nuclear translocation of Nrf2 is augmented by ISPP treatment. Consistently, ISPP increased ARE reporter gene activity and the protein levels of glutamate cysteine ligase (GCL) and hemeoxygenase (HO-1), resulting in increased intracellular glutathione levels. Cells pretreated with ISPP were rescued from tert-butylhydroperoxide-induced reactive oxygen species (ROS) production and glutathione depletion and consequently, apoptotic cell death. Moreover, ISPP ameliorated the mitochondrial dysfunction and apoptosis induced by rotenone which is an inhibitor of complex 1 of the mitochondrial respiratory chain. The specific role of Nrf2 activation by ISPP was demonstrated using an ARE-deletion mutant plasmid and Nrf2-knockout cells. Finally, we observed that extracellular signal-regulated kinase (ERK) and AMP-activated protein kinase (AMPK), but not protein kinase C (PKC)-? or other mitogen-activated protein kinases (MAPKs), are involved in the activation of Nrf2 by ISPP. Taken together, our results demonstrate that ISPP has a cytoprotective effect against oxidative damage mediated through Nrf2 activation and induction of its target gene expression in hepatocytes. PMID:26028482

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

    PubMed

    Fra?ková, Adéla; Marounek, Milan; Mozrová, V?ra; Weber, Jaroslav; Klou?ek, Pavel; Lukešová, Daniela

    2014-10-01

    Cronobacter sakazakii and C. malonaticus are opportunistic pathogens that cause infections in children and immunocompromised adults. In the present study, the antibacterial activity of 19 plant-derived compounds, 5 essential oils, and an extract of propolis were assessed against C. sakazakii and C. malonaticus. The effects of most of these antimicrobials have not been reported previously. Both strains were susceptible to thymol, carvacrol, thymoquinone, p-cymene, linalool, camphor, citral, eugenol, and trans-cinnamaldehyde as well as cinnamon, lemongrass, oregano, clove, and laurel essential oils; their minimum inhibitory concentrations varied between 0.1 and 2.0?mg/mL. As an alternative treatment method, vapors of the volatiles were tested as an indirect treatment. Vapors of trans-cinnamaldehyde, eugenol, oregano, and cinnamon essential oils inhibited both tested strains, while vapors of linalool were only active against C. sakazakii. To our knowledge, this study is the first time that the inhibitory activity of the vapors of these compounds and essential oils has been reported against Cronobacter spp. PMID:25062020

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

    PubMed Central

    Durak, Agata; Gawlik-Dziki, Urszula

    2014-01-01

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

  2. Marine Benthic Diatoms Contain Compounds Able to Induce Leukemia Cell Death and Modulate Blood Platelet Activity

    PubMed Central

    Prestegard, Siv Kristin; Oftedal, Linn; Coyne, Rosie Theresa; Nygaard, Gyrid; Skjærven, Kaja Helvik; Knutsen, Gjert; Døskeland, Stein Ove; Herfindal, Lars

    2009-01-01

    In spite of the high abundance and species diversity of diatoms, only a few bioactive compounds from them have been described. The present study reveals a high number of mammalian cell death inducing substances in biofilm-associated diatoms sampled from the intertidal zone. Extracts from the genera Melosira, Amphora, Phaeodactylum and Nitzschia were all found to induce leukemia cell death, with either classical apoptotic or autophagic features. Several extracts also contained inhibitors of thrombin-induced blood platelet activation. Some of this activity was caused by a high content of adenosine in the diatoms, ranging from 0.07 to 0.31 ?g/mg dry weight. However, most of the bioactivity was adenosine deaminase-resistant. An adenosine deaminase-resistant active fraction from one of the extracts was partially purified and shown to induce apoptosis with a distinct phenotype. The results show that benthic diatoms typically found in the intertidal zone may represent a richer source of interesting bioactive compounds than hitherto recognized. PMID:20098602

  3. Artifactual prolongation of activated partial thromboplastin time with PEGylated compounds in silica-based assays.

    PubMed

    Murphy, Bethanne; Parrula, Maria C M; Perigard, Christopher J; Li, Jinze

    2014-12-01

    Conjugation of polyethylene glycol (PEG) to another molecule prolongs its half-life in the body, but has a potential to artifactually increase the activated partial thromboplastin time (aPTT) as measured with certain assays. Studies conducted in-house at Bristol-Myers Squibb using the STA-PTT Automate 5 assay, the routine assay used to measure aPTT, demonstrated prolongation of aPTT in plasma samples spiked in vitro with 40-kDa branched PEG (PEG40) conjugated compounds or PEG40 alone, but not in samples spiked with vehicle or non-PEGylated compound, suggesting that the interference is because of the PEG40 moiety. To investigate the cause of this phenomenon, cynomolgus monkey and rat plasma samples were spiked with different concentrations of PEG40 and the aPTT was measured using different proprietary assays. With one exception, prolongation of aPTT was observed with all assays containing silica as the contact activator. No changes in aPTT were noted in assays using kaolin as a contact activator. The findings indicated that the observed prolongation of aPTT is largely because of interference of PEG40 with the silica, but other features of the reagent mixture may also influence aPTT times. PMID:25192241

  4. Activity-guided purification identifies lupeol, a pentacyclic triterpene, as a therapeutic agent multiple pathogenic factors of acne.

    PubMed

    Kwon, Hyuck Hoon; Yoon, Ji Young; Park, Seon Yong; Min, Seonguk; Kim, Yong-il; Park, Ji Yong; Lee, Yun-Sang; Thiboutot, Diane M; Suh, Dae Hun

    2015-06-01

    Acne vulgaris is a nearly universal cutaneous disease characterized by multifactorial pathogenic processes. Because current acne medications have various side effects, investigating new pharmacologically active molecules is important for treating acne. As natural products generally provide various classes of relatively safe compounds with medicinal potentials, we performed activity-guided purification after a series of screenings from the extracts of five medicinal plants to explore alternative acne medications. Lupeol, a pentacyclic triterpene, from the hexane extract of Solanum melongena L. (SM) was identified after instrumental analysis. Lupeol targeted most of the major pathogenic features of acne with desired physicochemical traits. It strongly suppressed lipogenesis by modulating the IGF-1R/phosphatidylinositide 3 kinase (PI3K)/Akt/sterol response element-binding protein-1 (SREBP-1) signaling pathway in SEB-1 sebocytes, and reduced inflammation by suppressing the NF-?B pathway in SEB-1 sebocytes and HaCaT keratinocytes. Lupeol exhibited a marginal effect on cell viability and may have modulated dyskeratosis of the epidermis. Subsequently, histopathological analysis of human patients' acne tissues after applying lupeol for 4 weeks demonstrated that lupeol markedly attenuated the levels of both the number of infiltrated cells and major pathogenic proteins examined in vitro around comedones or sebaceous glands, providing solid evidence for suggested therapeutic mechanisms. These results demonstrate the clinical feasibility of applying lupeol for the treatment of acne. PMID:25647437

  5. Highly selective palladium–benzothiazole carbene-catalyzed allylation of active methylene compounds under neutral conditions

    PubMed Central

    Cotugno, Pietro; Zambonin, Carlo Giorgio; Ciminale, Francesco

    2015-01-01

    Summary The Pd–benzothiazol-2-ylidene complex I was found to be a chemoselective catalyst for the Tsuji–Trost allylation of active methylene compounds carried out under neutral conditions and using carbonates as allylating agents. The proposed protocol consists in a simplified procedure adopting an in situ prepared catalyst from Pd2dba3 and 3-methylbenzothiazolium salt V as precursors. A comparison of the performance of benzothiazole carbene with phosphanes and an analogous imidazolium carbene ligand is also proposed. PMID:26199653

  6. Synthesis and anti-influenza virus activity of tricyclic compounds with a unique amine moiety.

    PubMed

    Oka, M; Ishiwata, Y; Iwata, N; Honda, N; Kakigami, T

    2001-04-01

    Several novel tricyclic compounds with a unique amine moiety (1, 2a--i) were designed and prepared based on the structure of triperiden for the development of anti-influenza virus agents. An in vitro antiviral assay showed that 1-(1-azabicyclo[3.3.0]octan-5-yl)-1-(4-fluorophenyl)-1-(2-tricyclo[3.3.1.1(3.7)]decyl)methan-1-ol hydrochloride (2f) has a potent anti-influenza A virus activity. Furthermore, since 2f was well tolerated in mice, 2f is promising as a novel anti-influenza virus agent for humans. PMID:11310661

  7. Organocatalytic Michael and Friedel-Crafts reactions in enantioselective synthesis of biologically active compounds

    NASA Astrophysics Data System (ADS)

    Maltsev, O. V.; Beletskaya, Irina P.; Zlotin, Sergei G.

    2011-11-01

    Recent applications of organocatalytic Michael and Friedel-Crafts reactions in enantioselective synthesis of biologically active compounds: natural products, pharmaceutical agents and plant protection agents are reviewed. The key mechanisms of stereoinduction, types of organocatalysts and reagents used in these reactions are considered. The material is classified according to the type of newly formed bonds incorporating the asymmetric carbon atom, and the information for the most numerous C-C coupling reactions is systematized according to the natures of the electrophile and the nucleophile. The bibliography includes 433 references. Dedicated to Academician O M Nefedov on the occasion of his 80th birthday.

  8. Synthesis and structure-activity relationships of 1,5-diazaanthraquinones as antitumour compounds.

    PubMed

    Avendaño, Carmen; Pérez, José María; Blanco, Maria del Mar; de la Fuente, Jesús Angel; Manzanaro, Sonia; Vicent, María Jesús; Martín, María Jesús; Salvador-Tormo, Nélida; Menéndez, J Carlos

    2004-08-01

    1,5-Diazaanthraquinone derivatives were synthesized employing single and double hetero Diels-Alder strategies. Their in vitro antitumour activity was assayed using three cell lines. Some of these compounds, specially those bearing methyl or ethyl groups at the C-3,7 positions or chloro at C-4 and methyl at C-7, showed IC(50) values in the 10(-8)M range for human lung carcinoma and human melanoma, which makes them attractive candidates for further development as anticancer agents. PMID:15225700

  9. Silver oxynitrate, an unexplored silver compound with antimicrobial and antibiofilm activity.

    PubMed

    Lemire, Joe A; Kalan, Lindsay; Bradu, Alexandru; Turner, Raymond J

    2015-07-01

    Historically it has been accepted, and recent research has established, that silver (Ag) is an efficacious antimicrobial agent. A dwindling pipeline of new antibiotics, combined with an increase in the number of antibiotic-resistant infections, is bringing Ag to the fore as a therapeutic compound to treat infectious diseases. Currently, many formulations of Ag are being deployed for commercial and medical purposes, with various degrees of effectiveness at killing microbial cells. Here, we evaluated the antimicrobial and antibiofilm capacity of our lead compound, silver oxynitrate [Ag(Ag3O4)2NO3 or Ag7NO11], against other metal compounds with documented antimicrobial activity, including Ag2SO4, AgNO3, silver sulfadiazine (AgSD), AgO, Ag2O, and CuSO4. Our findings reveal that Ag7NO11 eradicates biofilm and planktonic populations of Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, uropathogenic Escherichia coli (UPEC), fluoroquinolone-resistant Pseudomonas aeruginosa (FQRP), and methicillin-resistant Staphylococcus aureus (MRSA) at lower concentrations than those of the other tested metal salts. Altogether, our results demonstrate that Ag7NO11 has an enhanced efficacy for the treatment of biofilm-forming pathogens. PMID:25918137

  10. Silver Oxynitrate, an Unexplored Silver Compound with Antimicrobial and Antibiofilm Activity

    PubMed Central

    Lemire, Joe A.; Kalan, Lindsay; Bradu, Alexandru

    2015-01-01

    Historically it has been accepted, and recent research has established, that silver (Ag) is an efficacious antimicrobial agent. A dwindling pipeline of new antibiotics, combined with an increase in the number of antibiotic-resistant infections, is bringing Ag to the fore as a therapeutic compound to treat infectious diseases. Currently, many formulations of Ag are being deployed for commercial and medical purposes, with various degrees of effectiveness at killing microbial cells. Here, we evaluated the antimicrobial and antibiofilm capacity of our lead compound, silver oxynitrate [Ag(Ag3O4)2NO3 or Ag7NO11], against other metal compounds with documented antimicrobial activity, including Ag2SO4, AgNO3, silver sulfadiazine (AgSD), AgO, Ag2O, and CuSO4. Our findings reveal that Ag7NO11 eradicates biofilm and planktonic populations of Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, uropathogenic Escherichia coli (UPEC), fluoroquinolone-resistant Pseudomonas aeruginosa (FQRP), and methicillin-resistant Staphylococcus aureus (MRSA) at lower concentrations than those of the other tested metal salts. Altogether, our results demonstrate that Ag7NO11 has an enhanced efficacy for the treatment of biofilm-forming pathogens. PMID:25918137

  11. Neural cell activation by phenolic compounds from the Siberian larch (Larix sibirica).

    PubMed

    Loers, Gabriele; Yashunsky, Dmitry V; Nifantiev, Nikolay E; Schachner, Melitta

    2014-07-25

    Small organic phenolic compounds from natural sources have attracted increasing attention due to their potential to ameliorate the serious consequences of acute and chronic traumata of the mammalian nervous system. In this contribution, it is reported that phenols from the knot zones of Siberian larch (Larix sibirica) wood, namely, the antioxidant flavonoid (+)-dihydroquercetin (1) and the lignans (-)-secoisolariciresinol (2) and (+)-isolariciresinol (3), affect migration and outgrowth of neurites/processes from cultured neurons and glial cells of embryonic and early postnatal mice. Compounds 1-3, which were available in preparative amounts, enhanced neurite outgrowth from cerebellar granule neurons, dorsal root ganglion neurons, and motoneurons, as well as process formation of Schwann cells in a dose-dependent manner in the low nanomolar range. Migration of cultured astrocytes was inhibited by 1-3, and migration of neurons out of cerebellar explants was enhanced by 1. These observations provide evidence for the neuroactive features of these phenolic compounds in enhancing the beneficial properties of neurons and reducing the inhibitory properties of activated astrocytes in an in vitro setting and encourage the further investigation of these effects in vivo, in animal models of acute and chronic neurological diseases. PMID:24963869

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

    PubMed

    Kosti?, Miroslav; Popovi?, Zorica; Brki?, Dejan; Milanovi?, Slobodan; Sivcev, Ivan; Stankovi?, Sladjan

    2008-11-01

    Ethanol solutions of essential oil of Ocimum basilicum and its main component, linalool (both isomer forms), all in three concentrations, as well as botanical standard Bioneem (0.5%), were tested for their toxicity and antifeedant activity against the second instar gypsy moth larvae in the laboratory bioassay. The essential oil of O. basilicum was subjected to gas chromatography analysis, and totally 37 compounds were detected, of which linalool was predominantly present. All tested solutions showed low to moderate larvicidal effect in both residual toxicity test and in chronic larval mortality bioassay. Chronic mortality tests showed that obtained mortality was a consequence of starving rather than ingestion of treated leaves. However, antifeedant index achieved by application of tested solutions in feeding choice assay was remarkable. Foliar application of all tested compounds deterred feeding by L2 in the same percent as Bioneem. Antifeedant index was relatively high at all tested treatments (85-94%); moreover, the larval desensitization to repelling volatiles has not occurred after five days of observation. Low toxic and high antifeedant properties make these plant-derived compounds suitable for incorporation in integrated pest management programs, especially in urban environments. PMID:18364253

  13. Anti-tumour activity of two novel compounds in cisplatin-resistant testicular germ cell cancer

    PubMed Central

    Nitzsche, B; Gloesenkamp, C; Schrader, M; Hoffmann, B; Zengerling, F; Balabanov, S; Honecker, F; Höpfner, M

    2012-01-01

    Background: Resistance to cisplatin-based chemotherapy is associated with poor prognosis in testicular germ cell cancer, emphasising the need for new therapeutic approaches. In this respect, the therapeutic concept of anti-angiogenesis is of particular interest. In a previous study, we presented two novel anti-angiogenic compounds, HP-2 and HP-14, blocking the tyrosine kinase activity of angiogenic growth factor receptors, such as vascular endothelial growth factor receptor-2 (VEGFR-2), and related signalling pathways in testicular cancer. In this study, we investigated the efficacy of these new compounds in platinum-resistant testicular germ cell tumours (TGCTs), in vitro and in vivo. Methods and results: Drug-induced changes in cell proliferation of the cisplatin-sensitive TGCT cell line 2102EP and its cisplatin-resistant counterpart 2102EP-R, both expressing the VEGFR-2, were evaluated by crystal violet staining. Both compounds inhibited the growth of cisplatin-resistant TGCT cells in a dose-dependent manner. In combination experiments with cisplatin, HP-14 revealed additive growth-inhibitory effects in TGCT cells, irrespective of the level of cisplatin resistance. Anti-angiogenic effects of HP compounds were confirmed by tube formation assays with freshly isolated human umbilical vein endothelial cells. Using TGCT cells inoculated onto the chorioallantoic membrane of fertilised chicken eggs (chicken chorioallantoic membrane assay), the anti-angiogenic and anti-proliferative potency of the novel compounds was also demonstrated in vivo. Gene expression profiling revealed changes in the expression pattern of genes related to DNA damage detection and repair, as well as in chaperone function after treatment with both cisplatin and HP-14, alone or in combination. This suggests that HP-14 can revert the lost effectiveness of cisplatin in the resistant cells by altering the expression of critical genes. Conclusion: The novel compound HP-14 effectively inhibits the growth of cisplatin-resistant TGCT cells and suppresses tumour angiogenesis. Thus, HP-14 may be an interesting new agent that should be further explored for TGCT treatment, especially in TGCTs that are resistant to cisplatin. PMID:23169338

  14. Validation of mercury tip-switch and accelerometer activity sensors for identifying resting and active behavior in bears

    USGS Publications Warehouse

    Jasmine Ware; Rode, Karyn D.; Pagano, Anthony M.; Bromaghin, Jeffrey; Charles T Robbins; Joy Erlenbach; Shannon Jensen; Amy Cutting; Nicole Nicassio-Hiskey; Amy Hash; Owen, Megan A.; Heiko Jansen

    2015-01-01

    Activity sensors are often included in wildlife transmitters and can provide information on the behavior and activity patterns of animals remotely. However, interpreting activity-sensor data relative to animal behavior can be difficult if animals cannot be continuously observed. In this study, we examined the performance of a mercury tip-switch and a tri-axial accelerometer housed in collars to determine whether sensor data can be accurately classified as resting and active behaviors and whether data are comparable for the 2 sensor types. Five captive bears (3 polar [Ursus maritimus] and 2 brown [U. arctos horribilis]) were fitted with a collar specially designed to internally house the sensors. The bears’ behaviors were recorded, classified, and then compared with sensor readings. A separate tri-axial accelerometer that sampled continuously at a higher frequency and provided raw acceleration values from 3 axes was also mounted on the collar to compare with the lower resolution sensors. Both accelerometers more accurately identified resting and active behaviors at time intervals ranging from 1 minute to 1 hour (?91.1% accuracy) compared with the mercury tip-switch (range = 75.5–86.3%). However, mercury tip-switch accuracy improved when sampled at longer intervals (e.g., 30–60 min). Data from the lower resolution accelerometer, but not the mercury tip-switch, accurately predicted the percentage of time spent resting during an hour. Although the number of bears available for this study was small, our results suggest that these activity sensors can remotely identify resting versus active behaviors across most time intervals. We recommend that investigators consider both study objectives and the variation in accuracy of classifying resting and active behaviors reported here when determining sampling interval.

  15. Phenolic compounds from the flowers of Nepalese medicinal plant Aconogonon molle and their DPPH free radical-scavenging activities.

    PubMed

    Joshi, Khem Raj; Devkota, Hari Prasad; Watanabe, Takashi; Yahara, Shoji

    2014-01-01

    Eleven phenolic compounds, quercetin (1), quercetin 3-O-?-d-galactopyranoside (2), quercetin 3-O-(6?-O-galloyl)-?-d-galactopyranoside (3), quercetin 3-O-(6?-O-caffeoyl)-?-d-galactopyranoside (4), quercetin 3-O-?-d-glucopyranoside (5), rutin (6) quercetin 3-O-?-l-arabinopyranoside (7), quercetin 3-O-?-l-arabinofuranoside (8), protocatechulic acid (9), gallic acid (10) and chlorogenic acid (11), were isolated from the flowers of Aconogonon molle, a Nepalese medicinal plant. Structures of these compounds were elucidated on the basis of spectroscopic methods. All these compounds were isolated for the first time from flowers, and five compounds (4, 5, 8, 9 and 11) were isolated for the first time from A. molle. All of these isolated compounds were evaluated for their in vitro antioxidant activity by using the 1,1-diphenyl-2-picrylhydrazyl radical-scavenging method. Quercetin (1), quercetin glycosides (2-8) and gallic acid (10) exhibited potent antioxidant activity. PMID:24825068

  16. A c-Myc activation sensor-based high-throughput drug screening identifies an antineoplastic effect of nitazoxanide.

    PubMed

    Fan-Minogue, Hua; Bodapati, Sandhya; Solow-Cordero, David; Fan, Alice; Paulmurugan, Ramasamy; Massoud, Tarik F; Felsher, Dean W; Gambhir, Sanjiv S

    2013-09-01

    Deregulation of c-Myc plays a central role in the tumorigenesis of many human cancers. Yet, the development of drugs regulating c-Myc activity has been challenging. To facilitate the identification of c-Myc inhibitors, we developed a molecular imaging sensor-based high-throughput screening (HTS) system. This system uses a cell-based assay to detect c-Myc activation in a HTS format, which is established from a pure clone of a stable breast cancer cell line that constitutively expresses a c-Myc activation sensor. Optimization of the assay performance in the HTS format resulted in uniform and robust signals at the baseline. Using this system, we conducted a quantitative HTS against approximately 5,000 existing bioactive compounds from five different libraries. Thirty-nine potential hits were identified, including currently known c-Myc inhibitors. There are a few among the top potent hits that are not known for anti-c-Myc activity. One of these hits is nitazoxanide, a thiazolide for treating human protozoal infections. Validation of nitazoxanide in different cancer cell lines revealed a high potency for c-Myc inhibition with IC50 ranging between 10 and 500 nmol/L. Oral administration of nitazoxanide in breast cancer xenograft mouse models significantly suppressed tumor growth by inhibition of c-Myc and induction of apoptosis. These findings suggest a potential of nitazoxanide to be repurposed as a new antitumor agent for inhibition of c-Myc-associated neoplasia. Our work also demonstrated the unique advantage of molecular imaging in accelerating discovery of drugs for c-Myc-targeted cancer therapy. PMID:23825064

  17. Phenolic compounds and antioxidant activities of selected species of seaweeds from Danish coast.

    PubMed

    Sabeena Farvin, K H; Jacobsen, Charlotte

    2013-06-01

    Water and ethanolic extracts of 16 species of seaweeds collected along the Danish coasts were screened for antioxidant activities using four in vitro antioxidant assays (2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, reducing power, ferrous ion-chelating and liposome model system). Furthermore their effectiveness in retarding lipid peroxidation in fish oil was evaluated by an accelerated stability test. Significant differences were observed in total and individual phenolic content and the antioxidant activities of seaweed species evaluated. Ethanol was more efficient for polyphenol extraction than water. Polysiphonia fucoides and all the Fucus species tested showed highest radical scavenging activity, reducing power, inhibition of oxidation in liposome model system and in fish oil and were high in phenolic content. These seaweeds could be potential rich sources of natural antioxidants for protection of foods against oxidation. In general, the various antioxidative assays correlated well with the total phenolic content, indicating that algal polyphenols are active components in these extracts. However, in some of the antioxidative assays some species with low total phenolic content also showed good antioxidative effects indicating that some other co-extracted active compounds such as pigments and tocopherols in ethanolic extracts and sulphated polysaccharides, proteins or peptides in water extracts may also contribute to the overall antioxidant properties and this needs further investigation. PMID:23411297

  18. Pine Bark and Green Tea Concentrated Extracts: Antioxidant Activity and Comprehensive Characterization of Bioactive Compounds by HPLC–ESI-QTOF-MS

    PubMed Central

    Cádiz-Gurrea, María de la Luz; Fernández-Arroyo, Salvador; Segura-Carretero, Antonio

    2014-01-01

    The consumption of polyphenols has frequently been associated with low incidence of degenerative diseases. Most of these natural antioxidants come from fruits, vegetables, spices, grains and herbs. For this reason, there has been increasing interest in identifying plant extract compounds. Polymeric tannins and monomeric flavonoids, such as catechin and epicatechin, in pine bark and green tea extracts could be responsible for the higher antioxidant activities of these extracts. The aim of the present study was to characterize the phenolic compounds in pine bark and green tea concentrated extracts using high-performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC–ESI-QTOF-MS). A total of 37 and 35 compounds from pine bark and green tea extracts, respectively, were identified as belonging to various structural classes, mainly flavan-3-ol and its derivatives (including procyanidins). The antioxidant capacity of both extracts was evaluated by three complementary antioxidant activity methods: Trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC). Higher antioxidant activity values by each method were obtained. In addition, total polyphenol and flavan-3-ol contents, which were determined by Folin–Ciocalteu and vanillin assays, respectively, exhibited higher amounts of gallic acid and (+)-catechin equivalents. PMID:25383680

  19. Inhibitory activities of the marine streptomycete-derived compound SF2446A2 against Chlamydia trachomatis and Schistosoma mansoni.

    PubMed

    Reimer, Anastasija; Blohm, Ariane; Quack, Thomas; Grevelding, Christoph G; Kozjak-Pavlovic, Vera; Rudel, Thomas; Hentschel, Ute; Abdelmohsen, Usama Ramadan

    2015-11-01

    Infectious diseases caused by chlamydia or schistosomes are a major health problem worldwide, and particularly so in developing countries. The lack of appropriate vaccines renders the search for potent natural products against these disease-causing agents an urgent endeavor. Sponge-associated actinomycetes represent a rich reservoir for natural products. Among them, members of the genus Streptomyces are capable of synthesizing an impressive array of diverse natural products with a wide variety of biological activities. The naphthacene glycoside SF2446A2 was isolated from the calcium alginate beads culture of Streptomyces sp. strain RV15 that had originally been obtained from the Mediterranean sponge Dysidea tupha. Its structure was identified by spectroscopic analysis and MS and comparison with the literature data. SF2446A2 showed inhibitory activity against Chlamydia trachomatis and was able to inhibit the primary infection in a dose-dependent manner, as well as progeny formation. Moreover, it caused disruptive effects on the surface area of Schistosoma mansoni and affected the gonads by impairing oogenesis and spermatogenesis. Our current study demonstrates that sponge-associated actinomycetes are capable of providing compounds with new pharmacological activities and with relevance to drug discovery. PMID:25990954

  20. 30 CFR 285.803 - How must I conduct my approved activities to protect essential fish habitats identified and...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...approved activities to protect essential fish habitats identified and described under the Magnuson-Stevens...activities to protect essential fish habitats identified and described under the Magnuson-Stevens...activities, MMS finds that essential fish habitat or habitat areas of particular...

  1. 30 CFR 585.803 - How must I conduct my approved activities to protect essential fish habitats identified and...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...approved activities to protect essential fish habitats identified and described under the Magnuson-Stevens...activities to protect essential fish habitats identified and described under the Magnuson-Stevens...activities, BOEM finds that essential fish habitat or habitat areas of particular...

  2. 30 CFR 585.803 - How must I conduct my approved activities to protect essential fish habitats identified and...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...approved activities to protect essential fish habitats identified and described under the Magnuson-Stevens...activities to protect essential fish habitats identified and described under the Magnuson-Stevens...activities, BOEM finds that essential fish habitat or habitat areas of particular...

  3. 30 CFR 285.803 - How must I conduct my approved activities to protect essential fish habitats identified and...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...approved activities to protect essential fish habitats identified and described under the Magnuson-Stevens...activities to protect essential fish habitats identified and described under the Magnuson-Stevens...activities, MMS finds that essential fish habitat or habitat areas of particular...

  4. 30 CFR 585.803 - How must I conduct my approved activities to protect essential fish habitats identified and...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...approved activities to protect essential fish habitats identified and described under the Magnuson-Stevens...activities to protect essential fish habitats identified and described under the Magnuson-Stevens...activities, BOEM finds that essential fish habitat or habitat areas of particular...

  5. A Method to Find Generic Thresholds for Identifying Relevant Physical Activity Events in Sensor Data.

    PubMed

    Marschollek, Michael

    2016-01-01

    The increasing use of wearable actimetry devices in cohort studies can provide a deep and objective insight in physical activity (PA) patterns. For reliable and reproducible pattern recognition, and to minimize the influence of specific device characteristics, there is a need for a generic method to identify relevant PA events in sensor data sets on the basis of comprehensive features such as PA duration and intensity. The objectives of this paper are to present a method to identify universal event detection thresholds for such parameters, and to attempt to find stable meta-clusters of PA behaviour. PA events of 5, 10, 20 and 30 min with low, medium and high intensity thresholds found in literature and intensity deciles were computed for a random sample (N?=?100) of the NHANES 2005-06 accelerometer data set (N?=?7457). On the basis of all combinations of the above, activity events were detected, and parameters mean duration, mean intensity and event regularity were computed. Results were clustered using x-Means clustering and visualized for 5-, 10-, 20-, and 30-min events. Stable clustering results are obtained with intensity thresholds up to the 8th decile and for event durations up to 10 min. Two stable meta-clusters were detected: 'irregularly active' (intensity at 52nd percentile) and 'regularly active' (intensity at 42nd percentile). Distinct generic thresholds could be identified and are proposed. They may prove useful for further investigations of similar actimetry data sets, minimising the influence of specific device characteristics. The results also confirm that distinct PA event patterns - including event regularity - can be identified using wearable sensor devices, especially when regarding low-intensity, short-term activities which do not correspond to current PA recommendations. Further research is necessary to evaluate actual associations between sensor-based PA parameters and health outcome. The author identified generic intensity and duration thresholds for analysing objective PA data from wearable devices. This may contribute to further analyses of PA patterns along with their relations with health outcome parameters. PMID:26547849

  6. Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds.

    PubMed

    Alves, Vinicius M; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H; Tropsha, Alexander

    2015-04-15

    Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using Random Forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers was 71-88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR Toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the Scorecard database of possible skin or sense organ toxicants as primary candidates for experimental validation. PMID:25560674

  7. Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds

    PubMed Central

    Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

    2015-01-01

    Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using random forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers were 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the ScoreCard database of possible skin or sense organ toxicants as primary candidates for experimental validation. PMID:25560674

  8. An Automated High-Throughput Cell-Based Multiplexed Flow Cytometry Assay to Identify Novel Compounds to Target Candida albicans Virulence-Related Proteins

    PubMed Central

    Bernardo, Stella M.; Allen, Christopher P.; Waller, Anna; Young, Susan M.; Oprea, Tudor; Sklar, Larry A.; Lee, Samuel A.

    2014-01-01

    Although three major classes of systemic antifungal agents are clinically available, each is characterized by important limitations. Thus, there has been considerable ongoing effort to develop novel and repurposed agents for the therapy of invasive fungal infections. In an effort to address these needs, we developed a novel high-throughput, multiplexed screening method that utilizes small molecules to probe candidate drug targets in the opportunistic fungal pathogen Candida albicans. This method is amenable to high-throughput automated screening and is based upon detection of changes in GFP levels of individually tagged target proteins. We first selected four GFP-tagged membrane-bound proteins associated with virulence or antifungal drug resistance in C. albicans. We demonstrated proof-of-principle that modulation of fluorescence intensity can be used to assay the expression of specific GFP-tagged target proteins to inhibitors (and inducers), and this change is measurable within the HyperCyt automated flow cytometry sampling system. Next, we generated a multiplex of differentially color-coded C. albicans strains bearing C-terminal GFP-tags of each gene encoding candidate drug targets incubated in the presence of small molecules from the Prestwick Chemical Library in 384-well microtiter plate format. Following incubation, cells were sampled through the HyperCyt system and modulation of protein levels, as indicated by changes in GFP-levels of each strain, was used to identify compounds of interest. The hit rate for both inducers and inhibitors identified in the primary screen did not exceed 1% of the total number of compounds in the small-molecule library that was probed, as would be expected from a robust target-specific, high-throughput screening campaign. Secondary assays for virulence characteristics based on null mutant strains were then used to further validate specificity. In all, this study presents a method for the identification and verification of new antifungal drugs targeted to fungal virulence proteins using C. albicans as a model fungal pathogen. PMID:25350399

  9. Impairment of benthic diatom adhesion and photosynthetic activity by allelopathic compounds from a green alga: involvement of free fatty acids?

    PubMed

    Allen, Joey L; Ten-Hage, Loïc; Leflaive, Joséphine

    2015-09-01

    The role of chemical interactions in shaping microbial communities has raised increasing interest over the last decade. Many benthic microorganisms are known to develop chemical strategies to overcome competitors, but the real importance of chemical interactions within freshwater biofilm remains unknown. This study focused on the biological and chemical mechanisms of an interaction involving two benthic microorganisms, an allelopathic filamentous green alga, Uronema confervicolum, and a common diatom, Fistulifera saprophila. Our results showed that functions critical for benthic phototrophic microorganisms were inhibited by U. confervicolum extracts. Growth, cell motility, adhesion, and photosynthetic activity were impaired at extract concentrations ranging between 5 and 20 ?g ml(-1). The adhesion inhibition was mediated by intracellular nitric oxide (NO) induction. A bioassay-guided fractionation of the extract with HPLC helped to identify two C18 fatty acids present in the growth-inhibiting fractions: linoleic (LA) and ?-linolenic (LNA) acids. These compounds represented 77% of the total free fatty acids of U. confervicolum and were present in the culture medium (1.45 ?g l(-1) in total). Both could inhibit the diatom growth at concentrations higher than 0.25 ?g ml(-1), but had no effect on cell adhesion. The discrepancy between the effective concentrations of fatty acids and the concentration found in culture medium may be explained by the presence of high-concentration microenvironments. The compounds involved in adhesion inhibition remain to be identified. Though further experiments with complex biofilms are needed, our results suggest that U. confervicolum may participate to the control of biofilm composition by inhibiting diatom adhesion. PMID:25430012

  10. Activated by Combined Magnrtic Field Gravitropic Reaction Reply on Nanodose of Biologicaly Active Compounds

    NASA Astrophysics Data System (ADS)

    Sheykina, Nadezhda; Bogatina, Nina

    The new science direction nanotechnologies initiated a big jump in the pharmacology and medicine. This leads to the big development of homeopathy. The most interest appeared while investigating of the reaction of biological object on the nano dose of iologically substances. The changing of concentration (in nmol/l) of biologically active material is also possible during weak energy action. For instance, weak combined magnetic field may change a little the concentration of ions that are oriented parallel to the external magnetic field and, by the analogy with said above, lead to the similar effects. Simple estimations give the value for the threshold to the magnetic field by two orders smaller than the geomagnetic field. By this investigation we wanted to understand whether the analogy in the action of nano dose of biologically active substances and weak combined magnetic field presents and whether the action of one of these factors may be replaced by other one. The effect of one of biologically active substances NPA (Naphtyl-Phtalame Acid) solution with the concentration 0.01 mol/l on the gravitropic reaction of cress roots was investigated. It was shown that its effect was the inhibition of cress roots gravitropic reaction. The same inhibition was achieved by the combined magnetic field action on the cress roots, germinated in water. The alternative component of the combined magnetic field coincided formally with the cyclotron frequency of NPA ions. So the analogy in the action of nano dose of biologically active substances and weak combined magnetic field was shown. The combined magnetic field using allows to decrease sufficiently the dose of biologically active substances. This fact can be of great importance in pharmacy and medicine.

  11. Antifungal activity of organotin compounds with functionalized carboxylates evaluated by the microdilution bioassay in vitro.

    PubMed

    Dylag, Mariusz; Pruchnik, Hanna; Pruchnik, Florian; Majkowska-Skrobek, Grazyna; U?aszewski, Stanis?aw

    2010-03-01

    We investigated the susceptibility of 96 well-characterized strains of yeast-like and filamentous fungi towards new organotin compounds: (1) [Sn(C4H9)3(OOCC6H4SO3H-2)], (2) Sn(C4H9)3{OOC(CH2)3P(C6H5)3}]Br, and (3) [Sn(C6H5)3[OOC(CH2)3N(CH3)3}]Cl. In the case of yeast-like fungi, the in vitro susceptibility tests were carried out according to the Clinical Laboratory Standards Institute (CLSI, formerly NCCLS) reference method M27-A2, while for filamentous fungi the investigations were conducted according to the M38-A and M38-P methods. The organotin complexes 1, 2 and 3 are active antifungal agents. Minimal inhibitory concentrations (MIC) were in the range of 0.25-4.68 microg/ml for all tested fungal strains. Considerably larger differences were found for minimal fungicidal concentrations (MFC). In the case of yeast-like fungi, the fungicidal effect was generally observed at organotin compounds concentrations of 2.34-9.37 microg/ml. The MFC values for filamentous fungi were considerably higher and were in the range of 18.74-50 microg/ml. In conclusion, organotin compounds 1, 2 and 3 showed high fungistatic and fungicidal activities against different species of pathogenic and nonpathogenic fungi. However, they were also highly cytotoxic towards two mammalian cell lines. PMID:19688632

  12. In vitro antitumoral activity of compounds isolated from Artemisia gorgonum Webb.

    PubMed

    Martins, Alice; Mignon, Rukmini; Bastos, Marina; Batista, Daniela; Neng, Nuno R; Nogueira, José M F; Vizetto-Duarte, Catarina; Custódio, Luísa; Varela, João; Rauter, Amélia P

    2014-09-01

    Artemisia gorgonum (Asteraceae) is an endemic plant to the Cape Verde islands and plays an important role in traditional medicine. The chloroform extract of the plant aerial parts afforded six sesquiterpene lactones, two methoxylated flavonoids, two lignans, and one tetracyclic triterpene, which were isolated by chromatographic methods and their structure established by physical and spectroscopic techniques. The cytotoxic activity of the three major constituents, namely, arborescin, artemetin, and sesamin, was evaluated on neuroblastoma (SH-SY5Y), hepatocarcinoma (HepG2), and nontumoral bone marrow stromal (S17) cell lines. The application of different concentrations of the compounds significantly decreased tumor cells viability at different extents, especially at the highest concentrations tested. Arborescin is the most promising compound as it was able to reduce tumoral cell viability with an IC50 significantly lower (229-233??M; p?activity in vitro, more pronounced on the cancer cell lines, confirming A.?gorgonum as a source of potential antitumoral molecules. PMID:24633846

  13. Pozzolanic behaviour of compound-activated red mud-coal gangue mixture

    SciTech Connect

    Zhang Na; Liu Xiaoming; Sun Henghu; Li Longtu

    2011-03-15

    The pozzolanic behaviour of compound-activated red mud-coal gangue has been investigated through TG, DTA, XRD, FTIR and {sup 27}Al MAS NMR. From viewpoint of reaction kinetics, it is found that the pozzolanic reaction mechanism of the compound-activated red mud-coal gangue - lime system is clearly consistent with diffusion control up to 14 days, and the reaction rate constant calculated from Jander equation decreases with the increase of CaO addition in the system. The hydration products formed in the red mud-coal gangue - lime systems at ambient temperature are essentially aluminous C-S-H and Ca{sub 3}Al{sub 2}O{sub 6}.xH{sub 2}O. From TG analysis results, it is thought that the high amount of Ca(OH){sub 2} in the pastes of studied system is not conducive to the continual increase of non-evaporable water content of the hydration products. Of particular interest, {sup 27}Al MAS NMR proved to be an effective technique to obtain valuable information of Al{sup [4]} in C-S-H and Al{sup [6]} in Ca{sub 3}Al{sub 2}O{sub 6}.xH{sub 2}O.

  14. Assessment of wild mint from Tunceli as source of bioactive compounds, and its antioxidant Activity.

    PubMed

    Turkoglu, S

    2015-01-01

    The types of wild mint (Mentha spicata L.) were sampled from different geographical regions in Tunceli (Turkey) in order to find out their vitamin, mineral, phenolic contents and their antioxidant properties. The total phenol varied from 77.7±0.242 to 52.34±0.351 mg of GAEs/g of dry mint. The highest radical effect of scavenging was observed in Mazgirt parting of the ways 7.5 km with 6.17±0.245 mg/mL. The highest reducing power and metal chelating were observed in the mint from Cicekli parting of the ways 6.5 km Demirkap?. Among the various macronutrients which were estimated in the plant samples, potassium was presented in the highest quantity followed by calcium and phosphate. Although rutin and resveratrol were not determined in any samples, kaempferol and catechin levels were found out in almost all samples. The concentrations of vitamin A ranged between 42,14±5.70 and 13.61±3.00 (mg/kg dry weight). These results show that plants of mint are quite rich in phenolic compounds, and these have been appeared to have antioxidant activity, which agrees with this work, since the extract showed a higher content of phenolic compounds and higher antioxidant activity and mint may be considered as a natural alternative source for food, pharmacology and medicine sectors. PMID:26718431

  15. Controlling the release of active compounds from the inorganic carrier halloysite

    NASA Astrophysics Data System (ADS)

    Tescione, F.; Buonocore, G. G.; Stanzione, M.; Oliviero, M.; Lavorgna, M.

    2014-05-01

    Halloysite (HNTs), a natural material characterized by a nanotube structure, has been used as an inorganic carrier of active compounds in several applications from medicine to anticorrosion coatings. In this present work, vanillin (VAN) used as a antimicrobial model, has been encapsulated within HNTs for exploiting its applicability in the active food packaging sector. The molecule release rate has been controlled by crosslinking at the tube ends the loaded vanillin with copper ions, thus producing a stopper network. The vanillin-loaded HNTs were characterized using transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and thermo gravimetric analysis. The antimicrobial release kinetics from the loaded nanoparticles (VAN/HNTs) in water was investigated using UV-vis spectroscopy. The results show that the vanillin crosslinked with cupper ions is a feasible method to tailor the release rate of antimicrobial model from HTNs nanoparticles.

  16. Controlling the release of active compounds from the inorganic carrier halloysite

    SciTech Connect

    Tescione, F.; Buonocore, G. G.; Stanzione, M.; Oliviero, M.; Lavorgna, M.

    2014-05-15

    Halloysite (HNTs), a natural material characterized by a nanotube structure, has been used as an inorganic carrier of active compounds in several applications from medicine to anticorrosion coatings. In this present work, vanillin (VAN) used as a antimicrobial model, has been encapsulated within HNTs for exploiting its applicability in the active food packaging sector. The molecule release rate has been controlled by crosslinking at the tube ends the loaded vanillin with copper ions, thus producing a stopper network. The vanillin-loaded HNTs were characterized using transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and thermo gravimetric analysis. The antimicrobial release kinetics from the loaded nanoparticles (VAN/HNTs) in water was investigated using UV-vis spectroscopy. The results show that the vanillin crosslinked with cupper ions is a feasible method to tailor the release rate of antimicrobial model from HTNs nanoparticles.

  17. A new antibacterial compound produced by an indigenous marine bacteria--fermentation, isolation, and biological activity.

    PubMed

    Uzair, Bushra; Ahmed, Nuzhat; Ahmad, Viqar Uddin; Kousar, Farzana

    2006-12-01

    The use of microorganisms for biological purpose has become an effective alternative to control pathogens. A marine bacterium Pseudomonas aeruginosa was isolated from Eal fish of Baluchistan coast of Pakistan. This strain produced a bactericidal antibiotic against environmental and clinical isolates. In this study, we purified bactericidal antibiotic from the ethyl acetate extract of the cells of P. aeruginosa and analyzed its chemical structure. Based on spectrometric analysis, this compound 1 is proposed to be 1-methyl-1,4 dihydroquinoline and is active against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive S. aureus (MSSA), Salmonella typhi, Shigella flexneri, Escherichia coli, Proteus mirabilis, Vibrio aliginolyticus, Micrococcus luteus, Enterococcus faecalis, Enterobacter faecium but it is not active against G streptococci, Candida albicans, Aspergillus niger. Minimal inhibitory concentration for Gram-positive bacteria was between 50 and 75 microg mL(-1) and for Gram-negative bacteria 75-100 microg mL(-1). PMID:17393659

  18. Inhibitory effect of rice bran extracts and its phenolic compounds on polyphenol oxidase activity and browning in potato and apple puree.

    PubMed

    Sukhonthara, Sukhontha; Kaewka, Kunwadee; Theerakulkait, Chockchai

    2016-01-01

    Full-fatted and commercially defatted rice bran extracts (RBE and CDRBE) were evaluated for their ability to inhibit enzymatic browning in potato and apple. RBE showed more effective inhibition of polyphenol oxidase (PPO) activity and browning in potato and apple as compared to CDRBE. Five phenolic compounds in RBE and CDRBE (protocatechuic acid, vanillic acid, p-coumaric acid, ferulic acid and sinapic acid) were identified by HPLC. They were then evaluated for their important role in the inhibition using a model system which found that ferulic acid in RBE and p-coumaric acid in CDRBE were active in enzymatic browning inhibition of potato and apple. p-Coumaric acid exhibited the highest inhibitory effect on potato and apple PPO (p ? 0.05). Almost all phenolic compounds showed higher inhibitory effect on potato and apple PPO than 100 ppm citric acid. PMID:26213057

  19. Evaluation of wheat gluten hydrolysates as taste-active compounds with antioxidant activity.

    PubMed

    Koo, Seung Hyun; Bae, In Young; Lee, Suyong; Lee, Dae-Hee; Hur, Byung-Serk; Lee, Hyeon Gyu

    2014-03-01

    Wheat gluten was subjected to enzymatic hydrolysis with various proteases (Alcalase, Flavourzyme, Protamex) and the taste-enhancing properties and antioxidant activities of the resulting wheat gluten hydrolysates (WGHs) were characterized. The contents of the hydrophobic amino acid of the WGHs were highly correlated with the degree of hydrolysis by Flavourzyme and Protamex, except Alcalase. The taste profiles of the Alcalase-treated WGHs showed decreased bitterness while umami and overall acceptability increased. On the other hand, the WGHs produced by Flavourzyme and Protamex showed increased bitterness with increasing hydrolysis duration. However, taste profiles, such as umami, kokumi, and overall acceptability of the WGHs by Flavourzyme and Protamex were unaffected by the degree of hydrolysis. The WGH treated by Alcalase for 24 h (A24h) exhibited taste-enhancing property and its antioxidant effects were concentration-dependent. As a result, the A24h may be used as a multi-functional seasoning ingredient having potential antioxidant activity. PMID:24587529

  20. Discovery of Compound A - a selective activator of the glucocorticoid receptor with anti-inflammatory and anti-cancer activity.

    PubMed

    Lesovaya, Ekaterina; Yemelyanov, Alexander; Swart, Amanda C; Swart, Pieter; Haegeman, Guy; Budunova, Irina

    2015-10-13

    Glucocorticoids are among the most effective anti-inflammatory drugs, and are widely used for cancer therapy. Unfortunately, chronic treatment with glucocorticoids results in multiple side effects. Thus, there was an intensive search for selective glucocorticoid receptor (GR) activators (SEGRA), which retain therapeutic potential of glucocorticoids, but with fewer adverse effects. GR regulates gene expression by transactivation (TA), by binding as homodimer to gene promoters, or transrepression (TR), via diverse mechanisms including negative interaction between monomeric GR and other transcription factors. It is well accepted that metabolic and atrophogenic effects of glucocorticoids are mediated by GR TA. Here we summarized the results of extensive international collaboration that led to discovery and characterization of Compound A (CpdA), a unique SEGRA with a proven "dissociating" GR ligand profile, preventing GR dimerization and shifting GR activity towards TR both in vitro and in vivo. We outlined here the unusual story of compound's discovery, and presented a comprehensive overview of CpdA ligand properties, its anti-inflammatory effects in numerous animal models of inflammation and autoimmune diseases, as well as its anti-cancer effects. Finally, we presented mechanistic analysis of CpdA and glucocorticoid effects in skin, muscle, bone, and regulation of glucose and fat metabolism to explain decreased CpdA side effects compared to glucocorticoids. Overall, the results obtained by our and other laboratories underline translational potential of CpdA and its derivatives for treatment of inflammation, autoimmune diseases and cancer. PMID:26436695

  1. Characterization of the potent in vitro and in vivo antimalarial activities of ionophore compounds.

    PubMed Central

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

    1997-01-01

    Large-scale in vitro screening of different types of ionophores previously pinpointed nine compounds that were very active and selective in vitro against Plasmodium falciparum; their in vitro and in vivo antimalarial effects were further studied. Addition of the ionophores to synchronized P. falciparum suspensions revealed that all P. falciparum stages were sensitive to the drugs. However, the schizont stages were three- to ninefold more sensitive, and 12 h was required for complete parasite clearance. Pretreatment of healthy erythrocytes with toxic doses of ionophores for 24 to 48 h showed that the activity was not due to an irreversible effect on the host erythrocyte. No preferential ionophore adsorption in infected or uninfected erythrocytes occurred. On the other hand, ionophore molecules strongly bound to serum proteins since increasing the serum concentration from 2 to 50% led to almost a 25-fold parallel increase in the ionophore 50% inhibitory concentration. Mice infected with the malaria parasites Plasmodium vinckei petteri or Plasmodium chabaudi were successfully treated with eight ionophores in a 4-day suppressive test. The 50% effective dose after intraperitoneal administration ranged from 0.4 to 4.1 mg/kg of body weight, and the therapeutic indices were about 5 for all ionophores except monensin A methyl ether, 5-bromo lasalocid A, and gramicidin D, whose therapeutic indices were 12, 18, and 344, respectively. These three compounds were found to be curative, with no recrudescence. Gramicidin D, which presented impressive antimalarial activity, requires parenteral administration, while 5-bromo lasalocid A has the major advantage of being active after oral administration. Overall, the acceptable levels of toxicity and the good in vivo therapeutic indices in the rodent model highlight the interesting potential of these ionophores for the treatment of malaria in higher animals. PMID:9055986

  2. Biomedical Activity and Related Volatile Compounds of Thai Honeys from 3 Different Honeybee Species.

    PubMed

    Pattamayutanon, Praetinee; Angeli, Sergio; Thakeow, Prodpran; Abraham, John; Disayathanoowat, Terd; Chantawannakul, Panuwan

    2015-10-01

    This study investigated the effect of 3 factors (floral source, honeybee species, and postcollection processing) that influence the antibacterial activity, free radical reduction, and other biochemical compositions of different honey types typical of Thailand. Honey samples from 3 honeybee species (Apis mellifera, Apis cerana, and Apis dorsata) were obtained from 9 floral sources (longan, wild flower, lychee, coffee, sunflower, sesame, bitter bush, para-rubber, and manuka as a control) in different regions of Thailand. These samples were evaluated for both their total and nonperoxide antibacterial activity against 10 human pathogens by agar incorporation technique. Honey samples were further analyzed to evaluate the capacity for free radical-scavenging activity, total phenolic content, and the total flavonoid contents by the 2,2-diphenyl-1-picrylhydrazyl assay, Folin-Ciocalteu method, and aluminum chloride colorimetric assay, respectively. Furthermore, the volatile organic compounds (VOCs) of Thai honey samples were investigated by headspace solid-phase microextraction and gas chromatography-mass spectrometry analysis. Findings of this study suggest a strong correlation between floral origin and honeybee species on one hand, and differences in %Brix, total acidity, protein content, antimicrobial activities, free radical reduction, phenolic, and flavonoid contents on the other hand. Moreover, VOCs of wild and coffee honey types were remarkably different, depending on the floral source. Both honeys contained characteristics of VOCs, some of which are involved in antibacterial and antioxidant activities. PMID:26317173

  3. Identification of the possible new odor-active compounds "12-methyltridecanal and its analogs" responsible for the characteristic aroma of ripe Gouda-type cheese.

    PubMed

    Inagaki, Satsuki; Fujikawa, Seiji; Wada, Yoshiyuki; Kumazawa, Kenji

    2015-12-01

    The aroma concentrates of the three maturation stages of Gouda-type cheeses were prepared by combining the solvent extraction and the solvent assisted flavor evaporation techniques. The aroma extract dilution analysis applied to the volatile fraction revealed 31 odorants that were identified or tentatively identified from the 38 odor-active peaks with FD factors between 4(3) and 4(8). By comparison with the FD factors in the three maturation stages of the cheeses, 16 odorants, including 12-methyltridecanal, which is a newly identified odorant from the cheese, increased with the increasing maturation stage of the cheese. In addition, many iso- and anteiso-methyl-branched long-chain aliphatic aldehydes could be identified as the analogs of 12-methyltridecanal, which have a unique odor note. It may be then expected that these aldehydes were able to influence the flavor of the highly ripened Gouda cheese, since these compounds also increased with the increasing maturation stage. PMID:26223460

  4. Design, synthesis and biological evaluation of hydroxy substituted amino chalcone compounds for antityrosinase activity in B16 cells.

    PubMed

    Radhakrishnan, Sini; Shimmon, Ronald; Conn, Costa; Baker, Anthony

    2015-10-01

    A series of hydroxy substituted amino chalcone compounds have been synthesized. These compounds were then evaluated for their inhibitory activities on tyrosinase and melanogenesis in murine B16F10 melanoma cell lines. The structures of the compounds synthesized were confirmed by (1)H NMR, (13)C NMR, FTIR and HRMS. Two novel amino chalcone compounds exhibited higher tyrosinase inhibitory activities (IC50 values of 9.75?M and 7.82?M respectively) than the control kojic acid (IC50: 22.83?M). Kinetic studies revealed them to act as competitive tyrosinase inhibitors with their Ki values of 4.82?M and 1.89?M respectively. Both the compounds inhibited melanin production and tyrosinase activity in B16 cells. Docking results confirm that the active inhibitors strongly interact with mushroom tyrosinase residues. This study suggests that the depigmenting effect of novel amino chalcone compounds might be attributable to inhibition of tyrosinase activity, suggesting amino chalcones to be a promising candidate for use as depigmentation agents or as anti-browning food additives. PMID:26333206

  5. Differential activation of an identified motor neuron and neuromodulation provide Aplysia's retractor muscle an additional function

    PubMed Central

    McManus, Jeffrey M.; Lu, Hui; Cullins, Miranda J.

    2014-01-01

    To survive, animals must use the same peripheral structures to perform a variety of tasks. How does a nervous system employ one muscle to perform multiple functions? We addressed this question through work on the I3 jaw muscle of the marine mollusk Aplysia californica's feeding system. This muscle mediates retraction of Aplysia's food grasper in multiple feeding responses and is innervated by a pool of identified neurons that activate different muscle regions. One I3 motor neuron, B38, is active in the protraction phase, rather than the retraction phase, suggesting the muscle has an additional function. We used intracellular, extracellular, and muscle force recordings in several in vitro preparations as well as recordings of nerve and muscle activity from intact, behaving animals to characterize B38's activation of the muscle and its activity in different behavior types. We show that B38 specifically activates the anterior region of I3 and is specifically recruited during one behavior, swallowing. The function of this protraction-phase jaw muscle contraction is to hold food; thus the I3 muscle has an additional function beyond mediating retraction. We additionally show that B38's typical activity during in vivo swallowing is insufficient to generate force in an unmodulated muscle and that intrinsic and extrinsic modulation shift the force-frequency relationship to allow contraction. Using methods that traverse levels from individual neuron to muscle to intact animal, we show how regional muscle activation, differential motor neuron recruitment, and neuromodulation are key components in Aplysia's generation of multifunctionality. PMID:24805081

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

    PubMed Central

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

    2015-01-01

    Objectives To investigate the antistaphylococcal/antibiofilm activity and mode of action (MOA) of a panel of redox-active (RA) compounds with a history of human use and to provide a preliminary preclinical assessment of their potential for topical treatment of staphylococcal infections, including those involving a biofilm component. Methods Antistaphylococcal activity was evaluated by broth microdilution and by time–kill studies with growing and slow- or non-growing cells. The antibiofilm activity of RA compounds, alone and in combination with established antibacterial agents, was assessed using the Calgary Biofilm Device. Established assays were used to examine the membrane-perturbing effects of RA compounds, to measure penetration into biofilms and physical disruption of biofilms and to assess resistance potential. A living skin equivalent model was used to assess the effects of RA compounds on human skin. Results All 15 RA compounds tested displayed antistaphylococcal activity against planktonic cultures (MIC 0.25–128 mg/L) and 7 eradicated staphylococcal biofilms (minimum biofilm eradication concentration 4–256 mg/L). The MOA of all compounds involved perturbation of the bacterial membrane, whilst selected compounds with antibiofilm activity caused destructuring of the biofilm matrix. The two most promising agents [celastrol and nordihydroguaiaretic acid (NDGA)] in respect of antibacterial potency and selective toxicity against bacterial membranes acted synergistically with gentamicin against biofilms, did not damage artificial skin following topical application and exhibited low resistance potential. Conclusions In contrast to established antibacterial drugs, some RA compounds are capable of eradicating staphylococcal biofilms. Of these, celastrol and NDGA represent particularly attractive candidates for development as topical antistaphylococcal biofilm treatments. PMID:25368206

  7. Cerebroside D, a glycoceramide compound, improves experimental colitis in mice with multiple targets against activated T lymphocytes

    SciTech Connect

    Wu, Xue-Feng; Wu, Xing-Xin; Guo, Wen-Jie; Luo, Qiong; Gu, Yan-Hong; Shen, Yan; Tan, Ren-Xiang; Sun, Yang; Xu, Qiang

    2012-09-15

    In the present paper, we aimed to examine the novel effects of cerebroside D, a glycoceramide compound, on murine experimental colitis. Cerebroside D significantly reduced the weight loss, mortality rate and alleviated the macroscopic and microscopic appearances of colitis induced by dexran sulfate sodium. This compound also decreased the levels of TNF-?, IFN-? and IL-1? in intestinal tissue of mice with experimental colitis in a concentration-dependent manner, accompanied with markedly increased serum level of IL-10. Cerebroside D inhibited proliferation and induced apoptosis of T cells activated by concanavalin A or anti-CD3 plus anti-CD28 antibodies. The compound did not show an effect on naive lymphocytes but prevented cells from entering S phase and G2/M phase during T cells activation. Moreover, the treatment of cerebroside D led to apoptosis of activated T cells with the cleavage of caspase 3, 9, 12 and PARP. These results showed multiple effects of cerebroside D against activated T cells for a novel approach to treatment of colonic inflammation. Highlights: ? Cerebroside D, a glycoceramide compound, alleviated DSS induced colitis. ? The mechanism of the compound involved multiple effects against activated T cells. ? It regulated cytokine profiles in mice with experimental colitis. ? It prevented T cells from entering S and G2/M phases during activation. ? It led to apoptosis of activated T cells with the cleavage of caspases and PARP.

  8. Identifying functional co-activation patterns in neuroimaging studies via poisson graphical models.

    PubMed

    Xue, Wenqiong; Kang, Jian; Bowman, F DuBois; Wager, Tor D; Guo, Jian

    2014-12-01

    Studying the interactions between different brain regions is essential to achieve a more complete understanding of brain function. In this article, we focus on identifying functional co-activation patterns and undirected functional networks in neuroimaging studies. We build a functional brain network, using a sparse covariance matrix, with elements representing associations between region-level peak activations. We adopt a penalized likelihood approach to impose sparsity on the covariance matrix based on an extended multivariate Poisson model. We obtain penalized maximum likelihood estimates via the expectation-maximization (EM) algorithm and optimize an associated tuning parameter by maximizing the predictive log-likelihood. Permutation tests on the brain co-activation patterns provide region pair and network-level inference. Simulations suggest that the proposed approach has minimal biases and provides a coverage rate close to 95% of covariance estimations. Conducting a meta-analysis of 162 functional neuroimaging studies on emotions, our model identifies a functional network that consists of connected regions within the basal ganglia, limbic system, and other emotion-related brain regions. We characterize this network through statistical inference on region-pair connections as well as by graph measures. PMID:25147001

  9. Antioxidant activity of phenolics compounds from sugar cane (Saccharum officinarum L.) juice.

    PubMed

    Maurício Duarte-Almeida, Joaquim; Novoa, Alexis Vidal; Linares, Adyary Fallarero; Lajolo, Franco M; Inés Genovese, Maria

    2006-12-01

    Phenolic compounds in sugar cane (Saccharum officinarum L.) juice were identified and quantified by analytical high performance liquid chromatography and photodiode array detection, showing the predominance of flavones (apigenin, luteolin and tricin derivatives), among flavonoids, and of hydroxycinnamic, caffeic and sinapic acids, among phenolic acids, representing a total content of around 160 mg/L. A tricin derivative was present in the highest proportion (>10% of the total). The phenolic extract obtained from sugar cane juice showed a protective effect against in vivo MeHgCl intoxication and potent inhibition of ex vivo lipoperoxidation of rat brain homogenates, indicating a potential use for beneficial health effects and/or therapeutic applications. PMID:17123161

  10. Transcriptome Analysis of Pseudomonas syringae Identifies New Genes, Noncoding RNAs, and Antisense Activity? †

    PubMed Central

    Filiatrault, Melanie J.; Stodghill, Paul V.; Bronstein, Philip A.; Moll, Simon; Lindeberg, Magdalen; Grills, George; Schweitzer, Peter; Wang, Wei; Schroth, Gary P.; Luo, Shujun; Khrebtukova, Irina; Yang, Yong; Thannhauser, Theodore; Butcher, Bronwyn G.; Cartinhour, Samuel; Schneider, David J.

    2010-01-01

    To fully understand how bacteria respond to their environment, it is essential to assess genome-wide transcriptional activity. New high-throughput sequencing technologies make it possible to query the transcriptome of an organism in an efficient unbiased manner. We applied a strand-specific method to sequence bacterial transcripts using Illumina's high-throughput sequencing technology. The resulting sequences were used to construct genome-wide transcriptional profiles. Novel bioinformatics analyses were developed and used in combination with proteomics data for the qualitative classification of transcriptional activity in defined regions. As expected, most transcriptional activity was consistent with predictions from the genome annotation. Importantly, we identified and confirmed transcriptional activity in areas of the genome inconsistent with the annotation and in unannotated regions. Further analyses revealed potential RpoN-dependent promoter sequences upstream of several noncoding RNAs (ncRNAs), suggesting a role for these ncRNAs in RpoN-dependent phenotypes. We were also able to validate a number of transcriptional start sites, many of which were consistent with predicted promoter motifs. Overall, our approach provides an efficient way to survey global transcriptional activity in bacteria and enables rapid discovery of specific areas in the genome that merit further investigation. PMID:20190049

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

    PubMed Central

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

    2014-01-01

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

  12. Review of the Inhibition of Biological Activities of Food-Related Selected Toxins by Natural Compounds

    PubMed Central

    Friedman, Mendel; Rasooly, Reuven

    2013-01-01

    There is a need to develop food-compatible conditions to alter the structures of fungal, bacterial, and plant toxins, thus transforming toxins to nontoxic molecules. The term ‘chemical genetics’ has been used to describe this approach. This overview attempts to survey and consolidate the widely scattered literature on the inhibition by natural compounds and plant extracts of the biological (toxicological) activity of the following food-related toxins: aflatoxin B1, fumonisins, and ochratoxin A produced by fungi; cholera toxin produced by Vibrio cholerae bacteria; Shiga toxins produced by E. coli bacteria; staphylococcal enterotoxins produced by Staphylococcus aureus bacteria; ricin produced by seeds of the castor plant Ricinus communis; and the glycoalkaloid ?-chaconine synthesized in potato tubers and leaves. The reduction of biological activity has been achieved by one or more of the following approaches: inhibition of the release of the toxin into the environment, especially food; an alteration of the structural integrity of the toxin molecules; changes in the optimum microenvironment, especially pH, for toxin activity; and protection against adverse effects of the toxins in cells, animals, and humans (chemoprevention). The results show that food-compatible and safe compounds with anti-toxin properties can be used to reduce the toxic potential of these toxins. Practical applications and research needs are suggested that may further facilitate reducing the toxic burden of the diet. Researchers are challenged to (a) apply the available methods without adversely affecting the nutritional quality, safety, and sensory attributes of animal feed and human food and (b) educate food producers and processors and the public about available approaches to mitigating the undesirable effects of natural toxins that may present in the diet. PMID:23612750

  13. Antimalarial Activity of Allicin, a Biologically Active Compound from Garlic Cloves

    PubMed Central

    Coppi, Alida; Cabinian, Melissa; Mirelman, David; Sinnis, Photini

    2006-01-01

    The incidence of malaria is increasing, and there is an urgent need to identify new drug targets for both prophylaxis and chemotherapy. Potential new drug targets include Plasmodium proteases that play critical roles in the parasite life cycle. We have previously shown that the major surface protein of Plasmodium sporozoites, the circumsporozoite protein (CSP), is proteolytically processed by a parasite-derived cysteine protease, and this processing event is temporally associated with sporozoite invasion of host cells. E-64, a cysteine protease inhibitor, inhibits CSP processing and prevents invasion of host cells in vitro and in vivo. Here we tested allicin, a cysteine protease inhibitor found in garlic extracts, for its ability to inhibit malaria infection. At low concentrations, allicin was not toxic to either sporozoites or mammalian cells. At these concentrations, allicin inhibited CSP processing and prevented sporozoite invasion of host cells in vitro. In vivo, mice injected with allicin had decreased Plasmodium infections compared to controls. When sporozoites were treated with allicin before injection into mice, malaria infection was completely prevented. We also tested allicin on erythrocytic stages and found that a 4-day regimen of allicin administered either orally or intravenously significantly decreased parasitemias and increased the survival of infected mice by 10 days. Together, these experiments demonstrate that the same cysteine protease inhibitor can target two different life cycle stages in the vertebrate host. PMID:16641443

  14. Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies

    PubMed Central

    de Souza, Nicolli Bellotti; de Andrade, Isabel M; Carneiro, Paula F; Jardim, Guilherme AM; de Melo, Isadora MM; da Silva, Eufrânio N; Krettli, Antoniana Ursine

    2014-01-01

    Due to the recent advances of atovaquone, a naphthoquinone, through clinical trials as treatment for malarial infection, 19 quinone derivatives with previously reported structures were also evaluated for blood schizonticide activity against the malaria parasite Plasmodium falciparum. These compounds include 2-hydroxy-3-methylamino naphthoquinones (2-9), lapachol (10), nor-lapachol (11), iso-lapachol (12), phthiocol (13) and phenazines (12-20). Their cytotoxicities were also evaluated against human hepatoma and normal monkey kidney cell lines. Compounds 2 and 5 showed the highest activity against P. falciparum chloroquine-resistant blood-stage parasites (clone W2), indicated by their low inhibitory concentration for 50% (IC50) of parasite growth. The therapeutic potential of the active compounds was evaluated according to the selectivity index, which is a ratio of the cytotoxicity minimum lethal dose which eliminates 50% of cells and the in vitro IC50. Naphthoquinones 2 and 5, with activities similar to the reference antimalarial chloroquine, were also active against malaria in mice and suppressed parasitaemia by more than 60% in contrast to compound 11 which was inactive. Based on their in vitro and in vivo activities, compounds 2 and 5 are considered promising molecules for antimalarial treatment and warrant further study. PMID:25099332

  15. Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies.

    PubMed

    de Souza, Nicolli Bellotti; de Andrade, Isabel M; Carneiro, Paula F; Jardim, Guilherme A M; de Melo, Isadora M M; da Silva Júnior, Eufrânio N; Krettli, Antoniana Ursine

    2014-08-01

    Due to the recent advances of atovaquone, a naphthoquinone, through clinical trials as treatment for malarial infection, 19 quinone derivatives with previously reported structures were also evaluated for blood schizonticide activity against the malaria parasite Plasmodium falciparum. These compounds include 2-hydroxy-3-methylamino naphthoquinones (2-9), lapachol (10), nor-lapachol (11), iso-lapachol (12), phthiocol (13) and phenazines (12-20). Their cytotoxicities were also evaluated against human hepatoma and normal monkey kidney cell lines. Compounds 2 and 5 showed the highest activity against P. falciparum chloroquine-resistant blood-stage parasites (clone W2), indicated by their low inhibitory concentration for 50% (IC50) of parasite growth. The therapeutic potential of the active compounds was evaluated according to the selectivity index, which is a ratio of the cytotoxicity minimum lethal dose which eliminates 50% of cells and the in vitro IC50. Naphthoquinones 2 and 5, with activities similar to the reference antimalarial chloroquine, were also active against malaria in mice and suppressed parasitaemia by more than 60% in contrast to compound 11 which was inactive. Based on their in vitro and in vivo activities, compounds 2 and 5 are considered promising molecules for antimalarial treatment and warrant further study. PMID:25099332

  16. A computational approach predicting CYP450 metabolism and estrogenic activity of an endocrine disrupting compound (PCB-30).

    PubMed

    Harris, Jason B; Eldridge, Melanie L; Sayler, Gary; Menn, Fu-Min; Layton, Alice C; Baudry, Jerome

    2014-07-01

    Endocrine disrupting chemicals influence growth and development through interactions with the hormone system, often through binding to hormone receptors such as the estrogen receptor. Computational methods can predict endocrine disrupting chemical activity of unmodified compounds, but approaches predicting activity following metabolism are lacking. The present study uses a well-known environmental contaminant, PCB-30 (2,4,6-trichlorobiphenyl), as a prototype endocrine disrupting chemical and integrates predictive (computational) and experimental methods to determine its metabolic transformation by cytochrome P450 3A4 (CYP3A4) and cytochrome P450 2D6 (CYP2D6) into estrogenic byproducts. Computational predictions suggest that hydroxylation of PCB-30 occurs at the 3- or 4-phenol positions and leads to metabolites that bind more strongly than the parent molecule to the human estrogen receptor alpha (hER-?). Gas chromatography-mass spectrometry experiments confirmed that the primary metabolite for CYP3A4 and CYP2D6 is 4-hydroxy-PCB-30, and the secondary metabolite is 3-hydroxy-PCB-30. Cell-based bioassays (bioluminescent yeast expressing hER-?) confirmed that hydroxylated metabolites are more estrogenic than PCB-30. These experimental results support the applied model's ability to predict the metabolic and estrogenic fate of PCB-30, which could be used to identify other endocrine disrupting chemicals involved in similar pathways. PMID:24687371

  17. Using time-driven activity-based costing to identify value improvement opportunities in healthcare.

    PubMed

    Kaplan, Robert S; Witkowski, Mary; Abbott, Megan; Guzman, Alexis Barboza; Higgins, Laurence D; Meara, John G; Padden, Erin; Shah, Apurva S; Waters, Peter; Weidemeier, Marco; Wertheimer, Sam; Feeley, Thomas W

    2014-01-01

    As healthcare providers cope with pricing pressures and increased accountability for performance, they should be rededicating themselves to improving the value they deliver to their patients: better outcomes and lower costs. Time-driven activity-based costing offers the potential for clinicians to redesign their care processes toward that end. This costing approach, however, is new to healthcare and has not yet been systematically implemented and evaluated. This article describes early time-driven activity-based costing work at several leading healthcare organizations in the United States and Europe. It identifies the opportunities they found to improve value for patients and demonstrates how this costing method can serve as the foundation for new bundled payment reimbursement approaches. PMID:25647962

  18. Organotin Compound Derived from 3-Hydroxy-2-formylpyridine Semicarbazone: Synthesis, Crystal Structure, and Antiproliferative Activity

    PubMed Central

    Wiecek, Joanna; Kovala-Demertzi, Dimitra; Ciunik, Zbigniew; Wietrzyk, Joanna; Zervou, Maria; Demertzis, Mavroudis A.

    2010-01-01

    The novel diphenyltin(IV) compound [Ph2(HyFoSc)Sn] (2), where H2HyFoSc (1) is 3-hydroxy-2-formylpyridine semicarbazone, was prepared and characterized by vibrational and NMR (1H, 13C) spectroscopy. The structure of [Ph2(HyFoSc)Sn] was confirmed by single-crystal X-ray crystallography. The doubly deprotonated ligand is coordinated to the tin atom through the enolic-oxygen, the azomethine-nitrogen, and phenolic-oxygen, and so acts as an anionic tridentate ligand with the ONO donors. Two carbon atoms complete the fivefold coordination at the tin(IV) center. Intermolecular hydrogen bonding, C–H ? ?, and ? ? ? interactions combine to stabilize the crystal structure. Compounds 1 and 2 have been evaluated for antiproliferative activity in vitro against the cells of three human tumor cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A549 (nonsmall cell lung carcinoma), and a mouse fibroblast L-929 cancer cell line. PMID:20490260

  19. Assessing the Protective Activity of a Recently Discovered Phenolic Compound against Oxidative Stress Using Computational Chemistry.

    PubMed

    Villuendas-Rey, Yenny; Alvarez-Idaboy, Juan Raul; Galano, Annia

    2015-12-28

    The protection exerted by 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), a phenolic compound recently isolated from the Pacific oyster, against oxidative stress (OS) is investigated using the density functional theory. Our results indicate that DHMBA is an outstanding peroxyl radical scavenger, being about 15 times and 4 orders of magnitude better than Trolox for that purpose in lipid and aqueous media, respectively. It was also found to react faster with HOO(•) than other known antioxidants such as resveratrol and ascorbic acid. DHMBA is also predicted to be able to sequester Cu(II) ions, consequently inhibiting the OS induced by Cu(II)-ascorbate mixtures and downgrading the (•)OH production via the Haber-Weiss reaction. However, it is proposed that DHMBA is more efficient as a primary antioxidant (free radical scavenger), than as a secondary antioxidant (metal ion chelator). In addition, it was found that DHMBA can be efficiently regenerated in aqueous solution, at physiological pH. Such regeneration is expected to contribute to increase the antioxidant protection exerted by DHMBA. These results suggest that probably synthetic routes for this compound should be pursued, because albeit its abundance in nature is rather low, its antioxidant activity is exceptional. PMID:26624520

  20. Comparative study of phenolic compounds and antioxidant activity in different species of cherries.

    PubMed

    Liu, Yun; Liu, Xinyan; Zhong, Fei; Tian, Rongrong; Zhang, Kaichun; Zhang, Xiaoming; Li, Tianhong

    2011-05-01

    A new spectrometric method ultra performance liquid chromatography-tandem mass spectrometric with high precision and rapid analysis was developed to separate 17 phenolic compounds. Different species of cherries, including 10 sweet cherry (Prunus avium L.) cultivars, a tart cherry (P. cerasus L.) rootstock (CAB), and a hybrid rootstock 'Colt' (P. avium × P. pseudocerasus), were analyzed for phenolics contents by this method. The results showed that significant differences were observed among the phenolic compound contents in different cherry species. In 10 sweet cherry cultivars, the contents of neochlorogenic acid and cyanidin-3O-rutinoside were much higher in red-colored fruits (for example, 64.60 and 44.50 mg/100 g fresh weight in Burlat, respectively) than those in bicolored ones. Principal component analysis revealed that cyanidin-3O-rutinoside was an effective index for grouping the cultivars with similar species and fruit colors. Moreover, there were strong positive correlations between phenolics content and antioxidant activity, which was higher in red-colored cherries. PMID:22417346

  1. Effect of Polymer Micelles on Antifungal Activity of Geranylorcinol Compounds against Botrytis cinerea.

    PubMed

    Taborga, Lautaro; Díaz, Katy; Olea, Andrés F; Reyes-Bravo, Paula; Flores, Mario E; Peña-Cortés, Hugo; Espinoza, Luis

    2015-08-12

    Herein, we explore the potential use of two micelle-forming block copolymers, i.e., Pluronic F-127 and poly(ethylene oxide)-b-poly(caprolactone), for application of fungicide agents. The polymer effect on the in vitro fungicide activity of a series of geranyl orcinol derivatives against Botrytis cinerea has been assessed. The results show that, for all test compounds, the incorporation into micelles, formed by Pluronic F-127, produces a great enhancement of the inhibitory effect on the growth of B. cinerea. For some compounds, at the lowest tested concentration (50 ppm), the percentage of inhibition increases significantly (from 0-10 to 80-90%) when the application is made using a polymer solution instead of an ethanol/water mixture. The synthesis and structural determination of a series of eight geranylphenols/diacetates, which were used as fungicide agents, are also discussed. These results suggest that polymer micelles are promising systems for application of crop-protecting agents. PMID:26196664

  2. Occurrence, bioaccumulation, and trophic magnification of pharmaceutically active compounds in Taihu Lake, China.

    PubMed

    Xie, Zhengxin; Lu, Guanghua; Liu, Jianchao; Yan, Zhenhua; Ma, Binni; Zhang, Zhenghua; Chen, Wei

    2015-11-01

    The occurrence, bioaccumulation, and trophic magnification of pharmaceutically active compounds, (PhACs) including antibiotics (roxithromycin and erythromycin), non-steroidal anti-inflammatory drugs (ibuprofen and diclofenac), a non-selective ?-adrenoceptor blocker (propranolol), an antiepileptic drug (carbamazepine), and steroid estrogens (17?-estradiol and 17?-ethynylestradiol), were investigated in Taihu Lake, China. All eight PhACs were widely detected in surface water and sediment samples with maximal concentrations in the range of 8.74-118 ng L(-1) and 0.78-42.5 ng g(-1) dry weight (dw), respectively. The investigated organisms in the natural freshwater food web in Taihu Lake included phytoplankton, zooplankton, zoobenthos, and fish, and the maximal concentrations of target compounds in these biota samples ranged from 0.65 to 132 ng g(-1) dw. Bioaccumulation factors (BAFs) for all target PhACs were lower than 1000 L kg(-1), suggesting their low bioaccumulation potential in aquatic organisms from Taihu Lake. Trophic magnification factors (TMFs) were estimated at 1.11 for roxithromycin, 0.31 for propranolol, and 1.06 for diclofenac, indicating none of these PhACs underwent trophic magnification in this freshwater food web. PMID:26070079

  3. Follow-up: Prospective compound design using the 'SAR Matrix' method and matrix-derived conditional probabilities of activity.

    PubMed

    Gupta-Ostermann, Disha; Hirose, Yoichiro; Odagami, Takenao; Kouji, Hiroyuki; Bajorath, Jürgen

    2015-01-01

    In a previous Method Article, we have presented the 'Structure-Activity Relationship (SAR) Matrix' (SARM) approach. The SARM methodology is designed to systematically extract structurally related compound series from screening or chemical optimization data and organize these series and associated SAR information in matrices reminiscent of R-group tables. SARM calculations also yield many virtual candidate compounds that form a "chemical space envelope" around related series. To further extend the SARM approach, different methods are developed to predict the activity of virtual compounds. In this follow-up contribution, we describe an activity prediction method that derives conditional probabilities of activity from SARMs and report representative results of first prospective applications of this approach. PMID:25949808

  4. Follow-up: Prospective compound design using the ‘SAR Matrix’ method and matrix-derived conditional probabilities of activity

    PubMed Central

    Gupta-Ostermann, Disha; Hirose, Yoichiro; Odagami, Takenao; Kouji, Hiroyuki; Bajorath, Jürgen

    2015-01-01

    In a previous Method Article, we have presented the ‘Structure-Activity Relationship (SAR) Matrix’ (SARM) approach. The SARM methodology is designed to systematically extract structurally related compound series from screening or chemical optimization data and organize these series and associated SAR information in matrices reminiscent of R-group tables. SARM calculations also yield many virtual candidate compounds that form a “chemical space envelope” around related series. To further extend the SARM approach, different methods are developed to predict the activity of virtual compounds. In this follow-up contribution, we describe an activity prediction method that derives conditional probabilities of activity from SARMs and report representative results of first prospective applications of this approach. PMID:25949808

  5. Functional analysis of TPM domain containing Rv2345 of Mycobacterium tuberculosis identifies its phosphatase activity.

    PubMed

    Sinha, Avni; Eniyan, Kandasamy; Sinha, Swati; Lynn, Andrew Michael; Bajpai, Urmi

    2015-07-01

    Mycobacterium tuberculosis (Mtb) is the causal agent of tuberculosis, the second largest infectious disease. With the rise of multi-drug resistant strains of M. tuberculosis, serious challenge lies ahead of us in treating the disease. The availability of complete genome sequence of Mtb has improved the scope for identifying new proteins that would not only further our understanding of biology of the organism but could also serve to discover new drug targets. In this study, Rv2345, a hypothetical membrane protein of M. tuberculosis H37Rv, which is reported to be a putative ortholog of ZipA cell division protein has been assigned function through functional annotation using bioinformatics tools followed by experimental validation. Sequence analysis showed Rv2345 to have a TPM domain at its N-terminal region and predicted it to have phosphatase activity. The TPM domain containing region of Rv2345 was cloned and expressed using pET28a vector in Escherichia coli and purified by Nickel affinity chromatography. The purified TPM domain was tested in vitro and our results confirmed it to have phosphatase activity. The enzyme activity was first checked and optimized with pNPP as substrate, followed by using ATP, which was also found to be used as substrate by the purified protein. Hence sequence analysis followed by in vitro studies characterizes TPM domain of Rv2345 to contain phosphatase activity. PMID:25782739

  6. Altered Endoribonuclease Activity of Apurinic/Apyrimidinic Endonuclease 1 Variants Identified in the Human Population

    PubMed Central

    Kim, Wan Cheol; Ma, Conan; Li, Wai-Ming; Chohan, Manbir; Wilson III, David M.; Lee, Chow H.

    2014-01-01

    Apurinic/apyrimidinic endonuclease 1 (APE1) is the major mammalian enzyme in the DNA base excision repair pathway and cleaves the DNA phosphodiester backbone immediately 5? to abasic sites. APE1 also has 3?-5? DNA exonuclease and 3? DNA phosphodiesterase activities, and regulates transcription factor DNA binding through its redox regulatory function. The human APE1 has recently been shown to endonucleolytically cleave single-stranded regions of RNA. Towards understanding the biological significance of the endoribonuclease activity of APE1, we examined eight different amino acid substitution variants of APE1 previously identified in the human population. Our study shows that six APE1 variants, D148E, Q51H, I64V, G241R, R237A, and G306A, exhibit a 76–85% reduction in endoribonuclease activity against a specific coding region of the c-myc RNA, yet fully retain the ability to cleave apurinic/apyrimidinic DNA. We found that two APE1 variants, L104R and E126D, exhibit a unique RNase inhibitor-resistant endoribonuclease activity, where the proteins cleave c-myc RNA 3? of specific single-stranded guanosine residues. Expression of L104R and E126D APE1 variants in bacterial Origami cells leads to a 60–80% reduction in colony formation and a 1.5-fold increase in cell doubling time, whereas the other variants, which exhibit diminished endoribonuclease activity, had no effect. These data indicate that two human APE1 variants exhibit a unique endoribonuclease activity, which correlates with their ability to induce cytotoxicity or slow down growth in bacterial cells and supports the notion of their biological functionality. PMID:24595156

  7. Inter- and intraspecific activities of compounds derived from sex pheromone glands of currant borer, Synanthedon tipuliformis (Clerck) (Lepidoptera: Sesiidae).

    PubMed

    Moz?raitis, Raimondas; Karalius, Vidmantas; B?da, Vincas; Borg-Karlson, Anna-Karin

    2006-01-01

    Gas chromatography and mass spectrometry analyses of crude sex pheromone gland extracts revealed that virgin Synanthedon tipuliformis (Clerck), currant borer (Lepidoptera: Sesiidae) females, produced 6 compounds, structurally related to sex pheromone components of clearwing moths. By comparison of retention times and mass spectra of natural products with corresponding properties of synthetic standards, these compounds were identified as: (2E,13Z)-octadeca-2,13-dien-1-yl acetate (E2,Z13-18:OAc), (3E,13Z)-octadeca-3,13-dien-1-yl acetate (E3,Z13-18:OAc), (13Z)-octadec-13-en-1-yl acetate (Z13-18:OAc), (2E,13Z)-octadeca-2,13-dien-1-ol (E2,Z13-18:OH), (13Z)-octadec-13-en-1-ol (Z13-18:OH) and octadecan-1-ol (18:OH) in the ratio 100:0.7:2.7:3.2:traces:traces. The first 3 compounds were previously known to occur in the sex pheromone gland extracts of currant borers, while the last 3 chemicals are now reported for the first time. Trapping tests carried out in the black currant field revealed that E2,Z13-18:OAc, when tested separately, attracted S. tipuliformis males, while addition of E3,Z13-18:OAc to the main component increased the effectiveness of E2,Z13-18:OAc over seven times. The attractiveness of 6 component lures did not differ significantly from the one of the binary mixture, confirming that E2,Z13-18:OAc and E3,Z13-18:OAc in the ratio100:0.7 are essential sex pheromone components of S. tipuliformis. Trapping tests carried out at the dwelling place of Synanthedon scoliaeformis (Borkhausen) (Lepidoptera: Sesiidae) revealed that, in addition to intraspecific synergistic effect, E3,Z13-18:OAc increased the specificity of the pheromone signal of S. tipuliformis, acting by intraspecific mode as an attraction antagonist against S. scoliaeformis males. By this way, it ensured the specificity of the sex attraction signal of the currant borer. Consequently, both compounds E2,Z13-18:OAc and E3,Z13-18:OAc have to be present in pheromone formulations used for monitoring and/or control of S. tipuliformis to avoid effecting non-target species. Other compounds identified from the sex pheromone gland of S. tipuliformis did not show any significant interspecific activity for males of S. scoliaeformis, however, they provide a basis to achieve specificity of a pheromone signal of S. tipuliformis and could act as attraction antagonists against other clearwing moth species which, like S. tipuliformis, employ E2,Z13-18:OAc as their sex pheromone component. PMID:16729590

  8. Volatile Compounds in Honey: A Review on Their Involvement in Aroma, Botanical Origin Determination and Potential Biomedical Activities

    PubMed Central

    Manyi-Loh, Christy E.; Ndip, Roland N.; Clarke, Anna M.

    2011-01-01

    Volatile organic compounds (VOCs) in honey are obtained from diverse biosynthetic pathways and extracted by using various methods associated with varying degrees of selectivity and effectiveness. These compounds are grouped into chemical categories such as aldehyde, ketone, acid, alcohol, hydrocarbon, norisoprenoids, terpenes and benzene compounds and their derivatives, furan and pyran derivatives. They represent a fingerprint of a specific honey and therefore could be used to differentiate between monofloral honeys from different floral sources, thus providing valuable information concerning the honey’s botanical and geographical origin. However, only plant derived compounds and their metabolites (terpenes, norisoprenoids and benzene compounds and their derivatives) must be employed to discriminate among floral origins of honey. Notwithstanding, many authors have reported different floral markers for honey of the same floral origin, consequently sensory analysis, in conjunction with analysis of VOCs could help to clear this ambiguity. Furthermore, VOCs influence honey’s aroma described as sweet, citrus, floral, almond, rancid, etc. Clearly, the contribution of a volatile compound to honey aroma is determined by its odor activity value. Elucidation of the aroma compounds along with floral origins of a particular honey can help to standardize its quality and avoid fraudulent labeling of the product. Although only present in low concentrations, VOCS could contribute to biomedical activities of honey, especially the antioxidant effect due to their natural radical scavenging potential. PMID:22272147

  9. Research Resource: Modulators of Glucocorticoid Receptor Activity Identified by a New High-Throughput Screening Assay

    PubMed Central

    Blackford, John A.; Brimacombe, Kyle R.; Dougherty, Edward J.; Pradhan, Madhumita; Shen, Min; Li, Zhuyin; Auld, Douglas S.; Chow, Carson C.; Austin, Christopher P.

    2014-01-01

    Glucocorticoid steroids affect almost every type of tissue and thus are widely used to treat a variety of human pathological conditions. However, the severity of numerous side effects limits the frequency and duration of glucocorticoid treatments. Of the numerous approaches to control off-target responses to glucocorticoids, small molecules and pharmaceuticals offer several advantages. Here we describe a new, extended high-throughput screen in intact cells to identify small molecule modulators of dexamethasone-induced glucocorticoid receptor (GR) transcriptional activity. The novelty of this assay is that it monitors changes in both GR maximal activity (Amax) and EC50 (the position of the dexamethasone dose-response curve). Upon screening 1280 chemicals, 10 with the greatest changes in the absolute value of Amax or EC50 were selected for further examination. Qualitatively identical behaviors for 60% to 90% of the chemicals were observed in a completely different system, suggesting that other systems will be similarly affected by these chemicals. Additional analysis of the 10 chemicals in a recently described competition assay determined their kinetically defined mechanism and site of action. Some chemicals had similar mechanisms of action despite divergent effects on the level of the GR-induced product. These combined assays offer a straightforward method of identifying numerous new pharmaceuticals that can alter GR transactivation in ways that could be clinically useful. PMID:24850414

  10. Identifying transcription start sites and active enhancer elements using BruUV-seq

    PubMed Central

    Magnuson, Brian; Veloso, Artur; Kirkconnell, Killeen S.; Lima, Leonardo Carmo de Andrade; Paulsen, Michelle T.; Ljungman, Emily A.; Bedi, Karan; Prasad, Jayendra; Wilson, Thomas E.; Ljungman, Mats

    2015-01-01

    BruUV-seq utilizes UV light to introduce transcription-blocking DNA lesions randomly in the genome prior to bromouridine-labeling and deep sequencing of nascent RNA. By inhibiting transcription elongation, but not initiation, pre-treatment with UV light leads to a redistribution of transcription reads resulting in the enhancement of nascent RNA signal towards the 5?-end of genes promoting the identification of transcription start sites (TSSs). Furthermore, transcripts associated with arrested RNA polymerases are protected from 3?–5? degradation and thus, unstable transcripts such as putative enhancer RNA (eRNA) are dramatically increased. Validation of BruUV-seq against GRO-cap that identifies capped run-on transcripts showed that most BruUV-seq peaks overlapped with GRO-cap signal over both TSSs and enhancer elements. Finally, BruUV-seq identified putative enhancer elements induced by tumor necrosis factor (TNF) treatment concomitant with expression of nearby TNF-induced genes. Taken together, BruUV-seq is a powerful new approach for identifying TSSs and active enhancer elements genome-wide in intact cells. PMID:26656874

  11. Interaction of active compounds from Aegle marmelos CORREA with histamine-1 receptor

    PubMed Central

    Nugroho, Agung Endro; Agistia, Dany Dwi; Tegar, Maulana; Purnomo, Hari

    2013-01-01

    The aim of this study is to determine the affinity of six active compounds of Aegle Marmelos Correa, they are (E, R)-Marmin, skimmianine, (S)-aegeline, aurapten, zeorin, and dustanin as antihistamines in histamine H1 receptor in comparison to cetirizin, diphenhydramine and chlorpheniramine as ligands comparison. Previously, in the in vitro study marmin obviously antagonized the histamine H1 receptor in a competitive manner. Methods: molecular docking to determine the interaction of ligand binding to its receptor. Lower docking score indicates more stable binding to that protein. Results: Marmin, skimmianine, aegeline, aurapten, zeorin, and dustanin were potential to develop as antihistamine agents, especially as histamine H1 receptor antagonists by interacting with amino acid residues, Asp107, Lys179, Lys191, Asn198, and Trp428 of histamine H1 receptor. Conclusions: Based on molecular docking, Amino acid residues involved in ligand protein interactions were Asp107, Lys179, Lys191, Asn198, and Trp428. PMID:23750086

  12. Distribution of Phenolic Compounds and Antioxidative Activities of Rice Kernel and Their Relationships with Agronomic Practice

    PubMed Central

    Kesarwani, Amit; Chiang, Po-Yuan; Chen, Shih-Shiung

    2014-01-01

    The phenolic and antioxidant activity of ethanolic extract of two Japonica rice cultivars, Taikeng no. 16 (medium and slender grain) and Kaohsiung no. 139 (short and round grain), grown under organic and conventional farming were examined. Analyses shows that Kaohsiung no. 139 contains the highest amount of secondary metabolites and continuous farming can increase its production. Results also suggest that phenolic content under different agronomic practices, has not shown significant differences but organically grown rice has proven to be better in higher accumulation of other secondary metabolites (2,2-diphenyl-1-picrylhydrazyl (DPPH), flavonoid content, and ferrous chelating capacity). In nutshell, genetic traits and environment have significant effect on phenolic compounds and the least variation reported under agronomic practices. PMID:25506072

  13. Characterization of taste-active compounds of various cherry wines and their correlation with sensory attributes.

    PubMed

    Niu, Yunwei; Zhang, Xiaoming; Xiao, Zuobing; Song, Shiqing; Jia, Chengsheng; Yu, Haiyan; Fang, Lingling; Xu, Chunhua

    2012-08-01

    Five cherry wines exhibiting marked differences in taste and mouthfeel were selected for the study. The taste and mouthfeel of cherry wines were described by four sensory terms as sour, sweet, bitter and astringent. Eight organic acids, seventeen amino acids, three sugars and tannic acid were determined by high performance liquid chromatography (HPLC). Five phenolic acids were determined by ultra performance liquid chromatography coupled with mass spectrometry (UPLC-MS). The relationship between these taste-active compounds, wine samples and sensory attributes was modeled by partial least squares regression (PLSR). The regression analysis indicated tartaric acid, methionine, proline, sucrose, glucose, fructose, asparagines, serine, glycine, threonine, phenylalanine, leucine, gallic acid, chlorogenic acid, vanillic acid, arginine and tannic acid made a great contribution to the characteristic taste or mouthfeel of cherry wines. PMID:22795555

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

    PubMed Central

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

    2015-01-01

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

  15. Anaerobic activated carbon filter for the degradation of polycyclic N-aromatic compounds

    SciTech Connect

    Wang, Y.T.

    1984-12-01

    A simulated coal gasification wastewater containing polycyclic N-aromatics was successfully treated by a pilot-scale, anaerobic expanded-bed granular activated carbon filter. The wastewater contained 3 equal concentrations of indole, quinoline and methylquinoline: 50 mg/l, 150 mg/l and 300 mg/l, and the filter operated under these feed conditions for 881 days. Steady-state removal of COD and DOC exceeded 97 and 98%, respectively. The polycyclic N-aromatic compounds in the effluent were below detection limits until the last stage of the investigation: methylquinoline was the first influent to break through, followed by indole and quinoline. Methane was not detected until after 7 months of start-up. Gas production was reduced and later ceased.

  16. Separation of hydrophobic organic compound from surfactant solutions with activated carbon in a fixed bed.

    PubMed

    Liu, Jianfei; Chen, Jiajun; Jiang, Lin; Chen, Cheng

    2013-01-01

    The adsorption behavior of phenanthrene (PHE) in Triton X-100 (TX100) solutions with fixed activated carbon (AC) bed was studied to recover the surfactant. The effect of various parameters like bed depths, flow rates, influent TX100 concentration, and influent PHE concentration were investigated. The breakthrough time of both TX100 and PHE increased with the increase of bed height and decrease of flow rate and influent concentration. In the case of fixed length, a lower flow rate, higher concentration of TX100, and lower concentration of PHE will benefit the longer effective surfactant recovery time. The adsorption data were integrated into bed depth service time models. The height of exchange zone of TX100 should be much shorter than that of PHE, which provides conditions to separate the hydrophobic organic compound from surfactant solutions with AC in a fixed bed. It is likely that the adsorption process is controlled by hydrophobic interaction. PMID:24292481

  17. Analysis of phenolic compounds and radical scavenging activity of Echinacea spp.

    PubMed

    Pellati, Federica; Benvenuti, Stefania; Magro, Lara; Melegari, Michele; Soragni, Fabrizia

    2004-04-16

    The aim of this study was to set up and validate an RP-LC method with DAD-detection to quantify caffeic acid derivatives in various Echinacea spp. Samples were extracted with 80% methanol. The analyses were carried out on a Lichrospher RP-18 column (125 mm x 4 mm i.d., 5 microm), with a mobile phase gradient, which increases the acetonitrile level in a phosphoric acid solution (0.1%). The flow rate was 1.5 ml/min. Detection was set at 330 nm. This method allowed the identification and quantification of caftaric acid, chlorogenic acid, caffeic acid, cynarin, echinacoside and cichoric acid in Echinacea roots and derivatives. The total phenolic content was 10.49 mg/g for E. angustifolia, 17.83 mg/g for E. pallida and 23.23 mg/g for E. purpurea. Among Echinacea commercial herbal medicines, a certain variability in the concentrations of phenolic compounds was observed. The radical scavenging activity of Echinacea methanolic extracts was evaluated in vitro with a spectrophotometric method based on the reduction of an alcoholic 2,2-diphenyl-1-picrylhydrazyl (DPPH*) radical solution at 517 nm in the presence of a hydrogen donating antioxidant. As for pure compounds, echinacoside had the highest capacity to quench DPPH* radicals (EC50 = 6.6 microM), while caftaric acid had the lowest (EC50 = 20.5 microM). The average EC50 values for E. purpurea, E. pallida and E. angustifolia were 134, 167 and 231 microg/ml, respectively. The radical scavenging activity of Echinacea root extracts reflected their phenolic composition. The results indicate that Echinacea roots and derivatives are a good source of natural antioxidants and could be used to prevent free-radical-induced deleterious effects. PMID:15063463

  18. Activity of the Pinus elliottii resin compounds against Lernaea cyprinacea in vitro.

    PubMed

    Tóro, Rosa M; Gessner, Alaíde A F; Furtado, Niege A J C; Ceccarelli, Paulo S; de Albuquerque, Sérgio; Bastos, Jairo K

    2003-12-01

    Lernaea cyprinacea infestation is a major problem for fishing culture in Brazil, which was introduced in the mid-eighties. To attempt controlling this parasite, an evaluation of the activity of the Pinus elliottii resin constituents against it was undertaken. To run the bioassay, fish infested with L. cyprinaceae were transferred to aquaria and kept at room temperature and ventilation for 15 days for adaptation. Afterwards, fish were sacrificed and the parasites were kept under water to run the experiments by evaluating the activities of the steamed oil and the chloroform fraction of the resin at concentrations of 0.5, 1.0, 2.0 and 5.0 ppm. The crude resin was also evaluated at concentrations of 1.0, 5.0 and 10 ppm, as well as the major components of its steamed oil, alpha and beta-pinenes, both at concentrations of 0.5 and 1.0 ppm. The results showed that both fractions from the resin were effective at 0.5 ppm concentration, while the pure compounds were less active. Moreover, the acute toxicity (DL(50)) of the crude resin for the fish Leptorinus piau, aged 1 month, was established at 200.0 ppm, which ensures its safe use. PMID:14651883

  19. Evaluation of antioxidant activity of some natural polyphenolic compounds using the Briggs-Rauscher reaction method.

    PubMed

    Cervellati, Rinaldo; Renzulli, Cecilia; Guerra, Maria Clelia; Speroni, Ester

    2002-12-18

    A new method based on the inhibitory effects of antioxidants on the oscillations of the hydrogen peroxide, acidic iodate, malonic acid, and Mn(II)-catalyzed system (known as the Briggs-Rauscher reaction), was used for the evaluation of antioxidative capacity. With this method, which works near the pH of the fluids in the stomach (pH approximately 2), a group of natural compounds present in fruits and vegetables or in medicinal plants assumed to have antioxidant capacity, was tested successfully. The aim of the present study is to evaluate the antioxidative properties of some active principles contained in vegetables and aromatic plants, namely, cynarin (from Cynara scolymus), rosmarinic acid (from Rosmarinus officinalis), echinacoside (from Echinacea species), puerarin (from Pueraria lobata), and oleuropein (from Olea europea). Also studied with the Briggs-Rauscher reaction method was the antioxidant activity of cyanidin 3-O-beta-glucopyranoside (from Citrus aurantium) in order to compare the results with those obtained by other methods. The conclusions on the dependency of the antioxidative activity on the pH of the testing system are given. PMID:12475261

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

    PubMed Central

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

    2011-01-01

    Supercritical carbon dioxide (SC-CO2) extraction of bioactive