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1

T-Screen as a tool to identify thyroid hormone receptor active compounds.  

PubMed

The T-Screen represents an in vitro bioassay based on thyroid hormone dependent cell proliferation of a rat pituitary tumour cell line (GH3) in serum-free medium. It can be used to study interference of compounds with thyroid hormone at the cellular level, thus bridging the gap between limitations of assays using either isolated molecules (enzymes, transport proteins) or complex in vivo experiments with all the complex feedback mechanisms present. Compounds are tested both in the absence and presence of thyroid hormone (EC(50) concentration of T(3)) to test for both agonistic and antagonistic potency. Thyroid hormones (3,3'-5-triiodothyronine: T(3) and 3,3',5,5'-tetraiodothyroxine: T(4)) and compounds resembling the structure of thyroid hormones (3,3'-5-triiodothyroacetic acid: Triac; 3,3',5,5'-tetraiodothyroacetic acid: Tetrac) induced cell growth, with the rank order Triac > T(3) > Tetrac > T(4) (relative potency = 1.35 > 1 > 0.29 > 0.07), which is identical to published affinities of these compounds for nuclear thyroid hormone receptors. Exposure to 5,5'-diphenylhydantoin (DPH) in the presence of 0.25nM T(3) resulted in up to 60% decreased cell growth at 200?M DPH. No effect of DPH on basal metabolic activity of GH3 cells was observed at this concentration. Fentinchloride (IC(50) = 21nM) decreased cell growth induced by 0.25nM T(3), whereas parallel exposure to these concentrations in the absence of T(3) did not alter basal metabolic activities of GH3 cells. Apolar sediment extracts from the Dommel (34%) and Terneuzen (14%) decreased cell growth in the presence of 0.25nM T(3), whereas the extract from Hoogeveen increased cell growth (26%) and the extract from North Sea Channel had no effect. The T-Screen proved to be a fast and functional assay for assessing thyroid hormone receptor active potencies of pure chemicals or environmental mixtures. PMID:21783481

Gutleb, Arno C; Meerts, Ilonka A T M; Bergsma, Joost H; Schriks, Merijn; Murk, Albertinka J

2005-02-01

2

Molecular recognition: identifying compounds and their targets.  

PubMed

As a result of gene sequencing and proteomic efforts, thousands of new genes and proteins are now available as potential drug targets. The milieu of these proteins is complex and interactive; thousands of proteins activate, inhibit, and control each other's actions. The effect of blocking or activating a protein in a cell is far-reaching, and can affect whole, as well as adjacent pathways. This network of pathways is dynamic and a cellular response can change depending on the stimulus. In this section, the identification and role of individual proteins within the context of networked pathways, and the regulation of the activity of these proteins is discussed. Diverse chemical libraries, combinatorial libraries, natural products, as well as unnatural natural products that are derived from combinatorial biology (Chiu [2001] Proc. Natl. Acad. Sci. USA. 98:8548-8553), provide the chemical diversity in the search for new drugs to block new targets. Identifying new compounds that can become drugs is a long, expensive, and arduous task and potential targets must be carefully defined so as not to waste valuable resources. Equally important is the selection of compounds to be future drug candidates. Target selectivity in no way guarantees clinical efficacy, as the compound must meet pharmaceutical requirements, such as solubility, absorption, tissue distribution, and lack of toxicity. Thus matching biological diversity with chemical diversity involves something more than tight interactions, it involves interactions of the compounds with a variety host factors that can modulate its activity. PMID:11842421

Fernandes, P B

2001-01-01

3

Detection of dopaminergic modulators in a tier I screening battery for identifying endocrine-active compounds (EACs)  

Microsoft Academic Search

Apomorphine (APO; D2 receptor agonist), haloperidol (HAL; D2 receptor antagonist), and reserpine (RES; a dopamine depletor that acts to lower brain dopamine levels by depleting central nervous system monoamines via disrupting storage vesicle function) have been examined in a Tier I screening battery, which has been designed to detect endocrine-active compounds (EACs). The Tier I battery incorporates two short-term in

John C O’Connor; Leonard G Davis; Steven R Frame; Jon C Cook

2000-01-01

4

Small-molecule screening using a human primary cell model of HIV latency identifies compounds that reverse latency without cellular activation  

PubMed Central

The development of highly active antiretroviral therapy (HAART) to treat individuals infected with HIV-1 has dramatically improved patient outcomes, but HAART still fails to cure the infection. The latent viral reservoir in resting CD4+ T cells is a major barrier to virus eradication. Elimination of this reservoir requires reactivation of the latent virus. However, strategies for reactivating HIV-1 through nonspecific T cell activation have clinically unacceptable toxicities. We describe here the development of what we believe to be a novel in vitro model of HIV-1 latency that we used to search for compounds that can reverse latency. Human primary CD4+ T cells were transduced with the prosurvival molecule Bcl-2, and the resulting cells were shown to recapitulate the quiescent state of resting CD4+ T cells in vivo. Using this model system, we screened small-molecule libraries and identified a compound that reactivated latent HIV-1 without inducing global T cell activation, 5-hydroxynaphthalene-1,4-dione (5HN). Unlike previously described latency-reversing agents, 5HN activated latent HIV-1 through ROS and NF-?B without affecting nuclear factor of activated T cells (NFAT) and PKC, demonstrating that TCR pathways can be dissected and utilized to purge latent virus. Our study expands the number of classes of latency-reversing therapeutics and demonstrates the utility of this in vitro model for finding strategies to eradicate HIV-1 infection.

Yang, Hung-Chih; Xing, Sifei; Shan, Liang; O'Connell, Karen; Dinoso, Jason; Shen, Anding; Zhou, Yan; Shrum, Cynthia K.; Han, Yefei; Liu, Jun O.; Zhang, Hao; Margolick, Joseph B.; Siliciano, Robert F.

2009-01-01

5

Antifungal Chemical Compounds Identified Using a C. elegans Pathogenicity Assay  

PubMed Central

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 (?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.

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

2007-01-01

6

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

PubMed

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

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

2007-02-01

7

FREQUENCY OF ORGANIC COMPOUNDS IDENTIFIED IN WATER  

EPA Science Inventory

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

8

A combinatorial in silico and cellular approach to identify a new class of compounds that target VEGFR2 receptor tyrosine kinase activity and angiogenesis  

PubMed Central

BACKGROUND AND PURPOSE Vascular endothelial growth factor receptor 2 (VEGFR2) is an attractive therapeutic target for the treatment of diseases such as cancer. Small-molecule VEGFR2 inhibitors of a variety of chemical classes are currently under development or in clinical use. In this study, we describe the de novo design of a new generation pyrazole-based molecule (JK-P3) that targets VEGFR2 kinase activity and angiogenesis. EXPERIMENTAL APPROACH JK-P compound series were designed using de novo structure-based identification methods. Compounds were tested in an in vitro VEGFR2 kinase assay. Using primary endothelial cells, JK-P compounds were assessed for their ability to inhibit VEGF-A-stimulated VEGFR2 activation and intracellular signalling. We tested these compounds in cell migration, proliferation and angiogenesis assays. KEY RESULTS JK-P3 and JK-P5 were predicted to bind the VEGFR2 kinase domain with high affinity, and both compounds showed pronounced inhibition of endogenous VEGFR2 kinase activity in primary human endothelial cells. Only JK-P3 inhibited VEGF-A-stimulated VEGFR2 activation and intracellular signalling. Interestingly, JK-P3 inhibited endothelial monolayer wound closure and angiogenesis but not endothelial cell proliferation. Both compounds inhibited fibroblast growth factor receptor kinase activity in vitro, but not basic fibroblast growth factor-mediated signalling in endothelial cells. CONCLUSIONS AND IMPLICATIONS This is the first report that describes an anti-angiogenic inhibitor based on such a pyrazole core. Using a de novo structure-based identification approach is an attractive method to aid such drug discovery. These results thus provide an important basis for the development of multi-tyrosine kinase inhibitors for clinical use in the near future.

Kankanala, J; Latham, AM; Johnson, AP; Homer-Vanniasinkam, S; Fishwick, CWG; Ponnambalam, S

2012-01-01

9

A quantitative high throughput assay for identifying gametocytocidal compounds.  

PubMed

Current antimalarial drug treatment does not effectively kill mature Plasmodium falciparum gametocytes, the parasite stage responsible for malaria transmission from human to human via a mosquito. Consequently, following standard therapy malaria can still be transmitted for over a week after the clearance of asexual parasites. A new generation of malaria drugs with gametocytocidal properties, or a gametocytocidal drug that could be used in combinational therapy with currently available antimalarials, is needed to control the spread of the disease and facilitate eradication efforts. We have developed a 1536-well gametocyte viability assay for the high throughput screening of large compound collections to identify novel compounds with gametocytocidal activity. The signal-to-basal ratio and Z'-factor for this assay were 3.2-fold and 0.68, respectively. The IC(50) value of epoxomicin, the positive control compound, was 1.42±0.09 nM that is comparable to previously reported values. This miniaturized assay significantly reduces the number of gametocytes required for the AlamarBlue viability assay, and enables high throughput screening for lead discovery efforts. Additionally, the screen does not require a specialized parasite line, gametocytes from any strain, including field isolates, can be tested. A pilot screen utilizing the commercially available LOPAC library, consisting of 1280 known compounds, revealed two selective gametocytocidal compounds having 54- and 7.8-fold gametocytocidal selectivity in comparison to their cell cytotoxicity effect against the mammalian SH-SY5Y cell line. PMID:23454872

Tanaka, Takeshi Q; Dehdashti, Seameen J; Nguyen, Dac-Trung; McKew, John C; Zheng, Wei; Williamson, Kim C

2013-02-27

10

The EPI bioassay identifies natural compounds with estrogenic activity that are potent inhibitors of androgenic pathways in human prostate stromal and epithelial cells.  

PubMed

The reactive stromal phenotype is an important factor for prostate cancer progression and may be a new target for treatment and prevention. A new high efficiency preclinical protocol, the EPI bioassay, reflects the interaction of endocrine, paracrine and immune, (EPI) factors on induced androgen metabolism in human prostate reactive stroma. The bioassay is based on co-culturing human primary prostate stromal cells and LAPC-4 prostatic adenocarcinoma cells in a downscaled format of 96-well-plates for testing multiple doses of multiple target compounds. Metabolism of dehydroepiandrosterone (DHEA) with or without TGF?1-induced stimulation (D+T) of the reactive stroma phenotype was assessed by increased testosterone in the media and PSA production of the epithelial prostate cancer cells. Using the non-metabolizable androgen R1881, effects from direct androgen action were distinguished from stromal androgen production from DHEA. Stromal cell androgenic bioactivity was confirmed using conditioned media from D+T-treated stromal cell monocultures in an androgen-inducible AR screening assay. We further showed that both agonists to estrogen receptor (ER), DPN (ER?) and PPT (ER?), as well as estrogenic natural compounds including soy isoflavones attenuated D+T-induced PSA production. Studies with the pure ER agonists showed that activating either ER? or ER? could inhibit both D+T-mediated and R1881-mediated PSA production with the D+T effect being more pronounced. In conclusion, natural compounds with estrogenic activity and pure ER agonists are very potent inhibitors of stromal conversion of DHEA to androgenic metabolites. More studies are needed to characterize the mechanisms involved in estrogenic modulation of the endocrine-immune-paracrine balance of the prostate microenvironment. PMID:22207083

Vollmer, Günter; Helle, Janina; Amri, Hakima; Liu, Xunxian; Arnold, Julia T

2011-12-22

11

The EPI Bioassay identifies natural compounds with estrogenic activity that are potent inhibitors of androgenic pathways in human prostate stromal and epithelial cells  

PubMed Central

The reactive stromal phenotype is an important factor for prostate cancer progression and may be a new target for treatment and prevention. A new high efficiency preclinical protocol, the EPI bioassay, reflects the interaction of endocrine, paracrine and immune, (EPI) factors on induced androgen metabolism in human prostate reactive stroma. The bioassay is based on co-culturing human primary prostate stromal cells and LAPC-4 prostatic adenocarcinoma cells in a downscaled format of 96-well-plates for testing multiple doses of multiple target compounds. Metabolism of dehydroepiandrosterone (DHEA) with or without TGF?1–induced stimulation (D+T) of the reactive stroma phenotype was assessed by increased testosterone in the media and PSA production of the epithelial prostate cancer cells. By using the non-metabolizable androgen R1881, effects from direct androgen action were distinguished from stromal androgen production from DHEA. Stromal cell androgenic bioactivity was confirmed using conditioned media from D+T-treated stromal cell monocultures in an androgen-inducible AR screening assay. We further showed that both agonists to estrogen receptor (ER), DPN (ER?) and PPT (ER?), as well as estrogenic natural compounds including soy isoflavones attenuated D+T-induced PSA production. Studies with the pure ER agonists showed that activating either ER? or ER? could inhibit both D+T-mediated and R1881-mediated PSA production with the D+T effect being more pronounced. In conclusion, natural compounds with estrogenic activity and pure ER agonists are very potent inhibitors of stromal conversion of DHEA to androgenic metabolites. More studies are needed to characterize the mechanisms involved in estrogenic modulation of the endocrine-immune-paracrine balance of the prostate microenvironment.

Vollmer, Gunter; Helle, Janina; Amri, Hakima; Liu, Xunxian; Arnold, Julia T.

2012-01-01

12

Chemical Genetic Screening Identifies Tricyclic Compounds that Decrease Cellular Melanin Content  

Microsoft Academic Search

A screen of a library of 2,000 drugs and natural products in murine melanocytes identified 10 tricyclic antidepressants (TCAs) as compounds that potently decreased intracellular melanin content. The rank order of potency of these compounds for decreasing melanin content was different than their relative potencies as antidepressants. These compounds had no effect on either the level or the enzymatic activity

Li Ni-Komatsu; Seth J Orlow

2008-01-01

13

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...

14

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...

15

Nitro musk compounds genotoxic activity  

Microsoft Academic Search

s  Five nitro musk compounds are widely used as fragrance ingredients in perfumes, lotions and detergents; as food additives\\u000a in cigarettes and fish baits, and in such technical products as herbicide formulations and explosives. Several studies identified\\u000a nitro musk compounds in aquatic environment samples, human milk and fat samples as highly lipophilic and persistent bioaccumulating\\u000a environmental pollutants. To examine the compounds

Sebastian Kevekordes; Kathrin Grahl; Antonia Zaulig; Hartmut Dunkelberg

1996-01-01

16

Zebrafish screen identifies novel compound with selective toxicity against leukemia  

PubMed Central

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

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

2012-01-01

17

Autotaxin inhibition: development and application of computational tools to identify site-selective lead compounds.  

PubMed

Autotaxin (ATX) catalyzes the conversion of lysophosphatidyl choline (LPC) to lysophosphatidic acid (LPA). Both ATX and LPA have been linked to pathophysiologies ranging from cancer to neuropathic pain. Inhibition of LPA production by ATX is therefore of therapeutic interest. Here we report the application of previously-developed, subsite-targeted pharmacophore models in a screening workflow that involves either docking or binary QSAR as secondary filters to identify ATX inhibitors from previously unreported structural types, four of which have sub-micromolar inhibition constants. Cell-based assays demonstrate that ATX inhibition and cytotoxicity structure-activity-relationships (SAR) exhibit selectivity cliffs, characterized by structurally similar compounds exhibiting similar biological activities with respect to ATX inhibition but very different biological activities with respect to cytotoxicity. Thus, general cytotoxicity should not be used as an early filter to eliminate candidate ATX inhibitor scaffolds from further SAR studies. Assays using two substrates of vastly different sizes demonstrate that the tools developed to identify compounds binding outside the central core of the active site did identify compounds acting at an allosteric site. In contrast, tools developed to identify active-site directed compounds did not identify active-site directed compounds. The stronger volume overlap imposed when selecting screening candidates expected to bind outside the active site is likely responsible for the stronger match between intended and actual target site. PMID:23816044

Norman, Derek D; Ibezim, Ayolah; Scott, Whitney E; White, Stanley; Parrill, Abby L; Baker, Daniel L

2013-06-11

18

A high content screening assay for identifying lysosomotropic compounds.  

PubMed

Lysosomes are acidic organelles that are essential for the degradation of old organelles and engulfed microbes. Furthermore, lysosomes play a key role in cell death. Lipophilic or amphiphilic compounds with a basic moiety can become protonated and trapped within lysosomes, causing lysosomal dysfunction. Therefore, high-throughput screens to detect lysosomotropism, the accumulation of compounds in lysosomes, are desirable. Hence, we developed a 96-well format, high content screening assay that measures lysosomotropism and cytotoxicity by quantitative image analysis. Forty drugs, including antidepressants, antipsychotics, antiarrhythmics and anticancer agents, were tested for their effects on lysosomotropism and cytotoxicity in H9c2 cells. The assay correctly identified drugs known to cause lysosomotropism and revealed novel information showing that the anticancer drugs, gefitinib, lapatinib, and dasatinib, caused lysosomotropism. Although structurally and pharmacologically diverse, drugs that were lysosomotropic shared certain physicochemical properties, possessing a ClogP>2 and a basic pKa between 6.5 and 11. In contrast, drugs which did not lie in this physicochemical property space were not lysosomotropic. The assay is a robust, rapid screen that can be used to identify lysosomotropic, as well as, cytotoxic compounds, and can be positioned within a screening paradigm to understand the role of lysosomotropism as a contributor to drug-induced toxicity. PMID:21184822

Nadanaciva, Sashi; Lu, Shuyan; Gebhard, David F; Jessen, Bart A; Pennie, William D; Will, Yvonne

2010-12-22

19

Identifying organic nitrogen compounds in Rocky Mountain National Park aerosols  

NASA Astrophysics Data System (ADS)

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

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

2010-12-01

20

Biological activity of vanadium compounds  

Microsoft Academic Search

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

Anna Goc

2006-01-01

21

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

EPA Science Inventory

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

22

Odour-active compounds in papaya fruit cv. Red Maradol.  

PubMed

Application of solid-phase microextraction and simultaneous distillation-extraction combined with GC-FID, GC-MS, aroma extract dilution analysis, and odour activity value were used to analyse volatile compounds from papaya fruit cv. Red Maradol and to estimate the most odour-active compounds. The analyses led to the identification of 137 compounds; 118 of them were positively identified. Twenty-five odorants were considered as odour-active compounds and contribute to the typical papaya aroma, from which ethyl butanoate, benzyl isothiocyanate, 1-hexen-3-one, (E)-?-ionone, and methyl benzoate were the most odour-active compounds. PMID:24176322

Pino, Jorge A

2013-09-13

23

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

PubMed

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

Pino, Jorge A; Febles, Yanet

2013-03-26

24

Identifying Sexual Harassment: A Classroom Activity  

ERIC Educational Resources Information Center

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

Madson, Laura; Shoda, Jennifer

2002-01-01

25

[Anticancer activity of oxovanadium compounds].  

PubMed

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

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

26

A high content screening assay for identifying lysosomotropic compounds  

Microsoft Academic Search

Lysosomes are acidic organelles that are essential for the degradation of old organelles and engulfed microbes. Furthermore, lysosomes play a key role in cell death. Lipophilic or amphiphilic compounds with a basic moiety can become protonated and trapped within lysosomes, causing lysosomal dysfunction. Therefore, high-throughput screens to detect lysosomotropism, the accumulation of compounds in lysosomes, are desirable.Hence, we developed a

Sashi Nadanaciva; Shuyan Lu; David F. Gebhard; Bart A. Jessen; William D. Pennie; Yvonne Will

2011-01-01

27

Data mining of protein-binding profiling data identifies structural modifications that distinguish selective and promiscuous compounds.  

PubMed

Activity profiling of compound collections across multiple targets is increasingly being used in probe and drug discovery. Herein, we discuss an approach to systematically analyzing the structure-activity relationships of a large screening profile data with emphasis on identifying structural changes that have a significant impact on the number of proteins to which a compound binds. As a case study, we analyzed a recently released public data set of more than 15?000 compounds screened across 100 sequence-unrelated proteins. The screened compounds have different origins and include natural products, synthetic molecules from academic groups, and commercial compounds. Similar synthetic structures from academic groups showed, overall, greater promiscuity differences than do natural products and commercial compounds. The method implemented in this work readily identified structural changes that differentiated highly specific from promiscuous compounds. This approach is general and can be applied to analyze any other large-scale protein-binding profile data. PMID:22856455

Yongye, Austin B; Medina-Franco, José L

2012-08-17

28

Identifying producers of antibacterial compounds by screening for antibiotic resistance.  

PubMed

Microbially derived natural products are major sources of antibiotics and other medicines, but discovering new antibiotic scaffolds and increasing the chemical diversity of existing ones are formidable challenges. We have designed a screen to exploit the self-protection mechanism of antibiotic producers to enrich microbial libraries for producers of selected antibiotic scaffolds. Using resistance as a discriminating criterion we increased the discovery rate of producers of both glycopeptide and ansamycin antibacterial compounds by several orders of magnitude in comparison with historical hit rates. Applying a phylogeny-based screening filter for biosynthetic genes enabled the binning of producers of distinct scaffolds and resulted in the discovery of a glycopeptide antibacterial compound, pekiskomycin, with an unusual peptide scaffold. This strategy provides a means to readily sample the chemical diversity available in microbes and offers an efficient strategy for rapid discovery of microbial natural products and their associated biosynthetic enzymes. PMID:24056948

Thaker, Maulik N; Wang, Wenliang; Spanogiannopoulos, Peter; Waglechner, Nicholas; King, Andrew M; Medina, Ricardo; Wright, Gerard D

2013-09-22

29

Natural compounds with anti-ageing activity.  

PubMed

Covering: up to the end of June 2013Ageing is a complex molecular process driven by diverse molecular pathways and biochemical events that are promoted by both environmental and genetic factors. Specifically, ageing is defined as a time-dependent decline of functional capacity and stress resistance, associated with increased chance of morbidity and mortality. These effects relate to age-related gradual accumulation of stressors that result in increasingly damaged biomolecules which eventually compromise cellular homeostasis. Nevertheless, the findings that genetic or diet interventions can increase lifespan in evolutionarily diverse organisms indicate that mortality can be postponed. Natural compounds represent an extraordinary inventory of high diversity structural scaffolds that can offer promising candidate chemical entities in the major healthcare challenge of increasing healthspan and/or delaying ageing. Herein, those natural compounds (either pure forms or extracts) that have been found to delay cellular senescence or in vivo ageing will be critically reviewed and summarized according to affected cellular signalling pathways. Moreover, the chemical structures of the identified natural compounds along with the profile of extracts related to their bioactive components will be presented and discussed. Finally, novel potential molecular targets for screening natural compounds for anti-ageing activity, as well as the idea that anti-ageing interventions represent a systemic approach that is also effective against age-related diseases will be discussed. PMID:24056714

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

2013-10-11

30

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

PubMed

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

Tresch, Stefan

2013-08-29

31

Yeast-based automated high-throughput screens to identify anti-parasitic lead compounds.  

PubMed

We have developed a robust, fully automated anti-parasitic drug-screening method that selects compounds specifically targeting parasite enzymes and not their host counterparts, thus allowing the early elimination of compounds with potential side effects. Our yeast system permits multiple parasite targets to be assayed in parallel owing to the strains' expression of different fluorescent proteins. A strain expressing the human target is included in the multiplexed screen to exclude compounds that do not discriminate between host and parasite enzymes. This form of assay has the advantages of using known targets and not requiring the in vitro culture of parasites. We performed automated screens for inhibitors of parasite dihydrofolate reductases, N-myristoyltransferases and phosphoglycerate kinases, finding specific inhibitors of parasite targets. We found that our 'hits' have significant structural similarities to compounds with in vitro anti-parasitic activity, validating our screens and suggesting targets for hits identified in parasite-based assays. Finally, we demonstrate a 60 per cent success rate for our hit compounds in killing or severely inhibiting the growth of Trypanosoma brucei, the causative agent of African sleeping sickness. PMID:23446112

Bilsland, Elizabeth; Sparkes, Andrew; Williams, Kevin; Moss, Harry J; de Clare, Michaela; Pir, Pinar; Rowland, Jem; Aubrey, Wayne; Pateman, Ron; Young, Mike; Carrington, Mark; King, Ross D; Oliver, Stephen G

2013-02-27

32

Electrophysiological and Behavioral Responses of Female Helicoverpa armigera to Compounds Identified in Flowers of African Marigold, Tagetes erecta  

Microsoft Academic Search

Seven electrophysiologically active compounds were detected in air-entrained headspace samples of live flowers of Tagetes erectaanalyzed by gas chromatography (GC) linked to a female Helicoverpa armigeraelectroantennograph (EAG) using polar and nonpolar capillary columns. These compounds were subsequently identified using GC linked to mass spectrometry as benzaldehyde, (S)-(-)-limonene, (R,S)-(±)-linalool, (E)-myroxide, (Z)-ß-ocimene, phenylacetaldehyde, and (R)-(-)-piperitone. Electrophysiological activity was confirmed by EAG with

Toby J. Bruce; Alan Cork

2001-01-01

33

Novel Dual-Reporter Preclinical Screen for Anti-Astrocytoma Agents Identifies Cytostatic and Cytotoxic Compounds  

PubMed Central

Astrocytoma/glioblastoma is the most common malignant form of brain cancer and is often unresponsive to current pharmacological therapies and surgical interventions. Despite several potential therapeutic agents against astrocytoma and glioblastoma (1), there are currently no effective therapies for astrocytoma, creating a great need for the identification of effective anti-tumor agents. We have developed a novel dual-reporter system in Trp53/Nf1-null astrocytoma cells to simultaneously and rapidly assay cell viability and cell cycle progression as evidenced by activity of the human E2F1 promoter in vitro. The dual-reporter high-throughput assay was used to screen experimental therapeutics for activity in Trp53/Nf1-null astrocytoma. Several compounds were identified demonstrating selectivity for astrocytoma over primary astrocytes. The dual-reporter system described here may be a valuable tool for identifying potential anti-tumor treatments that specifically target astrocytoma.

Hawes, Jessica J.; Nerva, John D.; Reilly, Karlyne M.

2009-01-01

34

Nematicidal activities of acetylene compounds from Coreopsis lanceolata L.  

PubMed

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

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

35

Active faults newly identified in Pacific Northwest  

NASA Astrophysics Data System (ADS)

The Bellingham Basin, which lies north of Seattle and south of Vancouver around the border between the United States and Canada in the northern part of the Cascadia subduction zone, is important for understanding the regional tectonic setting and current high rates of crustal deformation in the Pacific Northwest. Using a variety of new data, Kelsey et al. identified several active faults in the Bellingham Basin that had not been previously known. These faults lie more than 60 kilometers farther north of the previously recognized northern limit of active faulting in the area. The authors note that the newly recognized faults could produce earthquakes with magnitudes between 6 and 6.5 and thus should be considered in hazard assessments for the region. (Journal of Geophysical Reserch-Solid Earth, doi:10.1029/2011JB008816, 2012)

Balcerak, Ernie

2012-05-01

36

Evolution of phenolic compounds and antioxidant activity during malting.  

PubMed

Two barley varieties, Gan4 and Hamelin, were malted to investigate the evolution of phenolic compounds and antioxidant activity during malting. The antioxidant activity was evaluated with DPPH radical scavenging activity, ABTS radical cation scavenging activity, reducing power, and metal chelating activity. Results showed that malting had significant influences on individual and total phenolic contents as well as antioxidant activities of two barley varieties. The contents of some phenolic compounds and the antioxidant activities decreased significantly during steeping and the early stages of germination and then increased remarkably during the later stages of germination and subsequent kilning. The most phenolic compounds identified in barley were (+)-catechin and ferulic acid, which both changed significantly during malting. Moreover, results from the Pearson correlation analysis showed that there were good correlations among DPPH radical scavenging activity, ABTS radical cation scavenging activity, reducing power, total phenolic content and sum of individual phenolic contents during malting. PMID:18038990

Lu, Jian; Zhao, Haifeng; Chen, Jian; Fan, Wei; Dong, Jianjun; Kong, Weibao; Sun, Junyong; Cao, Yu; Cai, Guolin

2007-11-27

37

Toward an efficient approach to identify molecular scaffolds possessing selective or promiscuous compounds.  

PubMed

The concept of a recurrent scaffold present in a series of structures is common in medicinal drug discovery. We present a scaffold analysis of compounds screened across 100 sequence-unrelated proteins to identify scaffolds that drive promiscuity or selectivity. Selectivity and promiscuity play a major role in traditional and poly-pharmacological drug design considerations. The collection employed here is the first publicly available data set containing the complete screening profiles of more than 15 000 compounds from different sources. In addition, no scaffold analysis of this data set has been reported. The protocol described here employs the Molecular Equivalence Index tool to facilitate the selection of Bemis-Murcko frameworks in the data set, which contain at least five compounds and Scaffold Hunter to generate a hierarchical tree of scaffolds. The annotation of the scaffold tree with protein-binding profile data enabled the successful identification of mostly highly specific compounds, due to data set constraints. We also applied this approach to a public set of 1497 small molecules screened non-uniformly across a panel of 172 protein kinases. The approach is general and can be applied to any other data sets and activity readout. PMID:23659738

Yongye, Austin B; Medina-Franco, José L

2013-09-10

38

A predictive nuclear translocation assay for spliced x-box-binding protein 1 identifies compounds with known organ toxicities.  

PubMed

Compound toxicity is still the main cause of attrition, emphasizing the need for novel predictive assays to identify toxic compounds early during drug development. Endoplasmic reticulum (ER) stress has recently been discovered as a molecular event that links cellular dysfunction to drug-induced organ toxicity in humans. Among higher organisms the inositol-requiring transmembrane kinase/endoribonuclease pathway plays a major role in mediating the ER stress response. Inositol-requiring transmembrane kinase/endoribonuclease achieves this through its endoribonuclease activity causing a frameshift in the translation of the X-box-binding protein 1 (XBP1) to produce spliced XBP1 (XBP1s), which translocates into the nucleus, where it initiates transcription of ER stress response genes. Based on this biology, we have designed a novel ?-galactosidase-based XBP1s-enzyme fragment complementation assay, which enables identification of compound-induced ER stress in human U2OS cells. The XBP1s-enzyme fragment complementation assay was established in a 384-well format and validated using a library of 1280 pharmacologically active compounds. Importantly, the library of pharmacologically active compounds screen identified both well-established ER stress inducers and several compounds that are known organ toxicants but not previously reported to induce ER stress. Implementation of this assay to assess compound-induced ER stress will facilitate decision making for compound selection and we believe that it will significantly increase the ability to reduce toxicity of preclinical drug candidates. PMID:20858054

Hahmann, Christa; Weiser, Amiee; Duckett, Derek; Schroeter, Thomas

2010-09-21

39

Antibacterial activity of dipropofol and related compounds.  

PubMed

Phenolic compounds, in general, exhibit antioxidant and antibacterial activities. We studied antimicrobial activity of the phenolic antioxidants, propofol (2,6-diisopropylphenol), tocopherol, eugenol, butylated hydroxyanisole (BHA), and several of their dimer compounds. Dipropofol (dimer of 2,6-diisopropylphenol) showed strong antibacterial activity against gram-positive strains including methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococci (VRE), while propofol and other monomeric and dimeric phenols having methyl or tert-butyl groups showed no remarkable activity. The results indicated that the dimeric structure of 2,6-diisopropylphenol moiety may play an important role in the antibacterial activity. PMID:15930760

Ogata, Masahiro; Tutumimoto Sato, Kanae; Kunikane, Takao; Oka, Kentaro; Seki, Masako; Urano, Shiro; Hiramatsu, Keiichi; Endo, Toyoshige

2005-06-01

40

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...

41

A High-Throughput Method to Identify Novel Senescence-Inducing Compounds  

PubMed Central

Cellular senescence is a persistently growth-arrested phenotype in normal and transformed cells induced by non-cytotoxic stress. Cytostasis as a method of cancer treatment has recently generated significant interest. Research into the induction of cellular senescence as cancer therapy has been hindered by a lack of compounds that efficiently induce this response. We describe a semiautomated high-throughput method to identify library compounds that induce senescence using prostate cancer cells cultured in 96 well plates. Primary hits are identified by low cell numbers after 3 days in culture, measured by Hoechst 33342 fluorescence. A secondary visual assessment of senescence-associated ?-galactosidase staining and cellular morphology in the same wells distinguishes senescence from quiescence, apoptosis and other false-positives. This method was used to screen a 4160 compound library of known bioactive compounds and natural products at a 10?M dose. Candidate compounds were further selected based on persistent growth arrest after drug removal and increased expression of previously described senescence marker genes. Four lead compounds not previously associated with senescence were identified for further investigation. This is the first successful assay to identify novel agents from compound libraries based on senescence-induction in cancer cells.

Ewald, Jonathan A.; Peters, Noel; Desotelle, Joshua A.; Hoffmann, F. Michael; Jarrard, David F.

2010-01-01

42

Forward chemical genetic screens in Arabidopsis identify genes that influence sensitivity to the phytotoxic compound sulfamethoxazole  

PubMed Central

Background The sulfanilamide family comprises a clinically important group of antimicrobial compounds which also display bioactivity in plants. While there is evidence that sulfanilamides inhibit folate biosynthesis in both bacteria and plants, the complete network of plant responses to these compounds remains to be characterized. As such, we initiated two forward genetic screens in Arabidopsis in order to identify mutants that exhibit altered sensitivity to sulfanilamide compounds. These screens were based on the growth phenotype of seedlings germinated in the presence of the compound sulfamethoxazole (Smex). Results We identified a mutant with reduced sensitivity to Smex, and subsequent mapping indicated that a gene encoding 5-oxoprolinase was responsible for this phenotype. A mutation causing enhanced sensitivity to Smex was mapped to a gene lacking any functional annotation. Conclusions The genes identified through our forward genetic screens represent novel mediators of Arabidopsis responses to sulfanilamides and suggest that these responses extend beyond the perturbation of folate biosynthesis.

2012-01-01

43

Activities for Identifying Similarities and Differences  

NSDL National Science Digital Library

This article discusses the four forms of identifying similarities and differences: comparing, classifying, creating metaphors, and creating analogies and how these strategies can be used in an elementary classroom.

Fries-Gaither, Jessica

44

Biologically active compounds from Aphyllophorales (polypore) fungi.  

PubMed

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

Zjawiony, Jordan K

2004-02-01

45

Antiosteoporotic activity of phenolic compounds from Curculigo orchioides.  

PubMed

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

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

2009-03-27

46

Activity: Identifying a solid using density  

NSDL National Science Digital Library

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

Greg Schmidt, Henry S.

47

Sulfonamides identified as plant immune-priming compounds in high-throughput chemical screening increase disease resistance in Arabidopsis thaliana  

PubMed Central

Plant activators are agrochemicals that protect crops from diseases by activating the plant immune system. To isolate lead compounds for use as practical plant activators, we screened two different chemical libraries composed of various bioactive substances by using an established screening procedure that can selectively identify immune-priming compounds. We identified and characterized a group of sulfonamide compounds – sulfameter, sulfamethoxypyridazine, sulfabenzamide, and sulfachloropyridazine – among the various isolated candidate molecules. These sulfonamide compounds enhanced the avirulent Pseudomonas-induced cell death of Arabidopsis suspension cell cultures and increased disease resistance in Arabidopsis plants against both avirulent and virulent strains of the bacterium. These compounds did not prevent the growth of pathogenic bacteria in minimal liquid media at 200 ?M. They also did not induce the expression of defense-related genes in Arabidopsis seedlings, at least not at 24 and 48 h after treatment, suggesting that they do not act as salicylic acid analogs. In addition, although sulfonamides are known to be folate biosynthesis inhibitors, the application of folate did not restore the potentiation effects of the sulfonamides on pathogen-induced cell death. Our data suggest that sulfonamides potentiate Arabidopsis disease resistance by their novel chemical properties.

Noutoshi, Yoshiteru; Ikeda, Mika; Saito, Tamio; Osada, Hiroyuki; Shirasu, Ken

2012-01-01

48

Identifying Interesting Networks of Criminal Activity  

Microsoft Academic Search

While Electronic Records Management Systems (RMS) make it possible for investigators to quickly query large volumes of Law\\u000a Enforcement (LE) data, much more can be done to effectively use police records to support investigational processes. Detectives\\u000a frequently identify interesting networks of association and draw them up in link charts to help generate leads, focus investigations,\\u000a and facilitate communication. A variety

Byron Marshall

2008-01-01

49

Degraded Lignin Compounds Identified in Silicified Wood 200 Million Years Old  

Microsoft Academic Search

Degraded lignin compounds have been identified in Triassic age (about 200 million years) silicified wood from the Petrified Forest National Park in Arizona. The pyrolysis products from black carbonaceous samples include carbon dioxide, low-molecular-weight alkanes and alkenes, benzene, alkyl-substituted benzenes, phenol, cresol, xylenols, indenes, benzofurans, trimethylindanone, and naphthalenes. These compounds are also the primary pyrolyzates of modern lignin above 500

Anne Colberg Sigleo

1978-01-01

50

Degraded lignin compounds identified in silicified wood 200 million years old.  

PubMed

Degraded lignin compounds have been identified in Triassic age (about 200 million years) silicified wood from the Petrified Forest National Park in Arizona. The pyrolysis products from black carbonaceous samples include carbon dioxide, low-molecular-weight alkanes and alkenes, benzene, alkyl-substituted benzenes, phenol, cresol, xylenols, indenes, benzofurans, trimethylindanone, and naphthalenes. These compounds are also the primary pyrolyzates of modern lignin above 500 degrees C. PMID:17740698

Sigleo, A C

1978-06-01

51

Structural Determination of Two Active Compounds That Bind to the Muscarinic M 3 Receptor in Beer  

Microsoft Academic Search

Background: It is known that beer accelerates gastrointestinal motility in humans. Our previous studies showed that beer congener stimulates gastrointestinal motility by directly stimulating the muscarinic M3 receptor. Further, we isolated 2 active compounds (compounds A and B) from beer by liquid chromatography. The objective of the present study was to identify the 2 active compounds that bind to the

Nahoko Yamaji; Yoshiaki Yokoo; Takashi Iwashita; Asuka Nemoto; Minako Koike; Yoshihide Suwa; Toshiyuki Wakimoto; Kuniro Tsuji; Haruo Nukaya

2007-01-01

52

Mechanomyogram for identifying muscle activity and fatigue  

Microsoft Academic Search

Mechanomyogram is the recording of the acoustic activity associated with the muscle contraction. While discovered nearly a decade ago with the intention of providing an alternate to the surface electromyogram, it has not yet been investigated thoroughly and there are no current applications associated with MMG. This paper reports an experimental study of MMG against force of contraction and muscle

Zhao Feng Yang; Dinesh Kant Kumar; Sridhar Poosapadi Arjunan

2009-01-01

53

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

PubMed

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

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

2008-06-05

54

Novel Plant Immune-Priming Compounds Identified via High-Throughput Chemical Screening Target Salicylic Acid Glucosyltransferases in Arabidopsis[W][OA  

PubMed Central

Plant activators are compounds, such as analogs of the defense hormone salicylic acid (SA), that protect plants from pathogens by activating the plant immune system. Although some plant activators have been widely used in agriculture, the molecular mechanisms of immune induction are largely unknown. Using a newly established high-throughput screening procedure that screens for compounds that specifically potentiate pathogen-activated cell death in Arabidopsis thaliana cultured suspension cells, we identified five compounds that prime the immune response. These compounds enhanced disease resistance against pathogenic Pseudomonas bacteria in Arabidopsis plants. Pretreatments increased the accumulation of endogenous SA, but reduced its metabolite, SA-O-?-d-glucoside. Inducing compounds inhibited two SA glucosyltransferases (SAGTs) in vitro. Double knockout plants that lack both SAGTs consistently exhibited enhanced disease resistance. Our results demonstrate that manipulation of the active free SA pool via SA-inactivating enzymes can be a useful strategy for fortifying plant disease resistance and may identify useful crop protectants.

Noutoshi, Yoshiteru; Okazaki, Masateru; Kida, Tatsuya; Nishina, Yuta; Morishita, Yoshihiko; Ogawa, Takumi; Suzuki, Hideyuki; Shibata, Daisuke; Jikumaru, Yusuke; Hanada, Atsushi; Kamiya, Yuji

2012-01-01

55

Antimicrobial activity of extractable conifer heartwood compounds toward Phytophthora ramorum.  

PubMed

Ethyl acetate extracts from heartwood of seven western conifer trees and individual volatile compounds in the extracts were tested for antimicrobial activity against Phytophthora ramorum. Extracts from incense and western redcedar exhibited the strongest activity, followed by yellow-cedar, western juniper, and Port-Orford-cedar with moderate activity, and no activity for Douglas-fir and redwood extracts. Chemical composition of the extracts varied both qualitatively and quantitatively among the species with a total of 37 compounds identified by mass spectrometry. Of the 13 individual heartwood compounds bioassayed, three showed strong activity with a Log(10) EC(50) less than or equal to 1.0 ppm (hinokitiol, thymoquinone, and nootkatin), three expressed moderate activity ranging from 1.0-2.0 ppm (nootkatol, carvacrol, and valencene-11,12-diol), four compounds had weak activity at 2.0-3.0 ppm [alpha-terpineol, valencene-13-ol, (+)-beta-cedrene, (-)-thujopsene], and three had no activity [(+)-cedrol, delta-cadinene, and methyl carvacrol]. All of the most active compounds contained a free hydroxyl group, except thymoquinone. The importance of a free hydroxyl was demonstrated by the tremendous difference in activity between carvacrol (Log(10) EC(50) 1.81 +/- 0.08 ppm) and methyl carvacrol (Log(10) EC(50) >3.0 ppm). A field trial in California, showed that heartwood chips from redcedar placed on the forest floor for 4 months under Umbellularia californica (California bay laurel) with symptoms of P. ramorum leaf blight significantly limited the accumulation of P. ramorum DNA in the litter layer, compared with heartwood chips from redwood. PMID:17929093

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

2007-10-11

56

Biological Activity of Grapevine Phenolic Compounds  

Microsoft Academic Search

Phenolic compounds present in nearly all parts of grape berries are increasingly believed to exhibit antioxidant and antimicrobial\\u000a activities and to play a significant role in the prevention of diseases including cancer and cardiovascular diseases (Bagchi\\u000a et al. 2000, Ariga 2004). The majority of studies on grape phenolics properties has been conducted using proanthocyanidin-rich\\u000a seeds extracts (GSEs).

R. Amarowicz; S. Weidner

57

A disease-relevant high-content screening assay to identify anti-inflammatory compounds for use in cystic fibrosis.  

PubMed

Chronic lung inflammation caused by bacterial pathogenesis through activation of nuclear factor kappa B (NF?B)-responsive proinflammatory genes is a major hurdle in the management of lung disease in cystic fibrosis (CF) patients. The authors generated a disease-relevant cell-based high-content screen to identify novel anti-inflammatory compounds for treating lung inflammation in CF. The human bronchial epithelial cell line KKLEB, harboring the most common form of mutation that causes CF, was modified to express an NF?B-responsive green fluorescent protein (GFP) reporter. After creation, the cell line was tested for its ability to respond to disease-relevant inflammatory stimuli elicited by treatment of cells with filtrates of Pseudomonas aeruginosa isolated from the airways of a CF patient. P. aeruginosa filtrates potently activated NF?B-responsive GFP reporter expression in cells. Subsequently, the assay was optimized for high-throughput screening (HTS) through generation of a Z factor (~0.5) and by testing its tolerance to the commonly used solvents ethanol and DMSO. A pilot library of clinically approved compounds was screened for assay validation. Several compounds with known NF?B inhibitory activity were identified, including several steroidal compounds that have been clinically tested in CF. Thus, the assay can be used in a broader HTS campaign to find anti-inflammatory agents for use in CF. PMID:20944057

Giddings, Angela M; Maitra, Rangan

2010-10-13

58

Compounds active against cell walls of medically important fungi.  

PubMed Central

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.

Hector, R F

1993-01-01

59

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...

60

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...

61

High-throughput screening of libraries of compounds to identify CFTR modulators.  

PubMed

Small molecules acting as selective activators (potentiators), inhibitors, or "correctors" of the CFTR chloride channel represent candidate drugs for various pathological conditions including cystic fibrosis and secretory diarrhea. The identification of CFTR pharmacological modulators may be achieved by screening highly diverse synthetic or natural compound libraries using high-throughput methods. A convenient assay for CFTR function is based on the halide sensitivity of the yellow fluorescent protein (YFP). CFTR activity can be simply assessed by measuring the rate of YFP signal decrease caused by iodide influx. This assay can be automated to test thousands of compounds per day. PMID:21594775

Pedemonte, Nicoletta; Zegarra-Moran, Olga; Galietta, Luis J V

2011-01-01

62

Identification of Chemical Compounds that Induce HIF-1? Activity  

PubMed Central

Cellular metabolism depends on the availability of oxygen and the major regulator of oxygen homeostasis is hypoxia-inducible factor 1 (HIF-1), a highly conserved transcription factor that plays an essential role in cellular and systemic homeostatic responses to hypoxia. HIF-1 is a heterodimeric transcription factor composed of hypoxia-inducible HIF-1? and constitutively expressed HIF-1?. Under hypoxic conditions, the two subunits dimerize, allowing translocation of the HIF-1 complex to the nucleus where it binds to hypoxia-response elements (HREs) and activates expression of target genes implicated in angiogenesis, cell growth, and survival. The HIF-1 pathway is essential to normal growth and development, and is involved in the pathophysiology of cancer, inflammation, and ischemia. Thus, there is considerable interest in identifying compounds that modulate the HIF-1 signaling pathway. To assess the ability of environmental chemicals to stimulate the HIF-1 signaling pathway, we screened a National Toxicology Program collection of 1408 compounds using a cell-based ?-lactamase HRE reporter gene assay in a quantitative high-throughput screening (qHTS) format. Twelve active compounds were identified. These compounds were tested in a confirmatory assay for induction of vascular endothelial growth factor, a known hypoxia target gene, and confirmed compounds were further tested for their ability to mimic the effect of a reduced-oxygen environment on hypoxia-regulated promoter activity. Based on this testing strategy, three compounds (o-phenanthroline, iodochlorohydroxyquinoline, cobalt sulfate heptahydrate) were confirmed as hypoxia mimetics, whereas two compounds (7-diethylamino-4-methylcoumarin and 7,12-dimethylbenz(a)anthracence) were found to interact with HIF-1 in a manner different from hypoxia. These results demonstrate the effectiveness of qHTS in combination with secondary assays for identification of HIF-1? inducers and for distinguishing among inducers based on their pattern of activated hypoxic target genes. Identification of environmental compounds having HIF-1? activation activity in cell-based assays may be useful for prioritizing chemicals for further testing as hypoxia-response inducers in vivo.

Xia, Menghang; Huang, Ruili; Sun, Yi; Semenza, Gregg L.; Aldred, Shelley Force; Witt, Kristine L.; Inglese, James; Tice, Raymond R.; Austin, Christopher P.

2009-01-01

63

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

PubMed Central

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

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

2012-01-01

64

Microarray Compound Screening (&mgr;ARCS) to Identify Inhibitors of HIV Integrase  

Microsoft Academic Search

A novel high-throughput strand transfer assay has been developed, using Microarray Compound Screening (&mgr;ARCS) technology, to identify inhibitors of human immunodeficiency virus (HIV) integrase. This technology utilizes agarose matrices to introduce a majority of the reagents throughout the assay. Integration of biotinylated donor DNA with fluorescein isothiocyanate (FITC)-labeled target DNA occurs on a SAM membrane in the presence of integrase.

Caroline A. David; Tim Middleton; Debra Montgomery; Hock Ben Lim; Warren Kati; Akhter Molla; Xiaoling Xuei; Usha Warrior; James L. Kofron; David J. Burns

2002-01-01

65

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

PubMed

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

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

2012-08-26

66

Identification of Oct4-activating compounds that enhance reprogramming efficiency  

PubMed Central

One of the hurdles for practical application of induced pluripotent stem cells (iPSC) is the low efficiency and slow process of reprogramming. Octamer-binding transcription factor 4 (Oct4) has been shown to be an essential regulator of embryonic stem cell (ESC) pluripotency and key to the reprogramming process. To identify small molecules that enhance reprogramming efficiency, we performed a cell-based high-throughput screening of chemical libraries. One of the compounds, termed Oct4-activating compound 1 (OAC1), was found to activate both Oct4 and Nanog promoter-driven luciferase reporter genes. Furthermore, when added to the reprogramming mixture along with the quartet reprogramming factors (Oct4, Sox2, c-Myc, and Klf4), OAC1 enhanced the iPSC reprogramming efficiency and accelerated the reprogramming process. Two structural analogs of OAC1 also activated Oct4 and Nanog promoters and enhanced iPSC formation. The iPSC colonies derived using the Oct4-activating compounds along with the quartet factors exhibited typical ESC morphology, gene-expression pattern, and developmental potential. OAC1 seems to enhance reprogramming efficiency in a unique manner, independent of either inhibition of the p53-p21 pathway or activation of the Wnt-?-catenin signaling. OAC1 increases transcription of the Oct4-Nanog-Sox2 triad and Tet1, a gene known to be involved in DNA demethylation.

Li, Wendong; Tian, E; Chen, Zhao-Xia; Sun, GuoQiang; Ye, Peng; Yang, Su; Lu, Dave; Xie, Jun; Ho, Thach-Vu; Tsark, Walter M.; Wang, Charles; Horne, David A.; Riggs, Arthur D.; Yip, M. L. Richard; Shi, Yanhong

2012-01-01

67

Identification of Oct4-activating compounds that enhance reprogramming efficiency.  

PubMed

One of the hurdles for practical application of induced pluripotent stem cells (iPSC) is the low efficiency and slow process of reprogramming. Octamer-binding transcription factor 4 (Oct4) has been shown to be an essential regulator of embryonic stem cell (ESC) pluripotency and key to the reprogramming process. To identify small molecules that enhance reprogramming efficiency, we performed a cell-based high-throughput screening of chemical libraries. One of the compounds, termed Oct4-activating compound 1 (OAC1), was found to activate both Oct4 and Nanog promoter-driven luciferase reporter genes. Furthermore, when added to the reprogramming mixture along with the quartet reprogramming factors (Oct4, Sox2, c-Myc, and Klf4), OAC1 enhanced the iPSC reprogramming efficiency and accelerated the reprogramming process. Two structural analogs of OAC1 also activated Oct4 and Nanog promoters and enhanced iPSC formation. The iPSC colonies derived using the Oct4-activating compounds along with the quartet factors exhibited typical ESC morphology, gene-expression pattern, and developmental potential. OAC1 seems to enhance reprogramming efficiency in a unique manner, independent of either inhibition of the p53-p21 pathway or activation of the Wnt-?-catenin signaling. OAC1 increases transcription of the Oct4-Nanog-Sox2 triad and Tet1, a gene known to be involved in DNA demethylation. PMID:23213213

Li, Wendong; Tian, E; Chen, Zhao-Xia; Sun, Guoqiang; Ye, Peng; Yang, Su; Lu, Dave; Xie, Jun; Ho, Thach-Vu; Tsark, Walter M; Wang, Charles; Horne, David A; Riggs, Arthur D; Yip, M L Richard; Shi, Yanhong

2012-12-03

68

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

PubMed

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

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

2012-08-23

69

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

Microsoft Academic Search

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

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

2006-01-01

70

Biologically active compounds of semi-metals  

Microsoft Academic Search

Semi-metals, viz. boron, silicon, arsenic, selenium, tellurium and astatine form organo-metal compounds, some of which are found in nature and have striking effects on the physiology of living organisms. Representatives of these compounds are, e.g., four boron-containing antibiotics (aplasmomycin, borophycin, boromycin, and tatrolon). Silicon compounds, frequently present in \\

T. ?ezanka; K. Sigler

2008-01-01

71

Apparent Activity in High-Throughput Screening: Origins of Compound-Dependent Assay Interference  

PubMed Central

Summary of recent advances Expansive compound collections made up of structurally heterogeneous chemicals, the activities of which are largely undefined, present challenging problems for high-throughput screening (HTS). Foremost is differentiating whether the activity for a given compound in an assay is directed against the targeted biology, or is the result of surreptitious compound activity involving the assay detection system. Such compound interference can be especially difficult to identify if it is reproducible and concentration-dependent – characteristics generally attributed to compounds with genuine activity. While reactive chemical groups on compounds were once thought to be the primary source of compound interference in assays used in HTS, recent work suggests that other factors, such as compound aggregation, may play a more significant role in many assay formats. Considerable progress has been made to profile representative compound libraries in an effort to identify chemical classes susceptible to producing compound interference, such as compounds commonly found to inhibit the reporter enzyme firefly luciferase. Such work has also led to the development of practices that have the potential to significantly reduce compound interference, for example, through the addition of non-ionic detergent to assay buffer to reduce aggregation-based inhibition.

Thorne, Natasha; Auld, Douglas S.; Inglese, James

2010-01-01

72

Anticancer and antioxidant activity of synthetic chalcones and related compounds  

Microsoft Academic Search

Nineteen synthetic chalcones and ten structurally related compounds were investigated for their cytotoxic, tumour reducing and antioxidant activities. Methyl and hydroxy substituted chalcones were found to be cytotoxic in vitro whereas only hydroxy substituted chalcones could reduce ascites tumour in animals. Although most of the compounds analysed showed antioxidant activity, hydroxy and methyl substituted compounds were found to be the

Ruby John Anto; K. Sukumaran; Girija Kuttan; M. N. A. Rao; V. Subbaraju; Ramadasan Kuttan

1995-01-01

73

Compounds from Gum Ammoniacum with Acetylcholinesterase Inhibitory Activity  

PubMed Central

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

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

2013-01-01

74

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

PubMed

The aqueous extract of galls from Terminalia chebula Retz. (Combretaceae) was fractionated on Diaion and refractionated on octadecyl silica column. Six phenolic compounds were isolated and identified as gallic acid (1), punicalagin (2), isoterchebulin (3), 1,3,6-tri-O-galloyl-?-D-glucopyranose (4), chebulagic acid (5) and chebulinic acid (6). All of the compounds showed stronger 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and melanin inhibitory activities than ascorbic acid, butylated hydroxytoluene, ?-tocopherol, arbutin and kojic acid, the reference compounds. Gallic acid (1) exhibited inhibitory activity against nitric oxide production in lipopolysaccharide-activated macrophages. However, all isolated compounds exhibited less activity than the reference compounds in mushroom tyrosinase inhibition and human tumour cytotoxicity assays. This study has demonstrated that the phenolic compounds isolated from galls of T. chebula might contribute significantly due to their antioxidant and whitening activities. PMID:21108118

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

2010-12-01

75

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

PubMed Central

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

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

2009-01-01

76

Analysis of chlorocarbon compounds identified in the SAM Investigation of the Mars Science Laboratory mission  

NASA Astrophysics Data System (ADS)

The gas chromatograph mass spectrometer (GCMS) mode of the Sample Analysis at Mars (SAM) experiment was designed for the separation and identification of the chemical components of the gases released from a solid sample or trapped from the atmosphere. Gases from solid samples are either produced by heating a cell from ambient to >800-1100oC (EGA mode) or by wet chemistry extraction and reactions (not yet employed on Mars). Prior to EGA analysis of portions of the first 3 solid samples (Rocknest, John Klein and Cumberland) collected by MSL and delivered to SAM, an internal SAM blank run was carried out with an empty quartz cup. These blank analyses are required to understand the background signal intrinsic to the GCMS and its gas manifolds and traps. Several peaks have been identified as part of SAM background, some of them below the nmol level, which attests of the sensitivity of the instrument and as-designed performance of the GCMS. The origin of each peak has been investigated, and two major contributors are revealed; residual vapor from one of the chemicals used for SAM wet chemistry experiment: N-methyl-N-tert-butyldimethylsilyl-trifluoroacetamide (MTBSTFA), and the Tenax from the hydrocarbon trap. Supporting lab experiments are in progress to understand the reaction pathways of the molecules identified in the SAM background. These experiments help elucidate which molecules may be interpreted as indigenous to Mars. Of the three solid samples analyzed on 11 runs, it was possible to detect and identify several chlorinated compounds including several chlorohydrocarbons. The chlorine is likely derived from the decomposition of martian perchlorates or other indigenous Cl-containing species while the origin of the carbon is presently under investigation for each detected molecule. To date, a subset these molecules have been identified in lab studies and a terrestrial contribution to the observed products are more easily explained. The combined results from SAM and the associated laboratory studies represent a significant step forward in the search for near-surface organic compounds on Mars.

Freissinet, Caroline; Mahaffy, P.; Glavin, D.; Buch, A.; Brunner, A.; Eigenbrode, J.; Martin, M.; Miller, K.; Steele, A.; Szopa, C.; SAM; MSL science Team

2013-10-01

77

Biologically active compounds of semi-metals  

Microsoft Academic Search

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

Tomáš ?ezanka; Karel Sigler

2008-01-01

78

Compounds from Vitex polygama active against kidney diseases.  

PubMed

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

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

2007-09-29

79

A Novel Histone Deacetylase Inhibitor Identified by High-Throughput Transcriptional Screening of a Compound Library1  

Microsoft Academic Search

Libraries of compounds are increasingly becoming commercially avail- able for the use of individual academic laboratories. A high-throughput system based on a stably integrated transcriptional reporter was used to screen a library of random compounds to identify agents that conferred robust augmentation of a signal transduction pathway. A novel histone deacetylase (HDAC) inhibitor, termed scriptaid, conferred the greatest effect, a

Gloria H. Su; Taylor A. Sohn; Byungwoo Ryu; Scott E. Kern

2000-01-01

80

Cell-based small-molecule compound screen identifies fenretinide as potential therapeutic for translocation-positive rhabdomyosarcoma.  

PubMed

A subset of paediatric sarcomas are characterized by chromosomal translocations encoding specific oncogenic transcription factors. Such fusion proteins represent tumor specific therapeutic targets although so far it has not been possible to directly inhibit their activity by small-molecule compounds. In this study, we hypothesized that screening a small-molecule library might identify already existing drugs that are able to modulate the transcriptional activity of PAX3/FOXO1, the fusion protein specifically found in the pediatric tumor alveolar rhabdomyosarcoma (aRMS). Towards this end, we established a reporter cell line based on the well characterized PAX3/FOXO1 target gene AP2ß. A library enriched in mostly FDA approved drugs was screened using specific luciferase activity as read-out and normalized for cell viability. The most effective inhibitor identified from this screen was Fenretinide. Treatment with this compound resulted in down-regulation of PAX3/FOXO1 mRNA and protein levels as well as in reduced expression of several of its direct target genes, but not of wild-type FOXO1, in a dose- and time-dependent manner. Moreover, fenretinide induced reactive oxygen species and apoptosis as shown by caspase 9 and PARP cleavage and upregulated miR-9. Importantly, it demonstrated a significant anti-tumor effect in vivo. These results are similar to earlier reports for two other pediatric tumors, namely neuroblastoma and Ewing sarcoma, where fenretinide is under clinical development. Our results suggest that fenretinide might represent a novel treatment option also for translocation-positive rhabdomyosarcoma. PMID:23372815

Herrero Martín, David; Boro, Aleksandar; Schäfer, Beat W

2013-01-25

81

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

PubMed

The characteristic aroma-active compounds in raw and cooked pine-mushrooms (Tricholoma matsutake Sing.) were investigated by gas chromatography-olfactometry using aroma extract dilution analysis. 1-Octen-3-one (mushroom-like) was the major aroma-active compound in raw pine-mushrooms; this compound had the highest flavor dilution factor, followed by ethyl 2-methylbutyrate (floral and sweet), linalool (citrus-like), methional (boiled potato-like), 3-octanol (mushroom-like and buttery), 1-octen-3-ol (mushroom-like), (E)-2-octen-1-ol (mushroom-like), and 3-octanone (mushroom-like and buttery). By contrast, methional, 2-acetylthiazole (roasted), an unknown compound (chocolate-like), 3-hydroxy-2-butanone (buttery), and phenylacetaldehyde (floral and sweet), which could be formed by diverse thermal reactions during the cooking process, together with C8 compounds, were identified as the major aroma-active compounds in cooked pine-mushrooms. PMID:16910727

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

2006-08-23

82

Practical identifiability of a biokinetic model of activated sludge respiration  

Microsoft Academic Search

This paper deals with the estimation of the parameters of the Monod model for the activated sludge process on the basis of oxygen uptake rate data only. The objective of the paper is to concentrate on the practical identifiability properties of the model and on the design of informative experiments for parameter estimation. The results are illustrated by experimental data.

Peter A. Vanrolleghem; Marc Van Daele; D. Dochain

1995-01-01

83

Psilostachyin C: a natural compound with trypanocidal activity.  

PubMed

In this study, the antiprotozoal activity of the sesquiterpene lactone psilostachyin C was investigated. This natural compound was isolated from Ambrosia scabra by bioassay-guided fractionation and was identified by spectroscopic techniques. Psilostachyin C exerted in vitro trypanocidal activity against Trypanosoma cruzi epimastigotes, trypomastigotes and amastigotes, with 50% inhibitory concentration (IC(50)) values of 0.6, 3.5 and 0.9 ?g/mL, respectively, and displayed less cytotoxicity against mammalian cells, with a 50% cytotoxic concentration (CC(50)) of 87.5 ?g/mL. Interestingly, this compound induced ultrastructural alterations, as seen by transmission electron microscopy, in which vacuolisation and a structural appearance resembling multivesicular bodies were observed even at a concentration as low as 0.2 ?g/mL. In an in vivo assay, a significant reduction in the number of circulating parasites was found in T. cruzi-infected mice treated with psilostachyin C for 5 days compared with untreated mice (7.4 ± 1.2 × 10(5)parasites/mL vs. 12.8 ± 2.0 × 10(5)parasites/mL) at the peak of parasitaemia. According to these results, psilostachyin C may be considered a promising template for the design of novel trypanocidal agents. In addition, psilostachyin C inhibited the growth of Leishmania mexicana and Leishmania amazonensis promastigotes (IC(50)=1.2 ?g/mL and 1.5 ?g/mL, respectively). PMID:21497061

Sülsen, Valeria P; Frank, Fernanda M; Cazorla, Silvia I; Barrera, Patricia; Freixa, Blanca; Vila, Roser; Sosa, Miguel A; Malchiodi, Emilio L; Muschietti, Liliana V; Martino, Virginia S

2011-04-15

84

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

PubMed

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

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

2011-12-01

85

Discovering active compounds from mixture of natural products by data mining approach  

Microsoft Academic Search

Traditionally, active compounds were discovered from natural products by repeated isolation and bioassays, which can be highly\\u000a time consuming. Here, we have developed a data mining approach using the casual discovery algorithm to identify active compounds\\u000a from mixtures by investigating the correlation between their chemical composition and bioactivity in the mixtures. The efficacy\\u000a of our algorithm was validated by the

Yi Wang; Yecheng Jin; Chenguang Zhou; Haibin Qu; Yiyu Cheng

2008-01-01

86

Anti-Ulcerative Colitis Activity of Compounds from Euphorbia granuleta Forssk.  

PubMed

The aim of the present study was to evaluate the anti-ulcerative colitis (UC) activity of the total alcohol extracts of Euphorbia granuleta Forssk. (Euphorpiaceae), isolate and identify the active compounds that could be responsible for the activity, in addition to determination of the possible mechanism of action. Six compounds were isolated and identified from this plant: three phenolic compounds (kampferol, kampferol-3-glucoside and kampferol-3-galactoside) in addition to three steroidal compounds (1-ethoxypentacosane, heptacosan-1-ol and ?-sitosterol). Three compounds (heptacosan-1-ol, ?-sitosterol and kampferol-3-galactoside) were found to be responsible for the anti-UC activity of E. granuleta extract. The anti-UC activity of these compounds may be explained by reducing the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-?), in addition to reduction of colonic malondialdehyde (MDA) contents. No side effects were reported on liver and kidney functions. The active compounds reduced both serum TNF-? and mucosal MDA levels. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23580316

Awaad, Amani S; El-Meligy, Reham M; Al-Jaber, Nabila A; Al-Muteeri, Hanoof S; Zain, Mohamed E; Alqasoumi, Saleh I; Alafeefy, Ahmed M; Donia, Abd El Raheim M

2013-04-11

87

Fun with Compound Words  

NSDL National Science Digital Library

Identify and create compound words We will be studying compound words! First we need to find out what a compound word is, go to this website and read about compound words.What is a compound word Now that you have read about compound words lets do some fun activities to help us review. First go to Compound word flashcards, here you will ...

Huggins, Ms.

2012-04-12

88

Antioxidant activity of propofol and related monomeric and dimeric compounds.  

PubMed

This study was carried out to investigate the antioxidant activity of propofol (2,6-diisopropylphenol) and its related compounds, butylated hydroxyanisole (BHA), 2,6-dimethylphenol, 2,6-di-t-butylphenol, and their dimeric compounds. The degree of antioxidant activity was evaluated based on the degree of peroxidation induced with Fe-ascorbic acid in egg phosphatidylcholine through the determination of thiobarbituric acid-reactive substances (TBARS) formed during peroxidation. Their antioxidant activities were in the order of dipropofol>di(2,6-di-t-butylphenol)>diBHA>di(2,6-dimethylphenol). Dipropofol, a dimeric compound of propofol, showed the highest antioxidant activities. Dimeric compounds had higher activities than monomeric compounds, and the 1,1-diphenyl-p-picryhydrazyl-trapping ability of dimeric compounds was also greater than those of monomeric compounds (4-10-fold). These results suggest that dimeric phenols may increase their antioxidant activities along with increments in the conjugation system and play a inhibitory role in the propagation of free radical chain reactions. PMID:15744114

Ogata, Masahiro; Shin-Ya, Kazuo; Urano, Shiro; Endo, Toyoshige

2005-03-01

89

Leishmanicidal activity of some stilbenoids and related heterocyclic compounds  

Microsoft Academic Search

We have evaluated the leishmanicidal activity of some natural and semisynthetic dihydrostilbenoids and several compounds of other series of dihydrostilbamides, isoindoles, phthalazinones, imidazoisoindoles and pyrimidoisoindoles. The evaluation was performed in vitro, on cultures of cutaneous, mucocutaneous and visceral strains of Leishmania spp. The most potent and selective compounds of these series were the dihydrostilbene piperidides.

Esther del Olmo; Marlon Garc??a Armas; Jose Luis López-Pérez; Victoria Muñoz; Eric Deharo; Arturo San Feliciano

2001-01-01

90

Diversity through phosphine catalysis identifies octahydro-1,6-naphthyridin-4-ones as activators of endothelium-driven immunity.  

PubMed

The endothelium plays a critical role in promoting inflammation in cardiovascular disease and other chronic inflammatory conditions, and many small-molecule screens have sought to identify agents that prevent endothelial cell activation. Conversely, an augmented immune response can be protective against microbial pathogens and in cancer immunotherapy. Yet, small-molecule screens to identify agents that induce endothelial cell activation have not been reported. In this regard, a bioassay was developed that identifies activated endothelium by its capacity to trigger macrophage inflammatory protein 1 beta from primary monocytes. Subsequently, a 642-compound library of 39 distinctive scaffolds generated by a diversity-oriented synthesis based on the nucleophilic phosphine catalysis was screened for small molecules that activated the endothelium. Among the active compounds identified, the major classes were synthesized through the sequence of phosphine-catalyzed annulation, Tebbe reaction, Diels-Alder reaction, and in some cases, hydrolysis. Ninety-six analogs of one particular class of compounds, octahydro-1,6-naphthyridin-4-ones, were efficiently prepared by a solid-phase split-and-pool technique and by solution phase analog synthesis. Structure-function analysis combined with transcriptional profiling of active and inactive octahydro-1,6-naphthyridin-4-one analogs identified inflammatory gene networks induced exclusively by the active compound. The identification of a family of chemical probes that augment innate immunity through endothelial cell activation provides a framework for understanding gene networks involved in endothelial inflammation as well as the development of novel endothelium-driven immunotherapeutic agents. PMID:21383121

Cruz, Daniel; Wang, Zhiming; Kibbie, Jon; Modlin, Robert; Kwon, Ohyun

2011-03-07

91

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

PubMed

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

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

2004-03-01

92

StructureActivity Study and Design of Multidrug-resistant Reversal Compounds by a Computer Automated Structure Evaluation Methodology  

Microsoft Academic Search

We have studied the relation between the structure and the multidrug resistance-reversal activity of a set of diverse chemicals with the MUL- TICASE structure-activity program. A number of key structural fea tures were identified as being related to multidrug resistance reversal activity. Using these key features, we identified seven new compounds predicted to have substantial activity. These were obtained and

Gilles Klopman; Sanjay Srivastava; Istvan Kolossvary; Raquel F. Epand; Nadeem Ahmed; Richard M. Epand

93

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

Microsoft Academic Search

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

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

2006-01-01

94

Impact of Nitrogen Compounds on Catalyst Activity.  

National Technical Information Service (NTIS)

Second stage coal liquefaction catalysts lose greater than 75% of their hydrogenation activity as soon as coal processing begins. This rapid deactivation is due to the buildup of carbonaceous deposits on the catalyst. The objective of the research present...

F. V. Stohl

1986-01-01

95

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

PubMed

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

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

2011-06-24

96

Physiologically active compounds interacting with serotonin (5-hydroxytryptamine) receptors  

NASA Astrophysics Data System (ADS)

The data on the structures of organic compounds active with respect to serotonin (5-hydroxytryptamine) receptors are systematised. Various aspects of their design are considered. The bibliography includes 296 references.

Zefirova, Ol'ga N.; Zefirov, Nikolai S.

2001-04-01

97

Cytotoxicity and antiviral activity of the compounds from Euphorbia kansui.  

PubMed

Eleven compounds including four triterpenes, one sterol, and six diterpenes from E kansui had been assayed for their cytotoxicity and activiral activity. The relations between structures and bioactivities have also been noted. PMID:9933994

Zheng, W F; Cui, Z; Zhu, Q

1998-12-01

98

Chemistry of Natural and Anthropogenic Endocrine Active Compounds  

Microsoft Academic Search

Research over the past years has revealed that numerous compounds present in our environment exert hormonal activity and thus\\u000a have the potential to interfere with the endocrine system of humans and animals. These endocrine active compounds comprise\\u000a both naturally occurring substances and man-made chemicals, and their chemical structures are surprisingly diverse. This chapter\\u000a provides an overview of the chemical structures

Manfred Metzler; Erika Pfeiffer

99

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

SciTech Connect

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.

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

2010-09-20

100

Whole-organism screening for gluconeogenesis identifies activators of fasting metabolism  

PubMed Central

Improving the control of energy homeostasis can lower cardiovascular risk in metabolically compromised individuals. To identify new regulators of whole-body energy control, we conducted a high-throughput screen in transgenic reporter zebrafish for small molecules that modulate the expression of the fasting-inducible gluconeogenic gene pck1. We show that this in vivo strategy identified several drugs that impact gluconeogenesis in humans, as well as metabolically uncharacterized compounds. Most notably, we find that the Translocator Protein (TSPO) ligands PK 11195 and Ro5-4864 are glucose lowering agents despite a strong inductive effect on pck1 expression. We show that these drugs are activators of a fasting-like energy state, and importantly that they protect high-fat diet induced obese mice from hepatosteatosis and glucose intolerance, two pathological manifestations of metabolic dysregulation. Thus, using a whole-organism screening strategy, this study has identified new small molecule activators of fasting metabolism.

Gut, Philipp; Baeza-Raja, Bernat; Andersson, Olov; Hasenkamp, Laura; Hsiao, Joseph; Hesselson, Daniel; Akassoglou, Katerina; Verdin, Eric; Hirschey, Matthew D.; Stainier, Didier Y.R.

2012-01-01

101

Whole-organism screening for gluconeogenesis identifies activators of fasting metabolism.  

PubMed

Improving the control of energy homeostasis can lower cardiovascular risk in metabolically compromised individuals. To identify new regulators of whole-body energy control, we conducted a high-throughput screen in transgenic reporter zebrafish for small molecules that modulate the expression of the fasting-inducible gluconeogenic gene pck1. We show that this in vivo strategy identified several drugs that affect gluconeogenesis in humans as well as metabolically uncharacterized compounds. Most notably, we find that the translocator protein ligands PK 11195 and Ro5-4864 are glucose-lowering agents despite a strong inductive effect on pck1 expression. We show that these drugs are activators of a fasting-like energy state and, notably, that they protect high-fat diet-induced obese mice from hepatosteatosis and glucose intolerance, two pathological manifestations of metabolic dysregulation. Thus, using a whole-organism screening strategy, this study has identified new small-molecule activators of fasting metabolism. PMID:23201900

Gut, Philipp; Baeza-Raja, Bernat; Andersson, Olov; Hasenkamp, Laura; Hsiao, Joseph; Hesselson, Daniel; Akassoglou, Katerina; Verdin, Eric; Hirschey, Matthew D; Stainier, Didier Y R

2012-12-02

102

Human developmental exposure to endocrine active compounds  

Microsoft Academic Search

Quantification of exposure to environmental contaminants such as endocrine active chemicals (EACs) during critical periods of development, particularly in utero, remains largely unexplored. Therefore, we tested the hypothesis that EACs can be detected and quantified in second trimester human amniotic fluid. Amniotic fluid was obtained from women (n=175) undergoing routine amniocentesis between 14 and 21 weeks gestation. Samples were assayed

Warren G Foster; Claude L Hughes; Siu Chan; Lawrence Platt

2002-01-01

103

[Antioxidant and antibacterial activities of dimeric phenol compounds].  

PubMed

We studied the antioxidant and antibacterial activities of monomeric and dimeric phenol compounds. Dimeric compounds had higher antioxidant activities than monomeric compounds. Electron spin resonance spin-trapping experiments showed that phenol compounds with an allyl substituent on their aromatic rings directly scavenged superoxide, and that only eugenol trapped hydroxyl radicals. We developed a generation system of the hydroxyl radical without using any metals by adding L-DOPA and DMPO to PBS or MiliQ water in vitro. We found that eugenol trapped hydroxyl radicals directly and is metabolized to a dimer. On the other hand, dipropofol, a dimer of propofol, has strong antibacterial activity against Gram-positive bacteria. However, it lacks solubility in water and this property is assumed to limit its efficacy. We tried to improve the solubility and found a new solubilization method of dipropofol in water with the addition of a monosaccharide or ascorbic acid. PMID:18670180

Ogata, Masahiro

2008-08-01

104

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

PubMed

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

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

2012-01-18

105

Antimicrobial activity of the methanolic extracts and compounds from Treculia africana and Treculia acuminata (Moraceae)  

Microsoft Academic Search

The crude methanolic extracts from Treculia africana and Treculia acuminata, three compounds isolated from T. africana and identified as, Phyllocoumarin (1), Catechin (2) and 6, 9-dihydroxy-megastigmane-3-one (3), four compounds namely 2, 3, 2,3-dihydroxypropyl-heptadecanoate (4), and Ferulic acid (5) isolated from T. acuminata were tested for their antimicrobial activity against Gram-positive bacteria (six species), Gram-negative bacteria (12 species) and three Candida

V. Kuete; R. Metuno; B. Ngameni; A. T. Mbaveng; F. Ngandeu; M. Bezabih; F.-X. Etoa; B. T. Ngadjui; B. M. Abegaz; V. P. Beng

2008-01-01

106

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

107

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

PubMed Central

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

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

2012-01-01

108

An integrated approach for identification and target validation of antifungal compounds active against Erg11p.  

PubMed

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

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

2012-05-21

109

The OPTX Project. V. Identifying Distant Active Galactic Nuclei  

NASA Astrophysics Data System (ADS)

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

Trouille, L.; Barger, A. J.; Tremonti, C.

2011-11-01

110

Different phenolic compounds activate distinct human bitter taste receptors.  

PubMed

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

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

2013-02-06

111

Triorganosilicon (IV) compounds: synthesis, structural study, and biological activity.  

PubMed

A few coordination compounds of silicon (IV) have been synthesized by the interaction of trimethyl- and triphenyl-chlorosilane with nitrogen-sulphur donor ligands. These compounds are monomeric, as indicated by molecular weight determination, and they behave as nonelectrolytes in dry DMF. From the electronic, infrared, 1H, and 13C NMR spectral results, it has been concluded that in these compounds, silicon is penta-coordinated in a trigonal bipyramidal environment. An assessment of biological activity of these compounds has shown that some of them are very active against P. mirabilis and others against S. viridans bacteria, while all of them show good fungicidal action against F. oxysporum, A. alternata, and A. niger. PMID:8936423

Singh, D; Singh, R V; Jha, N K

1996-04-01

112

Use of reference compounds in antioxidant activity assessment.  

PubMed

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

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

2007-06-19

113

Removal of endocrine active compounds using layered double hydroxide material  

Microsoft Academic Search

A granular form of a layered double hydroxide (LDH) material was used as an anionic adsorbent in packed column and slurry experiments to remove endocrine active compounds (EACs) from river water downstream from wastewater treatment plants and from laboratory water spiked with 17?-estradiol (E2). The estrogenic activity of the samples was estimated using the biological yeast estrogen screen (YES) assay

J. M. Morris; S. Jin; K. Cui

2008-01-01

114

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

PubMed

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

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

2012-08-25

115

Antimalarial activity of compounds comprising a primary benzene sulfonamide fragment.  

PubMed

Despite the urgent need for effective antimalarial drugs with novel modes of action no new chemical class of antimalarial drug has been approved for use since 1996. To address this, we have used a rational approach to investigate compounds comprising the primary benzene sulfonamide fragment as a potential new antimalarial chemotype. We report the in vitro activity against Plasmodium falciparum drug sensitive (3D7) and resistant (Dd2) parasites for a panel of fourteen primary benzene sulfonamide compounds. Our findings provide a platform to support the further evaluation of primary benzene sulfonamides as a new antimalarial chemotype, including the identification of the target of these compounds in the parasite. PMID:24084158

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

2013-09-14

116

Antibacterial Activity of Phenolic Compounds Against the Phytopathogen Xylella fastidiosa  

Microsoft Academic Search

Xylella fastidiosa is a pathogenic bacterium that causes diseases in many crop species, which leads to considerable economic loss. Phenolic\\u000a compounds (a group of secondary metabolites) are widely distributed in plants and have shown to possess antimicrobial properties.\\u000a The anti-Xylella activity of 12 phenolic compounds, representing phenolic acid, coumarin, stilbene and flavonoid, was evaluated\\u000a using an in vitro agar dilution

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

2010-01-01

117

Synthesis and Radioprotective Activity of New Organosilicon and Germanium Compounds  

PubMed Central

Silathiazolidine and metalladithioacetals (M = Si, Ge) have been prepared by the interaction of dialkyldichloro- or bis(diethylamino)dialkylsilanes and -germanes with 3-[N-(2- thioethyl)]amino-propanamide (WR-2529) and [1-thioethyl-2-(1-naphtylmethyl)]-2- imidazoline. The study of these compounds in the field of chemical radioprotection has shown a notable decrease in the toxicity and a rather large increase in the radioprotective activity of these new derivatives in comparison with the starting organic compounds.

Rima, Ghassoub; Dagiral, Rodolphe; Lion, Claude; Fatome, Marc; Roman, Vincent; Laval, Jean-Denis

1998-01-01

118

Large-scale screening using familial dysautonomia induced pluripotent stem cells identifies compounds that rescue IKBKAP expression.  

PubMed

Patient-specific induced pluripotent stem cells (iPSCs) represent a novel system for modeling human genetic disease and could provide a source of cells for large-scale drug-discovery screens. Here we demonstrate the feasibility of performing a primary screen in neural crest precursors derived from iPSCs that were generated from individuals with familial dysautonomia (FD), a rare, fatal genetic disorder affecting neural crest lineages. We tested 6,912 small-molecule compounds and characterized eight that rescued expression of IKBKAP, the gene responsible for FD. One of the hits, SKF-86466, was found to induce IKBKAP transcription through modulation of intracellular cAMP levels and PKA-dependent CREB phosphorylation. SKF-86466 also rescued IKAP protein expression and the disease-specific loss of autonomic neuronal marker expression. Our data implicate alpha-2 adrenergic receptor activity in regulating IKBKAP expression and demonstrate that small-molecule discovery using an iPSC-based disease model can identify candidate drugs for potential therapeutic intervention. PMID:23159879

Lee, Gabsang; Ramirez, Christina N; Kim, Hyesoo; Zeltner, Nadja; Liu, Becky; Radu, Constantin; Bhinder, Bhavneet; Kim, Yong Jun; Choi, In Young; Mukherjee-Clavin, Bipasha; Djaballah, Hakim; Studer, Lorenz

2012-11-25

119

Frequency of occurrence and potency range distribution of activity cliffs in bioactive compounds.  

PubMed

We have systematically identified activity cliffs in bioactive compounds for which high-confidence potency data were available. Different molecular representations were utilized and similarity and potency difference criteria for activity cliffs were clearly defined. Cliff formation was studied across the global potency range observed for qualifying bioactive compounds. Depending on the specific representation of activity cliffs, between ?22% and 34% of all active compounds meeting the data selection criteria were involved in the formation of at least one activity cliff spanning a potency difference of at least two orders of magnitude. However, these cliffs involved only between ?4.7% and ?5.7% of all compound pairs meeting the similarity criteria. Hence, in light of these findings, the formation of well-defined activity cliffs is a relatively rare event. Moreover, the potency range distribution of activity cliffs was analyzed in detail, revealing that most activity cliffs were formed between compounds with micro- and nanomolar potency, consistent with the global distribution of potency data. On the basis of our analysis, we propose a general definition of activity cliffs for data mining. PMID:22866827

Stumpfe, Dagmar; Bajorath, Jürgen

2012-08-17

120

Utilization of Microarrayed Compound Screening (?ARCS) to Identify Inhibitors of p56lck Tyrosine Kinase  

Microsoft Academic Search

Protein tyrosine kinases play critical roles in cell signaling and are considered attractive targets for drug discovery. The authors have applied ?ARCS (microarrayed compound screening) technology to develop a high-throughput screen for finding inhibitors of the p56lck tyrosine kinase. Initial assay development was performed in a homogeneous time-resolved (LANCE™) format in 96-well microplates and then converted into the gel-based ?ARCS

Gail Freiberg; Julie Wilkins; Caroline David; James Kofron; Yong Jia; Gavin C. Hirst; David J. Burns; Usha Warrior

2004-01-01

121

Structure-Activity Relationships on Compounds Having Neuro-Muscular Activity.  

National Technical Information Service (NTIS)

The report deals with the biological activity of four different series of compounds which were developed to clarify the structure-activity relationships required for optimal biological activity. Three of the series were carbamates with potent antiesterase...

T. A. Loomis

1974-01-01

122

Plant compounds insecticide activity against Coleoptera pest s of stored products  

Microsoft Academic Search

The objective of this work was to screen plants with insecticide activity, in order to isolate, identify and assess the bioactivity of insecticide compounds present in these plants, against Coleoptera pests of stored products: Oryzaephilus surinamensis L. (Silvanidae), Rhyzopertha dominica F. (Bostrichidae) and Sitophilus zeamais Mots. (Curculionidae). The plant species used were: basil (Ocimum selloi Benth.), rue (Ruta graveolens L.),

P. H. Rolfs

123

Anti-Inflammatory Activity of Sulfur-Containing Compounds from Garlic  

PubMed Central

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

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

2012-01-01

124

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

PubMed Central

High-throughput screening (HTS) of chemical compounds to identify modulators of molecular targets is a mainstay of pharmaceutical development. Increasingly, HTS is being used to identify chemical probes of gene, pathway, and cell functions, with the ultimate goal of comprehensively delineating relationships between chemical structures and biological activities. Achieving this goal will require methodologies that efficiently generate pharmacological data from the primary screen and reliably profile the range of biological activities associated with large chemical libraries. Traditional HTS, which tests compounds at a single concentration, is not suited to this task, because HTS is burdened by frequent false positives and false negatives and requires extensive follow-up testing. We have developed a paradigm, quantitative HTS (qHTS), tested with the enzyme pyruvate kinase, to generate concentration–response curves for >60,000 compounds in a single experiment. We show that this method is precise, refractory to variations in sample preparation, and identifies compounds with a wide range of activities. Concentration–response curves were classified to rapidly identify pyruvate kinase activators and inhibitors with a variety of potencies and efficacies and elucidate structure–activity relationships directly from the primary screen. Comparison of qHTS with traditional single-concentration HTS revealed a high prevalence of false negatives in the single-point screen. This study demonstrates the feasibility of qHTS for accurately profiling every compound in large chemical libraries (>105 compounds). qHTS produces rich data sets that can be immediately mined for reliable biological activities, thereby providing a platform for chemical genomics and accelerating the identification of leads for drug discovery.

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

2006-01-01

125

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

PubMed

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 ((1)H- and (13)C-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

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

2013-07-17

126

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

PubMed Central

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.

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

2013-01-01

127

Unbiased probing of the entire hepatitis C virus life cycle identifies clinical compounds that target multiple aspects of the infection  

PubMed Central

Over 170 million people are chronically infected by the hepatitis C virus (HCV) and at risk for dying from liver cirrhosis and hepatocellular carcinoma. Current therapy is expensive, associated with significant side effects, and often ineffective. Discovery of antiviral compounds against HCV traditionally involves a priori target identification followed by biochemical screening and confirmation in cell-based replicon assays. Typically, this results in the discovery of compounds that address a few predetermined targets and are prone to select for escape variants. To attempt to identify antiviral compounds with broad target specificity, we developed an unbiased cell-based screening system involving multiple rounds of infection in a 96-well format. Analysis of a publicly available library of 446 clinically approved drugs identified 33 compounds that targeted both known and previously unexplored aspects of HCV infection, including entry, replication, and assembly. Discovery of novel viral and cellular targets in this manner will broaden the therapeutic armamentarium against this virus, allowing for the development of drug mixtures that should reduce the likelihood of mutational escape.

Gastaminza, Pablo; Whitten-Bauer, Christina; Chisari, Francis V.

2009-01-01

128

Inferring Genetic Networks and Identifying Compound Mode of Action via Expression Profiling  

Microsoft Academic Search

The complexity of cellular gene, protein, and metabolite networks can hinder attempts to elucidate their structure and function. To address this problem, we used systematic transcriptional perturbations to construct a first-order model of regulatory interactions in a nine-gene subnetwork of the SOS pathway in Escherichia coli. The model correctly identified the major regulatory genes and the transcriptional targets of mitomycin

Timothy S. Gardner; Diego di Bernardo; David Lorenz; James J. Collins

2003-01-01

129

Byrsonima fagifolia Niedenzu Apolar Compounds with Antitubercular Activity  

PubMed Central

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

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

2011-01-01

130

Antioxidant and antiproliferative activity of Diospyros lotus L. extract and isolated compounds.  

PubMed

The object of the study was to determine the chemical composition of Diospyros lotus L. extract and their antioxidant and antiproliferative properties. Eight compounds were isolated from D. lotus and identified as gallic acid, methylgallate, ellagic acid, kaempferol, quercetin,myricetin, myricetin 3-O-beta-glucuronide, and myricetin-3-O-alpha-rhamnoside. D. lotus extract tested in different in vitro systems (DPPH, ABTS, FRAP, and Fe2+ chelating activity assay) showed significant antioxidant activity. The potential antiproliferative properties of D. lotus extract and isolated compounds against nine human cancer cell lines such as COR-L23, CaCo-2, C32, ACHN, A375, A549, Huh-7D12, MCF-7, and LNCaP were investigated in vitro by SRB assay. D. lotus extract demonstrated the highest inhibitory activity against COR-L23 with an IC50 value of 12.2 microg/ml. Among identified hydrolysable tannins, ellagic acid evidenced strong antiproliferative activity against both C32 and A375 cells with IC50 values of 0.8 and 4.1 microg/ml, respectively. Interesting results were observed, also, with gallic acid that showed the highest cytotoxic activity against CaCo-2 (IC(50) 2.6 microg/ml). Overall, the results of this study suggest that D. lotus displays a good antioxidant activity and has antiproliferative effects. Both activities are related to identified phenolic compounds. PMID:19731038

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

2009-12-01

131

Pearson versus Spearman Kendall's Tau Correlation Analysis on StructureActivity Relationships of Biologic Active Compounds  

Microsoft Academic Search

Abstract Asample,of sixty-seven pyrimidine derivatives with inhibitory activity on E. coli dihydrofolate reductase (DHFR) was ,studied by the ,use of molecular descriptors family on structure-activity relationships. Starting from the results obtained by applying ,of MDF-SAR methodology ,on pyrimidine ,derivatives and from the assumption ,that the measured activity (compounds’ inhibitory activity) of a ,biologically active compounds ,is a semi-quantitative outcome (can

Sorana-daniela Bolboac?; Lorentz Jäntschi

132

Influence of endocrine active compounds on the developing rodent brain  

Microsoft Academic Search

Changes in the volumes of sexually dimorphic brain nuclei are often used as a biomarker for developmental disruption by endocrine-active compounds (EACs). However, these gross, morphological analyses do not reliably predict disruption of cell phenotype or neuronal function. Therefore, an experimental approach that simultaneously assesses anatomical, physiological and behavioral endpoints is required when developing risk assessment models for EAC exposure.

Heather B. Patisaul; Eva K. Polston

2008-01-01

133

Computer assisted design of potentially active anti-trypanosomal compounds  

Microsoft Academic Search

A computer assisted molecular modeling was used to design molecules having a shape complementary to the active site of glutathione reductase (GR) and trypanothione reductase (TR). The designed 5-nitro compound derivatives, were obtained from structural knowledge gleaned on glutathione (GSSG), trypanothione (T[S]2) and GSP disulfide (glutathionylspermidine disulfide). These molecules form complexes with the enzymes GR and TR. The theoretical lead

Margot Paulino; Federico Iribarne; Mar??a Hansz; Mauricio Vega; Gustavo Seoane; Hugo Cerecetto; Rossanna Di Maio; Ignez Caracelli; Julio Zukerman-Schpector; Claudio Olea; Andrés O. M. Stoppani; Mathew Berriman; Alan H. Fairlamb; Orlando Tapia

2002-01-01

134

Genotoxic Potential of Natural and Synthetic Endocrine Active Compounds  

Microsoft Academic Search

In addition to their hormonal activity, endocrine active compounds may have the potential to cause DNA adducts, oxidative\\u000a DNA damage, and disturbances of the mitotic apparatus of the cell. They can therefore give rise to gene mutations as well\\u000a as structural and numerical chromosomal aberrations in the same way as do chemical carcinogens. This genotoxic potential is\\u000a independent of the

Manfred Metzler

135

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

PubMed Central

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

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

2011-01-01

136

Synthesis and anti-inflammatory activity of celecoxib like compounds.  

PubMed

Nine novel 4-[3-(4-Dimethylamino-phenyl)-5-aryl-4,5-dihydro-pyrazol-1-yl]-benzenesulfonamides (2a-i) were synthesized and evaluated for their anti-inflammatory and antiproliferative activities. These compounds (2a-i) showed moderate to strong anti-inflammatory activity in carrageenan rat paw oedema test. Compounds 2b, 2d and 2g showing comparable anti-inflammatory activity to that of reference drug celecoxib were evaluated for their ulcerogenic and analgesic activities. The effect of 2b, 2d and 2g on the content of NO, TNF-? and PGE2 in exudates from rat paw stimulated by carrageenan was also evaluated. The compound 2c showed considerable antitumor activities against all 60 human tumor cell lines with effective GI50 (MG-MID) value of 3.63 µM. It exhibited maximum activity against melanoma (LOX IMVI and SK-MEL-5) cancer cell lines with GI50 value less than 2 ?M. PMID:22957719

Ovais, Syed; Yaseen, Shafiya; Bashir, Rafia; Rathore, Pooja; Samim, Mohammed; Singh, Surender; Nair, Vinod; Javed, Kalim

2012-09-07

137

A combined impedance and AlphaLISA-based approach to identify anti-inflammatory and barrier-protective compounds in human endothelium.  

PubMed

Chronic inflammation is at least partially mediated by the chemokine-mediated attraction and by the adhesion molecule-directed binding of leukocytes to the activated endothelium. Therefore, it is therapeutically important to identify anti-inflammatory compounds able to control the interaction between leukocytes and the endothelial compartments of the micro- and macrocirculation. When testing novel drug candidates, it is, however, of the utmost importance to detect side effects, such as potential cytotoxic and barrier-disruptive activities. Indeed, minor changes in the endothelial monolayer integrity may increase the permeability of small blood vessels and capillaries, which, in extreme cases, can lead to edema development. Here, we describe the development of a high-throughput screening (HTS) platform, based on AlphaLISA technology, able to identify anti-inflammatory nontoxic natural or synthetic compounds capable of reducing tumor necrosis factor (TNF)-induced chemokine (interleukin [IL]-8) and adhesion molecule (ICAM-1) expression in human lung microvascular endothelial cells. Quantification of cell membrane-expressed ICAM-1 and of cell culture supernatant-associated levels of IL-8 was analyzed in HTS. In parallel, we monitored monolayer integrity and endothelial cell viability using the electrical cell substrate impedance sensing method. This platform allowed us to identify natural secondary metabolites from cyanobacteria, capable of reducing ICAM-1 and IL-8 levels in TNF-activated human microvascular endothelial cells in the absence of endothelial monolayer barrier disruption. PMID:22941294

Pflüger, Maren; Kapuscik, Aleksandra; Lucas, Rudolf; Koppensteiner, Anita; Katzlinger, Michael; Jokela, Jouni; Eger, Andreas; Jacobi, Nico; Wiesner, Christoph; Hofmann, Elisabeth; Onder, Kamil; Kopecky, Jiri; Schütt, Wolfgang; Hundsberger, Harald

2012-08-30

138

Activation tag screening to identify novel genes for trichothecene resistance  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

139

Sorption of perfluorinated compounds from contaminated water to activated carbon  

Microsoft Academic Search

Introduction  Perfluorinated compounds (PFC) are toxic and bioaccumulative compounds that are ubiquitous in the environment. It is important\\u000a to develop effective techniques to remove PFC from water. This study is the first to investigate sorption of PFC to activated\\u000a carbon (AC) at environmentally relevant nanogram per liter concentrations.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Batch AC sorption isotherms were measured for water from a contaminated groundwater well,

Mona C. Hansen; Marion H. Børresen; Martin Schlabach; Gerard Cornelissen

2010-01-01

140

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

PubMed

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

Fernández-Ibáñez, V; Fearn, T; Soldado, A; de la Roza-Delgado, B

2009-06-17

141

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

PubMed Central

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

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

1997-01-01

142

Potent antifungal activity of extracts and pure compound isolated from pomegranate peels and synergism with fluconazole against Candida albicans  

Microsoft Academic Search

Activity-guided repeated fractionation of crude hydro alcoholic extract prepared from the fruit peel of Punica granatum on a silica-gel column yielded a compound that exhibited strong antifungal activity against Candida spp. Based on spectral analyses, the compound was identified as punicalagin. Punicalagin showed strong activity against Candida albicans and Candida parapsilosis, with MICs of 3.9 and 1.9 ?g\\/ml, respectively. The combination

Eliana Harue Endo; Diógenes Aparício Garcia Cortez; Tânia Ueda-Nakamura; Celso Vataru Nakamura; Benedito Prado Dias Filho

2010-01-01

143

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

PubMed

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

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

2010-02-10

144

Reliability of facial muscle activity to identify vowel utterance  

Microsoft Academic Search

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

Ganesh R Naik; Dinesh K Kumar; Sridhar P Arjunan

2008-01-01

145

Aqua mediated synthesis of bio-active compounds.  

PubMed

Recently the aqueous medium has attracted the interest of organic chemists, and many. Moreover, in the past 20 years, the drug-discovery process has undergone extraordinary changes, and high-throughput biological screening of potential drug candidates has led to an ever-increasing demand for novel drug-like compounds. Noteworthy advantages were observed during the course of study on aqua mediated synthesis of compounds of medicinal importance. The established advantages of water as a solvent for reactions are, water is the most abundant and available resource on the planet and many biochemical processes occur in aqueous medium. This review will focus on describing new developments in the application of water in medicinal chemistry for the synthesis of bio-active compounds possessing various biological properties. PMID:23544463

Panda, Siva S

2013-05-01

146

Active MMP-2 Effectively Identifies the Presence of Colorectal Cancer  

PubMed Central

Fully active MMP-2 is expressed at such low levels in human tissues that studies often fail to confirm its value as a cancer marker despite strong associations with malignancy. This study utilized careful extraction, accurate activity measurements, standardization to purified controls and a new statistical metric to determine whether active MMP-2 is an effective indicator of colorectal cancer compared to pro-MMP-2 or pro-MMP-9. MMP-2 and MMP-9 activities were analyzed in matched normal and cancer samples from 269 patients by gelatin zymography, computer-assisted image analysis, serial dilutions of strong samples and standardization to controls. An index of effect size was designed for comparative evaluation of active MMP-2, pro-MMP-2 and pro-MMP-9 activities. For each gelatinase, mean activity and protein levels/mg soluble protein in normal mucosa and colorectal cancer were calculated for the first time with respect to commercial standards. Active MMP-2 activity, detected in 99% of colorectal cancers, was higher in 95% of cancers (on average 10-fold) than in normal mucosa. Levels of pro-MMP-2 and pro-MMP-9, but not active MMP-9, activities were also significantly higher in cancers versus normal. However, active MMP-2 activity provided the most effective test for the presence of cancer (P< 0.0001) with an effect size statistically significantly larger than for either pro-MMP-2 or pro-MMP-9. Receiver operating characteristic (ROC) curves demonstrated that a cut-off for active MMP-2 of >44 SDU activity/mg soluble protein (>180 pg/mg), which is three times mean normal levels, would permit detection of colorectal cancer with an estimated sensitivity of 84% and estimated specificity of 93%.

Murnane, Mary Jo; Cai, Jinguo; Shuja, Sania; McAneny, David; Klepeis, Veronica; Willett, John B.

2009-01-01

147

Aldose reductase inhibitory activity of compounds from Zea mays L.  

PubMed

Aldose reductase (AR) inhibitors have a considerable therapeutic potential against diabetes complications and do not increase the risk of hypoglycemia. Through bioassay-guided fractionation of an EtOH extract of the kernel from purple corn (Zea mays L.), 7 nonanthocyanin phenolic compounds (compound 1-7) and 5 anthocyanins (compound 8-12) were isolated. These compounds were investigated by rat lens aldose reductase (RLAR) inhibitory assays. Kinetic analyses of recombinant human aldose reductase (rhAR) were performed, and intracellular galactitol levels were measured. Hirsutrin, one of 12 isolated compounds, showed the most potent RLAR inhibitory activity (IC(50), 4.78 ? M). In the kinetic analyses using Lineweaver-Burk plots of 1/velocity and 1/substrate concentration, hirsutrin showed competitive inhibition against rhAR. Furthermore, hirsutrin inhibited galactitol formation in rat lens and erythrocytes sample incubated with a high concentration of galactose; this finding indicates that hirsutrin may effectively prevent osmotic stress in hyperglycemia. Therefore, hirsutrin derived from Zea mays L. may be a potential therapeutic agent against diabetes complications. PMID:23586057

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

2013-03-17

148

Implementation of a high-throughput screen for identifying small molecules to activate the Keap1-Nrf2-ARE pathway.  

PubMed

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

Wu, Kai Connie; McDonald, Peter R; Liu, Jie Jerry; Chaguturu, Rathnam; Klaassen, Curtis D

2012-10-08

149

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

PubMed Central

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

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

2010-01-01

150

Screening of Bioactive Compounds from Moutan Cortex and Their Anti-Inflammatory Activities in Rat Synoviocytes  

PubMed Central

Moutan Cortex, a widely used traditional Chinese medicine for the treatment of various diseases, is the root bark of Paeonia suffruticosa Andrews (Paeoniaceae). Most of the pharmacological investigations of Moutan Cortex have been addressed to its central nervous system activities, anti-oxidative and sedative actions. Otherwise, there are few reports about the active compounds with anti-inflammatory activity of Moutan Cortex. The aim of the present study was to screen and identify bioactive compounds with anti-inflammatory effect from Moutan Cortex. With the aid of preparative high performance liquid chromatography (HPLC) technique, ethyl acetate and ethanol extract of Moutan Cortex were isolated into twenty-two fractions. Bioactivities of these fractions were evaluated by measuring expression of tumor necrosis factor-? (TNF-?) in rat synoviocytes subjected to interleukin-1? (IL-1?). Eight compounds were isolated from six active fractions and identified by HPLC/MSn. Purified compounds, paeoniflorin, paeonol and pentagalloylglucose resulted in dose-dependent inhibition of TNF-? synthesis and IL-6 production in synoviocytes treated with proinflammatory mediator. These results suggested that paeonol, paeoniflorin, glycosides and pentagalloylglucose contribute to the anti-inflammatory effect of Moutan Cortex.

Wu, Mengjie

2009-01-01

151

Screening of bioactive compounds from moutan cortex and their anti-inflammatory activities in rat synoviocytes.  

PubMed

Moutan Cortex, a widely used traditional Chinese medicine for the treatment of various diseases, is the root bark of Paeonia suffruticosa Andrews (Paeoniaceae). Most of the pharmacological investigations of Moutan Cortex have been addressed to its central nervous system activities, anti-oxidative and sedative actions. Otherwise, there are few reports about the active compounds with anti-inflammatory activity of Moutan Cortex. The aim of the present study was to screen and identify bioactive compounds with anti-inflammatory effect from Moutan Cortex. With the aid of preparative high performance liquid chromatography (HPLC) technique, ethyl acetate and ethanol extract of Moutan Cortex were isolated into twenty-two fractions. Bioactivities of these fractions were evaluated by measuring expression of tumor necrosis factor-alpha (TNF-alpha) in rat synoviocytes subjected to interleukin-1beta (IL-1beta). Eight compounds were isolated from six active fractions and identified by HPLC/MS(n). Purified compounds, paeoniflorin, paeonol and pentagalloylglucose resulted in dose-dependent inhibition of TNF-alpha synthesis and IL-6 production in synoviocytes treated with proinflammatory mediator. These results suggested that paeonol, paeoniflorin, glycosides and pentagalloylglucose contribute to the anti-inflammatory effect of Moutan Cortex. PMID:18955220

Wu, Mengjie; Gu, Zhiyuan

2007-06-15

152

Mechanism change in estimating of antioxidant activity of phenolic compounds.  

PubMed

The 2,2'-diphenyl-1-picrylhydrazyl (DPPH(•)) method is commonly applied for the estimation of antioxidant activity of single compounds and plant extracts. In this method, the amount of disappeared DPPH(•) in the examined system, determined spectrophotometrically, is a measure of the antioxidative (hydrogen-donating) activity of compounds. The present paper discusses the influence of buffer components on the estimation of antioxidant activity of phenolic compounds by this method. According to the obtained results, the change of hydrogen ion concentration changes the mechanism of scavenging process of DPPH radicals by phenolic antioxidants, and the introduction of metal ions into measuring system blocks the scavenging process of DPPH radicals. Both factors depend on the anion type used in the measuring system. The presented results may be especially important for the researches examining plant extract which differ in the content and composition of natural acids and metal ions, and for those who investigate the mechanisms of the reaction applied for the estimation of antioxidant properties. PMID:22841085

Dawidowicz, Andrzej L; Olszowy, Ma?gorzata

2012-04-26

153

In vitro antioxidant activity of coffee compounds and their metabolites.  

PubMed

In this paper we report the antioxidant activity of different compounds which are present in coffee or are produced as a result of the metabolism of this beverage. In vitro methods such as the ABTS*+ [ABTS = 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)] decolorization assay and the oxygen radical absorbance capacity assay (ORAC) were used to assess the capacity of coffee compounds to scavenge free radicals. The importance of caffeine metabolites and colonic metabolites in the overall antioxidant activity associated with coffee consumption is shown. Colonic metabolites such as m-coumaric acid and dihydroferulic acid showed high antioxidant activity. The ability of these compounds to protect human low-density lipoprotein (LDL) oxidation by copper and 2,2'-azobis(2-amidinopropane) dihydrochloride was also explored. 1-Methyluric acid was particularly effective at inhibiting LDL oxidative modification. Different experiments showed that this caffeine metabolite is not incorporated into LDL particles. However, at physiologically relevant concentrations, it was able to delay for more than 13 h LDL oxidation by copper. PMID:17655324

Gómez-Ruiz, José Angel; Leake, David S; Ames, Jennifer M

2007-07-27

154

A 3D-QSAR model based screen for dihydropyridine-like compound library to identify inhibitors of amyloid beta (A?) production.  

PubMed

Abnormal accumulation of amyloid beta peptide (A?) is one of the hallmarks of Alzheimer's disease progression. Practical limitations such as cost , poor hit rates and a lack of well characterized targets are a major bottle neck in the in vitro screening of a large number of chemical libraries and profiling them to identify A? inhibitors. We used a limited set of 1,4 dihydropyridine (DHP)-like compounds from our model set (MS) of 24 compounds which inhibit A? as a training set and built 3D-QSAR (Three-dimensional Quantitative Structure-Activity Relationship) models using the Phase program (SchrÖdinger, USA). We developed a 3D-QSAR model that showed the best prediction for A? inhibition in the test set of compounds and used this model to screen a 1,043 DHP-like small library set of (LS) compounds. We found that our model can effectively predict potent hits at a very high rate and result in significant cost savings when screening larger libraries. We describe here our in silico model building strategy, model selection parameters and the chemical features that are useful for successful screening of DHP and DHP-like chemical libraries for A? inhibitors. PMID:21364791

Mathura, Venkatarajan S; Patel, Nikunj; Bachmeier, Corbin; Mullan, Michael; Paris, Daniel

2010-09-20

155

A 3D-QSAR model based screen for dihydropyridine-like compound library to identify inhibitors of amyloid beta (A?) production  

PubMed Central

Abnormal accumulation of amyloid beta peptide (A?) is one of the hallmarks of Alzheimer's disease progression. Practical limitations such as cost , poor hit rates and a lack of well characterized targets are a major bottle neck in the in vitro screening of a large number of chemical libraries and profiling them to identify A? inhibitors. We used a limited set of 1,4 dihydropyridine (DHP)-like compounds from our model set (MS) of 24 compounds which inhibit A? as a training set and built 3D-QSAR (Three-dimensional Quantitative Structure-Activity Relationship) models using the Phase program (SchrÖdinger, USA). We developed a 3D-QSAR model that showed the best prediction for A? inhibition in the test set of compounds and used this model to screen a 1,043 DHP-like small library set of (LS) compounds. We found that our model can effectively predict potent hits at a very high rate and result in significant cost savings when screening larger libraries. We describe here our in silico model building strategy, model selection parameters and the chemical features that are useful for successful screening of DHP and DHP-like chemical libraries for A? inhibitors.

Mathura, Venkatarajan S; Patel, Nikunj; Bachmeier, Corbin; Mullan, Michael; Paris, Daniel

2010-01-01

156

MEG identifies dorsal medial brain activations during sleep  

Microsoft Academic Search

All sleep stages contain epochs with high-amplitude electrophysiological phasic events, alternating with quieter “core periods.” High-amplitude and core state properties cannot be disentangled with PET and fMRI. Here from high temporal resolution magnetoencephalography data, regional changes in neuronal activity were extracted during core periods in different frequency bands for each sleep stage and waking. We found that gamma-band activity increases

Andreas A. Ioannides; George K. Kostopoulos; Lichan Liu; Peter B. C. Fenwick

2009-01-01

157

A Potent Activator of Melanogenesis Identified from Small Molecule Screening  

PubMed Central

Small molecules that increase the cellular level of melanin can be used to study melanogenesis, and have therapeutic potential for melanin-related diseases such as albinism. We describe the identification of a potent activator of melanogenesis from a targeted combinatorial library. Treating melanocytes with our most active molecule results in a 1.8-fold increase in melanin, and an increase in tyrosinase-catalyzed oxidation of L-tyrosine, a key step in melanin biosynthesis.

McNaughton, Brian R.; Gareiss, Peter C.; Jacobs, Stacey E.; Fricke, Alex F.; Scott, Glynis A.

2012-01-01

158

Active Botnet Probing to Identify Obscure Command and Control Channels  

Microsoft Academic Search

We consider the problem of identifying obscure chat-like botnet command and control (C&C) communications, which are indistinguishable from human-human communi- cation using traditional signature-based techniques. Existing passive-behavior-based anomaly detection techniques are lim- ited because they either require monitoring multiple bot- infected machines that belong to the same botnet or require extended monitoring times. In this paper, we explore the potential

Guofei Gu; Vinod Yegneswaran; Phillip A. Porras; Jennifer Stoll; Wenke Lee

2009-01-01

159

Zebrafish promoter microarrays identify actively transcribed embryonic genes  

Microsoft Academic Search

We have designed a zebrafish genomic microarray to identify DNA-protein interactions in the proximal promoter regions of over\\u000a 11,000 zebrafish genes. Using these microarrays, together with chromatin immunoprecipitation with an antibody directed against\\u000a tri-methylated lysine 4 of Histone H3, we demonstrate the feasibility of this method in zebrafish. This approach will allow\\u000a investigators to determine the genomic binding locations of

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

2006-01-01

160

Phase analysis identifies compound heterozygous deletions of the PARK2 gene in patients with early-onset Parkinson disease.  

PubMed

Exon rearrangements and point mutations are common in PARK2, the most important causative gene of autosomal recessive early-onset Parkinson disease (EOPD). However, gene dosage analysis alone cannot conclusively determine the phase of exon rearrangements and the incidence of molecularly confirmed parkin-type EOPD may be underestimated. To fully characterize the mutation spectrum, we performed sequencing and gene dosage analyses of SNCA, PARK2, PINK1, and PARK7 in 114 unrelated EOPD patients with onset age ?40 years. Mutational phase of exon rearrangements was determined by reverse-transcriptase PCR (RT-PCR) and sequence analysis using a patient's own RNA. Fourteen different PARK2 mutations (3 point mutations plus 11 exon rearrangements) were identified in 18 patients, comprising 1 homozygote (0.9%), 13 compound heterozygotes (11.4%), 3 single heterozygotes (2.6%), and 1 with unknown phase (0.9%). By phase determination, more than 80% (5 of 6) of patients with apparently contiguous multi-exon deletions and 30% (5 of 18) of all PARK2 mutation carriers were additionally diagnosed as compound heterozygotes, respectively. This study shows that compound heterozygous mutations constituted a significant portion of patients with apparently contiguous multi-exon deletions. Phase determination is a prerequisite to molecular diagnosis for autosomal recessive EOPD, especially in subjects with PARK2 exon rearrangements. PMID:21534944

Kim, S Y; Seong, M W; Jeon, B S; Kim, S Y; Ko, H S; Kim, J Y; Park, S S

2011-05-29

161

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

PubMed Central

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

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

2011-01-01

162

On combining recursive partitioning and simulated annealing to detect groups of biologically active compounds.  

PubMed

Statistical data mining methods have proven to be powerful tools for investigating correlations between molecular structure and biological activity. Recursive partitioning (RP), in particular, offers several advantages in mining large, diverse data sets resulting from high throughput screening. When used with binary molecular descriptors, the standard implementation of RP splits on single descriptors. We use simulated annealing (SA) to find combinations of molecular descriptors whose simultaneous presence best separates off the most active, chemically similar group of compounds. The search is incorporated into a recursive partitioning design to produce a regression tree for biological activity on the space of structural fingerprints. Each node is characterized by a specific combination of structural features, and the terminal nodes with high average activities correspond, roughly, to different classes of compounds. Using LeadScope structural features as descriptors to mine a database from the National Cancer Institute, the merging of RP and SA consistently identifies structurally homogeneous classes of highly potent anticancer agents. PMID:11911709

Blower, Paul; Fligner, Michael; Verducci, Joseph; Bjoraker, Jeffrey

163

Activation Tagging Identifies a Conserved MYB Regulator of Phenylpropanoid Biosynthesis  

Microsoft Academic Search

Plants produce a wide array of natural products, many of which are likely to be useful bioactive structures. Unfortu- nately, these complex natural products usually occur at very low abundance and with restricted tissue distribution, thereby hindering their evaluation. Here, we report a novel approach for enhancing the accumulation of natural prod- ucts based on activation tagging by Agrobacterium-mediated transformation

Justin O. Borevitz; Yiji Xia; Jack Blount; Richard A. Dixon; Chris Lamb

2000-01-01

164

Creatinyl amino acids: new hybrid compounds with neuroprotective activity.  

PubMed

Prolonged oral creatine administration resulted in remarkable neuroprotection in experimental models of brain stroke. However, because of its polar nature creatine has poor ability to penetrate the blood-brain barrier (BBB) without specific creatine transporter (CRT). Thus, synthesis of hydrophobic derivatives capable of crossing the BBB by alternative pathway is of great importance for the treatment of acute and chronic neurological diseases including stroke, traumatic brain injury and hereditary CRT deficiency. Here we describe synthesis of new hybrid compounds-creatinyl amino acids, their neuroprotective activity in vivo and stability to degradation in different media. The title compounds were synthesized by guanidinylation of corresponding sarcosyl peptides or direct creatine attachment using isobutyl chloroformate method. Addition of lipophilic counterion (p-toluenesulfonate) ensures efficient creatine dissolution in DMF with simultaneous protection of guanidino group towards intramolecular cyclization. It excludes the application of expensive guanidinylating reagents, permits to simplify synthetic procedure and adapt it to large-scale production. The biological activity of creatinyl amino acids was tested in vivo on ischemic stroke and NaNO(2) -induced hypoxia models. One of the most effective compounds-creatinyl-glycine ethyl ester increases life span of experimental animals more than two times in hypoxia model and has neuroprotective action in brain stroke model when applied both before and after ischemia. These data evidenced that creatinyl amino acids can represent promising candidates for the development of new drugs useful in stroke treatment. PMID:21644247

Burov, Sergey; Leko, Maria; Dorosh, Marina; Dobrodumov, Anatoliy; Veselkina, Olga

2011-06-06

165

Degradation of volatile organic compounds with thermally activated persulfate oxidation.  

PubMed

This study investigated the extent and treatability of the degradation of 59 volatile organic compounds (VOCs) listed in the EPA SW-846 Method 8260B with thermally activated persulfate oxidation. Data on the degradation of the 59 VOCs (in mixture) reacted with sodium persulfate in concentrations of 1 g l(-1) and 5 g l(-1) and at temperatures of 20 degrees C, 30 degrees C, and 40 degrees C were obtained. The results indicate that persulfate oxidation mechanisms are effective in degrading many VOCs including chlorinated ethenes (CEs), BTEXs and trichloroethanes that are frequently detected in the subsurface at contaminated sites. Most of the targeted VOCs were rapidly degraded under the experimental conditions while some showed persistence to the persulfate oxidation. Compounds with "CC" bonds or with benzene rings bonded to reactive functional groups were readily degraded. Saturated hydrocarbons and halogenated alkanes were much more stable and difficult to degrade. For those highly persulfate-degradable VOCs, degradation was well fitted with a pseudo first-order decay model. Activation energies of reactions of CEs and BTEXs with persulfate were determined. The degradation rates increased with increasing reaction temperature and oxidant concentration. Nevertheless, to achieve complete degradation of persulfate-degradable compounds, the systems required sufficient amounts of persulfate to sustain the degradation reaction. PMID:16202809

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

2005-04-12

166

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

PubMed

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

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

2013-04-19

167

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

Microsoft Academic Search

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

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

2009-01-01

168

Development of a Tier I Screening Battery for Detecting Endocrine-Active Compounds (EACs)  

Microsoft Academic Search

One of the components of our research program is development of a mode-of-action screening battery to detect several different types of endocrine-active compounds (EACs). Our working hypothesis is that a comprehensive short-termin vivo\\/in vitrobattery can be developed to identify endocrine toxicants using a collection of endpoints. The goals of this battery are that it be quick, cost effective, and predictive.

Jon C Cook; A. Michael Kaplan; Leonard G Davis; John C O'connor

1997-01-01

169

Screening for Antiviral Activities of Isolated Compounds from Essential Oils  

PubMed Central

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

Astani, Akram; Reichling, Jurgen; Schnitzler, Paul

2011-01-01

170

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

PubMed Central

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

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

2013-01-01

171

Characterization of aroma-active compounds in rainbow trout (Oncorhynchus mykiss) eliciting an off-odor.  

PubMed

The aroma-active and off-flavor compounds of cooked rainbow trout (Oncorhynchus mykiss) were analyzed by sensory and instrumental analyses. Sensory analysis shows that the aromatic extract obtained by vacuum steam distillation was representative of rainbow trout odor. To obtain more information on odorants of volatile compounds, analyses were conducted on two gas chromatography columns of different polarities (DB-5 and DB-Wax). The results of the gas chromatography-olfactometry analysis showed that 38 odorous compounds were perceived when the DB-5 column was used and 36 with the DB-Wax column. Of these, 31 with the DB-5 and 28 with the DB-Wax were identified. (E)-2-Nonenal, 2-ethyl-1-hexanol, 2-methylisoborneol, geosmin, 2-methylnaphthalene, and 8-heptadecene were described as off-flavor compounds by the sniffing assessors. The most powerful off-flavor compounds identified in the extract were 2-methylisoborneol and geosmin, which were described as strong musty and earthy odors, respectively. PMID:17147438

Selli, Serkan; Rannou, Cecile; Prost, Carole; Robin, Joel; Serot, Thierry

2006-12-13

172

Identifying criminal activities at the operating system level  

NASA Astrophysics Data System (ADS)

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

Hussain, Khaled; Sapre, Sampada; Hajgude, Poonam

2005-05-01

173

Antifungal activity of tautomycin and related compounds against Sclerotinia sclerotiorum.  

PubMed

The potential of tautomycin to control oilseed rape stem rot was investigated in this paper. Tautomycin produced by Streptomyces spiroverticillatus strongly inhibited Sclerotinia sclerotiorum, which causes oilseed rape stem rot. Tautomycin showed great inhibition of the mycelial growth of S. sclerotiorum on potato dextrose agar (PDA) plates. The values of EC(50) and MIC were 3.26 × 10(-4) mM and 6.52 × 10(-4) mM, respectively. Tautomycin treatment also resulted in morphological abnormalities of S. sclerotiorum such as hyphal swellings and abnormally branched shapes, which were observed microscopically. Sclerotia of S. sclerotiorum soaked in the tautomycin solution for 24 h remained viable, but their ability to undergo myceliogenic germination on PDA plates was completely inhibited when the concentration of tautomycin reached 6.52 × 10(-4) mM. Tautomycin-treated oilseed rape leaves were found to have a low incidence of leaf blight caused by S. sclerotiorum. The activity of the protein phosphatase (PP) in S. sclerotiorum decreased by 41.6% and 52.6% when treated with 3.30 × 10(-4)?mM and 6.52 × 10(-4) mM tautomycin, respectively. Cellular constituents also leaked from S. sclerotiorum cells incubated with tautomycin. The results suggest that the antimicrobial activity of tautomycin is due to the inhibition of the PP and then a change of membrane permeability. This paper also investigated related compounds that possess either a maleic anhydride or maleic acid moiety. Results showed 2,3-dimethylmaleic anhydride, diphenylmaleic anhydride and dimethyl maleate demonstrated significant activity against S. sclerotiorum. The values of EC(50) for these three compounds were 0.31 mM, 0.15 mM and 3.99 mM, respectively. The MIC values obtained for these compounds were 1.11 mM, 0.56 mM and 9.58 mM, respectively. PMID:21772304

Chen, Xiaolong; Zhu, Xiaohui; Ding, Yicheng; Shen, Yinchu

2011-07-20

174

Hypochlorous Acid Scavenging Activities of Thioallyl Compounds from Garlic.  

PubMed

The hypochlorous acid (HOCl) scavenging capacities of 10 garlic compounds containing modifications in the thioallyl group (-S-CH(2)CH?CH(2)) were determined by a catalase protection assay, and the corresponding structure-activity relationships using molecular descriptors were calculated. This scavenging activity was enhanced by increasing the number of S atoms or by the alanyl group (-CH(2)CH-NH(2)-COOH) and decreased in the absence of the C?C bond or in the presence of a sulfoxide group in the thioallyl group. Interestingly, S-allylcysteine and its corresponding sulfoxide (alliin) showed the highest and lowest HOCl-scavenging capacities, respectively. Quantitative modeling by multiple regression analysis and partial least-squares projections showed that the topological descriptor polar surface area and two electronic properties, namely, highest occupied molecular orbital and total energy, contributed mainly to variations in the HOCl scavenging activity of thioallyl compounds. These observations provide new insights on the antioxidant mechanism of garlic derivatives in processes involving HOCl production. PMID:20942486

Argu?ello-Garci?a, Rau?l; Medina-Campos, Omar N; Pe?rez-Herna?ndez, Nury; Pedraza-Chaverri?, Jose?; Ortega-Pierres, Guadalupe

2010-10-13

175

Identification of major phenolic compounds from Nephelium lappaceum L. and their antioxidant activities.  

PubMed

Nephelium lappaceum is a tropical fruit whose peel possesses antioxidant properties. Experiments on the isolation and identification of the active constituents were conducted, and on their antioxidant activity using a lipid peroxidation inhibition assay. The methanolic extract of N. lappaceum peels exhibited strong antioxidant properties. Sephadex LH-20 chromatography was utilized in the isolation of each constituent and the antioxidant properties of each was studied. The isolated compounds were identified as ellagic acid (EA) (1), corilagin (2) and geraniin (3). These compounds accounted for 69.3% of methanolic extract, with geraniin (56.8%) as the major component, and exhibited much greater antioxidant activities than BHT in both lipid peroxidation (77-186 fold) and DPPH* (42-87 fold) assays. The results suggest that the isolated ellagitannins, as the principal components of rambutan peels, could be further utilized as both a medicine and in the food industry. PMID:20335993

Thitilertdecha, Nont; Teerawutgulrag, Aphiwat; Kilburn, Jeremy D; Rakariyatham, Nuansri

2010-03-09

176

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

PubMed

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

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

2007-04-25

177

Antinociceptive activity and preliminary structure-activity relationship of chalcone-like compounds.  

PubMed

Chalcones belong to a class of alpha,beta,-unsaturated aromatic ketones which occur abundantly in nature, especially in plants. They are promising and interesting compounds due to their vast applications in pharmaceuticals, agriculture and industry. Several studies have shown that these compounds exert important biological activities in different experimental models. The present work deals with the antinociceptive activity, evaluated against the writhing test, of three series of chalcone-like compounds obtained by the Claisen-Schmidt condensation, using different aldehydes and substituted acetophenones. The results reveal that the compounds synthesized show a significant antinociceptive effect compared with nonsteroidal drugs such as aspirin, paracetamol and diclofenac. They also show that the electronic demand of the substituents is the dominant factor of the biological activity. PMID:19227830

Corrêa, Rogério; Fenner, Bruna Proiss; Buzzi, Fátima de Campos; Cechinel Filho, Valdir; Nunes, Ricardo José

178

Identifying the Main Driver of Active Region Outflows  

NASA Astrophysics Data System (ADS)

Hinode's EUV Imaging Spectrometer (EIS) has discovered ubiquitous outflows of a few to 50 km s-1 from active regions (ARs). The characteristics of these outflows are very curious in that they are most prominent at the AR boundary and appear over monopolar magnetic areas. They are linked to strong non-thermal line broadening and are stronger in hotter EUV lines. The outflows persist for at least several days. Whereas red-shifted down flows observed in AR closed loops are well understood, to date there is no general consensus for the mechanism(s) driving blue-shifted AR-related outflows. We use Hinode EIS and X-Ray Telescope observations of AR 10942 coupled with magnetic modeling to demonstrate for the first time that the outflows originate from specific locations of the magnetic topology where field lines display strong gradients of magnetic connectivity, namely quasi-separatrix layers (QSLs), or in the limit of infinitely thin QSLs, separatrices. The strongest AR outflows were found to be in the vicinity of QSL sections located over areas of strong magnetic field. We argue that magnetic reconnection at QSLs, separating closed field lines of the AR and either large-scale externally connected or ‘open’ field lines, is a viable mechanism for driving AR outflows which are potentially sources of the slow solar wind. In fact, magnetic reconnection along QSLs (including separatricies) is the first theory to explain the most puzzling characteristics of the outflows, namely their occurrence over monopolar areas at the periphery of ARs and their longevity.

Baker, D.; van Driel-Gesztelyi, L.; Mandrini, C. H.; Démoulin, P.; Murray, M. J.

2012-08-01

179

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

PubMed Central

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

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

2009-01-01

180

Activity cliffs in PubChem confirmatory bioassays taking inactive compounds into account.  

PubMed

Activity cliffs are formed by pairs or groups of structurally similar compounds with significant differences in potency. They represent a prominent feature of activity landscapes of compound data sets and a primary source of structure-activity relationship (SAR) information. Thus far, activity cliffs have only been considered for active compounds, consistent with the principles of the activity landscape concept. However, from an SAR perspective, pairs formed by structurally similar active and inactive compounds should often also be informative. Therefore, we have extended the activity cliff concept to also take inactive compounds into consideration. As source of both confirmed active and inactive compounds, we have exclusively focused on PubChem confirmatory bioassays. Activity cliffs formed between pairs of active compounds (homogeneous pairs) and pairs of active and inactive compounds (heterogeneous pairs) were systematically analyzed on a per-assay basis, hence ensuring the currently highest possible degree of experimental consistency in activity measurement. Only very small numbers of large-magnitude activity cliffs formed between active compounds were detected in PubChem bioassays. However, when taking confirmed inactive compounds from confirmatory assays into account, the activity cliff frequency in assay data significantly increased, involving 11-15% of all qualifying pairs of similar compounds, depending on the molecular representations that were used. Hence, these non-conventional activity cliffs provide an additional source of SAR information. PMID:23296990

Hu, Ye; Maggiora, Gerald M; Bajorath, Jürgen

2013-01-08

181

Identification of electrophysiologically-active compounds for the malaria mosquito, Anopheles gambiae, in human sweat extracts.  

PubMed

Human sweat samples were chemically fractionated into acid and non-acid components. The most abundant volatile compounds present in the fractions were identified by linked gas chromatography mass spectrometry. The acid fractions were found to be composed of a range of twenty aliphatic and three aromatic carboxylic acids ranging, on average, from 0.02 to 20 micrograms per ml of sweat sampled. Non-acid fractions were found to contain: 6-methyl-5-hepten-2-one, 1-octen-3-ol, decanal, benzyl alcohol, dimethylsulphone, phenylethanol, phenol and 4-methylphenol, collectively amounting to 0.1 and 3 micrograms per ml of sweat. The major component of sweat was found to be L-lactic acid which constituted from 1 to 5 mg/ml. Using the intact antennae of the anthropophilic malaria vector mosquito Anopheles gambiae Giles, the peripheral olfactory activities of compounds identified in the sweat fractions were investigated by electroantennography (EAG). Short-chain saturated carboxylic acids, methanoic, ethanoic, propanoic, butanoic, pentanoic and hexanoic acids were found to elicit significantly larger EAG responses than longer chain saturated carboxylic acids from female An.gambiae. For a given dose the largest amplitude EAG response was elicited by methanoic acid. Pentanoic acid elicited larger EAG responses than either butanoic or hexanoic acids. Two non-acidic compounds, 1-octen-3-ol and 4-methylphenol, were found to elicit significant dose-dependent EAG responses from female An.gambiae. 1-Octen-3-ol elicited larger EAG responses than 4-methylphenol for a given dose, but both compounds elicited smaller EAG responses than the same dose of C1-C6 straight-chain aliphatic carboxylic acids. The possible behavioural significance of the EAG-active compounds identified in human sweat samples is discussed. PMID:8887339

Cork, A; Park, K C

1996-07-01

182

Evaluation of compounds for insecticidal activity on adult mosquitos*  

PubMed Central

The N,N-dimethylcarbamates are much less toxic and much more volatile than the corresponding N-methylcarbamates. N-acylation of N-methylcarbamates is also generally accompanied by a loss in intrinsic toxicity to adult mosquitos by topical application, but the reduction in toxicity may be relatively small and in some N-acetyl derivatives may not occur at all. N-acylation is also accompanied by changes in physical properties such as lipid solubility and partition coefficient, which influence contact toxicity, and volatility, which affects residual activity. In the series of compounds examined, contact toxicity is maximal in the N-acetyl derivatives but their volatility is often so high that they lack the persistence required of residual insecticides. This does not apply, however, to the N-acetyl derivatives of OMS-597 and OMS-708 because the volatility of the parent compound is so low that some degree of persistence can be sacrificed to obtain some improvement in contact activity. OMS-1064 is the only N-chloroacetyl derivative tested so far that shows promise as a residual insecticide.

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

1970-01-01

183

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

PubMed Central

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.

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

2012-01-01

184

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

SciTech Connect

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.

Steven B. Hawthorne

2007-04-15

185

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

PubMed

The estrogenic activities of ultraviolet absorbers and their related compounds were investigated using MCF-7 cell proliferation assay. Nine of 33 chemicals (benzophenone, 2,4-dihydroxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, 4-hydroxybenzophenone, 3-(4-methylbenzylidene) camphor, ethyl 2-cyano-3,3-diphenylacrylate (etocrylene) and 2-ethylhexyl-2-cyano-3,3-diphenylacrylate (octocrylene)) were positive compared with the vehicle control. Benzhydrol, ethyl cinnamate and 2,2'-dihydroxy-4-methoxybenzophenone were weakly active. When each xenoestrogen was added to the cells along with ICI 182780, an estrogen receptor (ER) antagonist, the cell growth was reduced according to its doses. Therefore, the cell proliferation was suggested to generate through ER. Most of these chemicals were also positive using CHOOSER assay, a new method of testing estrogenic activity of xenoestrogen. Each xenoestrogen was also confirmed to bind to ERalpha and ERbeta using a human ER competitive binding assay against 17beta-estradiol. The concentration order of the strength of its inhibitory effect using both ERalpha and ERbeta was similar to that of MCF-7 cell proliferation assay, except for benzyl 4-hydroxybenzoate (B4HB). B4HB showed a stronger activity on CHOOSER assay and the competitive binding assay using both ERalpha and ERbeta, although there was no activity observed on MCF-7 cell proliferation assay. Our findings were to detect the estrogenic activity of etocrylene and octocrylene in vitro, in addition to confirming the activities of some ultraviolet absorbers as previously reported. PMID:16079615

Matsumoto, Hisashi; Adachi, Shinichi; Suzuki, Yasuhiko

2005-08-01

186

Isolation of Bioactive Compounds That Relate to the Anti-Platelet Activity of Cymbopogon ambiguus  

PubMed Central

Infusions and decoctions of Cymbopogon ambiguus have been used traditionally in Australia for the treatment of headache, chest infections and muscle cramps. The aim of the present study was to screen and identify bioactive compounds from C. ambiguus that could explain this plant's anti-headache activity. A dichloromethane extract of C. ambiguus was identified as having activity in adenosine-diphosphate-induced human platelet aggregation and serotonin-release inhibition bioassays. Subsequent fractionation of this extract led to the isolation of four phenylpropenoids, eugenol, elemicin, eugenol methylether and trans-isoelemicin. While both eugenol and elemicin exhibited dose-dependent inhibition of ADP-induced human platelet serotonin release, only eugenol displayed potent inhibitory activity with an IC50 value of 46.6??M, in comparison to aspirin, with an IC50 value of 46.1??M. These findings provide evidence to support the therapeutic efficacy of C. ambiguus in the non-conventional treatment of headache and inflammatory conditions.

Grice, I. Darren; Rogers, Kelly L.; Griffiths, Lyn R.

2011-01-01

187

Highly Active Anti-Pneumocystis carinii Compounds in a Library of Novel Piperazine-Linked Bisbenzamidines and Related Compounds  

PubMed Central

Trimethoprim-sulfamethoxazole and pentamidine isethionate have been used extensively for the prophylaxis and therapy of pneumonia caused by Pneumocystis jirovecii. Problems associated with toxicity and potential emerging resistance for both therapies necessitate the development of safe and effective analogs or new treatment strategies. In the present study, a library of 36 compounds was synthesized by using the pentamidine molecule as the parent compound modified by a 1,4-piperazinediyl moiety as the central linker to restrict conformation flexibility. The compounds were evaluated for anti-Pneumocystis carinii activity in a bioluminescent ATP-driven assay. Four of the compounds were highly active, with 50% inhibitory concentration (IC50) values of <0.01 ?g/ml; four had very marked activity (IC50 < 0.10 ?g/ml); ten had marked activity (IC50 < 1.0 ?g/ml); nine had moderate activity (IC50 < 10 ?g/ml); one had slight activity (IC50 = 34.1 ?g/ml); and the remaining eight did not demonstrate activity in this assay system. The high level of activity was specifically associated with an alkyl chain length of five to six carbons attached to one of the nitrogens of the bisamidinium groups. None of the highly active compounds and only one of the very marked compounds exhibited any toxicity when evaluated in three mammalian cell lines. The strategy of substitution of 1,4-piperazine-linked bisbenzamidines produced compounds with the highest level of activity observed in the ATP assay and holds great promise for the development of efficacious anti-P. carinii therapy.

Cushion, Melanie T.; Walzer, Peter D.; Collins, Margaret S.; Rebholz, Sandra; Vanden Eynde, Jean Jacques; Mayence, Annie; Huang, Tien L.

2004-01-01

188

Luminescence of biologically active 24-epicastasterone and a model compound  

NASA Astrophysics Data System (ADS)

Biologically active brassinosteroid 24-epicastasterone, ring B of which contains a C=O group and has the n?*-configuration for a low-lying electronic excited state, exhibits rapid fluorescence. The wavelengths of the fluorescence maxima of the steroid dissolved in hexane and acetonitrile are equal to 332 and 394 nm, respectively. The fluorescence lifetime of the steroid dissolved in acetonitrile is ? = 9.9 nsec. Solutions of 24-epibrassinolide do not luminesce. The long-wavelength electronic absorption band ?{max/abs} = 340 nm in the absorption spectrum of an ethanol solution of model compound 2, ring D of which contains a C=O group ?*-conjugated with the C=C double bond of ring C, like in the spectrum of the steroid, has a low extinction coefficient. An ethanol solution of 2 does not fluoresce. 24-Epicastasterone at 77 K in ethanol solution exhibits phosphorescence with ?{max/phos} = 447 nm. The phosphorescence decay is exponential with ? = 0.79 msec. Compound 2 also phosphoresces. The phosphorescence spectrum of its ethanol solution has a maximum at 490 nm. The phosphorescence decay is nonexponential in the early stage. The phosphorescence lifetime is 25 msec in the exponential decay region.

Borisevich, N. A.; Bagnich, S. A.; Raichenok, T. F.; Knyukshto, V. N.; Baranovskii, A. V.; Zhabinskii, V. N.

2008-03-01

189

Irreversible adsorption of phenolic compounds by activated carbons  

SciTech Connect

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.

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

1988-12-01

190

In Vitro Antifungal Activities of Bis(Alkylpyridinium)Alkane Compounds against Pathogenic Yeasts and Molds?  

PubMed Central

Ten bis(alkylpyridinium)alkane compounds were tested for antifungal activity against 19 species (26 isolates) of yeasts and molds. We then determined the MICs and minimum fungicidal concentrations (MFCs) of four of the most active compounds (compounds 1, 4, 5, and 8) against 80 Candida and 20 cryptococcal isolates, in comparison with the MICs of amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, and caspofungin, using Clinical Laboratory and Standards Institutes broth microdulition M27-A3 (yeasts) or M38-A2 (filamentous fungi) susceptibility protocols. The compounds were more potent against Candida and Cryptococcus spp. (MIC range, 0.74 to 27.9 ?g/ml) than molds (0.74 to 59.7 ?g/ml). MICs against Exophiala were 0.37 to 5.9 ?g/ml and as low as 1.48 ?g/ml for Scedosporium but ?25 ?g/ml for zygomycetes, Aspergillus, and Fusarium spp. Compounds 1, 4, 5, and 8 exhibited good fungicidal activity against Candida and Cryptococcus, except for Candida parapsilosis (MICs of >44 ?g/ml). Geometric mean (GM) MICs were similar to those of amphotericin B and lower than or comparable to fluconazole GM MICs but 10- to 100-fold greater than those for the other azoles. GM MICs against Candida glabrata were <1 ?g/ml, significantly lower than fluconazole GM MICs (P < 0.001) and similar to those of itraconazole, posaconazole, and voriconazole (GM MIC range of 0.4 to 1.23 ?g/ml). The GM MIC of compound 4 against Candida guilliermondii was lower than that of fluconazole (1.69 ?g/ml versus 7.48 ?g/ml; P = 0.012). MICs against Cryptococcus neoformans and Cryptococcus gattii were similar to those of fluconazole. The GM MIC of compound 4 was significantly higher for C. neoformans (3.83 ?g/ml versus 1.81 ?g/ml for C. gattii; P = 0.015). This study has identified clinically relevant in vitro antifungal activities of novel bisalkypyridinium alkane compounds.

Chen, Sharon C.-A.; Biswas, Chayanika; Bartley, Robyn; Widmer, Fred; Pantarat, Namfon; Obando, Daniel; Djordjevic, Julianne T.; Ellis, David H.; Jolliffe, Katrina A.; Sorrell, Tania C.

2010-01-01

191

In vitro antifungal activities of bis(alkylpyridinium)alkane compounds against pathogenic yeasts and molds.  

PubMed

Ten bis(alkylpyridinium)alkane compounds were tested for antifungal activity against 19 species (26 isolates) of yeasts and molds. We then determined the MICs and minimum fungicidal concentrations (MFCs) of four of the most active compounds (compounds 1, 4, 5, and 8) against 80 Candida and 20 cryptococcal isolates, in comparison with the MICs of amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, and caspofungin, using Clinical Laboratory and Standards Institutes broth microdulition M27-A3 (yeasts) or M38-A2 (filamentous fungi) susceptibility protocols. The compounds were more potent against Candida and Cryptococcus spp. (MIC range, 0.74 to 27.9 microg/ml) than molds (0.74 to 59.7 microg/ml). MICs against Exophiala were 0.37 to 5.9 microg/ml and as low as 1.48 microg/ml for Scedosporium but >or=25 microg/ml for zygomycetes, Aspergillus, and Fusarium spp. Compounds 1, 4, 5, and 8 exhibited good fungicidal activity against Candida and Cryptococcus, except for Candida parapsilosis (MICs of >44 mug/ml). Geometric mean (GM) MICs were similar to those of amphotericin B and lower than or comparable to fluconazole GM MICs but 10- to 100-fold greater than those for the other azoles. GM MICs against Candida glabrata were <1 microg/ml, significantly lower than fluconazole GM MICs (P<0.001) and similar to those of itraconazole, posaconazole, and voriconazole (GM MIC range of 0.4 to 1.23 microg/ml). The GM MIC of compound 4 against Candida guilliermondii was lower than that of fluconazole (1.69 microg/ml versus 7.48 microg/ml; P=0.012). MICs against Cryptococcus neoformans and Cryptococcus gattii were similar to those of fluconazole. The GM MIC of compound 4 was significantly higher for C. neoformans (3.83 mug/ml versus 1.81 microg/ml for C. gattii; P=0.015). This study has identified clinically relevant in vitro antifungal activities of novel bisalkypyridinium alkane compounds. PMID:20530227

Chen, Sharon C-A; Biswas, Chayanika; Bartley, Robyn; Widmer, Fred; Pantarat, Namfon; Obando, Daniel; Djordjevic, Julianne T; Ellis, David H; Jolliffe, Katrina A; Sorrell, Tania C

2010-06-07

192

Antioxidant activity of an aminothiazole compound: possible mechanisms.  

PubMed

Oceans are among the richest natural sources of many bioactive compounds. Several of these compounds have shown pharmacological activities for many diseases. Dendrodoine (5-[(3-N-dimethylamino)-1,2,4-thiadiazolyl]-3-indanyl methanone) is an alkaloid extracted from the marine tunicate Dendrodoa grossularia. Aminothiazoles have a wide range of biological activities including anti-tumor and antioxidant properties. The aim of our study was to examine the antioxidant ability of an aminothiazole derivative, dendrodoine analogue (DA) [(4-amino-5-benzoyl-2-(4-methoxy phenylamino) thiazole] which has been chemically synthesized and is similar to dendrodoine. In all the biochemical assays used in our study, corresponding to different levels of protection, DA showed concentration dependent antioxidant ability. DA (3.07 microM) showed an ability to inhibit 2,2'-azobis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) radical formation to the extent of 0.17 microM of 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). The ferric complex reducing ability of 3.07 microM DA was equivalent to 110 microM Trolox. 3.07 microM DA gave 84% protection against deoxyribose degradation, a measure of hydroxyl radical scavenging. DA also has an ability to scavenge NO radical, 3.07 microM DA effecting 20% scavenging. Concentration dependent inhibition of lipid peroxidation and protein oxidation induced by 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) and ascorbate-Fe2+ was observed with low concentrations of DA (1.5-3.07 microM). Mechanistic studies using pulse radiolysis revealed that DA scavenges peroxyl radicals with a bimolecular rate constant of 3 x 10(8)M(-1)s(-1). Moreover, the initially formed nitrogen-centered radical gets transformed into sulfur-centered radical before furnishing any final product. Our results indicated that DA can be a free radical scavenger and potential antioxidant for future application. PMID:18466888

De, Strayo; Adhikari, S; Tilak-Jain, J; Menon, V P; Devasagayam, T P A

2008-03-26

193

Volatile compounds and antioxidative activity of Porophyllum tagetoides extracts.  

PubMed

Porophyllum tagetoides is an annual warm-weather herb that has an intense typical smell. Its leaves are commonly used in soup preparation and traditional medicine for treatment of inflammatory diseases. Its volatile compounds and antioxidant properties were evaluated in crude, aqueous and ethanol leaf extract and an oil emulsion using different antioxidant assays in vitro, such as: DPPH radical scavenging activity, redox potential, polyphenol content, reducing power and optical density. A high antioxidative activity was found when comparing leaves with stems. The crude extract from leaves showed a very high reducing power (2.88?±?0.20 O.D.) and DPPH radical-scavenging activity (54.63?±?4.80%), in concordance with a major concentration of vitamin C (23.97?±?0.36 mg/100 g). Instead, the highest polyphenol content (264.54?±?2.17 mg GAE/g of sample) and redox potential (561.23?±?0.15 mV) were found by the ethanol and aqueous extract, respectively. Aldehydes and terpenes such as nonanal, decanal, trans-pineno, ?-myrcene and D-limonene were the major volatiles found. This study suggests that Porophyllum tagetoides extracts could be used as antioxidants. PMID:22318745

Jimenez, M; Guzman, A P; Azuara, E; Garcia, O; Mendoza, M R; Beristain, C I

2012-03-01

194

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

PubMed

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

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

2009-02-27

195

Activation of human peripheral blood mononuclear cells by nitric oxide-generating compounds  

SciTech Connect

Recent work in this laboratory has identified immune-stimulatory properties of the oxidant hemin. In this study, the authors examined whether the nitrogen-based oxidant nitric oxide (NO) had inductive effects on human lymphocytes. They found that the NO-generating compounds sodium nitroprusside and S-nitroso-N acetylpenicillamine rapidly enhanced the rate of glucose transport in resting human PBMC. In addition, NF-[kappa]B binding activity was induced by these agents as was the secretion of TNF-[alpha]. The data suggest that a cGMP-independent mechanism is involved as the cell permeant cGMP analogue, 8-Br-cGMP, had no effect in eliciting these inductive events. Activation of lymphocytes by these NO-generating compounds may be mediated through the protein tyrosine phosphorylation signal transduction pathway. It was found that membrane-associated protein tyrosine phosphatase activity was enhanced in PBMC treated with sodium nitroprusside or S-nitroso-N-acetylpenicillamine and that the src family protein tyrosine kinase p56[sup lck] was activated in these cells. Inasmuch as p56[sup lck] activity is negatively controlled by tyrosine phosphorylation, its activation may be related to the enhancement of protein tyrosine phosphatase activity. 8Br-cGMP had no effect on these enzymes. Taken together, these data suggest that NO may have immune-stimulatory properties and may signal through a hitherto undescribed cGMP-independent pathway. 30 refs., 9 figs., 2 tabs.

Lander, H.M.; Sehajpal, P.; Levine, D.M.; Novogrodsky, A. (Cornell Univ. Medical College, NY (United States))

1993-02-15

196

Virtual screening against highly charged active sites: identifying substrates of alpha-beta barrel enzymes.  

PubMed

We have developed a virtual ligand screening method designed to help assign enzymatic function for alpha-beta barrel proteins. We dock a library of approximately 19,000 known metabolites against the active site and attempt to identify the relevant substrate based on predicted relative binding free energies. These energies are computed using a physics-based energy function based on an all-atom force field (OPLS-AA) and a generalized Born implicit solvent model. We evaluate the ability of this method to identify the known substrates of several members of the enolase superfamily of enzymes, including both holo and apo structures (11 total). The active sites of these enzymes contain numerous charged groups (lysines, carboxylates, histidines, and one or more metal ions) and thus provide a challenge for most docking scoring functions, which treat electrostatics and solvation in a highly approximate manner. Using the physics-based scoring procedure, the known substrate is ranked within the top 6% of the database in all cases, and in 8 of 11 cases, it is ranked within the top 1%. Moreover, the top-ranked ligands are strongly enriched in compounds with high chemical similarity to the substrate (e.g., different substitution patterns on a similar scaffold). These results suggest that our method can be used, in conjunction with other information including genomic context and known metabolic pathways, to suggest possible substrates or classes of substrates for experimental testing. More broadly, the physics-based scoring method performs well on highly charged binding sites and is likely to be useful in inhibitor docking against polar binding sites as well. The method is fast (<1 min per ligand), due largely to an efficient minimization algorithm based on the truncated Newton method, and thus, it can be applied to thousands of ligands within a few hours on a small Linux cluster. PMID:15697231

Kalyanaraman, Chakrapani; Bernacki, Katarzyna; Jacobson, Matthew P

2005-02-15

197

Pharmacologically active compounds in the Anoectochilus and Goodyera species.  

PubMed

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

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

2008-01-18

198

Aspergillus fumigatus activates thrombocytes by secretion of soluble compounds.  

PubMed

During invasive aspergillosis, platelets might be involved in immune defense, but they also might contribute to the pathology of the disease. We tested the hypothesis that Aspergillus secretes factors that influence the activity and functionality of thrombocytes. Platelets were incubated with medium wherein Aspergillus fumigatus was grown. This fungal culture supernatant potently stimulated thrombocytes in a time- and dose-dependent fashion, inducing release of alpha and dense granules, membrane alterations, aggregation, and formation of microparticles. Fungus-induced platelet activation could be confirmed in vivo: thrombocytes from mice infected with A. fumigatus showed a higher activation level than platelets from noninfected animals. Two stimulating components in the fungal culture supernatant were identified: a fungal serine protease and the mycotoxin gliotoxin. Activation of platelets by fungal factors stimulates antifungal functions: platelets gain the capacity to interact with foreign particles, and they become able to inhibit fungal growth, thus supporting the host immune network. However, some consequences of platelet activation might also be harmful, including excessive inflammation and induction of thrombosis. These findings imply that measuring platelet activation in patients might be an interesting diagnostic parameter. PMID:23225903

Speth, Cornelia; Hagleitner, Magdalena; Ott, Helmut W; Würzner, Reinhard; Lass-Flörl, Cornelia; Rambach, Günter

2012-12-07

199

Glucocorticoid Compounds Modify Smoothened Localization and Hedgehog Pathway Activity  

PubMed Central

Summary The Hedgehog signaling pathway is linked to a variety of diseases, notably a range of cancers. The first generation of drug screens identified Smoothened (Smo), a membrane protein essential for signaling, as an attractive drug target. Smo localizes to the primary cilium upon pathway activation, and this transition is critical for the response to Hedgehog ligands. In a high content screen directly monitoring Smo distribution in Hedgehog responsive cells, we identified different glucocorticoids as specific modulators of Smo ciliary accumulation. One class promoted Smo accumulation, conferring cellular hypersensitivity to Hedgehog stimulation. In contrast, a second class inhibited Smo ciliary localization and signaling activity by both wildtype Smo, and mutant forms of Smo, SmoM2 and SmoD473H, that are refractory to previously identified Smo antagonists. These findings point to the potential for developing glucocorticoid-based pharmacological modulation of Smo signaling to treat mutated drug-resistant forms of Smo, an emerging problem in long-term cancer therapy. They also raise a concern about potential crosstalk of glucocorticoid drugs in the Hedgehog pathway, if therapeutic administration exceeds levels associated with on-target transcriptional mechanisms of glucocorticoid action.

Wang, Yu; Davidow, Lance; Arvanites, Anthony C.; Blanchard, Joel; Lam, Kelvin; Xu, Ke; Oza, Vatsal; Yoo, Jin Woo; Ng, Jessica M.Y.; Curran, Tom; Rubin, Lee L.; McMahon, Andrew P.

2013-01-01

200

Polypharmacology directed compound data mining: identification of promiscuous chemotypes with different activity profiles and comparison to approved drugs.  

PubMed

Increasing evidence that many pharmaceutically relevant compounds elicit their effects through binding to multiple targets, so-called polypharmacology, is beginning to change conventional drug discovery and design strategies. In light of this paradigm shift, we have mined publicly available compound and bioactivity data for promiscuous chemotypes. For this purpose, a hierarchy of active compounds, atomic property based scaffolds, and unique molecular topologies were generated, and activity annotations were analyzed using this framework. Starting from ?35?000 compounds active against human targets with at least 1 ?M potency, 33 chemotypes with distinct topology were identified that represented molecules active against at least 3 different target families. Network representations were utilized to study scaffold-target family relationships and activity profiles of scaffolds corresponding to promiscuous chemotypes. A subset of promiscuous chemotypes displayed a significant enrichment in drugs over bioactive compounds. A total of 190 drugs were identified that had on average only 2 known target annotations but belonged to the 7 most promiscuous chemotypes that were active against 8-15 target families. These drugs should be attractive candidates for polypharmacological profiling. PMID:21070069

Hu, Ye; Bajorath, Jürgen

2010-11-12

201

Identification and Validation of Notch Pathway Activating Compounds through a Novel High-Throughput Screening Method  

PubMed Central

Carcinoids are neuroendocrine (NE) tumors with limited treatment options. Notch activation has been shown to suppress growth and hormone production in carcinoid cells. In this study, we provide a process for identifying Notch activating compounds using a high throughput screen (HTS), and we validate the effects of the strongest hit from the 7,264 compounds analyzed by HTS, resveratrol (RESV). Treatment of carcinoid cells with RESV resulted in upregulation of the Notch signaling pathway as measured by suppression of its downstream target achaete-scute complex-like 1 (ASCL1). Luciferase reporter assays incorporating the centromere-binding factor 1 binding site also confirmed the functional activity of RESV-induced Notch. As activation of the Notch pathway has been shown to suppress carcinoid proliferation, RESV treatment of carcinoid cells led to a dose-dependent inhibition of cellular growth. Immunoblotting revealed phosphorylation of cdc2 (Tyr15) and upregulation of p21Cip1/Waf, markers of cell cycle arrest, with RESV treatment. Flow cytometry confirmed the mechanism of RESV-induced growth inhibition is S phase cell cycle arrest. Furthermore, as Notch has been shown to inhibit bioactive hormone production from NE tumors, RESV also suppressed expression of the NE peptides/hormones chromogranin A and serotonin. RNA interference assays demonstrated that the hormone suppressing capacity of RESV was due to upregulation of the Notch2 isoform. Thus, this HTS can be utilized to identify novel Notch activating compounds which may have the potential to suppress carcinoid tumor growth and the associated endocrinopathies.

Pinchot, Scott N.; Jaskula-Sztul, Renata; Ning, Li; Peters, Noel R.; Cook, Mackenzie R.; Kunnimalaiyaan, Muthusamy; Chen, Herbert

2010-01-01

202

Evaluation of Biologically Active Compounds from Calendula officinalis Flowers using Spectrophotometry  

PubMed Central

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

2012-01-01

203

A fluorescence-based high-throughput screen to identify small compound inhibitors of the genotype 3a hepatitis C virus RNA polymerase.  

PubMed

The hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) plays an essential role in the replication of HCV and is a key target for novel antiviral therapies. Several RdRp inhibitors are in clinical trials and have increased response rates when combined with current interferon-based therapies for genotype 1 (G1) HCV patients. These inhibitors, however, show poor efficacy against non-G1 genotypes, including G3a, which represents ~20% of HCV cases globally. Here, we used a commercially available fluorescent dye to characterize G3a HCV RdRp in vitro. RdRp activity was assessed via synthesis of double-stranded RNA from the single-stranded RNA poly(C) template. The assay was miniaturized to a 384-well microplate format and a pilot high-throughput screen was conducted using 10,208 "lead-like" compounds, randomly selected to identify inhibitors of HCV G3a RdRp. Of 150 compounds demonstrating greatest inhibition, 10 were confirmed using both fluorescent and radioactive assays. The top two inhibitors (HAC001 and HAC002) demonstrated specific activity, with an IC50 of 12.7 µM and 1.0 µM, respectively. In conclusion, we describe simple, fluorescent-based high-throughput screening (HTS) for the identification of inhibitors of de novo RdRp activity, using HCV G3a RdRp as the target. The HTS system could be used against any positive-sense RNA virus that cannot be cultured. PMID:23708123

Eltahla, Auda A; Lackovic, Kurt; Marquis, Christopher; Eden, John-Sebastian; White, Peter A

2013-05-24

204

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

SciTech Connect

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.

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

2008-12-01

205

INSECTICIDAL ACTIVITY OF 23 ESSENTIAL OILS AND THEIR MAJOR COMPOUNDS AGAINST ADULT LIPAPHIS PSEUDOBRASSICAE (DAVIS) (APHIDIDAE: HOMOPTERA)  

Technology Transfer Automated Retrieval System (TEKTRAN)

Essential oils from 23 species of plants comprising 14 genera and 4 plant families were extracted by Clevenger-type water distillation. Major compounds of these essential oils were identified with gas chromatography-mass spectroscopy. Insecticidal activity of the oils and their major components was ...

206

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

PubMed

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

Seo, Seon-Mi; Park, Il-Kwon

2011-11-09

207

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

Microsoft Academic Search

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

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

2003-01-01

208

Arginine-containing compounds and thymic endocrine activity.  

PubMed

The frequent association of malnutrition, infectious disease and aging has stressed the role played by some nutrients on the immune efficiency and particularly on the age-dependent immunological decline. Since arginine has been proven to enhance immune efficiency as demonstrated by the observation that supplemental dietary arginine accelerates would healing and increases thymus weight, we have evaluated the influence of oral administration of arginine on the age-associated immune deficiencies and in particular on the reduced thymic endocrine activity, as measured by the circulating level of one of the best known thymic peptides, i.e. thymulin. Thirty days oral treatment with arginine at the dose of 0.03 g/Kg b.w./day in 20 month old mice induces a full recovery of thymic endocrine activity and a significant increase of PHA responsiveness by spleen cells, when compared with untreated age-matched controls. In humans, oral administration of a commercially available arginine-lysin combination (Lysargin, Baldacci, Pisa, Italia) at the dose of 4 gr. of arg. + 4 gr. of Lysine induces a significant increment of thymulin blood level both in elderly and in cancer patients and at peripheral level, an increase of CD4+ lymphocyte subpopulation. These findings confirm the immunomodulation role of arginine and suggest that on the target of arginine as the thymus and particularly its endocrine activity. Furthermore arginine and arginine-containing compounds may offer a new therapeutical approach to restore thymic immunodeficiencies associated with age or secondary to pathologies inducing thymic deterioration such as trauma, stress and cancer. PMID:1585417

Fabris, N; Mocchegiani, E

1992-01-01

209

Comparative Study of the Endocrine-Disrupting Activity of Bisphenol A and 19 Related Compounds  

Microsoft Academic Search

The endocrine-disrupting activities of bisphenol A (BPA) and 19 related compounds were comparatively examined by means of different in vitro and in vivo reporter assays. BPA and some related compounds exhibited estrogenic activity in human breast cancer cell line MCF-7, but there were remarkable differ- ences in activity. Tetrachlorobisphenol A (TCBPA) showed the highest activity, followed by bisphenol B, BPA,

Shigeyuki Kitamura; Tomoharu Suzuki; Seigo Sanoh; Ryuki Kohta; Norimasa Jinno; Kazumi Sugihara

2005-01-01

210

Comparative transcriptome analysis of tobacco (Nicotiana tabacum) leaves to identify aroma compound-related genes expressed in different cultivated regions.  

PubMed

To identify genes that are differentially expressed in tobacco in response to environmental changes and to decipher the mechanisms by which aromatic carotenoids are formed in tobacco, an Agilent Tobacco Gene Expression microarray was adapted for transcriptome comparison of tobacco leaves derived from three cultivated regions of China, Kaiyang (KY), Weining (WN) and Tianzhu (TZ). A total of 1,005 genes were differentially expressed between leaves derived from KY and TZ, 733 between KY and WN, and 517 between TZ and WN. Genes that were upregulated in leaves from WN and TZ tended to be involved in secondary metabolism pathways, and included several carotenoid pathway genes, e.g., NtPYS, NtPDS, and NtLCYE, whereas those that were down-regulated tended to be involved in the response to temperature and light. The expression of 10 differentially expressed genes (DEGs) was evaluated by real-time quantitative polymerase chain reaction (qRT-PCR) and found to be consistent with the microarray data. Gene Ontology and MapMan analyses indicate that the genes that were differentially expressed among the three cultivated regions were associated with the light reaction of photosystem II, response to stimuli, and secondary metabolism. High-performance liquid chromatography (HPLC) analysis showed that leaves derived from KY had the lowest levels of lutein, ?-carotene, and neoxanthin, whereas the total carotenoid content in leaves from TZ was greatest, a finding that could well be explained by the expression patterns of DEGs in the carotenoid pathway. These results may help elucidate the molecular mechanisms underlying environmental adaptation and accumulation of aroma compounds in tobacco. PMID:23079704

Lei, Bo; Zhao, Xue-Hua; Zhang, Kai; Zhang, Jie; Ren, Wei; Ren, Zhu; Chen, Yi; Zhao, Hui-Na; Pan, Wen-Jie; Chen, Wei; Li, Hong-Xun; Deng, Wen-Ya; Ding, Fu-Zhang; Lu, Kun

2012-10-19

211

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

Microsoft Academic Search

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

Wang Yuegang

2006-01-01

212

Antiproliferative and cell apoptosis-inducing activities of compounds from Buddleja davidii in Mgc-803 cells  

PubMed Central

Background Buddleja davidii is widely distributed in the southwestern region of China. We have undertaken a systematic analysis of B. davidii as a Chinese traditional medicine with anticancer activity by isolating natural products for their activity against the human gastric cancer cell line Mgc-803 and the human breast cancer cell line Bcap-37. Results Ten compounds were extracted and isolated from B. davidii, among which colchicine was identified in B. davidii for the first time. The inhibitory activities of these compounds were investigated in Mgc-803, Bcap-37 cells in vitro by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, and the results showed that luteolin and colchicine had potent inhibitory activities against the growth of Mgc-803 cells. Subsequent fluorescence staining and flow cytometry analysis indicated that these two compounds could induce apoptosis in Mgc-803 cells. The results also showed that the percentages of early apoptotic cells (Annexin V+/PI-, where PI is propidium iodide) and late apoptotic cells (Annexin V+/PI+) increased in a dose- and time-dependent manner. After 36 h of incubation with luteolin at 20 ?M, the percentages of cells were approximately 15.4% in early apoptosis and 43.7% in late apoptosis; after 36 h of incubation with colchicine at 20 ?M, the corresponding values were 7.7% and 35.2%, respectively. Conclusions Colchicine and luteolin from B. davidii have potential applications as adjuvant therapies for treating human carcinoma cells. These compounds could also induce apoptosis in tumor cells.

2012-01-01

213

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

SciTech Connect

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.

Lin, S.H.; Hsu, F.M. [Yuan Ze Inst. of Tech., Taoyuan (Taiwan, Province of China). Dept. of Chemical Engineering

1995-06-01

214

Quantitative High-Throughput Screening Identifies 8-Hydroxyquinolines as Cell-Active Histone Demethylase Inhibitors  

PubMed Central

Background Small molecule modulators of epigenetic processes are currently sought as basic probes for biochemical mechanisms, and as starting points for development of therapeutic agents. N?-Methylation of lysine residues on histone tails is one of a number of post-translational modifications that together enable transcriptional regulation. Histone lysine demethylases antagonize the action of histone methyltransferases in a site- and methylation state-specific manner. N?-Methyllysine demethylases that use 2-oxoglutarate as co-factor are associated with diverse human diseases, including cancer, inflammation and X-linked mental retardation; they are proposed as targets for the therapeutic modulation of transcription. There are few reports on the identification of templates that are amenable to development as potent inhibitors in vivo and large diverse collections have yet to be exploited for the discovery of demethylase inhibitors. Principal Findings High-throughput screening of a ?236,000-member collection of diverse molecules arrayed as dilution series was used to identify inhibitors of the JMJD2 (KDM4) family of 2-oxoglutarate-dependent histone demethylases. Initial screening hits were prioritized by a combination of cheminformatics, counterscreening using a coupled assay enzyme, and orthogonal confirmatory detection of inhibition by mass spectrometric assays. Follow-up studies were carried out on one of the series identified, 8-hydroxyquinolines, which were shown by crystallographic analyses to inhibit by binding to the active site Fe(II) and to modulate demethylation at the H3K9 locus in a cell-based assay. Conclusions These studies demonstrate that diverse compound screening can yield novel inhibitors of 2OG dependent histone demethylases and provide starting points for the development of potent and selective agents to interrogate epigenetic regulation.

Kawamura, Akane; Rose, Nathan R.; Ng, Stanley S.; Quinn, Amy M.; Rai, Ganesha; Mott, Bryan T.; Beswick, Paul; Klose, Robert J.; Oppermann, Udo; Jadhav, Ajit; Heightman, Tom D.; Maloney, David J.; Schofield, Christopher J.; Simeonov, Anton

2010-01-01

215

Pyrazole compound BPR1P0034 with potent and selective anti-influenza virus activity  

PubMed Central

Background Influenza viruses are a major cause of morbidity and mortality around the world. More recently, a swine-origin influenza A (H1N1) virus that is spreading via human-to-human transmission has become a serious public concern. Although vaccination is the primary strategy for preventing infections, influenza antiviral drugs play an important role in a comprehensive approach to controlling illness and transmission. In addition, a search for influenza-inhibiting drugs is particularly important in the face of high rate of emergence of influenza strains resistant to several existing influenza antivirals. Methods We searched for novel anti-influenza inhibitors using a cell-based neutralization (inhibition of virus-induced cytopathic effect) assay. After screening 20,800 randomly selected compounds from a library from ChemDiv, Inc., we found that BPR1P0034 has sub-micromolar antiviral activity. The compound was resynthesized in five steps by conventional chemical techniques. Lead optimization and a structure-activity analysis were used to improve potency. Time-of-addition assay was performed to target an event in the virus life cycle. Results The 50% effective inhibitory concentration (IC50) of BPR1P0034 was 0.42 ± 0.11 ?M, when measured with a plaque reduction assay. Viral protein and RNA synthesis of A/WSN/33 (H1N1) was inhibited by BPR1P0034 and the virus-induced cytopathic effects were thus significantly reduced. BPR1P0034 exhibited broad inhibition spectrum for influenza viruses but showed no antiviral effect for enteroviruses and echovirus 9. In a time-of-addition assay, in which the compound was added at different stages along the viral replication cycle (such as at adsorption or after adsorption), its antiviral activity was more efficient in cells treated with the test compound between 0 and 2 h, right after viral infection, implying that an early step of viral replication might be the target of the compound. These results suggest that BPR1P0034 targets the virus during viral uncoating or viral RNA importation into the nucleus. Conclusions To the best of our knowledge, BPR1P0034 is the first pyrazole-based anti-influenza compound ever identified and characterized from high throughput screening to show potent (sub-?M) antiviral activity. We conclude that BPR1P0034 has potential antiviral activity, which offers an opportunity for the development of a new anti-influenza virus agent.

2010-01-01

216

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

PubMed

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 noncytotoxic 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 ligand for PXR. Taken together, these results identify walrycin A as a novel human PXR activator. PMID:22314385

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

2012-02-07

217

Multiobjective particle swarm optimization: automated identification of structure-activity relationship-informative compounds with favorable physicochemical property distributions.  

PubMed

The selection of active compounds for chemical optimization efforts typically requires the consideration of multiple properties beyond potency. Herein we introduce a multiobjective particle swarm optimization approach to automatically extract compound subsets from large data sets that reveal structure-activity relationship (SAR) information and display physicochemical property distributions that are indicative of favorable absorption, distribution, metabolism, and excretion (ADME) characteristics. The approach is based on Pareto optimization of multiple objectives and does not require subjective intervention. It is automated and can be easily modified. We have applied the method to screen 10 compound data sets of different composition and global SAR phenotypes. In five of these data sets, between one and more than hundred compound subsets were identified that represented discontinuous local SARs and had desirable property distributions. PMID:23039232

Namasivayam, Vigneshwaran; Bajorath, Jürgen

2012-10-18

218

Influence of endocrine active compounds on the developing rodent brain.  

PubMed

Changes in the volumes of sexually dimorphic brain nuclei are often used as a biomarker for developmental disruption by endocrine-active compounds (EACs). However, these gross, morphological analyses do not reliably predict disruption of cell phenotype or neuronal function. Therefore, an experimental approach that simultaneously assesses anatomical, physiological and behavioral endpoints is required when developing risk assessment models for EAC exposure. Using this more comprehensive approach we have demonstrated that the disruption of nuclear volume does not necessarily coincide with disruption of cellular phenotype or neuroendocrine function in two sexually dimorphic brain nuclei: the anteroventral periventricular nucleus of the hypothalamus (AVPV) and the sexually dimorphic nucleus of the preoptic area (SDN). These results demonstrate that nuclear volume is likely not an appropriate biomarker for EAC exposure. We further demonstrated that neonatal exposure to the EACs genistein (GEN) and Bisphenol-A (BPA) can affect sexually dimorphic brain morphology and neuronal phenotypes in adulthood with regional and cellular specificity suggesting that effects observed in one brain region may not be predictive of effects within neighboring regions. Finally, developmental EAC exposure has been shown to affect a variety of sexually dimorphic behaviors including reproductive behavior. These effects are likely to have a broad impact as maladaptive behavior could translate to decreased fitness of entire populations. Collectively, these findings emphasize the need to employ a comprehensive approach that addresses anatomical, functional and behavioral endpoints when evaluating the potential effects of EAC exposure. PMID:17822772

Patisaul, Heather B; Polston, Eva K

2007-08-03

219

Persistence of biologically active compounds in aquatic systems: Final report  

SciTech Connect

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

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

1986-11-01

220

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

NASA Astrophysics Data System (ADS)

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

Peterson, B.; Wheeler, R.

221

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

SciTech Connect

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

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

2003-06-01

222

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

PubMed Central

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

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

2013-01-01

223

Antioxidant activity of lignin phenolic compounds extracted from kraft and sulphite black liquors.  

PubMed

The antioxidant activity of the phenolic compounds present in industrial black liquors obtained from the two cooking processes (kraft and sulphite) used in Portugal to produce Eucalyptus globulus pulp was evaluated. The black liquors treated at several pH values were extracted with ethyl acetate. Phenolic fractions were further separated by liquid chromatography of the crude extracts of kraft liquor at pH = 6 and sulphite liquor at the original pH. Total phenolic content was determined in terms of gallic acid equivalents (Folin-Ciocalteu colorimetric method), and the antioxidant activity in the crude extracts at several pH values and in the separated fractions was measured using the DPPH test for radical scavenging capacity. The total phenolic content of crude extracts and separated fractions ranged from 92.7 to 181.6 and from 91.6 to 1,099.6 mg GAE/g, respectively, while the antioxidant activity index (AAI) ranged from 2.20 to 3.41 and from 2.21 to 11.47 respectively, showing very strong antioxidant activity in all studied cases. The fractions separated by column chromatography were submitted to mass spectrometry analysis and the results were compared to others in the literature of natural products, mainly from Eucalyptus, and the characteristic bands of functional groups were identified by ¹H-NMR and FTIR. These methods allowed the identification of 17 phenolic compounds. PMID:21169882

Faustino, Hélio; Gil, Nuno; Baptista, Cecília; Duarte, Ana Paula

2010-12-16

224

Identifying physical activity patterns in chronic fatigue syndrome using actigraphic assessment  

Microsoft Academic Search

Objective: Changes in physical activity are thought to play an important role in maintaining symptoms in chronic fatigue syndrome (CFS). The aim of this study was to describe intraindividual physical activity patterns in more detail and to identify pervasively passive patients. Methods: With help of a movement-sensing device, physical activity levels were registered continuously over a 12-day period in 277

Sieberen P van der Werf; Judith B Prins; Jan H. M. M Vercoulen; Jos W. M van der Meer; Gijs Bleijenberg

2000-01-01

225

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

ERIC Educational Resources Information Center

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

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

2011-01-01

226

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

PubMed

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. PMID:19371625

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

2009-01-23

227

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...

228

Antibacterial activity of phenolic compounds and aromatic alcohols.  

PubMed

The antibacterial properties of phenolic compounds and aromatic alcohols (growth inhibition, lethal effect and cytological damage) were investigated. The role of protein and RNA synthesis in the bactericidal action was also determined. All compounds tested demonstrated lethal properties and the ability to alter membranes, especially in Gram-negative bacteria. Efficacious concentrations, however, varied greatly among the compounds. These data corroborate previous findings which suggest that the mechanism of action of these compounds is related to their lipophilia. Moreover, since it was demonstrated that the lethal effect of two aromatic alcohols (phenethyl alcohol and benzyl alcohol) stops when protein synthesis is inhibited, it is likely that both possess specific mechanisms of action. PMID:1697976

Lucchini, J J; Corre, J; Cremieux, A

1990-05-01

229

An array of Escherichia coli clones over-expressing essential proteins: A new strategy of identifying cellular targets of potent antibacterial compounds  

Microsoft Academic Search

With the advancement of high throughput screening, it has become easier and faster to discover hit compounds that inhibit proliferation of bacterial cells. However, development in technologies used to identify cellular targets of potent antibacterial inhibitors has lagged behind. Here, we describe a novel strategy of target identification for antibacterial inhibitors using an array of Escherichia coli clones each over-expressing

H. Howard. Xu; Lilian Real; Melissa Wu Bailey

2006-01-01

230

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

Microsoft Academic Search

Novel chemical entities (NCEs) may be investigated for emetic liability in a range of unpleasant experiments involving retching, vomiting or conditioned taste aversion\\/food avoidance in sentient animals. We have used a range of compounds with known emetic \\/aversive properties to examine the possibility of using the social amoeba, Dictyostelium discoideum, for research into identifying and understanding emetic liability, and hence

Steven Robery; Janina Mukanowa; Nathalie Percie Du Sert; Paul L. R. Andrews; Robin S. B. Williams; Adrian John Harwood

2011-01-01

231

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

PubMed

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

Dos Santos, Fernanda M; de Souza, Maria Gorete; Crotti, Antônio E Miller; Martins, Carlos H G; Ambrósio, Sérgio R; Veneziani, Rodrigo C S; E Silva, Márcio L Andrade; Cunha, Wilson R

2012-06-01

232

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

PubMed Central

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

dos Santos, Fernanda M.; de Souza, Maria Gorete; Crotti, Antonio E. Miller; Martins, Carlos H. G.; Ambrosio, Sergio R.; Veneziani, Rodrigo C. S.; e Silva, Marcio L. Andrade; Cunha, Wilson R.

2012-01-01

233

CHEMICAL ANALYSIS AND LABORATORY BIOASSAYS OF HOST ODORS TO IDENTIFY COMPOUNDS THAT ATTRACT OR INHIBIT THE ATTRACTION OF MOSQUITOES  

Technology Transfer Automated Retrieval System (TEKTRAN)

Using various sampling techniques and gas chromatography/mass spectrometry (GC/MS), a comprehensive profile of odors from hosts can be obtained. The differences in chemicals emanated by different hosts may provide a clue to the structures of compounds used by anthropophilic mosquitoes compared to t...

234

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

ERIC Educational Resources Information Center

|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…

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

2011-01-01

235

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

PubMed Central

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

2013-01-01

236

Identifying Subgroups That Succeed or Fail With Three Levels of Physical Activity Intervention: The Activity Counseling Trial  

Microsoft Academic Search

The authors used recursive partitioning methods to identify combinations of baseline characteristics that predict 2-year physical activity success in each of 3 physical activity interventions delivered in the multisite Activity Counseling Trial. The sample consisted of 874 initially sedentary primary care patients, ages 35–75 years, who were at risk for cardiovascular disease. Predictors of 2-year success were specific to each

Abby C. King; Bess Marcus; David Ahn; Andrea L. Dunn; W. Jack Rejeski; James F. Sallis; Mace Coday

2006-01-01

237

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

PubMed

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

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

2011-12-23

238

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

Microsoft Academic Search

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

H. Tunón; W. Thorsell; L. Bohlin

1994-01-01

239

Chemical reactivity and biological activity of chalcones and other ?,?-unsaturated carbonyl compounds.  

PubMed

Abstract 1. Chalcones are structural analogues of benzalacetophenone (BAP). Several derivatives have been identified in plants and anticarcinogenic and anti-inflammatory properties were attributed to the compounds, probably related to their direct antioxidant activity or stimulatory effects on the expression of endogenous defence enzymes like hemeoxygenase-1 (HO-1). HO-1 expression is triggered by the Nrf2-Keap1 signalling pathway, initiated by the addition of chalcones to thiol groups of Keap1 via Michael-type reaction. 2. The present study used a model system estimating the reactivity of different synthetic chalcones and other ?,?-unsaturated carbonyl compounds with thiols and compared the chemical reactivity with the biological activity, measured by HO-1 expression in human dermal fibroblasts. 3. Chemical reactivity with the thiol group of N-acetylcysteine was determined with 5,5'-dithiobis-(2-nitrobenzoic acid) and followed chemical principles of structure-reactivity relationship. Most reactive were sulforaphane, dimethylfumarate, chalcone 3 ((2E)-1-phenyl-3-pyrimidin-2-ylprop-2-en-1-one) and chalcone 7 (1,3-diphenylprop-2-yn-1-one). This result demonstrates that ?,?-unsaturated carbonyl derivatives react with thiols differently. All compounds were also biologically active; however, expression of HO-1 was not only related to the chemical reactivity but also to the lipophilicity of the molecules which likely affected transmembrane uptake. Most efficient inducers of HO-1 expression were BAP, 4-hydroxynonenal and chalcone 1 (4-[(1E)-3-oxo-3-phenylprop-1-en-1-yl]benzonitrile), chalcone 5 ((2E)-1-phenyl-3-[4-(trifluoromethyl)-phenyl]prop-2-en-1-one) and chalcone 7. PMID:23339572

Maydt, Daniela; De Spirt, Silke; Muschelknautz, Christian; Stahl, Wilhelm; Müller, Thomas J J

2013-01-23

240

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

Microsoft Academic Search

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

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

1996-01-01

241

Two-hybrid yeast test system for assessment of estrogenic activity of chemical compounds  

Microsoft Academic Search

The search for natural and synthetic compounds exhibiting estrogenic and antiestrogenic activity is a topical problem of modern biology and medicine. Compounds exhibiting estrogenic activity are widely used in medical practice to correct functioning and to treat a number of endocrine disorders and sexual diseases. Antagonists of steroid hormones may be used for designing antitumor preparation to treat hormonedependent malignancies.

V. B. Kozhemyako; S. N. Koval’chuk; V. A. Rasskazov; D. L. Aminin

2005-01-01

242

In vitro Effect of a Variety of Biologically Active Compounds on Human Cytomegalovirus  

Microsoft Academic Search

Anticytomegalovirus experiments were carried out on 38 classes of compounds containing 320 materials of known or potential biological activity. All experiments were carried out in tubes using WI-38 cells with the test compounds added within minutes after the virus and then at additional times in medium changes 2 and 4 days later. Antiviral activity was determined by microscopic demonstration of

R. W. Sidwell; G. Arnett

1972-01-01

243

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

ERIC Educational Resources Information Center

|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)|

Finer, Kim R.

1997-01-01

244

Characterization of phenolic compounds, carotenoids, vitamins and antioxidant activities of selected Malaysian wild edible plants.  

PubMed

This study was carried out to characterize phenolic compounds, carotenoids, vitamins and the antioxidant activity of selected wild edible plants. Plant extracts were purified, and phenolic compounds comprising 11 phenolic acids (hydroxybenzoic acid and hydrocinnamic acid) and 33 flavonoids (including catechin, glycosides and aglycones) were analysed using High Performance Liquid Chromatography - Diode Array Detector (HPLC-DAD). Furthermore, the contents of ascorbic acid and tocopherol ((? and ? tocopherol) and carotenoids (lutein and ?-carotene) were also determined. The major phenolics identified consisted of glycosides of flavones (apigenin and luteolin) and flavonols (kaempferol and quercetin). Among the phenolic acids identified after hydrolysis, coumaric acid was the predominant phenolic acid in all the extracts of wild plants. Ascorbic acid [53.8 mg/100 g fresh weight (FW)] and ?-carotene (656.5 mg/100 g FW) showed the highest content in the leaf of Heckeria umbellatum. In conclusion, the leaves of H. umbellatum, Aniseia martinicensis and Gonostegia hirta have excellent potential in the future to emerge as functional ingredients. PMID:23368987

Wong, Jin Yi; Matanjun, Patricia; Ooi, Yasmin Beng Houi; Chia, Kah Fei

2013-02-01

245

What is the likelihood of an active compound to be promiscuous? Systematic assessment of compound promiscuity on the basis of PubChem confirmatory bioassay data.  

PubMed

Compound promiscuity refers to the ability of small molecules to specifically interact with multiple targets, which represents the origin of polypharmacology. Promiscuity is thought to be a widespread characteristic of pharmaceutically relevant compounds. Yet, the degree of promiscuity among active compounds from different sources remains uncertain. Here, we report a thorough analysis of compound promiscuity on the basis of more than 1,000 PubChem confirmatory bioassays, which yields an upper-limit assessment of promiscuity among active compounds. Because most PubChem compounds have been tested in large numbers of assays, data sparseness has not been a limiting factor for the current analysis. We have determined that there is an overall likelihood of ?50% of an active PubChem compound to interact with two or more targets. The probability to interact with more than five targets is reduced to 7.6%. On average, an active PubChem compound was found to interact with ?2.5 targets. Moreover, if only activities consistently detected in all assays available for a given target were considered, this ratio was further reduced to ?2.3 targets per compound. For comparison, we have also analyzed high-confidence activity data from ChEMBL, the major public repository of compounds from medicinal chemistry, and determined that an active ChEMBL compound interacted on average with only ?1.5 targets. Taken together, our results indicate that the degree of compound promiscuity is lower than often assumed. PMID:23605807

Hu, Ye; Bajorath, Jürgen

2013-04-19

246

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

PubMed Central

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

2013-01-01

247

Identifying potential CSCW applications by means of activity theory concepts: a case example  

Microsoft Academic Search

The paper presents some novel concepts and models derived from Activity Theory for to identify a potential CSCW application. It is suggested that the six elements of the structure of the activity concept might be useful for differentiating between areas of support, and that three levels of support are needed in order to cope with both routine and emergent features

Kari Kuutti; Tuula Arvonen

1992-01-01

248

Novel Compounds from Shark and Stingray Epidermal Mucus With Antimicrobial Activity Against Wound Infection Pathogens.  

National Technical Information Service (NTIS)

A protective secretion produced by epidermal mucus cells in stingrays is being investigated to understand its role in wound healing and to identify mucus-associated antimicrobial compounds with the potential for development into novel therapeutics to trea...

C. Walsh C. A. Luer J. Wyffels K. Ritchie L. Edsberg

2013-01-01

249

Structural Activity of Bovidic Acid and Related Compounds as Feeding Deterrents against Aedes aegypti.  

National Technical Information Service (NTIS)

Natural products present in preferred and non-preferred animal hosts of biting insects can exhibit interesting semiochemical properties. Recently, a novel fatty acid compound that acts as a feeding deterrent for blood sucking insects was identified from t...

K. Tran K. R. Chauhan

2007-01-01

250

High throughput screening for compounds that alter muscle cell glycosylation identifies new role for N-glycans in regulating sarcolemmal protein abundance and laminin binding.  

PubMed

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

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

2012-05-08

251

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

PubMed Central

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

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

2012-01-01

252

Antioxidant activity in vitro of two aromatic compounds from Caesalpinia sappan L.  

PubMed

Two antioxidant compounds were isolated from C. sappan L by multiple steps of column chromatography and thin layer chromatography in succession with superoxide scavenging assay as activity monitor. Structures of the two compounds were determined by spectroscopic methods as 1',4'-dihydro-spiro[benzofuran-3(2H),3'-[3H-2]benzopyran]-1',6',6',7'-tetrol (compound 1) and 3-[[4,5-dihydroxy-2(hydroxymethyl) phenyl]-methyl]-2,3-dihydro-3,6-benzofurandiol (compound 2). Characterization of antioxidant properties of these two compounds was done by determining the inhibitory effect on xanthine oxidase activity as well as scavenging effect on superoxide anion and hydroxyl radicals. Our results indicated that compounds 1 and 2 inhibited xanthine oxidase activity and scavenged superoxide anion and hydroxyl radicals. Compounds 1 and 2 possessed similar radical scavenging activities as ascorbic acid, and they were more effective than other well-known antioxidants such as alpha-tocopherol, beta-carotene, and BHT. As inhibitors of free radical formation, compounds 1 and 2 were more effective than all the other antioxidants tested. In conclusion, compounds 1 and 2 can be regarded as primary antioxidants with radical-scavenging and chain-breaking activities as well as secondary antioxidants with inhibitory effect on radical generation. PMID:14757979

Safitri, Ratu; Tarigan, Ponis; Freisleben, Hans Joachim; Rumampuk, Rymond J; Murakami, Akira

2003-01-01

253

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

PubMed

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

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

2013-07-02

254

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

PubMed Central

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

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

2011-01-01

255

Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anti-cancer drug activity  

PubMed Central

Conventional anti-cancer drug screening is typically performed in the absence of accessory cells of the tumor microenvironment, which can profoundly alter anti-tumor drug activity. To address this major limitation, we developed the tumor cell-specific in vitro bioluminescence imaging (CS-BLI) assay. Tumor cells (e.g. myeloma, leukemia and solid tumors) stably expressing luciferase are co-cultured with non-malignant accessory cells (e.g. stromal cells) for selective quantification of tumor cell viability, in presence vs. absence of stromal cells or drug treatment. CS-BLI is high-throughput scalable and identifies stroma-induced chemoresistance in diverse malignancies, including imatinib-resistance in leukemic cells. A stromal-induced signature in tumor cells correlates with adverse clinical prognosis and includes signatures for activated Akt, Ras, NF-?B, HIF-1?, myc, hTERT, and IRF4; signatures for biological aggressiveness and for self-renewal. Unlike conventional screening, CS-BLI can also identify agents with increased activity against tumor cells interacting with stroma. One such compound, reversine, exhibits more potent activity in an orthotopic model of diffuse myeloma bone lesions than in conventional subcutaneous xenografts. Use of CS-BLI, therefore, enables refined screening of candidate anti-cancer agents to enrich preclinical pipelines with potential therapeutics that overcome stroma-mediated drug resistance and can act in a synthetic lethal manner in the context of tumor-stromal interactions.

McMillin, Douglas W.; Delmore, Jake; Weisberg, Ellen; Negri, Joseph M.; Geer, D. Corey; Klippel, Steffen; Mitsiades, Nicholas; Schlossman, Robert L.; Munshi, Nikhil C.; Kung, Andrew L.; Griffin, James D.; Richardson, Paul G.; Anderson, Kenneth C.; Mitsiades, Constantine S.

2013-01-01

256

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

Code of Federal Regulations, 2010 CFR

...activities to protect essential fish habitats identified and described under...activities to protect essential fish habitats identified and described under...activities, MMS finds that essential fish habitat or habitat areas of...

2009-07-01

257

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

Code of Federal Regulations, 2010 CFR

...activities to protect essential fish habitats identified and described under...activities to protect essential fish habitats identified and described under...activities, MMS finds that essential fish habitat or habitat areas of...

2010-07-01

258

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

Code of Federal Regulations, 2013 CFR

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

2013-07-01

259

Feasibility studies on newly identified LiCrP 2 O 7 compound for lithium insertion behavior  

Microsoft Academic Search

A new category of lithium intercalating cathode candidates, namely LiCrP2O7, was synthesized at 800°C using a citric acid assisted modified (CAM) sol–gel method and examined for possible lithium insertion\\u000a behavior. The formation of a phase pure and monoclinic LiCrP2O7 compound with finer crystallite size was confirmed from the X-ray diffraction patterns. The presence of nano-sized particles\\u000a as observed from a

Gangulibabu; D. Bhuvaneswari; N. Kalaiselvi

2009-01-01

260

Partition of Volatile Organic Compounds in Activated Sludge and Wastewater  

Microsoft Academic Search

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

Jun-Hong Lin; Ming-Shean Chou

2006-01-01

261

Nematicidal activity of Paecilomyces spp. and isolation of a novel active compound.  

PubMed

Many species of Paecilomyces are entomogenous fungi and several are efficacious toward nematodes. To study the potential of Paecilomyces species in controlling nematodes, fungal extracts of 40 Paecilomyces spp. were evaluated for their nematicidal activity against Bursaphelenchus xylophilus and Panagrellus redivivus. The extracts of six Paecilomyces spp. exhibited the nematicidal activity against P. redivivus, and 11 species exhibited the nematicidal activity against B. xylophilus. The methanol extract of strain 1.01761 incubating on Czapek solid medium killed more than 95% P. redivivus in 24 h at 5 mg/ml, and the filtrate of strain 1.01788 cultured in Sabouraud's broth medium resulted in 90% mortality of B. xylophilus in 24 h at 5 mg/ml. A novel nematicidal compound 4-(4'-carboxy-2'-ethyl-hydroxypentyl)-5,6-dihydro-6-methylcyclobuta[b]pyridine-3,6-dicarboxylic acid, was isolated from Paecilomyces sp. YMF1.01761. The LD(50) value of the compound within 24 h against P. redivivus was 50.86 mg/L, against Meloidogyne incognita was 47.1 mg/L, and against B. xylophilus was 167.7 mg/L. PMID:19557340

Liu, Ya-Jun; Zhai, Chong-Yan; Liu, Yi; Zhang, Ke-Qin

2009-06-26

262

Mechanism of inhibiting effect of biologically active compounds on the active forms of oxygen reduction.  

PubMed

The impulse voltammetry methods with recording short-living radical-natured products of the reduction (in particular, hydroxyl radicals) are used to study the process of oxygen reduction steps. A possibility to study mechanisms of antioxidative action of biologically active compounds (BAC) through studying their influence on the separate steps of oxygen reduction (initial molecular oxygen, radical particles and peroxides) is shown. It provides a possibility for the purposeful search of BAC capable to affect certain steps of chain oxidation in biosystems. PMID:8592792

Gromovaya, V F; Shapoval, C S; Luik, A I; Piven, V I

263

Activity-enhancing mutations in an E3 ubiquitin ligase identified by high-throughput mutagenesis  

PubMed Central

Although ubiquitination plays a critical role in virtually all cellular processes, mechanistic details of ubiquitin (Ub) transfer are still being defined. To identify the molecular determinants within E3 ligases that modulate activity, we scored each member of a library of nearly 100,000 protein variants of the murine ubiquitination factor E4B (Ube4b) U-box domain for auto-ubiquitination activity in the presence of the E2 UbcH5c. This assay identified mutations that enhance activity both in vitro and in cellular p53 degradation assays. The activity-enhancing mutations fall into two distinct mechanistic classes: One increases the U-box:E2-binding affinity, and the other allosterically stimulates the formation of catalytically active conformations of the E2?Ub conjugate. The same mutations enhance E3 activity in the presence of another E2, Ube2w, implying a common allosteric mechanism, and therefore the general applicability of our observations to other E3s. A comparison of the E3 activity with the two different E2s identified an additional variant that exhibits E3:E2 specificity. Our results highlight the general utility of high-throughput mutagenesis in delineating the molecular basis of enzyme activity.

Starita, Lea M.; Pruneda, Jonathan N.; Lo, Russell S.; Fowler, Douglas M.; Kim, Helen J.; Hiatt, Joseph B.; Shendure, Jay; Brzovic, Peter S.; Fields, Stanley; Klevit, Rachel E.

2013-01-01

264

Identification of Compounds in the Essential Oil of Nutmeg Seeds (Myristica fragrans Houtt.) That Inhibit Locomotor Activity in Mice.  

PubMed

The present study was designed to evaluate the inhibitory effect of nutmeg (Myristica fragrans Houtt.) seed essential oil on the locomotor activity of mice in a wheel cage. Active compounds in the essential oil were identified by off-line solid phase extraction (SPE-C18) and GC/MS analysis. The essential oil was administered by inhalation at doses of 0.1, 0.3, and 0.5 mL/cage. The results showed that inhalation of nutmeg seed essential oil at a dose of 0.5 mL/cage decreased locomotion by 68.62%; and inhalation of 0.1 and 0.3 mL/cage inhibited locomotion by 62.81% and 65.33%, respectively. Generally, larger doses and longer administrations of nutmeg seed essential oil exhibited greater locomotor inhibition. Subsequently, the plasma concentrations of essential oil compounds were measured. The most concentrated compound in the plasma was myristicin. Half an hour after the addition of 1 mL/cage of nutmeg seed oil, the plasma concentration of myristicin was 3.7 ?g/mL; one and two hours after the addition, the blood levels of myristicin were 5.2 ?g/mL and 7.1 ?g/mL, respectively. Other essential oil compounds identified in plasma were safrole (two-hour inhalation: 1.28 ?g/mL), 4-terpineol (half-hour inhalation: 1.49 ?g/mL, one-hour inhalation: 2.95 ?g/mL, two-hour inhalation: 6.28 ?g/mL) and fatty esters. The concentrations of the essential oil compounds in the blood plasma were relatively low (?g/mL or ppm). In conclusion, the volatile compounds of nutmeg seed essential oil identified in the blood plasma may correlate with the locomotor-inhibiting properties of the oil when administered by inhalation. PMID:21151471

Muchtaridi; Subarnas, Anas; Apriyantono, Anton; Mustarichie, Resmi

2010-11-23

265

Identification of Compounds in the Essential Oil of Nutmeg Seeds (Myristica fragrans Houtt.) That Inhibit Locomotor Activity in Mice  

PubMed Central

The present study was designed to evaluate the inhibitory effect of nutmeg (Myristica fragrans Houtt.) seed essential oil on the locomotor activity of mice in a wheel cage. Active compounds in the essential oil were identified by off-line solid phase extraction (SPE-C18) and GC/MS analysis. The essential oil was administered by inhalation at doses of 0.1, 0.3, and 0.5 mL/cage. The results showed that inhalation of nutmeg seed essential oil at a dose of 0.5 mL/cage decreased locomotion by 68.62%; and inhalation of 0.1 and 0.3 mL/cage inhibited locomotion by 62.81% and 65.33%, respectively. Generally, larger doses and longer administrations of nutmeg seed essential oil exhibited greater locomotor inhibition. Subsequently, the plasma concentrations of essential oil compounds were measured. The most concentrated compound in the plasma was myristicin. Half an hour after the addition of 1 mL/cage of nutmeg seed oil, the plasma concentration of myristicin was 3.7 ?g/mL; one and two hours after the addition, the blood levels of myristicin were 5.2 ?g/mL and 7.1 ?g/mL, respectively. Other essential oil compounds identified in plasma were safrole (two-hour inhalation: 1.28 ?g/mL), 4-terpineol (half-hour inhalation: 1.49 ?g/mL, one-hour inhalation: 2.95 ?g/mL, two-hour inhalation: 6.28 ?g/mL) and fatty esters. The concentrations of the essential oil compounds in the blood plasma were relatively low (?g/mL or ppm). In conclusion, the volatile compounds of nutmeg seed essential oil identified in the blood plasma may correlate with the locomotor-inhibiting properties of the oil when administered by inhalation.

Muchtaridi; Subarnas, Anas; Apriyantono, Anton; Mustarichie, Resmi

2010-01-01

266

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

PubMed

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

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

2006-12-15

267

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

Microsoft Academic Search

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

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

2011-01-01

268

Thiol-Reactive Metal Compounds Inhibit NF-kB Activation by Blocking IkB Kinase1  

Microsoft Academic Search

Gold compounds are used in the treatment of rheumatoid arthritis. NF-kB is a transcription factor implicated in the expression of many inflammatory genes. NF- kB is activated by signal-induced phosphorylation and subsequent degradation of inhibitory IkB (inhibitory protein that dissociates from NF-kB) proteins, and a multisubunit IkB kinase (IKK) has been identified previously. We tested the effect of various gold

Kye-Im Jeon; Jae-Yeon Jeong; Dae-Myung Jue

269

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

PubMed

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

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

2012-02-02

270

Identification of compounds with anti-proliferative activity against Trypanosoma brucei brucei strain 427 by a whole cell viability based HTS campaign.  

PubMed

Human African Trypanosomiasis (HAT) is caused by two trypanosome sub-species, Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Drugs available for the treatment of HAT have significant issues related to difficult administration regimes and limited efficacy across species and disease stages. Hence, there is considerable need to find new alternative and less toxic drugs. An approach to identify starting points for new drug candidates is high throughput screening (HTS) of large compound library collections. We describe the application of an Alamar Blue based, 384-well HTS assay to screen a library of 87,296 compounds against the related trypanosome subspecies, Trypanosoma brucei brucei bloodstream form lister 427. Primary hits identified against T.b. brucei were retested and the IC(50) value compounds were estimated for T.b. brucei and a mammalian cell line HEK293, to determine a selectivity index for each compound. The screening campaign identified 205 compounds with greater than 10 times selectivity against T.b. brucei. Cluster analysis of these compounds, taking into account chemical and structural properties required for drug-like compounds, afforded a panel of eight compounds for further biological analysis. These compounds had IC(50) values ranging from 0.22 µM to 4 µM with associated selectivity indices ranging from 19 to greater than 345. Further testing against T.b. rhodesiense led to the selection of 6 compounds from 5 new chemical classes with activity against the causative species of HAT, which can be considered potential candidates for HAT early drug discovery. Structure activity relationship (SAR) mining revealed components of those hit compound structures that may be important for biological activity. Four of these compounds have undergone further testing to 1) determine whether they are cidal or static in vitro at the minimum inhibitory concentration (MIC), and 2) estimate the time to kill. PMID:23209849

Sykes, Melissa L; Baell, Jonathan B; Kaiser, Marcel; Chatelain, Eric; Moawad, Sarah R; Ganame, Danny; Ioset, Jean-Robert; Avery, Vicky M

2012-11-29

271

Anti-HIV Activity of Extracts and Compounds from Algae and Cyanobacteria  

Microsoft Academic Search

The human immunodeficiency virus (HIV) is the retrovirus that causes the acquired immune deficiency disease syndrome (AIDS). This review discusses the anti-HIV activity of extracts and compounds isolated from freshwater and marine algae, and cyanobacteria (formerly called “blue-green algae”). Compounds and extracts with anti-HIV activity are also active against other retroviruses such as herpes simplex virus (HSV), but the amount

David J Schaeffer; Victor S Krylov

2000-01-01

272

Potato tuber-inducing activities of salicylic acid and related compounds  

Microsoft Academic Search

Salicylic acid (SA) induced potato tuberization in vitro at concentrations greater than 10?5 M. A comparison of the tuber-inducing activities of various related compounds suggested that derivatives of benzoic acid\\u000a with a free carboxyl group and a substituent at the C-2 position of the benzene ring have this activity. Although SA had the\\u000a strongest activity among the compounds tested, the

Yasunori Koda; Kiyoshi Takahashi; Yoshio Kikuta

1992-01-01

273

Multiple microbial activities for volatile organic compounds reduction by biofiltration.  

PubMed

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

Civilini, Marcello

2006-07-01

274

Review on Natural Coumarin Lead Compounds for Their Pharmacological Activity  

PubMed Central

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.

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

2013-01-01

275

High nuclearity nickel compounds with three, four or five metal atoms showing antibacterial activity  

Microsoft Academic Search

The effect on DNA and the antibacterial activity of a series of high nuclearity nickel compounds with three, four and five metal atoms were examined. The compounds have a mixed ligand composition with salicylhydroxamic acid and di-2-pyridyl-ketonoxime as chelate agents. In the trinuclear compound Ni3(shi)2(Hpko)2(py)2(1), two metal ions show a square planar geometry while the third one is in an

Maria Alexiou; Ioannis Tsivikas; Catherine Dendrinou-Samara; Anastasia A. Pantazaki; Pantelis Trikalitis; Nikolia Lalioti; Dimitris A. Kyriakidis; Dimitris P. Kessissoglou

2003-01-01

276

Phenolic compounds from Caesalpinia sappan heartwood and their anti-inflammatory activity.  

PubMed

Four new phenolic compounds, caesalpiniaphenols A-D (1-4), together with eight known compounds were isolated from Caesalpinia sappan heartwood. The chemical structures were established mainly by NMR, MS, ECD, and Mosher's method. Compounds 4, 5, and 7 showed weak inhibitory activity against the LPS-induced NO production in macrophage RAW264.7 cells with IC(50) values of 12.2, 3.5, and 5.7 ?M, respectively. PMID:23234407

Cuong, To Dao; Hung, Tran Manh; Kim, Jin Cheol; Kim, Eun Hee; Woo, Mi Hee; Choi, Jae Sue; Lee, Jeong Hyung; Min, Byung Sun

2012-12-12

277

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

SciTech Connect

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).

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

1982-04-01

278

Naphthoquinones and Bioactive Compounds from Tobacco as Modulators of Neuronal Nitric Oxide Synthase Activity  

PubMed Central

Studies were conducted with extracts of several varieties of tobacco in search of neuronal nitric oxide synthase (nNOS) inhibitors which may be of value in the treatment of stroke. Current therapies do not directly exploit modulation of nNOS activity due to poor selectivity of the currently available nNOS inhibitors. The properties of a potentially novel nNOS inhibitor(s) derived from tobacco extracts, and the concentration-dependent, modulatory effects of the tobacco-derived naphthoquinone compound, 2, 3, 6-trimethyl-1, 4-naphthoquinone (TMN), on nNOS activity were investigated, using 2-methyl-1, 4-naphthoquinone (menadione) as a control. Up to 31?M, both TMN and menadione stimulated nNOS-catalyzed L-citrulline production. However, at higher concentrations of TMN (62.5-500 ?M), the stimulation was lost in a concentration-dependent manner. With TMN, the loss of stimulation did not decrease beyond the control activity. With menadione (62.5-500 ?M), the loss of stimulation surpassed that of the control (78 ± 0.01%), indicating a complete inhibition of nNOS activity. This study suggests that potential nNOS inhibitors are present in tobacco, most of which remain to be identified.

Venkatakrishnan, Priya; Gairola, C. Gary; Castagnoli, Neal; Miller, R. Timothy

2009-01-01

279

The Dietary Compounds Resveratrol and Genistein Induce Activating Transcription Factor 3 While Suppressing Inhibitor of DNA Binding/Differentiation-1  

PubMed Central

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

Alston-Mills, Brenda

2011-01-01

280

Prediction of CNS activity of compound libraries using substructure analysis.  

PubMed

An in silico ADME/Tox prediction tool based on substructural analysis has been developed. The tool called SUBSTRUCT has been used to predict CNS activity. Data sets with CNS active and nonactive drugs were extracted from the World Drug Index (WDI). The SUBSTRUCT program predicts CNS activity as good as a much more complicated artificial neural network model. SUBSTRUCT separates the data sets with approximately 80% accuracy. Substructural analysis also shows surprisingly large differences in substructure profiles between CNS active and nonactive drugs. PMID:12546548

Engkvist, Ola; Wrede, Paul; Rester, Ulrich

281

Improving Maintenance Workflows Through the Use of Activity Sampling to Identify and Remove Barriers to Productivity  

Microsoft Academic Search

The way we design and implement our maintenance management processes directly impacts the productivity we can achieve from\\u000a our maintenance workforce. Activity sampling is a method that can be used to directly measure the direct utilisation achieved\\u000a in the field by the craft labour and more importantly help identify the delays and support activities that are preventing\\u000a craft from “getting

Steve Berquist

282

Identification of aroma active compounds in orange essence oil using gas chromatography-olfactometry and gas chromatography-mass spectrometry.  

PubMed

Using GC-MS and GC-flame ionization detection (FID)/olfactometry, 95 volatile components were detected in orange essence oil, of which 55 were aroma active. In terms of FID peak area the most abundant compounds were: limonene, 94.5%; myrcene, 1%; valencene, 0.8%; linalool, 0.7%, and octanal, decanal, and ethyl butyrate, 0.3% each. One hundred percent of the aroma activity was generated by slightly more than 4% of the total volatiles. The most intense aromas were produced by octanal, wine lactone, linalool, decanal, beta-ionone, citronellal, and beta-sinensal. Potent aroma components reported for the first time in orange essence oil include: E-2-octenal, 1-octen-3-ol, Z-4-decenal, E,E-2,4-nonadienal, guaiacol, gamma-octalactone, and m-cresol. Over 20 compounds were identified for the first time in orange essence oil using MS, however, most did not exhibit aroma activity. PMID:12862384

Högnadóttir, Aslaug; Rouseff, Russell L

2003-05-23

283

Detection of land-cover transitions in multitemporal images with active-learning based compound classification  

Microsoft Academic Search

This paper presents a novel active learning (AL) technique for the compound classification of multitemporal remotesensing images for the detection of land-cover transitions. The proposed AL technique is based on the selection of unlabeled pairs of samples that have maximum uncertainty on their labels assigned by a classifier implemented according to the Bayes rule for compound classification. Uncertainty of a

Begum Demir; Francesca Bovolo; Lorenzo Bruzzone

2011-01-01

284

Inhibitory activity for chitin synthase II from Saccharomyces cerevisiae by tannins and related compounds.  

PubMed

In the course of search for potent inhibitors of chitin synthase II from natural resources, seven tannins and related compounds were isolated from the aerial part of Euphorbia pekinensis and identified as gallic acid (1), methyl gallate (2), 3-O-galloyl-(-)-shikimic acid (3), corilagin (4), geraniin (5), quercetin-3-O-(2"-O-galloyl)-beta-D-glucoside (6), and kaempferol-3-O-(2"-O-galloyl)-beta-D-glucoside (7). These and nine related compounds, (-)-quinic acid (8), (-)-shikimic acid (9), ellagic acid (10), kaempferol (11), quercetin (12), quercitrin (13), rutin (14), quercetin-3-O-(2"-O-galloyl)-beta-D-rutinoside (15) and 1,3,4,6-tetra-O-galloyl-beta-D-glucose (16), were evaluated for the inhibitory activity against chitin synthase II and III. They inhibited chitin synthase II with IC(50) values of 18-206 microM, except for two organic acids, (-)-quinic acid (8) and (-)-shikimic acid (9). Among them, 3-O-galloyl-(-)-shikimic acid (3) was the most potent inhibitor against chitin synthase II of Saccharomyces cerevisiae with an IC(50) value of 18 microM. The inhibition appears to be selective for chitin synthase II, as they did not appreciably inhibit chitin synthase III. PMID:11509967

Hwang, E I; Ahn, B T; Lee, H B; Kim, Y K; Lee, K S; Bok, S H; Kim, Y T; Kim, S U

2001-08-01

285

Feasibility studies on newly identified LiCrP2O7 compound for lithium insertion behavior  

NASA Astrophysics Data System (ADS)

A new category of lithium intercalating cathode candidates, namely LiCrP2O7, was synthesized at 800°C using a citric acid assisted modified (CAM) sol-gel method and examined for possible lithium insertion behavior. The formation of a phase pure and monoclinic LiCrP2O7 compound with finer crystallite size was confirmed from the X-ray diffraction patterns. The presence of nano-sized particles as observed from a transmittance electron microscope image of LiCrP2O7 and the presence of a preferred local cation environment, evidenced from Fourier transform infra-red and 7Li nuclear magnetic resonance studies, are the added advantages of the present study. Further, cyclic voltametry study performed on 2016 coin cells consisting of the synthesized LiCrP2O7 cathode revealed an excellent cycling reversibility and structural stability. Hence, CAM sol-gel synthesized LiCrP2O7 is found to possess desirable physical as well as electrochemical properties, leading one to consider the same as a possible lithium intercalating cathode material.

Gangulibabu; Bhuvaneswari, D.; Kalaiselvi, N.

2009-08-01

286

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

PubMed Central

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

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

2013-01-01

287

Antibacterial compounds from mushrooms II: lanostane triterpenoids and an ergostane steroid with activity against Bacillus cereus isolated from Fomitopsis pinicola.  

PubMed

Anti- Bacillus cereus bioassay-guided fractionation of a crude extract of the American mushroom, Fomitopsis pinicola, was performed using thin-layer chromatography, Sephadex LH-20 column chromatography, and preparative-scale HPLC. Five lanostane triterpenoids (1-5) and one ergostane steroid (6) were isolated and identified. Compound 1 is a new lanostane triterpenoid, and its structure was determined using 1D and 2D NMR experiments, HR-MS, and physical data. Each of the purified compounds (1-6) was tested for antibacterial activity against B. cereus using standard MIC assays. Compounds 1-6 had MIC values of 32, 16, 32, 32, 128, and 64 microg/mL, respectively. PMID:19847745

Liu, Xue-Ting; Winkler, Abby L; Schwan, William R; Volk, Thomas J; Rott, Marc; Monte, Aaron

2009-10-21

288

IDENTIFYING AND EVALUATING PARALLEL DESIGN ACTIVITIES USING THE DESIGN STRUCTURE MATRIX  

Microsoft Academic Search

This paper describes an approach based upon the Design Structure Matrix (DSM) for identifying, evaluating and optimising one aspect of CE: activity parallelism. Concurrent Engineering (CE) has placed emphasis on the management of the product development process and one of its major benefits is the reduction in lead-time and product cost (1). One approach that CE promotes for the reduction

R. I. Whitfield; A. H. B. Duffy; L Kortabarria Gartzia-Etxabe

289

Identifying population subgroups at risk for underestimating weight health risks and overestimating physical activity health benefits  

Microsoft Academic Search

People may incorrectly perceive that their body weight or Physical Activity (PA) meets health recommendations; this provides an obstacle for change. In this study self-reported BMI and PA were assessed in relation to questions regarding perception of meeting weight and PA recommendations. Signal detection analysis was used to identify population subgroups. Study outcomes showed that 34.4 per cent of the

Corneel Vandelanotte; Mitch J. Duncan; Christine Hanley; W. Kerry Mummery

2011-01-01

290

A causal relationship discovery-based approach to identifying active components of herbal medicine  

Microsoft Academic Search

Herbal medicine is widely applied for clinical use in East Asia and other countries. However, unclear correlation between its complex chemical composition and bioactivity prevents its application in the West. In the present study, a stepwise causal adjacent relationship discovery algorithm has been developed to study correlation between composition and bioactivity of herbal medicine and identify active components from the

Yiyu Cheng; Yi Wang; Xuewei Wang

2006-01-01

291

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

PubMed Central

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.

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

292

Identifying Predictors of Activity Based Anorexia Susceptibility in Diverse Genetic Rodent Populations  

PubMed Central

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.

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

293

Investigation of the role of structural domains identified in sedimentary organic matter in the sorption of hydrophobic organic compounds.  

PubMed

The role of composition and structure of sedimentary organic matter (SOM) in the sorption of hydrophobic organic compounds (HOCs) was investigated by spiking 13C-labeled phenanthrene onto six estuarine sediments known to vary in SOM content and character. After equilibration and HF treatment, 13C NMR cross polarization and stable carbon isotope analyses indicated that the amount of desorption-resistant phenanthrene was related to aromatic carbon content. Application of the 13C NMR spectral editing technique proton spin relaxation editing (PSRE) demonstrated that all samples consisted of a rapidly relaxing and a slowly relaxing component, further evidence that SOM can be described as a structurally heterogeneous sorbent. Further, comparison of corresponding control and spiked PSRE subspectra revealed that, for each of the six sediments, desorption-resistant phenanthrene had become associated almost exclusively with the rapidly relaxing component. In only two of the sediments were there even small amounts of phenanthrene discernible in the slowly relaxing component, which is signficant as it was not always true that aromatic carbon was concentrated exclusively in the rapidly relaxing phase. The implication of these findings is that not all aromatic fractions have the same affinity for phenanthrene and that some fractions may indeed have little affinity at all. These results were interpreted as indicative that rapidly relaxing aromatic carbon associated with either sediment-associated charcoal or diagenetic organic matter plays a controlling role in the sorption of HOCs. However, the exact manner in which this rapidly relaxing aromatic phase relates to models presented elsewhere remains unclear. PMID:15984766

Golding, Christopher J; Smernik, Ronald J; Birch, Gavin F

2005-06-01

294

Pharmacologically active compounds in the Anoectochilus and Goodyera species  

Microsoft Academic Search

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

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

2008-01-01

295

Structure-activity relationships of alloxan-like compounds derived from uric acid.  

PubMed Central

The diabetogenic activity of a range of alloxan-like compounds derived from uric acid has been investigated. The classes of derivatives were: 5-substituted-isouric acids; 4,5-disubstituted-4, 5-dihydrouric acids; 5-substituted-pseudouric acids; salts of dehydro-uramil hydrate; salts of dehydro-isouramil hydrate; alloxan derivatives. Compounds were tested by intravenous injection into rats and diabetogenic activity assessed by production of persistent hyperglycaemia and glycosuria. The only essential structural feature common to all active compounds was the presence of a quinonoid pyrimidine system or its hydrated equivalent. The presence of the five-membered ring of uric acid (or an opened form thereof) did not abolish and in some compounds enhanced diabetogenic activity.

Ashcroft, S. J.; Harrison, D. E.; Poje, M.; Rocic, B.

1986-01-01

296

Tyrphostin-like compounds with ubiquitin modulatory activity as possible therapeutic agents for multiple myeloma.  

PubMed

With the goal of developing small molecules as novel regulators of signal transduction and apoptosis, a series of tyrphostin-like compounds were synthesized and screened for their activity against MM-1 (multiple myeloma) cells and other cell lines representing this malignancy. Synthesis was completed in solution-phase initially and then adopted to solid-phase for generating a more diverse set of compounds. A positive correlation was noted between compounds capable of inducing apoptosis and their modulation of protein ubiquitination. Further analysis suggested that ubiquitin modulation occurs through inhibition of cellular deubiquitinase activity. Bulky groups on the sidechain near the ?,?-unsaturated ketone caused a complete loss of activity, whereas cyclization on the opposite side was tolerated. Theoretical calculations at the B3LYP/LACV3P(??) level were completed on each molecule, and the resulting molecular orbitals and Fukui reactivity values for C(?) carbon were utilized in developing a model to explain the compound activity. PMID:22036213

Peng, Zhenghong; Pal, Ashutosh; Han, Dongmei; Wang, Shimei; Maxwell, David; Levitzki, Alexander; Talpaz, Moshe; Donato, Nicholas J; Bornmann, William

2011-10-07

297

A Review on the Radioprotective Activity of organogermanium and Organosilicon Compounds  

PubMed Central

The present review describes the work carried out during the last 20 years in the field of the radioprotective activity and toxicity of several classes of organosilicon and organogermanium compounds (i.e. metallathiazolidines, metalladithioacetals, metallatranes and germathianes).

Rima, Ghassoub; Dagiral, Rodolphe; Lion, Claude; Sentenac-Roumanou, Henri; Fatome, Marc; Roman, Vincent; Laval, Jean-Denis

1999-01-01

298

Drug Discovery for Schistosomiasis: Hit and Lead Compounds Identified in a Library of Known Drugs by Medium-Throughput Phenotypic Screening  

PubMed Central

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.

Wolff, Brian; Snedecor, June; Lim, Kee-Chong; Xu, Fengyun; Renslo, Adam R.; Williams, Janice; McKerrow, James H.; Caffrey, Conor R.

2009-01-01

299

Theoretical investigation of the antituberculosis activity of compounds of the dihydropyrimidine series  

Microsoft Academic Search

An analysis of the tuberculostatic activity of dihydropyrimidine derivatives has been carried out using the 3D QSAR algorithm\\u000a BiS\\/MC. Conformers responsible for the biological action of these compounds have been found and their complexes with receptors\\u000a have been modeled. It is shown that oxygen atoms of the podand chain or ether group of most biologically active compounds\\u000a interact with postiviely

E. S. Pereyaslavskaya; V. A. Potemkin; E. V. Bartashevich; M. A. Grishina; G. L. Rusinov; O. V. Fedorova; M. S. Zhidovinova; I. G. Ovchinnikova

2008-01-01

300

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

NASA Astrophysics Data System (ADS)

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

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

2007-11-01

301

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

PubMed

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

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

2013-07-16

302

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

PubMed Central

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

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

2009-01-01

303

Modulation of aflatoxin B 1 activated protein kinase C by phenolic compounds  

Microsoft Academic Search

Several natural phenolic compounds were tested in vitro for their effect on the activity of protein kinase C isolated from liver cytosol, particulate and nuclear fractions of normal and aflatoxin B1 treated rats. Quercetin and kaempferol inhibited the enzyme activity of all these fractions at very low dose levels. These phenolics were particularly effective in inhibiting the elevated enzyme activity

K. J Mistry; M Krishna; R. K Bhattacharya

1997-01-01

304

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

PubMed Central

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.

Cohen, G M

1990-01-01

305

Heterologous Expression Studies of Saccharomyces cerevisiae Reveal Two Distinct Trypanosomatid CaaX Protease Activities and Identify Their Potential Targets? †  

PubMed Central

The CaaX tetrapeptide motif typically directs three sequential posttranslational modifications, namely, isoprenylation, proteolysis, and carboxyl methylation. In all eukaryotic systems evaluated to date, two CaaX proteases (Rce1 and Ste24/Afc1) have been identified. Although the Trypanosoma brucei genome also encodes two putative CaaX proteases, the lack of detectable T. brucei Ste24 activity in trypanosome cell extracts has suggested that CaaX proteolytic activity within this organism is solely attributed to T. brucei Rce1 (J. R. Gillespie et al., Mol. Biochem. Parasitol. 153:115-124. 2007). In this study, we demonstrate that both T. brucei Rce1 and T. brucei Ste24 are enzymatically active when heterologously expressed in yeast. Using a-factor and GTPase reporters, we demonstrate that T. brucei Rce1 and T. brucei Ste24 possess partially overlapping specificities much like, but not identical to, their fungal and human counterparts. Of interest, a CaaX motif found on a trypanosomal Hsp40 protein was not cleaved by either T. brucei CaaX protease when examined in the context of the yeast a-factor reporter but was cleaved by both in the context of the Hsp40 protein itself when evaluated using an in vitro radiolabeling assay. We further demonstrate that T. brucei Rce1 is sensitive to small molecules previously identified as inhibitors of the yeast and human CaaX proteases and that a subset of these compounds disrupt T. brucei Rce1-dependent localization of our GTPase reporter in yeast. Together, our results suggest the conserved presence of two CaaX proteases in trypanosomatids, identify an Hsp40 protein as a substrate of both T. brucei CaaX proteases, support the potential use of small molecule CaaX protease inhibitors as tools for cell biological studies on the trafficking of CaaX proteins, and provide evidence that protein context influences T. brucei CaaX protease specificity.

Mokry, David Z.; Manandhar, Surya P.; Chicola, Kristen A.; Santangelo, George M.; Schmidt, Walter K.

2009-01-01

306

Identifying combinations of risk and protective factors predicting physical activity change in high school students.  

PubMed

Research sought to identify combinations of risk and protective factors predicting change in physical activity (PA) over one year in high school students. Adolescents (N = 344; M = 15.7 years) participated in a longitudinal study with assessment of demographics, substance use/smoking exposure, height and weight, psychological factors, and PA in 10th and 11th grade. PA participation in 11th grade was greatest for adolescents who engaged in PA and had high sports competence (78%), and least for adolescents who did not engage in or enjoy PA (13%) in 10th grade. Identifying adolescent subgroups at risk for decreasing PA can inform the development of tailored interventions. PMID:21467595

Dunton, Genevieve Fridlund; Atienza, Audie A; Tscherne, James; Rodriguez, Daniel

2011-02-01

307

Anti depressant activity of Mamsyadi Kwatha: An Ayurvedic compound formulation  

PubMed Central

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.

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

2013-01-01

308

[Phenol compounds from brown algae and their antioxidant activity].  

PubMed

The composition and content of phenolic substances were studied in 14 species of marine brown algae of the Canary Islands littoral (Spain). The highest content of phenolic substances was found in Cystoseira compressia and Sargassum furcatum. A high antioxidant activity was found in florotannin isolated from Cystoseira sp. PMID:10867955

Chkhikvishvili, I D; Ramazanov, Z M

309

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

PubMed

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

Shreevathsa, M; Ravishankar, B; Dwivedi, Rambabu

2013-01-01

310

Singing-related activity of identified HVC neurons in the zebra finch.  

PubMed

High vocal center (HVC) is part of the premotor pathway necessary for song production and is also a primary source of input to the anterior forebrain pathway (AFP), a basal ganglia-related circuit essential for vocal learning. We have examined the activity of identified HVC neurons of zebra finches during singing. Antidromic activation was used to identify three classes of HVC cells: neurons projecting to the premotor nucleus RA, neurons projecting to area X in the AFP, and putative HVC interneurons. HVC interneurons are active throughout the song and display tonic patterns of activity. Projection neurons exhibit highly phasic stereotyped firing patterns. X-projecting (HVC((X))) neurons burst zero to four times per motif, whereas RA-projecting neurons burst extremely sparsely--at most once per motif. The bursts of HVC projection neurons are tightly locked to the song and typically have a jitter of <1 ms. Population activity of interneurons, but not projection neurons, was significantly correlated with syllable patterns. Consistent with the idea that HVC codes for the temporal order in the song rather than for sound, the vocal dynamics and neural dynamics in HVC occur on different and uncorrelated time scales. We test whether HVC((X)) neurons are auditory sensitive during singing. We recorded the activity of these neurons in juvenile birds during singing and found that firing patterns of these neurons are not altered by distorted auditory feedback, which is known to disrupt learning or to cause degradation of song already learned. PMID:17182906

Kozhevnikov, Alexay A; Fee, Michale S

2006-12-20

311

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

PubMed Central

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

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

2009-01-01

312

Procaspase-3 Activation as an Anti-Cancer Strategy: Structure-Activity Relationship of Procaspase-Activating Compound 1 (PAC-1) and its Cellular Co-Localization with Caspase-3  

PubMed Central

A goal of personalized medicine as applied to oncology is to identify compounds that exploit a defined molecular defect in a cancerous cell. A compound called procaspase-activating compound 1 (PAC-1) was reported that enhances the activity of procaspase-3 in vitro and induces apoptotic death in cancer cells in culture and in mouse xenograft models. Experimental evidence indicates that PAC-1 activates procaspase-3 in vitro through chelation of inhibitory zinc ions. Described herein is the synthesis and biological activity of a family of PAC-1 derivatives where key functional groups have been systematically altered. Analysis of these compounds reveals a strong correlation between the in vitro procaspase-3 activating effect and their ability to induce death in cancer cells in culture. Importantly, we also show that a fluorescently-labeled version of PAC-1 co-localizes with sites of caspase-3 activity in cancer cells. The data presented herein further bolster the hypothesis that PAC-1 induces apoptosis in cancer cells through the direct activation of procaspase-3, has implications for the design and discovery of next-generation procaspase-3 activating compounds, and sheds light on the anti-apoptotic role of cellular zinc.

Peterson, Quinn P.; Hsu, Danny C.; Goode, David R.; Novotny, Chris J.; Totten, Ryan K.; Hergenrother, Paul J.

2009-01-01

313

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

PubMed

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

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

2008-07-01

314

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

PubMed

During our search to discover new antitrypanosomal compounds, eight known plant compounds (three phenolic compounds and five kawa lactones) were evaluated for in vitro activity against Trypanosoma brucei brucei. Among them, we found two phenolic compounds and three kawa lactones possessing an ?-pyrone influenced antitrypanosomal property. In particular, ?-phenethyl caffeate, farnesyl caffeate and dihydrokawain exhibited high or moderate selective and potent antitrypanosomal activity in vitro. We detail here the antitrypanosomal activity and cytotoxicities of the compounds, in comparison with two commonly used antitrypanosomal drugs (eflornithine and suramin). Our findings represent the first report of the promising trypanocidal activity of these compounds. PMID:22116743

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

2011-11-25

315

Antileishmanial activity of the hydroalcoholic extract of Miconia langsdorffii, isolated compounds, and semi-synthetic derivatives.  

PubMed

The in vitro activity of the crude hydroalcoholic extract of the aerial parts of Miconia langsdorffii Cogn. was evaluated against the promastigote forms of L. amazonensis, the causative agent of cutaneous leishmaniasis in humans. The bioassay-guided fractionation of this extract led to identification of the triterpenes ursolic acid and oleanolic acid as the major compounds in the fraction that displayed the highest activity. Several ursolic acid semi-synthetic derivatives were prepared, to find out whether more active compounds could be obtained. Among these ursolic acid-derived substances, the C-28 methyl ester derivative exhibited the best antileishmanial activity. PMID:21343887

Peixoto, Juliana A; Andrade E Silva, Márcio Luis; Crotti, Antônio E M; Cassio Sola Veneziani, Rodrigo; Gimenez, Valéria M M; Januário, Ana H; Groppo, Milton; Magalhães, Lizandra G; Dos Santos, Fransérgio F; Albuquerque, Sérgio; da Silva Filho, Ademar A; Cunha, Wilson R

2011-02-22

316

Hypervalent iodine compounds as potent antibacterial agents against ice nucleation active (INA) Pseudomonas syringae.  

PubMed

Twenty-three hypervalent iodine compounds belonging to aryliodonium salts, 1, aryliodonium ylides, 2, and (diacyloxyiodo)arenes, 3, were tested for their antibacterial activities against ice nucleation active (INA) Pseudomonas syringae, and the MIC and EC(50) values were determined. All of the compounds examined caused a dose-dependent decrease in bacterial growth rates. Aryliodonium salts, especially those with electron-withdrawing groups, exhibit higher antibacterial activities with MIC = 8-16 ppm, whereas the nature of the anion does not seem to affect the activities of the diaryliodonium salts. PMID:11513659

Menkissoglu-Spiroudi, U; Karamanoli, K; Spyroudis, S; Constantinidou, H I

2001-08-01

317

Global emissions and models of photochemically active compounds  

SciTech Connect

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

Penner, J.E.; Atherton, C.S. [Lawrence Livermore National Lab., CA (United States); Graedel, T.E. [AT and T Bell Labs., Murray Hill, NJ (United States)

1993-05-20

318

Two new xanthones from Hypericum sampsonii and biological activity of the isolated compounds.  

PubMed

Phytochemical investigation of the CH(2) Cl(2) extract of the aerial part of Hypericum sampsonii yielded two new prenylated xanthones, hypericumxanthone A and B, together with three known xanthones. Their structures were elucidated by analysis of physical and spectral (UV, IR, mass and NMR) data and comparison of spectroscopic data with those reported previously. All these compounds were evaluated for in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Two new compounds were also tested for their cytotoxicity against human breast (MCF-7), hepatoma (HepG2), colon (HT-29) and lung (A549) tumour cell lines. Two new compounds showed moderate antibacterial activities at minimum inhibitory concentrations (MIC) of 16 and 32?µg/mL, respectively, whereas the positive standard antibacterial drug, vancomycin, showed an MIC of 8?µg/mL. The other compounds were inactive against MRSA. In addition, hypericumxanthone B showed weak inhibitory activities against four human tumour cell lines. PMID:20839213

Xin, Wen-Bo; Mao, Zhu-Jun; Jin, Gui-Lin; Qin, Lu-Ping

2010-09-13

319

A multi-parameter imaging assay identifies different stages of ligand-induced androgen receptor activation.  

PubMed

Androgens exert their key function in development and maintenance of the male phenotype via the androgen receptor (AR). Ligand-activated ARs also play a role in prostate cancer. Despite initial success of treatment by testosterone depletion or blocking of androgen binding to the AR using antiandrogens, eventually all tumors escape to a therapy resistant stage. Development of novel therapies by other antagonistic ligands or compounds that target events subsequent to ligand binding is very important. Here, we validate a fluorescence resonance energy transfer (FRET) based imaging assay for ligand-induced AR activity, based on the conformational change in the AR caused by interaction between the FQNLF motif in the N-terminal domain and the cofactor binding groove in the ligand-binding domain (N/C-interaction). We test the assay using known agonistic and antagonistic ligands on wild type AR and specific AR mutants. Our data show a strong correlation between the ligand-induced AR N/C-interaction and transcriptional activity in wild type AR, but also in AR mutants with broadened ligand responsiveness. Moreover, we explore additional readouts of this assay that contribute to the understanding of the working mechanism of the ligands. Together, we present a sensitive assay that can be used to quantitatively assess the activity of agonistic and antagonistic AR ligands. © 2013 International Society for Advancement of Cytometry. PMID:23585273

van Royen, Martin E; van de Wijngaart, Dennis J; Cunha, Sónia M; Trapman, Jan; Houtsmuller, Adriaan B

2013-04-12

320

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

PubMed

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

Nantitanon, W; Okonogi, S

2012-02-01

321

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

PubMed

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

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

2013-09-01

322

Anti-Cancer Activity of a Novel Small Molecule Compound That Simultaneously Activates p53 and Inhibits NF-?B Signaling  

PubMed Central

The p53 and NF-?B pathways play important roles in diverse cellular functions, including cell growth, apoptosis, and tumorigenesis. Mutations that inactivate the p53 gene and constitutive NF-?B pathway activation are common occurrences in human cancers. Although many drugs are being developed that selectively activate p53 or inhibit NF-?B, there are few drug candidates that can do both. Simultaneous activation of p53 and inhibition of the NF-?B pathway is therefore a prime target for new cancer drug development. This study is the first report of a high-throughput approach with mass compounds that concurrently target both pathways. Using a cell-based screening assay and a library of 200,000 synthetic compounds, we identified 9 small molecules that simultaneously inhibit NF-?B and activate p53. One of these compounds, N-2, increased the expression of p53 target genes, including p21 and GADD45a. In addition, N-2 inhibited the transcriptional activity of NF-?B, concomitantly repressing interleukin-6 and monocyte chemotactic protein-1 (MCP-1) expression. When cell lines derived from a diverse range of cancers were treated in vitro with N-2, we observed increased cell death. N-2 also significantly inhibited allograft growth in murine models of melanoma and lung carcinoma. Our findings suggest that N-2 may act as a bivalent anti-cancer agent through simultaneous modulation of NF-?B and p53 activities.

Hwang, Sun Gwan; Park, Jinah; Park, Joo Young; Park, Cheol Hyoung; Lee, Ki-Ho; Cho, Jeong Woo; Hwang, Jong-Ik; Seong, Jae Young

2012-01-01

323

Identification strategy for unknown pollutants using high-resolution mass spectrometry: Androgen-disrupting compounds identified through effect-directed analysis  

Microsoft Academic Search

Effect-directed analysis has been applied to a river sediment sample of concern to identify the compounds responsible for\\u000a the observed effects in an in vitro (anti-)androgenicity assay. For identification after non-target analysis performed on\\u000a a high-resolution LTQ-Orbitrap, we developed a de novo identification strategy including physico-chemical parameters derived\\u000a from the effect-directed analysis approach. With this identification strategy, we were able

Jana M. Weiss; Eszter Simon; Gerard J. Stroomberg; Ronald de Boer; Jacob de Boer; Sander C. van der Linden; Pim E. G. Leonards; Marja H. Lamoree

2011-01-01

324

Structure-activity models of oral clearance, cytotoxicity, and LD50: a screen for promising anticancer compounds  

PubMed Central

Background Quantitative structure-activity relationship (QSAR) models have become popular tools to help identify promising lead compounds in anticancer drug development. Few QSAR studies have investigated multitask learning, however. Multitask learning is an approach that allows distinct but related data sets to be used in training. In this paper, a suite of three QSAR models is developed to identify compounds that are likely to (a) exhibit cytotoxic behavior against cancer cells, (b) exhibit high rat LD50 values (low systemic toxicity), and (c) exhibit low to modest human oral clearance (favorable pharmacokinetic characteristics). Models were constructed using Kernel Multitask Latent Analysis (KMLA), an approach that can effectively handle a large number of correlated data features, nonlinear relationships between features and responses, and multitask learning. Multitask learning is particularly useful when the number of available training records is small relative to the number of features, as was the case with the oral clearance data. Results Multitask learning modestly but significantly improved the classification precision for the oral clearance model. For the cytotoxicity model, which was constructed using a large number of records, multitask learning did not affect precision but did reduce computation time. The models developed here were used to predict activities for 115,000 natural compounds. Hundreds of natural compounds, particularly in the anthraquinone and flavonoids groups, were predicted to be cytotoxic, have high LD50 values, and have low to moderate oral clearance. Conclusion Multitask learning can be useful in some QSAR models. A suite of QSAR models was constructed and used to screen a large drug library for compounds likely to be cytotoxic to multiple cancer cell lines in vitro, have low systemic toxicity in rats, and have favorable pharmacokinetic properties in humans.

Boik, John C; Newman, Robert A

2008-01-01

325

Activity of compounds isolated from Baccharis dracunculifolia D.C. (Asteraceae) against Paracoccidioides brasiliensis.  

PubMed

Paracoccidioidomycosis is a prevalent systemic mycosis in Latin America which requires prolonged treatment with highly toxic antifungals. Baccharis dracunculifolia is a medicinal plant in Brazil that is a candidate in the search for new drugs. Fractions of the hexanic extracts were obtained using chromatographic procedures and assessed using an antifungal assay with Paracoccidioides brasiliensis (Pb18), tumor cell lines and amastigote forms of Leishmania, L. amazonensis. Four compounds were isolated, i.e., ursolic acid (1), methyl linolenate (2), caryophyllene oxide (3), and trans-nerolidol (4). Compounds 2, 3 and 4 displayed antifungal activity against four isolates of Paracocci dioides with MIC values ranging from 3.9-250 ?g/ml. Only caryophyllene oxide showed differences in the MIC values against Pb18 when the medium was supplemented with ergosterol, which suggested that the compound interacts with ergosterol. Ursolic acid was active in the cytotoxic assays and showed leishmanicidal activity. Scanning electron microscopy demonstrated that compounds 2, 3 and 4 decreased the cell size and produced an irregular cell wall surface on P. brasiliensis cells. The present results showed the biological activities of the isolated compounds and revealed that these compounds may affect the cell surface and growth of P. brasiliensis isolates. PMID:22548242

Johann, Susana; Oliveira, Flávia Beraldo; Siqueira, Ezequias P; Cisalpino, Patricia S; Rosa, Carlos A; Alves, Tânia M A; Zani, Carlos L; Cota, Betania B

2012-05-02

326

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

PubMed

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

Zhu, Xianfeng; Zhang, Hongxun; Lo, Raymond

2004-12-01

327

Activity-based Protein Profiling Identifies a Host Enzyme, Carboxylesterase 1, Which Is Differentially Active during Hepatitis C Virus Replication*  

PubMed Central

Hepatitis C virus (HCV) relies on many interactions with host cell proteins for propagation. Successful HCV infection also requires enzymatic activity of host cell enzymes for key post-translational modifications. To identify such enzymes, we have applied activity-based protein profiling to examine the activity of serine hydrolases during HCV replication. Profiling of hydrolases in Huh7 cells replicating HCV identified CES1 (carboxylesterase 1) as a differentially active enzyme. CES1 is an endogenous liver protein involved in processing of triglycerides and cholesterol. We observe that CES1 expression and activity were altered in the presence of HCV. The knockdown of CES1 with siRNA resulted in lower levels of HCV replication, and up-regulation of CES1 was observed to favor HCV propagation, implying an important role for this host cell protein. Experiments in HCV JFH1-infected cells suggest that CES1 facilitates HCV release because less intracellular HCV core protein was observed, whereas HCV titers remained high. CES1 activity was observed to increase the size and density of lipid droplets, which are necessary for the maturation of very low density lipoproteins, one of the likely vehicles for HCV release. In transgenic mice containing human-mouse chimeric livers, HCV infection also correlates with higher levels of endogenous CES1, providing further evidence that CES1 has an important role in HCV propagation.

Blais, David R.; Lyn, Rodney K.; Joyce, Michael A.; Rouleau, Yanouchka; Steenbergen, Rineke; Barsby, Nicola; Zhu, Lin-Fu; Pegoraro, Adrian F.; Stolow, Albert; Tyrrell, David L.; Pezacki, John Paul

2010-01-01

328

Identification and quantification of phenolic compounds in bambangan (Mangifera pajang Kort.) peels and their free radical scavenging activity.  

PubMed

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

Hassan, Fouad Abdulrahman; Ismail, Amin; Abdulhamid, Azizah; Azlan, Azrina

2011-08-17

329

IDENTIFICATION OF A NOVEL CLASS OF ANTI-INFLAMMATORY COMPOUNDS WITH ANTI-TUMOR ACTIVITY IN COLORECTAL AND LUNG CANCERS  

PubMed Central

Summary Chronic inflammation is associated with 25% of all cancers. In the inflammation-cancer axis, prostaglandin E2 (PGE2) is one of the major players. PGE2 synthases (PGES) are the enzymes downstream of the cyclooxygenases (COXs) in the PGE2 biosynthesis pathway. Microsomal prostaglandin E2 synthase 1 (mPGES-1) is inducible by pro-inflammatory stimuli and constitutively expressed in a variety of cancers. The potential role for this enzyme in tumorigenesis has been reported and mPGES-1 represents a novel therapeutic target for cancers. In order to identify novel small molecule inhibitors of mPGES-1, we screened the ChemBridge library and identified 13 compounds as potential hits. These compounds were tested for their ability to bind directly to the enzyme using surface plasmon resonance spectroscopy and to decrease cytokine-stimulated PGE2 production in various cancer cell lines. We demonstrate that the compound PGE0001 (ChemBridge ID number 5654455) binds to human mPGES-1 recombinant protein with good affinity (KD = 21.3 ± 7.8 ?M). PGE0001 reduces IL-1?-induced PGE2 release in human HCA-7 colon and A549 lung cancer cell lines with EC50 in the submicromolar range. Although PGE0001 may have alternative targets based on the results from in vitro assays, it shows promising effects in vivo. PGE0001 exhibits significant anti-tumor activity in SW837 rectum and A549 lung cancer xenografts in SCID mice. Single injection i.p. of PGE0001 at 100 mg/kg decreases serum PGE2 levels in mice within 5 h. In summary, our data suggest that the identified compound PGE0001 exerts anti-tumor activity via the inhibition of the PGE2 synthesis pathway.

Chang, Hui-Hua; Song, Zuohe; Wisner, Lee; Tripp, Tina; Gokhale, Vijay

2011-01-01

330

Innovative cosmeceuticals: sirtuin activators and anti-glycation compounds.  

PubMed

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

Farris, Patricia K

2011-09-01

331

A causal relationship discovery-based approach to identifying active components of herbal medicine.  

PubMed

Herbal medicine is widely applied for clinical use in East Asia and other countries. However, unclear correlation between its complex chemical composition and bioactivity prevents its application in the West. In the present study, a stepwise causal adjacent relationship discovery algorithm has been developed to study correlation between composition and bioactivity of herbal medicine and identify active components from the complex mixture. This approach was successfully applied in discovering active constituents from mixed extracts of Radix Salviae miltiorrhizae and Cortex Moutan. Moreover, advantage of the present approach compared with bioassay-guided isolation was demonstrated by its application on a typical herbal drug. The current work offers a new way to virtually screen active components of herbal medicine, and it might be helpful to accelerate the process of new drug discovery from natural products. PMID:16542877

Cheng, Yiyu; Wang, Yi; Wang, Xuewei

2006-03-20

332

Evaluation of anxiolytic activity of compound Valeriana jatamansi Jones in mice  

PubMed Central

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

2012-01-01

333

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

SciTech Connect

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.

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

2005-12-01

334

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

PubMed

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

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

2013-02-01

335

Synthesis and biological activity of natural thiazoles: An important class of heterocyclic compounds  

Microsoft Academic Search

The class of heterocyclic compounds known as thiazole is found in many natural and synthetic products with a wide range of pharmacological activities, such as antiviral, anticancer, antibacterial, antifungal, anticonvulsant, antiparkinsonian and anti-inflammatory activities that can be well illustrated by the large number of drugs in the market containing this function group. Due to its importance, the aim of this

Marcus Vinícius Nora de Souza

2005-01-01

336

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,...

337

Antiandrogenic Activity and Metabolism of the Organophosphorus Pesticide Fenthion and Related Compounds  

Microsoft Academic Search

tude 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.

Shigeyuki Kitamura; Tomoharu Suzuki; Shigeru Ohta; Nariaki Fujimoto

2003-01-01

338

Assessment of the developmental neurotoxicity of compounds by measuring locomotor activity in zebrafish embryos and larvae.  

PubMed

The developmental neurotoxic potential of the majority of environmental chemicals and drugs is currently undetermined. Specific in vivo studies provide useful data for hazard assessment but are not amenable to screen thousands of untested compounds. In this study, methods which use zebrafish embryos, eleutheroembryos and larvae as model organisms, were proposed as alternatives for developmental neurotoxicity (DNT) testing. The evaluation of spontaneous tail coilings in zebrafish embryos aged 24-26 hours post fertilization (hpf) and the swimming activity of eleutheroembryos at 120 and larvae at 144 hpf, i.e. parameters for locomotor activity, were investigated as potential endpoints for DNT testing, according to available standard protocols. The overall performance and predictive value of these methods was then examined by testing a training set of 10 compounds, including known developmental neurotoxicants and compounds not considered to be neurotoxic. The classification of the selected compounds as either neurotoxic or non-neurotoxic, based on the effects observed in zebrafish embryos and larvae, was compared to available mammalian data and an overall concordance of 90% was achieved. Furthermore, the specificity of the selected endpoints for DNT was evaluated as well as the potential similarities between zebrafish and mammals with regard to mechanisms of action for the selected compounds. Although further studies, including the screening of a large testing set of compounds are required, we suggest that the proposed methods with zebrafish embryos and larvae might be valuable alternatives for animal testing for the screening and prioritization of compounds for DNT. PMID:23357511

Selderslaghs, Ingrid W T; Hooyberghs, Jef; Blust, Ronny; Witters, Hilda E

2013-01-26

339

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

DOEpatents

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.

Vo-Dinh, T.

1994-06-07

340

One Lignanoid Compound and Four Triterpenoid Compounds with Anti-Inflammatory Activity from the Leaves of Elaeagnus oldhamii Maxim.  

PubMed

One lignanoid compound, isoamericanol B (1), along with four triterpenoid compounds-cis-3-O-p-hydroxycinnamoyloleanolic acid (2), trans-3-O-p-hydroxy cinnamoyloleanolic acid (3), cis-3-O-p-hydroxycinnamoylursolic acid (4), trans-3-O-p-hydroxycinnamoylursolic acid (5) have been isolated for the first time from the leaves of Elaeagnus oldhamii Maxim. Compounds 1-4 significantly inhibited the expression of NO (nitric oxide) produced in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The IC50 value for inhibition of nitrite production of compound 1 was about 10.3 ± 0.4 ?g/mL. In the cell viability test, however, among compounds 1-4 compound 1 did not significantly change cell viability. Therefore, in this study compound 1 possessed anti-inflammatory effects. The result suggests compound 1 as a potential lead compound for the treatment of inflammatory diseases. PMID:24165581

Liao, Chi-Ren; Ho, Yu-Ling; Huang, Guan-Jhong; Yang, Chang Syun; Chao, Che-Yi; Chang, Yuan-Shiun; Kuo, Yueh-Hsiung

2013-10-25

341

3D-quantitative structure-activity relationship study of organophosphate compounds  

Microsoft Academic Search

The biological effects of most organophosphate compounds (OP) are arising by inhibition of the enzyme acetylcholinesterase\\u000a (AChE). The 3D-quantitative structure-activity relationship (3D-QSAR) on the acute toxicity to housefly (Musca nobulo L.) of 35 dialkyl phenyl phosphate compounds are studied by using comparative molecular field analysis (CoMFA) and comparative\\u000a molecular similarity index analysis (CoMSIA) methods, and the reaction mechanism between the

Jinsong Zhao; Bin Wang; Zhaoxia Dai; Xiaodong Wang; Lingren Kong; Liansheng Wang

2004-01-01

342

Anti-Trypanosoma activity of some natural stilbenoids and synthetic related heterocyclic compounds  

Microsoft Academic Search

We report the anti-Chagasic activity of the natural dihydrostilbenoid isonotholaenic acid and several simple derivatives, as well as that of some representative compounds of related synthetic series, with basic structures of benzalphthalides, dihydrostilbamides, isoindoles, phthalazin-1-ones, imidazo[2,1-a]isoindoles and pyrimido[2,1-a]isoindoles. The evaluation was performed in vitro on cultures of epimastigote and trypomastigote forms of Trypanosoma cruzi. Some of the tested compounds resulted

Esther del Olmo; Marlon Garc??a Armas; Jose Luis López-Pérez; Grace Ruiz; Fernando Vargas; Alberto Giménez; Eric Deharo; Arturo San Feliciano

2001-01-01

343

Study on synthesis and herbicidal activity of heterocyclic compounds containing PP bond  

Microsoft Academic Search

N,N?-diphenylurea reacted with phosphorus trichloride and phenyl dichlorophosphane giving the heterocyclic compounds 1 and\\u000a 2 with a direct phosphorus-phosphorus bond (P-P bond), respectively. The new compounds were characterized by elementary analysis,\\u000a NMR and IR spectra. The results of preliminary bioassay showed that these heterocycles possess selective herbicidal activity\\u000a at 1.5 kg\\/hm2.

He Liangnian; Zhuo Renxi; Cai Lei; Lu Alhong

1998-01-01

344

New Biologically Active N-(Tetrahydrobenzothienopyrimidin-4-YL)Amino Acids, Thiourethane, Sulfonamides and Related Compounds  

Microsoft Academic Search

Some derivatives of thieno[2,3-d]pyrimidine containing amino acids 3a-i, imidazoles 4a-f, isothiocyanate 5, thiourethane 6, triazine 8, pyrimidine 10, sulphonamides 13a-d, 14, pyrazole 16 and pyrazolone 17 were synthesized. The structural assignments of the new compounds were based on analytical, spectroscopic measurements and chemical reactions. Some of the obtained compounds showed interesting antimicrobial activities.

M. M. Ghorab

2000-01-01

345

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

Microsoft Academic Search

The objective of this research was to determine the effectiveness of using pecan and almond shell-based granular activated carbons (GACs) in the adsorption of volatile organic compounds (VOCs) of health concern and known toxic compounds (such as bromo-dichloromethane, benzene, carbon tetrachloride, 1,1,1-trichloromethane, chloroform, and 1,1-dichloromethane) compared to the adsorption efficiency of commercially used carbons (such as Filtrasorb 200, Calgon GRC-20,

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

2003-01-01

346

Antifungal properties of new quaternary ammonium compounds in relation to their surface activity  

Microsoft Academic Search

The biological activity of 17 potential wood preservatives—quaternary ammonium and imidazolium compounds—was determined employing screening agar-plate and agar-block methods. Experiments were carried out on Scots pine (Pinus sylvestris L.) wood. The fungicidal value of new compounds with cycloalkyl substituents for Coniophora puteana ranged from 0.64 kg\\/m3 to 2.2 kg\\/m3. Aspergillus niger turned out to be the most resistant fungus to the action

Jadwiga Zabielska-Matejuk

2005-01-01

347

Antioxidant and Antibacterial Activity of Nutraceutical Compounds from Chlorella vulgaris Extracted in Hydrothermal Condition  

Microsoft Academic Search

Water in hydrothermal condition has been used for extraction of nutraceutical compounds from Chlorella vulgaris. Hydrothermal extraction was carried out in a semi-batch and a batch extractor at various temperatures (120–200°C), pressures (2–10 MPa), and extraction times (30–300 min) to extract antioxidant and antibacterial compounds. The effect of extraction condition on the yield of extract was investigated. The antioxidant and antibacterial activity

Kiwa Kitada; Siti Machmudah; Mitsuru Sasaki; Motonobu Goto; Yuya Nakashima; Shoichiro Kumamoto; Takashi Hasegawa

2009-01-01

348

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

Microsoft Academic Search

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

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

2004-01-01

349

An Ongoing Validation of a Tier I Screening Battery for Detecting Endocrine-Active Compounds (EACs)  

Microsoft Academic Search

After previously examining an estrogen receptor agonist (17?-estradiol), several additional compounds have been evaluated in a Tier I screening battery for detecting endocrine-active compounds (EACs): an estrogen receptor antagonist (ICI-182,780, ICI), an androgen receptor antagonist (flutamide, FLUT), a testosterone biosynthesis inhibitor (ketoconazole, KETO), a 5?-reductase inhibitor (finasteride, FIN), and an aromatase inhibitor (anastrozole, ANA). The Tier I battery incorporates two

John C. O'Connor; Jon C. Cook; Theodore W. Slone; G. Tracy Makovec; Steven R. Frame; Leonard G. Davis

1998-01-01

350

The rejection of endocrine disrupting and pharmaceutically active compounds by NF and RO membranes as a function of compound and water matrix properties  

Microsoft Academic Search

This study examined the rejection of 22 endocrine disrupting compounds (EDCs) and pharmaceutically active compounds (PhAC) from raw and 5-?m filtered Lake Ontario water, membrane bioreactor effluent and laboratory-grade water (Milli-Q®) by ‘loose’ and ‘tight’ nanofiltration (NF) membranes and a reverse osmosis (RO) membrane. Rejection by the ‘tight’ NF membrane was most strongly correlated with compound logKow and water solubility

Anna M. Comerton; Robert C. Andrews; David M. Bagley; Chunyan Hao

2008-01-01

351

Novel orally active NPY Y5 receptor antagonists: Synthesis and structure-activity relationship of spiroindoline class compounds.  

PubMed

Spiroindoline urea derivatives, designed to act as NPY Y5 receptor antagonists, were synthesized and their structure-activity relationships were investigated. Of these derivatives, compound 3a showed good Y5 binding affinity with favorable pharmacokinetic properties. Compound 3a significantly inhibited bPP Y5 agonist-induced food intake in rats, and suppressed body weight gain in DIO mice. PMID:19525116

Sakamoto, Toshihiro; Moriya, Minoru; Tsuge, Hiroyasu; Takahashi, Toshiyuki; Haga, Yuji; Nonoshita, Katsumasa; Okamoto, Osamu; Takahashi, Hirobumi; Sakuraba, Aya; Hirohashi, Tomoko; Shibata, Takunobu; Kanno, Tetsuya; Ito, Junko; Iwaasa, Hisashi; Gomori, Akira; Ishihara, Akane; Fukuroda, Takahiro; Kanatani, Akio; Fukami, Takehiro

2009-06-02

352

Antioxidant Activity of Phenolics Compounds From Sugar Cane ( Saccharum officinarum L.) Juice  

Microsoft Academic Search

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

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

2006-01-01

353

Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers.  

PubMed

Activation of normally silent tissue-specific genes and the resulting cell "identity crisis" are the unexplored consequences of malignant epigenetic reprogramming. We designed a strategy for investigating this reprogramming, which consisted of identifying a large number of tissue-restricted genes that are epigenetically silenced in normal somatic cells and then detecting their expression in cancer. This approach led to the demonstration that large-scale "off-context" gene activations systematically occur in a variety of cancer types. In our series of 293 lung tumors, we identified an ectopic gene expression signature associated with a subset of highly aggressive tumors, which predicted poor prognosis independently of the TNM (tumor size, node positivity, and metastasis) stage or histological subtype. The ability to isolate these tumors allowed us to reveal their common molecular features characterized by the acquisition of embryonic stem cell/germ cell gene expression profiles and the down-regulation of immune response genes. The methodical recognition of ectopic gene activations in cancer cells could serve as a basis for gene signature-guided tumor stratification, as well as for the discovery of oncogenic mechanisms, and expand the understanding of the biology of very aggressive tumors. PMID:23698379

Rousseaux, Sophie; Debernardi, Alexandra; Jacquiau, Baptiste; Vitte, Anne-Laure; Vesin, Aurélien; Nagy-Mignotte, Hélène; Moro-Sibilot, Denis; Brichon, Pierre-Yves; Lantuejoul, Sylvie; Hainaut, Pierre; Laffaire, Julien; de Reyniès, Aurélien; Beer, David G; Timsit, Jean-François; Brambilla, Christian; Brambilla, Elisabeth; Khochbin, Saadi

2013-05-22

354

Methods for Identifying and Averaging Variable Molecular Conformations in Tomograms of Actively Contracting Insect Flight Muscle  

PubMed Central

During active muscle contraction, tension is generated through many simultaneous, independent interactions between the molecular motor myosin and the actin filaments. The ensemble of myosin motors displays heterogeneous conformations reflecting different kinetic steps of the ATPase pathway. We used electron tomography of actively contracting insect flight muscle fast-frozen, freeze-substituted, Araldite embedded, thin sectioned and stained, to obtain 3-D snapshots of the multiplicity of actin-attached myosin structures. We describe procedures for alignment of the repeating lattice of sub-volumes (38.7 nm cross-bridge repeats bounded by troponin) and multivariate data analysis to identify self-similar repeats for computing class averages. Improvements in alignment and classification of repeat sub-volumes reveals (for the first time in active muscle images) the helix of actin subunits in the thin filament and the troponin density with sufficient clarity that a quasiatomic model of the thin filament can be built into the class averages independent of the myosin cross-bridges. We show how quasiatomic model building can identify both strong and weak myosin attachments to actin. We evaluate the accuracy of image classification to enumerate the different types of actin-myosin attachments.

Wu, Shenping; Liu, Jun; Reedy, Mary C.; Winkler, Hanspeter; Reedy, Michael K.; Taylor, Kenneth A.

2009-01-01

355

Activation of different signals identified with glia cells contribute to the progression of hyperalgesia.  

PubMed

Hyperalgesia results from a decreased pain threshold, often subsequent to peripheral tissue damage. Recent reports revealed several promising mechanisms of hyperalgesia, but many issues remain unclear. The glial activation accompanying inflammation of neurotransmission in the spinal cord might be related to the initiation and maintenance of hyperalgesia. The present study investigated the pharmacological pain-modifying effects of mitogen-associated protein kinase (MAPK)-related inhibitors identified with glia cells over time during inflammatory pain. A model of inflammatory pain was produced by injecting mustard oil (MO) into the hind paws of rats. Following MO injection, the changes in paws flinching as the early onset of pain and paw withdrawal latency (PWL) in response to thermal stimulation were measured as delayed-onset hyperalgesia. Before and after the MO injection, one of the inhibitors, a p38-MAPK (SB), nuclear factor (NF)-?B (PDTC), BDNF-trk-B (K252a), or JNK-1 (SP), was administered and flinching and PWL were measured. In the SB, PDTC, and k252a groups, early flinching following MO injection was moderately suppressed. Hyperalgesia was significantly suppressed in the left-right difference of PWL in animals receiving SB, k252a, or PDTC pre-treatment. In animals receiving post-treatment, the suppressive effects were most potent in the SP group. The present results revealed that microglial activation resulting from the release of the phosphatase p38-MAPK, the transcription factor NF-?B, and BDNF contributes to the early stage of inflammatory pain. Astrocyte activation accompanying JNK activation contributes to subsequent hyperalgesia. Activation of different signals identified with glia cells is thought to contribute to the progression of hyperalgesia, which represents an applicable finding for the treatment of hyperalgesia. PMID:23208699

Yamamoto, Satoru; Kishishita, Yusuke; Yoshida, Mitsuhiro; Miura, Daisuke; Suzuki, Hidenori; Ishikawa, Kozo; Miyazaki, Hirofumi; Nojima, Junzo; Yamamoto, Misa; Ishikawa, Toshizo

2012-10-23

356

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

NASA Astrophysics Data System (ADS)

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.

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

357

Polyphenolic compounds and in vitro antimicrobial and antioxidant activity of aqueous extracts from leaves of some Cirsium species.  

PubMed

Crude aqueous extracts from leaves of Cirsium arvense, C. oleraceum, C. palustre, C. rivulare and C. vulgare were investigated. The content of tannins in mentioned sources, determined by the weight method with hide powder, varied between 1 and 7.63%. Total phenolic content, analysed by using Folin-Ciocalteau's method, ranged between 54 and 96 mg g(-1), was expressed as milligrams of gallic acid per gram of dry extract. Phenolic acids were identified by HPLC method. Antimicrobial activity of those extracts was examined. Cirsium palustre extract was the most active against investigated microorganisms. It was observed that the content of small-molecular phenolic compounds had greater influence on the activity of extracts than tannins. The total antioxidant activity indicated by radical cation 2,2'-azini-di-(3-ethylbenzthiazoline sulphonate) ABTS(*+), expressed as total antioxidant status (TAS) ranged from 2.31 to 2.78 mM L(-1). PMID:19085412

Nazaruk, Jolanta; Czechowska, Sylwia K; Markiewicz, Renata; Borawska, Maria H

2008-12-01

358

Intermolecular interactions identify ligand-selective activity of estrogen receptor alpha/beta dimers.  

PubMed

Estrogen receptor (ER) dimerization is prerequisite for its activation of target gene transcription. Because the two forms of ER, ERalpha and ERbeta, exhibit opposing functions in cell proliferation, the ability of ligands to induce ERalpha/beta heterodimers vs. their respective homodimers is expected to have profound impacts on transcriptional outcomes and cellular growth. However, there is a lack of direct methods to monitor the formation of ERalpha/beta heterodimers in vivo and to distinguish the ability of estrogenic ligands to promote ER homo- vs. heterodimerization. Here, we describe bioluminescence resonance energy transfer (BRET) assays for monitoring the formation of ERalpha/beta heterodimers and their respective homodimers in live cells. We demonstrate that although both partners contribute to heterodimerization, ligand-bound ERalpha plays a dominant role. Furthermore, a bioactive component was found to induce ERbeta/beta homodimers, and ERalpha/beta heterodimers but had minimal activity on ERalpha/alpha homodimers, posing a model that compounds promoting ERalpha/beta heterodimer formation might have therapeutic value. Thus, ER homodimer and heterodimer BRET assays are applicable to drug screening for dimer-selective selective ER modulators. Furthermore, this strategy can be used to study other nuclear receptor dimers. PMID:19022902

Powell, Emily; Xu, Wei

2008-11-20

359

Intermolecular interactions identify ligand-selective activity of estrogen receptor ?/? dimers  

PubMed Central

Estrogen receptor (ER) dimerization is prerequisite for its activation of target gene transcription. Because the two forms of ER, ER? and ER?, exhibit opposing functions in cell proliferation, the ability of ligands to induce ER?/? heterodimers vs. their respective homodimers is expected to have profound impacts on transcriptional outcomes and cellular growth. However, there is a lack of direct methods to monitor the formation of ER?/? heterodimers in vivo and to distinguish the ability of estrogenic ligands to promote ER homo- vs. heterodimerization. Here, we describe bioluminescence resonance energy transfer (BRET) assays for monitoring the formation of ER?/? heterodimers and their respective homodimers in live cells. We demonstrate that although both partners contribute to heterodimerization, ligand-bound ER? plays a dominant role. Furthermore, a bioactive component was found to induce ER?/? homodimers, and ER?/? heterodimers but had minimal activity on ER?/? homodimers, posing a model that compounds promoting ER?/? heterodimer formation might have therapeutic value. Thus, ER homodimer and heterodimer BRET assays are applicable to drug screening for dimer-selective selective ER modulators. Furthermore, this strategy can be used to study other nuclear receptor dimers.

Powell, Emily; Xu, Wei

2008-01-01

360

Modulation of aflatoxin B1 activated protein kinase C by phenolic compounds.  

PubMed

Several natural phenolic compounds were tested in vitro for their effect on the activity of protein kinase C isolated from liver cytosol, particulate and nuclear fractions of normal and aflatoxin B1 treated rats. Quercetin and kaempferol inhibited the enzyme activity of all these fractions at very low dose levels. These phenolics were particularly effective in inhibiting the elevated enzyme activity following aflatoxin B1 administration. Ellagic acid and curcumin were found to be inhibitory only towards particulate enzymes obtained after carcinogen treatment, while curcumin and rutin were moderately active against nuclear enzymes. Constitutive activation of protein kinase C can drive the cell to a proliferative state, thereby initiating the process of carcinogenesis, however, suppression of this activation by phenolic compounds may be an effective way to control carcinogenesis. PMID:9459180

Mistry, K J; Krishna, M; Bhattacharya, R K

1997-12-16

361

Antioxidant activity of various solvent fractions from edible brown alga, Eisenia bicyclis and its active compounds.  

PubMed

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

Kwon, Tae-Hyung; Kim, Tae-Wan; Kim, Choong-Gon; Park, Nyun-Ho

2013-04-04

362

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

PubMed

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

Thuaytong, W; Anprung, P

2011-06-07

363

The stimulatory activities of polysaccharide compounds derived from algae extracts on insulin secretion in vitro.  

PubMed

We prepared two series of polysaccharide compounds derived from algae extracts and investigated their stimulatory activity on insulin secretion in vitro using the rat pancreatic cell line, RIN-5F. Several of the compounds exhibited significant stimulatory activity in a dose-dependent manner without apparent cytotoxicity at concentrations above 10 microM. Glybenclamide, a commonly prescribed sulfonylurea (SU) against diabetes mellitus type II, was used as a positive control and showed moderate cytotoxicity in the cell culture assay system. Amylin (IAPP; islet amyloid polypeptide), an inhibitor for glybenclamide, did not inhibit the activity of the isolated compounds, suggesting that they act through a mechanism(s) different from glybenclamide. Algae-derived extracts could be candidates for a new class of anti-diabetic drugs. PMID:18451519

Zhang, Dandan; Fujii, Isao; Lin, Changzheng; Ito, Kaori; Guan, Huashi; Zhao, Ji'en; Shinohara, Makoto; Matsukura, Makoto

2008-05-01

364

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

PubMed

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

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

2006-11-15

365

Synthesis and antitumor activity of water-soluble enediyne compounds related to dynemicin A.  

PubMed

The enediyne compounds 9-14, simple dynemicin A (1) analogues equipped with aryl carbamate moieties with various aliphatic amino or hydroxy groups at the C9 position, were synthesized and evaluated for DNA-cleaving ability, in vitro cytotoxicity, and in vivo antitumor activity. We found that the water-soluble compounds, in which the tert-amines such as the 2-(dimethylamino)ethyl (10b, 14b), 2-(pyrrolidino)ethyl (10c), or 1-azabicyclo[3.3.0]oct-5-ylmethyl (10d, 12d, 14d) group were attached, showed not only the enhanced in vivo antitumor activity but also the decreased toxicity compared to the corresponding 9-acetoxy enediyne compounds 6-8. In particular, compound 10c showed the most enhanced in vivo antitumor activity (T/C = 222% at a daily dose of 1.25 mg/kg for 4 days) at about half of the dose of 6. These results suggest that both the enhanced antitumor activity and the reduced toxicity might be due to the improved bioavailability or disposition of compounds 6-8 by their water-solubilization. PMID:9208107

Unno, R; Michishita, H; Inagaki, H; Suzuki, Y; Baba, Y; Jomori, T; Nishikawa, T; Isobe, M

1997-05-01

366

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

PubMed

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

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

2013-07-03

367

A functional screen to identify novel effectors of hematopoietic stem cell activity.  

PubMed

Despite tremendous progress made toward the identification of the molecular circuitry that governs cell fate in embryonic stem cells, genes controlling this process in the adult hematopoietic stem cell have proven to be more difficult to unmask. We now report the results of a novel gain-of-function screening approach, which identified a series of 18 nuclear factors that affect hematopoietic stem cell activity. Overexpression of ten of these factors resulted in an increased repopulating activity compared to unmanipulated cells. Interestingly, at least four of the 18 factors, Fos, Tcfec, Hmgb1, and Sfpi1, show non-cell-autonomous functions. The utilization of this screening method together with the creation of a database enriched for potential determinants of hematopoietic stem cell self-renewal will serve as a resource to uncover regulatory networks in these cells. PMID:19379700

Deneault, Eric; Cellot, Sonia; Faubert, Amélie; Laverdure, Jean-Philippe; Fréchette, Mélanie; Chagraoui, Jalila; Mayotte, Nadine; Sauvageau, Martin; Ting, Stephen B; Sauvageau, Guy

2009-04-17

368

Small-Molecule Activators of Insulin-Degrading Enzyme Discovered through High-Throughput Compound Screening  

Microsoft Academic Search

BackgroundHypocatabolism of the amyloid ?-protein (A?) by insulin-degrading enzyme (IDE) is implicated in the pathogenesis of Alzheimer disease (AD), making pharmacological activation of IDE an attractive therapeutic strategy. However, it has not been established whether the proteolytic activity of IDE can be enhanced by drug-like compounds.Methodology\\/Principal FindingsBased on the finding that ATP and other nucleotide polyphosphates modulate IDE activity at

Christelle Cabrol; Malwina A. Huzarska; Christopher Dinolfo; Maria C. Rodriguez; Lael Reinstatler; Jake Ni; Li-An Yeh; Gregory D. Cuny; Ross L. Stein; Dennis J. Selkoe; Malcolm A. Leissring; Andreas Hofmann

2009-01-01

369

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

PubMed

We found that several solid-state cuprous compounds, including cuprous oxide (Cu(2)O), sulfide (Cu(2)S), iodide (CuI), and chloride (CuCl), have highly efficient antiviral activities, whereas those of solid-state silver and cupric compounds are markedly lower. On a Cu(2)O-loaded glass substrate, for example, the infectious activity of bacteriophages was reduced by 5-orders of magnitude within 30 min and by 3-orders of magnitude within 1h for bacteria. In contrast, the infectious activities of both phages and bacteria were not markedly reduced on CuO-loaded substrates within a similar time frame. To determine the origin of this inhibitory activity, we investigated the effects of reactive oxygen species (ROS), leached copper ions, and the solid-state compound itself against bacteriophages, and concluded that infectious activity is lost following direct contact with the solid-state surface of cuprous compounds, but not ROS or copper ions. Furthermore, we found that Cu(2)O adsorbed and denatured more proteins than CuO, which suggests the difference of the inhibitory activity between Cu(2)O and CuO. PMID:22902129

Sunada, Kayano; Minoshima, Masafumi; Hashimoto, Kazuhito

2012-08-06

370

Phytogrowth-inhibitory activities of 2-thiophenecarboxylic acid and its related compounds.  

PubMed

2-Thiophenecarboxylic acid (I) exhibited growth-inhibitory activity in five kinds of plants. In particular, I strongly inhibited the growth of the roots of Lactuca sativa L. var. longifolia LAM and Echinochloa utilis OHWI et YABUNO, even at the low concentration of 5.0 x 10(-3) M. Furthermore, all of the I-related compounds (II-V and VII-X) except for VI, showed more or less obvious inhibitory activity on the seeds of Sesamum indicum L. Compounds VII-X, in which the carboxyl group of I was replaced by acetic acid, propionic acid, butyric acid and acrylic acid, and exhibited more potent phytogrowth-inhibitory activity than I. Among these compounds, 2-thiophenebutyric acid (IX) showed the strongest activity. Esterification of the carboxyl group in I increased the inhibitory activity relative to that of I, while amidation and reduction of this group markedly decreased its inhibitory activity. The radicles of the plants treated with each of the compounds except for VI showed negative geotropism, even though germination occurred. PMID:8148810

Inamori, Y; Muro, C; Funakoshi, Y; Usami, Y; Tsujibo, H; Numata, A

1994-01-01

371

The Antimicrobial Activities of Extract and Compounds Isolated from Brillantaisia lamium  

PubMed Central

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

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

2011-01-01

372

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

PubMed

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

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

2012-07-31

373

New synthesis of two tridentate bipyrazolic compounds and their cytotoxic activity tumor cell lines.  

PubMed

Two new tripodal compounds - 4-{bis[(3,5-dimethyl-1H-pyrazole-1-yl)methyl]amino}butane-1-ol (1); ethyl 1-[((2-hydroxyethyl){[3-(ethoxycarbonyl)-5-methyl-1H-pyrazole-1-yl]methyl} amino)methyl]-5-methyl-1H-pyrazole-3-carboxylate (2) were reported. The evaluation of the cytotoxic properties in vitro of these ligands, was examined on two tumor cell lines - P815 (mastocytome murine) and Hep (carcinoma of human larynx). The concentration required to induce 50% of lysis (IC(50)) was more pronounced against P815 cell line (IC(50): 39.42 microg mL(-1) for the compound 1 and 97.74 microg mL(-1) for the compound 2) than the Hep cell line (IC(50): 83.49 microg mL(-1) for compound 1 and 185.30 microg mL(-1) for compound 2). Statistical analysis shows that the compound 1 is two to three folds more cytotoxic than the compound 2 (p < 0.05). Interestingly, the cytotoxic activity depends strongly on both the substituents linked to the aminic nitrogen and pyrazolic rings. PMID:17691042

El Kodadi, Mohamed; Benamar, Malika; Ibrahim, Bouabdallah; Zyad, Abdelmajid; Malek, Fouad; Touzani, Rachid; Ramdani, Abdelkrim; Melhaoui, Ahmed

2007-09-01

374

Neuroprotective and free radical scavenging activities of phenolic compounds from Hovenia dulcis  

Microsoft Academic Search

The EtOAc-soluble fraction from a methanolic extract ofHovenia dulcis Thunb. exhibited neuroprotective activity against glutamate-induced neurotoxicity in mouse hippocampal HT22 cells. The neuroprotective\\u000a 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, compounds6 and8 had a

Gao Li; Byung-Sun Min; Changji Zheng; Joongku Lee; Sei-Ryang Oh; Kyung-Seop Ahn; Hyeong-Kyu Lee

2005-01-01

375

Identifying patterns of eating and physical activity in children: a latent class analysis of obesity risk.  

PubMed

We used latent class analysis (LCA) to identify heterogeneous subgroups with respect to behavioral obesity risk factors in a sample of 4th grade children (n = 997) residing in Southern California. Multiple dimensions assessing physical activity, eating and sedentary behavior, and weight perceptions were explored. A set of 11 latent class indicators were used in the analysis. The final model yielded a five-class solution: "High-sedentary, high-fat/high-sugar (HF/HS) snacks, not weight conscious," "dieting without exercise, weight conscious," "high-sedentary, HF/HS snacks, weight conscious," "active, healthy eating," and "low healthy, snack food, inactive, not weight conscious." The results suggested distinct subtypes of children with respect to obesity-related risk behaviors. Ethnicity, gender, and a socioeconomic status proxy variable significantly predicted the above latent classes. Overweight or obese weight status was determined based on the Centers for Disease Control and Prevention BMI (kg/m²)-for-age-and-sex percentile (overweight, 85th percentile ? BMI < 95th percentile; obese, 95th percentile ? BMI). The identified latent subgroup membership, in turn, was associated with the children's weight categories. The results suggest that intervention programs could be refined or targeted based on children's characteristics to promote effective pediatric obesity interventions. PMID:20930718

Huh, Jimi; Riggs, Nathaniel R; Spruijt-Metz, Donna; Chou, Chih-Ping; Huang, Zhaoqing; Pentz, Maryann

2010-10-07

376

[Studies on the antimould activity of compound TBZ and its application in paint].  

PubMed

The compound TBZ is a new antimould agent, which contains mainly [2-(4-thiazolyl) benzoimidazole (TBZ)], ethanoic acid and propionic acid. It was shown in laboratory experiment that the compound TBZ had excellent mycostatic effect on all the 10 fungi tested with 70% of the mycostatic zones larger than 6.0 cm. It had obvious inhibitary activity on Alternaria Nees and Aureobasidium Pullulans isolated from mouldy wall. In laboratory condition the surface of fibreboard painted with compound TBZ did not become mouldy in 120 days, while the 20% of that coated with TBZ directly mixed in the paint became mouldy. In practical use, the antimould effect of the wall painted with compound TBZ could maintain more than two years. PMID:10325606

Wang, S; Han, C P; Xu, N; Xing, X

1997-03-01

377

Indole and other aromatic compounds activate the yeast TRPY1 channel.  

PubMed

The yeast TRPY1 (Yvc1p) channel is activated by membrane stretch to release vacuolar Ca2+ into the cytoplasm upon osmotic upshock. Exogenously added indole greatly enhances the upshock-induced Ca2+ release in vivo. Indole also reversibly activates the channels under patch clamp. A minimum of 10(-6)M Ca2+ is needed for membrane stretch force to open TPRY1, but indole activation appears to be Ca2+ independent. A deletion of 30 residues at the predicted cytoplasmic domain, 570-600Delta, renders TRPY1 insensitive to stretch force upto 10(-3)M Ca2+. Nonetheless, indole readily activates this mutant channel. Several other aromatic compounds, e.g. the antimicrobial parabens, also activate TRPY1. These compounds likely alter the innate forces in the lipid bilayer received by the channel. PMID:18396169

John Haynes, W; Zhou, Xin-Liang; Su, Zhen-Wei; Loukin, Stephen H; Saimi, Yoshiro; Kung, Ching

2008-04-07

378

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

PubMed

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

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

2007-08-19

379

Neuroprotective and free radical scavenging activities of phenolic compounds from Hovenia dulcis.  

PubMed

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

Li, Gao; Min, Byung-Sun; Zheng, Changji; Lee, Joongku; Oh, Sei-Ryang; Ahn, Kyung-Seop; Lee, Hyeong-Kyu

2005-07-01

380

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

PubMed Central

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.

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

2003-01-01

381

Monitoring of pharmaceutically active compounds on the Guadalquivir River basin (Spain): occurrence and risk assessment.  

PubMed

Guadalquivir River (South of Spain) is among the major freshwater sources of the European Atlantic basin. Until now scientific efforts have been focused on contamination by heavy metals and some priority pollutants in Guadalquivir River. However, the presence of "emerging contaminants", such as pharmaceutically active compounds, has not yet been studied. In this work the occurrence and risk assessment of sixteen pharmaceutically active compounds, belonging to different therapeutic groups, in Guadalquivir River during its course through Seville city are reported. Wastewater effluents from four wastewater treatment plants discharging into Guadalquivir River and river water samples were analyzed. All studied pharmaceutically active compounds, except sulfamethoxazole, trimethoprim, estrone and clofibric acid, were detected in effluent wastewaters at concentration levels up to 28.9 ?g L(-1). Among the pharmaceutically active compounds found in effluent wastewater, seven were present in Guadalquivir River samples at concentration levels up to 0.75 ?g L(-1), which indicated an important dilution from effluent discharge. Environmental risk assessment reveals that potential ecotoxicological risk cannot be expected on Guadalquivir River at measured concentration levels. Only, the lipid regulator gemfibrozil showed a medium risk for the environment. The risk for acute toxic effects in the environment with the current use of active pharmaceutical ingredients is unlikely. However, the results do not rule out the potential for chronic environmental effects. PMID:21666922

Martín, J; Camacho-Muñoz, D; Santos, J L; Aparicio, I; Alonso, E

2011-06-13

382

Antimicrobial activities of the methanol extract and compounds from the twigs of Dorstenia mannii (Moraceae)  

PubMed Central

Background Dorstenia mannii (Moraceae) is a medicinal herb used traditionally for the treatment of many diseases. In the present study, the methanol extract of D. mannii and nine of its isolated compounds, namely dorsmanin A (1), B (2), C (3), D (4), E (6), F (7), G (8) dorsmanin I (9) and 6,8-diprenyleriodictyol (5), were tested for their antimicrobial activities against yeast, Mycobacteria and Gram-negative bacteria. Methods The microplate alamar blue assay (MABA) and the broth microdilution method were used to determine the minimal inhibitory concentration (MIC) and minimal microbicidal concentration (MMC) of the above extract and compounds on a panel of bacterial species. Results The results of the MIC determinations demonstrated that the methanol extract as well as compounds 3 and 8 were able to prevent the growth of all the fourteen studied microorganisms within the concentration range of 4 to 1024??g/ml. The lowest MIC value for the methanol extract (64??g/ml) was obtained on Candida albicans. The lowest value for individual compounds (4??g/ml) was recorded with compounds 3 on Pseudomonas aeruginosa PA01 and 7 on Eschericia coli ATCC strain. The MIC values recorded with compounds 3 on P. aeruginosa PA01, 6 on C. albicans,7 on P. aeruginosa PA01 and K. pneumoniae ATCC strain and C. albicans,and 8 on P. aeruginosa PA01, PA124, P. stuartii, M. tuberculosis MTCS1 were lower than or equal to those of the reference drugs. MMC values not greater than 1024??g/ml were recorded on all studied microorganisms with compounds 3 and 8. Conclusion The overall results of the present investigation provided evidence that the crude extract of D. mannii as well as some of its compounds such compounds 3 and 8 could be a potential source of natural antimicrobial products.

2012-01-01

383

Rethinking molecular similarity: comparing compounds on the basis of biological activity.  

PubMed

Since the advent of high-throughput screening (HTS), there has been an urgent need for methods that facilitate the interrogation of large-scale chemical biology data to build a mode of action (MoA) hypothesis. This can be done either prior to the HTS by subset design of compounds with known MoA or post HTS by data annotation and mining. To enable this process, we developed a tool that compares compounds solely on the basis of their bioactivity: the chemical biological descriptor "high-throughput screening fingerprint" (HTS-FP). In the current embodiment, data are aggregated from 195 biochemical and cell-based assays developed at Novartis and can be used to identify bioactivity relationships among the in-house collection comprising ~1.5 million compounds. We demonstrate the value of the HTS-FP for virtual screening and in particular scaffold hopping. HTS-FP outperforms state of the art methods in several aspects, retrieving bioactive compounds with remarkable chemical dissimilarity to a probe structure. We also apply HTS-FP for the design of screening subsets in HTS. Using retrospective data, we show that a biodiverse selection of plates performs significantly better than a chemically diverse selection of plates, both in terms of number of hits and diversity of chemotypes retrieved. This is also true in the case of hit expansion predictions using HTS-FP similarity. Sets of compounds clustered with HTS-FP are biologically meaningful, in the sense that these clusters enrich for genes and gene ontology (GO) terms, showing that compounds that are bioactively similar also tend to target proteins that operate together in the cell. HTS-FP are valuable not only because of their predictive power but mainly because they relate compounds solely on the basis of bioactivity, harnessing the accumulated knowledge of a high-throughput screening facility toward the understanding of how compounds interact with the proteome. PMID:22594495

Petrone, Paula M; Simms, Benjamin; Nigsch, Florian; Lounkine, Eugen; Kutchukian, Peter; Cornett, Allen; Deng, Zhan; Davies, John W; Jenkins, Jeremy L; Glick, Meir

2012-05-31

384

Optimization of the culture condition for an antitumor bacterium Serratia proteamacula 657 and identification of the active compounds.  

PubMed

Exploration of novel active anti-tumor compounds from marine microbes for pharmaceutical applications has been a continuously hot spot in natural product research. Bacterial growth and metabolites may greatly vary under different culture conditions. In this study, the effects of different culture conditions and medium components on the growth and bioactive metabolites of Serratia proteamacula 657, an anti-tumor bacterium found in our previous study, were investigated. The results showed that lower temperature, weak acidic condition and solid fermentation favored the bacterial growth and the production of active compounds. Four components in the culture medium, NaCl, peptone, yeast extract and MgSO4, were found important to the bacterial growth and active compounds production in medium optimization. Under the optimized condition of solid state fermentation at pH 6.0-7.0, 23-25 °C, with the MgSO4-free medium containing 10.0 g/L peptone, 1.0 g/L yeast extract and 19.45 g/L NaCl, the antitumor activity of S. proteamacula 657 and the yield of crude extracts increased about 15 times and 6 times than the sample obtained in the original liquid fermentation, respectively. The active components in the metabolites of S. proteamacula 657 were identified as a homolog of prodigiosin, a red bacterial pigment, based on the analysis of the NMR and GC-MS. The bacterium S. proteamacula 657, which is adapted to lower temperature, produced prodigiosin-like pigments with highly antitumor activity, suggesting the bacterium is a potential new source for prodigiosin production. PMID:23271461

Miao, Li; Wang, Xueling; Jiang, Wei; Yang, Shengping; Zhou, Huiru; Zhai, Youpeng; Zhou, Xiaojian; Dong, Kunming

2012-12-28

385

Compounds and Methods for the Treatment of Ubiquitin Conjugating Disorders.  

National Technical Information Service (NTIS)

The present invention provides methods for identifying compounds that selectively bind one or more active sites within an ubiquitin conjugating enzyme. The compounds identified by the methods are useful in the treatment of disorders attributed to dysregul...

A. Banerjee

2004-01-01

386

Physicochemical and biological attributes of nickel compounds in relationship to carcinogenic activities.  

PubMed

Nickel compounds that possess similar elemental compositions but vary in physicochemical properties can elicit markedly different biological effects. The crystalline nickel sulfides and oxides that slowly dissolve in body fluids and readily enter cells by phagocytosis tend to be most active in producing morphological transformation of SHE cells in vitro and stimulating erythrocytosis and carcinogenesis following ir administration to rats. The capacities of particulate nickel compounds to induce erythropoietin-mediated erythrocytosis in rats are closely correlated with their carcinogenic activities; hence erythrocytosis stimulation can serve as a screening test for carcinogenicity. Although water-soluble nickel salts have not been shown to initiate carcinogenesis in rodents, the soluble nickel salts are evidently effective as cancer promotors following initiation of tumorigenesis by aromatic hydrocarbons and nitrosoamines. Growing evidence suggests that the Ni(III)/Ni(II) redox-couple facilitates oxygen free-radical reactions, which may represent one of the molecular mechanisms for genotoxicity and carcinogenicity of nickel compounds. PMID:3602750

Sunderman, F W

1987-03-20

387

Activation Tagging in Tomato Identifies a Transcriptional Regulator of Anthocyanin Biosynthesis, Modification, and Transport  

PubMed Central

We have developed a high-throughput T-DNA insertional mutagenesis program in tomato using activation tagging to identify genes that regulate metabolic pathways. One of the activation-tagged insertion lines (ant1) showed intense purple pigmentation from the very early stage of shoot formation in culture, reflecting activation of the biosynthetic pathway leading to anthocyanin accumulation. The purple coloration resulted from the overexpression of a gene that encodes a MYB transcription factor. Vegetative tissues of ant1 plants displayed intense purple color, and the fruit showed purple spotting on the epidermis and pericarp. The gene-to-trait relationship of ant1 was confirmed by the overexpression of ANT1 in transgenic tomato and in tobacco under the control of a constitutive promoter. Suppression subtractive hybridization and RNA hybridization analysis of the purple tomato plants indicated that the overexpression of ANT1 caused the upregulation of genes that encode proteins in both the early and later steps of anthocyanidin biosynthesis as well as genes involved in the glycosylation and transport of anthocyanins into the vacuole.

Mathews, Helena; Clendennen, Stephanie K.; Caldwell, Colby G.; Liu, Xing Liang; Connors, Karin; Matheis, Nikolaus; Schuster, Debra K.; Menasco, D. J.; Wagoner, Wendy; Lightner, Jonathan; Wagner, D. Ry

2003-01-01

388

A pair of identified giant visual projection neurons demonstrates rhythmic activities before eclosion.  

PubMed

A small set of neurons acting as an internal clock in the Drosophila brain is critical for regulating circadian activities behavior and pre-adult development. However, the cell basis for the circadian rhythm in correlation with light sensitivity is not fully understood. Here we identified a pair of giant visual projection neurons located laterally to the calyx of the mushroom bodies, and investigated their electrophysiological, morphological characteristics, as well as the development pathways during eclosion. The typical morphology of these giant neurons showed the size of the soma (16.0±0.6 microns in diameter) and its processes. Interestingly during development, the three major branches shrunk significantly along with gradually decreased rhythmic spikes. Furthermore, the electrical activity of the giant visual projection neurons is circadian-regulated, shown with significantly higher resting membrane potential, increase in frequency of spontaneous action potential firing, and burst firing pattern during circadian day and night time. The similarities in the morphological characteristics with other visual projection neurons highly suggest that this neuron is a type of novel visual projection neurons in this area, which has special properties in light sensitivities and rhythmic activities. Our data provided supporting evidence for the visual projection neurons with light sensitivities, and pointed to the potential correlation of visual projection neurons and circadian rhythms during the eclosion period or an adaptive development for higher sensitivity of light in adult visual systems. PMID:23827229

Yan, Ying; Xu, Ye; Deng, Shengwen; Huang, Naya; Yang, Ying; Qiu, Jiahe; Liu, Jinchao; Wang, Xutian; Yang, Guangxin; Gu, Huaiyu

2013-07-01

389

Synthesis, pharmacological activity evaluation and molecular modeling of new polynuclear heterocyclic compounds containing benzimidazole derivatives.  

PubMed

Novel heterocyclic compounds containing benzimidazole derivatives were synthesized from 2-(1H-benzimidazol-2-yl) acetonitrile (1) and arylhydrazononitrile derivative 2 was obtained via coupling of 1 with 4-methyl phenyldiazonium salt, which was then reacted with hydroxylamine hydrochloride to give amidooxime derivative 3. This product was cyclized into the corresponding oxadiazole derivative 4 upon reflux in acetic anhydride. Compound 4 was refluxed in DMF in the presence of triethylamine to give the corresponding 5-(1H-benzimidazol-2-yl)-2-p-tolyl-2H-1,2,3-triazol-4-amine 6. Treatment of compound 6 with ethyl chloroformate afforded 2,6-dihydro-2-(4-methylphenyl)-1,2,3-triazolo[4",5"-4',5']pyrimido[1,6-a]benzimidazole-5(4H)-one (8). 1,2-bis(2-cyanomethyl-1H-benzimidazol-1-yl)ethane-1,2-dione (10) was synthesized via the condensation reaction of 2-(1H-benzimidazol-2-yl) acetonitrile (1) and diethyloxalate. The reactivity of compound 10 towards some diamine reagents was studied. The in vitro antimicrobial activity of the synthesized compounds was investigated against several pathogenic bacterial strains such as Escherichia coli O157, Salmonella typhimurium, E. coli O119, S. paratyphi, Pseudomonas aeruginosa, Staphylococcus aureus, Listeria monocytogenes and Bacillus cereus. The results of MIC revealed that compounds 12a-c showed the most effective antimicrobial activity against tested strains. On the other hand, compounds 12a, b exhibited high activity against rotavirus Wa strain while compounds 12b, c exhibited high activity against adenovirus type 7. In silico target prediction, docking and validation of the compounds 12a-c were performed. The dialkylglycine decarboxylase bacterial enzyme was predicted as a potential bacterial target receptor using pharmacophore-based correspondence with previous leads; giving the highest normalized scores and a high correlation docking score with mean inhibition concentrations. A novel binding mechanism was predicted after docking using the MOE software and its validation. PMID:23263801

Bassyouni, Fatma A; Saleh, Tamer S; ElHefnawi, Mahmoud M; Abd El-Moez, Sherein I; El-Senousy, Waled M; Abdel-Rehim, Mohamed E

2012-12-21

390

Inhibitory effects of key compounds isolated from Corni fructus on BACE1 Activity.  

PubMed

Progressive cerebral deposition of A? in the brain is a seminal event in the pathogenesis of Alzheimer's disease (AD). A? is generated from the amyloid precursor protein (APP) by proteolytic processing of ?-secretase (BACE1) and ?-secretase. Consequently, BACE1, a key enzyme in the production of A?, is a prime target for therapeutic intervention in AD. In the course of screening for natural BACE1 inhibitors from Corni fructus, the ethyl acetate (EtOAc) fraction showed significant inhibitory activity against BACE1. By activity guided purification, three compounds of BACE1 inhibitors p-coumaric acid, gallic acid and ursolic acid were isolated from Corni fructus EtOAc fraction. All isolated compounds suppressed BACE1 in a dose dependent manner. p-Coumaric acid, in particular, exhibited significant inhibitory activity against BACE1 with 9.0?×?10(-5) ?m and a K(i) value of 1.9?×?10(-6) ?m. Also this compound was non-competitive with a substrate in the Dixon plot, suggesting that it might bind either to the ?-secretase subsite or to another regulatory site. All compounds showed no significant attenuation of TACE (?-secretase) and other serine proteases such as chymotrypsin and trypsin, demonstrating that they were relatively selective and specific inhibitors of BACE1. These novel findings suggest that Corni fructus contains biologically active components that may be used to attenuate the progression and/or prevention of Alzheimer's disease. PMID:22407769

Youn, Kumju; Jun, Mira

2012-03-09

391

Laboratory Animal Science Issues in the Design and Conduct of Studies with Endocrine-active Compounds  

Microsoft Academic Search

The use of rodent models for research and testing on endo- crine-active compounds necessitates an awareness of a number of laboratory animal science issues to standardize bioassay methods and facilitate reproducibility of results between laboratories. These issues are not unique to endo- crine research but are particularly important in this field due to the complexities and interdependencies of the endocrine

Jeffrey I. Everitt; Paul M. D. Foster

2004-01-01

392

Note: Characterization of Yeast Strains on the Basis of Autolytic Activity and Volatile Compounds  

Microsoft Academic Search

Autolytic activity and the production of several major volatile compounds were studied for a set of 18 commercial and non-commercial Saccharomyces cerevisiæ strains isolated from sparkling wine, cider and sherry fermentations. No correlation was found between the autolytic capacity of the strains and isobutanol production levels, in contrast with results published by other authors for a limited number of S.

J. M. Barcenilla; P. J. Martín-Álvarez; A. Vian; R. Gonzalez

2003-01-01

393

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 ...