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1

Pharmacological and chemical study to identify wound-healing active compounds in Ageratina pichinchensis.  

PubMed

The aerial parts of Ageratina pichinchensis are used in Mexican traditional medicine for the treatment of skin wounds. Recently, it was demonstrated that the aqueous extract of this plant reduced the time required to cicatrize a wound induced in the rat. The same extract showed a capability to induce overgrowth in normal fetal lung cells (MRC-5). The objective of the present study was isolating and identifying the active compounds in A. pichinchensis that are capable of inducing cellular overgrowth, as well as performing a preliminary evaluation of their anti-inflammatory and toxic effects. By means of bioguided chemical separation of an aqueous extract of A. pichinchensis, the most active compound capable of inducing cellular overgrowth was identified as 7-O-(?-D-glucopyranosyl)-galactin. In vivo inflammation induced with carrageenan in mice was significantly reduced by the aqueous extract of A. pichinchensis, reaching a decrease of up to 60.6 %. Acute (2 g/kg) and subchronic (1 g/kg for 28 days) oral administration of the aqueous extract of this plant did not affect hepatic function (through alanine aminotransferase and aspartate aminotransferase activity evaluation), while no alterations of the histologic samples of liver and kidney were evidenced. PMID:23599006

Romero-Cerecero, Ofelia; Zamilpa, Alejandro; González-Cortazar, Manasés; Alonso-Cortés, Daniel; Jiménez-Ferrer, Enrique; Nicasio-Torres, Pilar; Aguilar-Santamaría, Lucía; Tortoriello, Jaime

2013-05-01

2

Spiperone, identified through compound screening, activates calcium-dependent chloride secretion in the airway  

PubMed Central

Cystic fibrosis (CF) is caused by mutations in the gene producing the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR functions as a Cl? channel. Its dysfunction limits Cl? secretion and enhances Na+ absorption, leading to viscous mucus in the airway. Ca2+-activated Cl? channels (CaCCs) are coexpressed with CFTR in the airway surface epithelia. Increases in cytosolic Ca2+ activate the epithelial CaCCs, which provides an alternative Cl? secretory pathway in CF. We developed a screening assay and screened a library for compounds that could enhance cytoplasmic Ca2+, activate the CaCC, and increase Cl? secretion. We found that spiperone, a known antipsychotic drug, is a potent intracellular Ca2+ enhancer and demonstrated that it stimulates intracellular Ca2+, not by acting in its well-known role as an antagonist of serotonin 5-HT2 or dopamine D2 receptors, but through a protein tyrosine kinase-coupled phospholipase C-dependent pathway. Spiperone activates CaCCs, which stimulates Cl? secretion in polarized human non-CF and CF airway epithelial cell monolayers in vitro and in CFTR-knockout mice in vivo. In conclusion, we have identified spiperone as a new therapeutic platform for correction of defective Cl? secretion in CF via a pathway independent of CFTR.

Liang, Lihua; MacDonald, Kelvin; Schwiebert, Erik M.; Zeitlin, Pamela L.; Guggino, William B.

2009-01-01

3

Pheromonal activity of compounds identified from male Phyllotreta cruciferae: field tests of racemic mixtures, pure enantiomers, and combinations with allyl isothiocyanate.  

PubMed

Four himachalene sesquiterpenes and (+)-gamma-cadinene, previously identified as possible pheromone components from males of a North American population of Phyllotreta cruciferae Goeze (Coleoptera, Chrysomelidae), were tested for attractiveness in field trapping experiments in Hungary. A mixture of the four synthetic racemic himachalene derivatives and (+)-gamma-cadinene from a botanical source was slightly attractive to beetles, but much more attractive when blended with the known host-plant-derived attractant allyl isothiocyanate. This result was consistent with a previous study in North America. In tests with optically pure synthetic compounds, a blend of the same himachalene enantiomers found from male beetles was equivalent to the corresponding blend of racemic compounds, whereas a blend of the opposite enantiomers was not active. Through subtraction tests, it was found that the single compound, (6R,7S)-2,2,6,10-tetramethylbicyclo[5.4.0.]undeca-9,11-diene [compound (+)-A in this study], was as active as the whole mixture, suggesting that this compound is the key pheromone component of the European population of P. cruciferae. During field trials, several congeneric species, including P. vittula, P. nemorum, P. nodicornis, and P. ochripes, also were caught, suggesting that the same compound(s) may be relatively widespread as pheromone components in this genus. PMID:16273436

Tóth, Miklós; Csonka, Eva; Bartelt, Robert J; Cossé, Allard A; Zilkowski, Bruce W; Muto, Shin-Etsu; Mori, Kenji

2005-11-01

4

Identifying new volatile compounds in toasted oak.  

PubMed

Toasting wood to be used in barrels for aging wine produces a great number of volatile and odiferous compounds. Three new volatile odorous compounds in toasted oak were identified. Analysis by high-performance gas chromatography of toasted oak extracts, combined with olfactory detection, enabled various chromatographic peaks with these specific aromas to be isolated. These same odors were simultaneously studied by heating glucose both with and without proline and phenylalanine. Aromatic compounds of interest were identified thanks to a combination of gas chromatography and both mass and infrared spectrometry. An analysis RMN was also used. Hydroxymaltol, 2,5-furanedicarbaldehyde, and furylhydroxymethyl ketone have been detected in extract of toasted oak wood. These molecules may be formed by direct pyrolysis of sugar or Maillard reactions. The acetylformoine was not detected in extract of toasted oak wood, whereas it was detected in heated extracts of various sugars and sugars mixtures with amino acids. PMID:10564035

Cutzach, I; Chatonnet, P; Henry, R; Dubourdieu, D

1999-04-01

5

Screening for Inhibition of Vibrio cholerae VipA-VipB Interaction Identifies Small-Molecule Compounds Active against Type VI Secretion.  

PubMed

The type VI secretion system (T6SS) is the most prevalent bacterial secretion system and an important virulence mechanism utilized by Gram-negative bacteria, either to target eukaryotic cells or to combat other microbes. The components show much variability, but some appear essential for the function, and two homologues, denoted VipA and VipB in Vibrio cholerae, have been identified in all T6SSs described so far. Secretion is dependent on binding of an ?-helical region of VipA to VipB, and in the absence of this binding, both components are degraded within minutes and secretion is ceased. The aim of the study was to investigate if this interaction could be blocked, and we hypothesized that such inhibition would lead to abrogation of T6S. A library of 9,600 small-molecule compounds was screened for their ability to block the binding of VipA-VipB in a bacterial two-hybrid system (B2H). After excluding compounds that showed cytotoxicity toward eukaryotic cells, that inhibited growth of Vibrio, or that inhibited an unrelated B2H interaction, 34 compounds were further investigated for effects on the T6SS-dependent secretion of hemolysin-coregulated protein (Hcp) or of phospholipase A1 activity. Two compounds, KS100 and KS200, showed intermediate or strong effects in both assays. Analogues were obtained, and compounds with potent inhibitory effects in the assays and desirable physicochemical properties as predicted by in silico analysis were identified. Since the compounds specifically target a virulence mechanism without affecting bacterial replication, they have the potential to mitigate the virulence with minimal risk for development of resistance. PMID:24798289

Sun, Kun; Bröms, Jeanette; Lavander, Moa; Gurram, Bharat Kumar; Enquist, Per-Anders; Andersson, C David; Elofsson, Mikael; Sjöstedt, Anders

2014-07-01

6

Active compound combinations  

US Patent & Trademark Office Database

The invention relates to active compound combinations, in particular within a composition, which comprises (A) an amidine compound of formula (I) and a further fungicidally (B-1), insecticidally (B-2) active or plant growth regulating compound (B-3). Moreover, the invention relates to a method for curatively or preventively controlling the phytopathogenic fungi of plants or reducing the mycotoxin contamination of plant or plant parts, to the use of a combination according to the invention for the treatment of seed, to a method for protecting a seed and not at least to the treated seed. ##STR00001##

2013-09-10

7

A cell-based screening identifies compounds from the stem of Momordica charantia that overcome insulin resistance and activate AMP-activated protein kinase.  

PubMed

Treatment of insulin resistance is a critical strategy in the prevention and management of type 2 diabetes. The crude extracts from all parts of Momordica charantia L. have been reported by many studies for the effective treatment of diabetes and related complications. However, the exact ingredients responsible for the hypoglycemic effect and the underlying mechanism of their actions have not been well characterized because of the lack of a proper assay and screening system. A new cell-based, nonradioactive, and nonfluorescent screening method was demonstrated in this study to screen for natural products from the stem of M. charantia, aiming to identify hypoglycemic components that can overcome cellular insulin resistance. The results suggest triterpenoids being potential hypoglycemic components of the plant and the mechanism underlying their action involving AMP-activated protein kinase. PMID:18656931

Cheng, Hsueh-Ling; Huang, Hsin-Kai; Chang, Chi-I; Tsai, Chung-Pao; Chou, Chang-Hung

2008-08-27

8

Using Properties to Identify Ionic and Molecular Compounds  

NSDL National Science Digital Library

An inquiry activity for students to test physical properties of several compounds to analyze data and determine if the compound is ionic or covalent. This is ideal for an introduction to ionic and molecular compound nomenclature.

Tamara Ellsworth, Parkers Prairie High School, Parkers Prairie, MN, based on a lab for pre-ap chemistry at the westlake high school website.

9

A Quantitative High Throughput Assay for Identifying Gametocytocidal Compounds  

PubMed Central

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 1,536-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 IC50 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 1,280 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.

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

2013-01-01

10

Active compound combinations  

US Patent & Trademark Office Database

The invention relates to active compound combinations, in particular a fungicidal and/or insecticidal composition, comprising Isotianil (3,4-dichloro-N-(2-cyanophenyl)-5-isothiazolecarboxamide) and at least one further insecticide of the tetronic acid derivatives group and optionally one further insecticide of the neonicotinoids. Moreover, the invention relates to a method for curatively or preventively controlling the phytopathogenic fungi and/or microorganisms and/or pests of plants or crops, to the use of a combination according to the invention for the treatment of seed, to a method for protecting a seed and not at least to the treated seed.

2014-02-18

11

Odor-active compounds in cardboard.  

PubMed

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

Czerny, Michael; Buettner, Andrea

2009-11-11

12

IDENTIFYING COMPOUNDS DESPITE CHROMATOGRAPHY LIMITATIONS: ORGANOPHOSPHATES IN TREATED SEWAGE  

EPA Science Inventory

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

13

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

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

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...

16

Compounds exhibiting an antibiotic activity  

US Patent & Trademark Office Database

The present invention relates to compounds having antibiotic activity which are obtained from body fluids of mollusks, namely of certain West-African snails, to therapeutic drugs comprising these compounds, and to the use thereof for the preparation of a therapeutic drug for controlling infectious pathogens in humans and animals.

2006-01-03

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

2013-09-01

18

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

PubMed Central

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

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

2012-01-01

19

Phenyl-Adenine, Identified in a LIGHT-DEPENDENT SHORT HYPOCOTYLS4-Assisted Chemical Screen, Is a Potent Compound for Shoot Regeneration through the Inhibition of CYTOKININ OXIDASE/DEHYDROGENASE Activity1[W][OA  

PubMed Central

In vitro shoot regeneration is implemented in basic plant research and commercial plant production, but for some plant species, it is still difficult to achieve by means of the currently available cytokinins and auxins. To identify novel compounds that promote shoot regeneration, we screened a library of 10,000 small molecules. The bioassay consisted of a two-step regeneration protocol adjusted and optimized for high-throughput manipulations of root explants of Arabidopsis (Arabidopsis thaliana) carrying the shoot regeneration marker LIGHT-DEPENDENT SHORT HYPOCOTYLS4. The screen revealed a single compound, the cytokinin-like phenyl-adenine (Phe-Ade), as a potent inducer of adventitious shoots. Although Phe-Ade triggered diverse cytokinin-dependent phenotypical responses, it did not inhibit shoot growth and was not cytotoxic at high concentrations. Transcript profiling of cytokinin-related genes revealed that Phe-Ade treatment established a typical cytokinin response. Moreover, Phe-Ade activated the cytokinin receptors ARABIDOPSIS HISTIDINE KINASE3 and ARABIDOPSIS HISTIDINE KINASE4 in a bacterial receptor assay, albeit at relatively high concentrations, illustrating that it exerts genuine but weak cytokinin activity. In addition, we demonstrated that Phe-Ade is a strong competitive inhibitor of CYTOKININ OXIDASE/DEHYDROGENASE enzymes, leading to an accumulation of endogenous cytokinins. Collectively, Phe-Ade exhibits a dual mode of action that results in a strong shoot-inducing activity.

Motte, Hans; Galuszka, Petr; Spichal, Lukas; Tarkowski, Petr; Plihal, Ondrej; Smehilova, Maria; Jaworek, Pavel; Vereecke, Danny; Werbrouck, Stefaan; Geelen, Danny

2013-01-01

20

Impact of nitrogen compounds on catalyst activity  

SciTech Connect

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 presented in this paper, which is part of a larger study aimed at extending catalyst life by mitigating the effects of carbonaceous deposits, is to identify the hydrotreater feed components that are responsible for the greatest deactivation. Previous studies at Sandia to determine the effects on catalyst activity of various chemical classes of compounds found in hydrotreater feed have shown that the nitrogen polycyclic aromatic compounds cause the greatest deactivation (95% loss of hydrogenation activity), but the effect of the hydroxy polycyclic hydrocarbons (81% loss) is also important. Research is therefore being carried out to identify the properties of nitrogen and hydroxy compounds responsible for this deactivation. Nitrogen model compounds with different properties have been hydrotreated with presulfided Shell 324M catalyst. Hydrogenation activity testing of the aged catalysts from these runs has shown that the greatest deactivation is due to quinoline and the least deactivation is due to carbazole. Both a 5 minute run and a 2 hour run with quinoline at 400/sup 0/C caused about 80% losses of hydrogenation activity, whereas hydrotreating carbazole for 2 hours only caused a 48% loss. The greater deactivation due to hydrotreating quinoline is probably due to the basicity of this compound. Results of studies on other nitrogen compounds with different properties and on hydroxy compounds are also discussed. 10 refs., 4 tabs.

Stohl, F.V.

1986-01-01

21

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

22

Identifying calcineurin activators for treatment of schizophrenia  

US Patent & Trademark Office Database

The present invention provides targets, methods, and reagents for the diagnosis and treatment of schizophrenia and related conditions. The invention provides methods for the diagnosis of schizophrenia and susceptibility to schizophrenia by detection of polymorphisms, mutations, variations, alterations in expression, etc., in calcineurin genes or calcineurin interacting genes, or polymorphisms linked to such genes. The invention provides oligonucleotides, arrays, and antibodies for detection of polymorphisms and variants. The invention provides transgenic mice having alterations in such genes. The invention also provides methods of treating schizophrenia by administering compounds that target these genes. The invention further provides screening methods for identifying such compounds and compounds obtained by performing the screens.

2011-05-03

23

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

EPA Science Inventory

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

24

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...

25

Water maze testing to identify compounds for cognitive enhancement.  

PubMed

The water maze task is widely used to evaluate spatial learning and memory in rodents. The basic paradigm requires an animal to swim in a pool until it finds a hidden escape platform. The animals learn to find the platform using extra-maze cues and, after several training trials, are able to swim directly to it from any starting location. Memory for the platform location is assessed by examining swimming behavior with the platform removed from the maze, while sensory, motor and motivational aspects of the task can be examined by making the platform visible to the animals. Described in this unit is the use of the water maze to identify rats with age-related spatial learning and memory impairments. The efficacy of potential pharmacological treatments for alleviating these deficits is then evaluated. This assay provides a means for studying the neurobiology of spatial learning and memory, and to identify potential pharmacotherapies for treating memory-impaired humans. While the use of aged rats is described in this unit, the protocol can also be employed for compound screening with other rodent models that have spatial learning and memory impairments, such as transgenic mouse models of Alzheimer's disease. PMID:23258600

Rose, Gregory M; Rowe, Wayne B

2012-12-01

26

Chemical proteomics to identify molecular targets of small compounds.  

PubMed

Most drug targets are cellular proteins that selectively interact with chemicals administered to treat diseases. Chemical proteomics, as an interdisciplinary technology that integrates synthetic and analytic chemistry, biochemistry and cell biology, has recently emerged as a powerful platform to specifically enrich and comprehensively profile drug-binding proteins, and thus has been extensively applied in the identification of drug targets. In addition, chemical proteomics can also provide information for researchers to understand the poly-pharmacological activities of the pharmaceutical compounds, and thus help in maximizing the efficacy and minimizing the side effects of the drugs. In this manuscript, we summarized several popular approaches of chemical proteomics by illustrating their essential features in drug target-fishing through specific profiling of drug-protein interaction. Alternative technologies for target identification were also discussed. PMID:23826922

Sun, B; He, Q-Y

2013-08-01

27

High content screening of diverse compound libraries identifies potent modulators of tubulin dynamics.  

PubMed

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

Laraia, Luca; Stokes, Jamie; Emery, Amy; McKenzie, Grahame J; Venkitaraman, Ashok R; Spring, David R

2014-05-01

28

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

2014-03-01

29

Criteria for identifying endogenous compounds as digoxin-like immunoreactive factors in humans.  

PubMed

Endogenous digoxin-like immunoreactive factors (DLIF) are factors in plasma that interact with anti-digoxin antibodies. In this report we propose specific empirical criteria that must be satisfied by any group of endogenous compounds purported to account for DLIF activity in human plasma. These criteria include immunoreactive potency relative to existing physiologic concentrations as well as the biochemical and protein binding properties of these compounds. Recent studies have identified several congeners of fatty acids and phospholipids, hydrocortisone, and dehydroepiandrosterone-sulfate as compounds likely to account for DLIF activity in plasma. Using the above criteria we demonstrate that the highest reported plasma concentrations of these compounds combined account for less than 25% of DLIF reported in healthy adult subjects, less than 11% in newborns, less than 27% in pregnant women, and less than 39% in patients with renal failure. Human serum albumin at a concentration of 40 g/l completely abolished any detectable interaction of these compounds with both anti-digoxin antibodies or canine kidney Na/K-ATPase. The immunoreactive and physical properties of these compounds are also not consistent with those reported for DLIF. We conclude that these compounds do not account for the plasma DLIF concentrations measured in human subjects nor are they likely to play a role as specific endogenous regulators of Na/K-ATPase. PMID:2844442

Lau, B W; Valdes, R

1988-06-30

30

A Screen for Kinetochore-Microtubule Interaction Inhibitors Identifies Novel Antitubulin Compounds  

Microsoft Academic Search

BackgroundProtein assemblies named kinetochores bind sister chromatids to the mitotic spindle and orchestrate sister chromatid segregation. Interference with kinetochore activity triggers a spindle checkpoint mediated arrest in mitosis, which frequently ends in cell death. We set out to identify small compounds that inhibit kinetochore-microtubule binding for use in kinetochore-spindle interaction studies and to develop them into novel anticancer drugs.Methodology\\/Principal FindingsA

Emanuela Screpanti; Stefano Santaguida; Tam Nguyen; Romano Silvestri; Rick Gussio; Andrea Musacchio; Ernest Hamel; Peter de Wulf; Daniela Cimini

2010-01-01

31

Antifungal Chemical Compounds Identified Using a C. elegans Pathogenicity Assay  

Microsoft Academic Search

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

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

2007-01-01

32

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

2013-10-01

33

A small molecule screen identifies a novel compound that induces a homeotic transformation in Hydra.  

PubMed

Developmental processes such as morphogenesis, patterning and differentiation are continuously active in the adult Hydra polyp. We carried out a small molecule screen to identify compounds that affect patterning in Hydra. We identified a novel molecule, DAC-2-25, that causes a homeotic transformation of body column into tentacle zone. This transformation occurs in a progressive and polar fashion, beginning at the oral end of the animal. We have identified several strains that respond to DAC-2-25 and one that does not, and we used chimeras from these strains to identify the ectoderm as the target tissue for DAC-2-25. Using transgenic Hydra that express green fluorescent protein under the control of relevant promoters, we examined how DAC-2-25 affects tentacle patterning. Genes whose expression is associated with the tentacle zone are ectopically expressed upon exposure to DAC-2-25, whereas those associated with body column tissue are turned off as the tentacle zone expands. The expression patterns of the organizer-associated gene HyWnt3 and the hypostome-specific gene HyBra2 are unchanged. Structure-activity relationship studies have identified features of DAC-2-25 that are required for activity and potency. This study shows that small molecule screens in Hydra can be used to dissect patterning processes. PMID:24255098

Glauber, Kristine M; Dana, Catherine E; Park, Steve S; Colby, David A; Noro, Yukihiko; Fujisawa, Toshitaka; Chamberlin, A Richard; Steele, Robert E

2013-12-01

34

Antithrombogenic activity of antioxidant compounds.  

PubMed

Antithrombotic activities of enoxifol, a new antioxidant with antiaggregant activity demonstrated in vitro and in vivo, and antioxidant mexidol were compared on the rat model of arterial thrombosis induced by application of 50% ferric chloride. Acetylsalicylic acid (antiaggregant) served as the reference drug. All drugs exhibited dose-dependent antithrombotic activity. Enoxifol was more effective than mexidol, both drugs being more active than the reference drug (acetylsalicylic acid). Taking into account the pathogenesis of the thrombosis in this experimental model, we can hypothesize that the pronounced antithrombotic effect of enoxifol was due to its antiaggregant and antioxidant activities. PMID:24288764

Spasov, A A; Kucheryavenko, A F; Kosolapov, V A; Anisimova, V A

2013-10-01

35

Mutagenicity of Polycyclic Aromatic Compounds (PAC), Identified in Source Emissions and Ambient Air.  

National Technical Information Service (NTIS)

Several polycyclic aromatic compounds including nitrated and oxygenated derivatives of polycyclic aromatic hydrocarbons were tested for mutagenic activity in the Salmonella/ microsome assay. Among the compounds tested the isomer mix of nitro-1-hydroxypyre...

M. Moeller I. Hagen T. Randahl

1985-01-01

36

Identifying Crucial Parameter Correlations Maintaining Bursting Activity  

PubMed Central

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

Doloc-Mihu, Anca; Calabrese, Ronald L.

2014-01-01

37

An isogenic cell panel identifies compounds that inhibit proliferation of mTOR-pathway addicted cells by different mechanisms.  

PubMed

The mTOR pathway is a critical integrator of nutrient and growth factor signaling. Once activated, mTOR promotes cell growth and proliferation. Several components of the mTOR pathway are frequently deregulated in tumors, leading to constitutive activation of the pathway and thus contribute to uncontrolled cell growth. We performed a high-throughput screen with an isogenic cell line system to identify compounds specifically inhibiting proliferation of PTEN/mTOR-pathway addicted cells. We show here the characterization and mode of action of two such compound classes. One compound class inhibits components of the PTEN/mTOR signaling pathway, such as S6 ribosomal protein phosphorylation, and leads to cyclin D3 downregulation. These compounds are not adenosine triphosphate competitive inhibitors for kinases in the pathway, nor do they require FKBP12 for activity like rapamycin. The other compound class turned out to be a farnesylation inhibitor, blocking the activity of GTPases, as well as an inducer of oxidative stress. Our results demonstrate that an isogenic cell system with few specific mutations in oncogenes and tumor suppressor genes can identify different classes of compounds selectively inhibiting proliferation of PTEN/mTOR pathway-addicted isogenic clones. The identified mechanisms are in line with the known cellular signaling networks activated by the altered oncogenes and suppressor genes in the isogenic system. PMID:23954931

Wyder Peters, Lorenza; Molle, Klaus D; Thiemeyer, Anke; Knopf, Agnes; Goxe, Marie; Guerry, Philippe; Brodbeck, Daniela; Colombi, Marco; Hall, Michael N; Moroni, Christoph; Regenass, Urs

2014-01-01

38

[Endogenous digitalis compounds and adrenal gland activity].  

PubMed

Endogenous inhibitors of the Na+,K+-pump have been postulated to participate in Na+ and water homeostasis. When present in high amounts, they have been proposed to induce a rise in blood pressure. There is no general agreement concerning their chemical structure and their possible tissue origin has not been well defined. In an attempt to identify a tissue source, (i) the digitalis-like contents of various organs (cross reactivity with digoxin antibodies and inhibition of ouabain binding to the Na+ pump) were determined and (ii) the circulating digitalis-like activity was analyzed under various conditions known to alter the activity of the putative source organs. High levels of digitalis-like compounds were present in the adrenal and pituitary glands (4.1 +/- 0.1, n = 15 and 3.7 +/- 0.4, n = 13 ng digoxin equivalents/g) or 328 +/- 66, n = 6 and 460 +/- 76, n = 6 ng ouabain equivalents/g) respectively. Much lower levels were found in heart, kidney, brain and hypothalamus. Plasma digitalis-like activity was measured in 5 groups of rats: control, ACTH treated, hypophysectomised, and in DOCA-salt treated animals with and without bilateral adrenalectomy. Changes in the plasma digitalis-like activity measured by the crossreactivity with anti-digoxin antibodies or by the inhibition of ouabain binding followed the same pattern. When compared to the control values, the plasma digitalis-like activity was partially decreased after hypophysectomy, markedly decreased after adrenalectomy and enhanced in ACTH-treated animals. These results suggest that the pituitary-adrenal axis plays a major role in the control of the circulating "digitalis-like" activity. PMID:3116999

Mohammad Ali, R; Pernollet, M G; Meyer, P; Devynck, M A

1987-06-01

39

Isolation of opioid-active compounds from Tabernaemontana pachysiphon leaves.  

PubMed

A procedure for prefractionation of crude plant extracts by centrifugal partition chromatography (CPC) has been developed to enable rapid identification of known-positive compounds or false-positive compounds and to increase the chance of identifying minor unknown-active compounds. The study explored the use of CPC as a tool in the prefractionation step before investigation of bioactivity. Fractions obtained by CPC from an ethanolic extract of Tabernaemontana pachysiphon Stapf (Apocynaceae) were screened by means of an opiate-receptor-binding assay and an adenosine A1-receptor-binding assay. Fractions containing fatty acids, which had false-positive effects on the assay, were identified, as were unknown-positive fractions from which two opioid-active compounds, tubotaiwine and apparicine, were subsequently isolated. The affinities (Ki) of tubotaiwine and apparicine at the opiate receptor were 1.65 +/- 0.81 and 2.65 +/- 1.56 micromol, respectively. Both alkaloids had analgesic activity in the abdominal constriction test in mice. CPC prefractionation led to the rapid isolation of two opioid-active compounds, tubotaiwine and apparicine, from the unknown-positive fraction; false-positive fractions were rapidly identified. Both tubotaiwine and apparicine had affinity for adenosine receptors in the micromolar range and also had in-vivo analgesic activity in mice. PMID:10678501

Ingkaninan, K; Ijzerman, A P; Taesotikult, T; Verpoorte, R

1999-12-01

40

Bio-active compounds from Psychotria camponutans.  

PubMed

A new benzoquinone (1-hydroxybenzoisochromanquinone) and benz [g]isoquinoline-5, 10-dione have been isolated from the woody parts of Psychotria camponutans, as a result of bioactivity-guided fractionation. The compounds were characterized by UV, IR, EI-mass, 1H-, and 13C-NMR, and HETCOR NMR spectroscopy. Both compounds, together with acetylbenzoisochromanquinone, showed in vitro strong activity against brine shrimp, KB cells, and chloroquine-resistant P. falciparum. PMID:7700994

Solis, P N; Lang'at, C; Gupta, M P; Kirby, G C; Warhusrst, D C; Phillipson, J D

1995-02-01

41

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

EPA Science Inventory

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

42

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

43

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

44

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

PubMed Central

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

2014-01-01

45

Virtual Screening for LPA2-Specific Agonists Identifies a Nonlipid Compound with Antiapoptotic ActionsS?  

PubMed Central

Lysophosphatidic acid (LPA) is a highly potent endogenous lipid mediator that protects and rescues cells from programmed cell death. Earlier work identified the LPA2 G protein-coupled receptor subtype as an important molecular target of LPA mediating antiapoptotic signaling. Here we describe the results of a virtual screen using single-reference similarity searching that yielded compounds 2-((9-oxo-9H-fluoren-2-yl)carbamoyl)benzoic acid (NSC12404), 2-((3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propyl)thio)benzoic acid (GRI977143), 4,5-dichloro-2-((9-oxo-9H-fluoren-2-yl)carbamoyl)benzoic acid (H2L5547924), and 2-((9,10-dioxo-9,10-dihydroanthracen-2-yl)carbamoyl) benzoic acid (H2L5828102), novel nonlipid and drug-like compounds that are specific for the LPA2 receptor subtype. We characterized the antiapoptotic action of one of these compounds, GRI977143, which was effective in reducing activation of caspases 3, 7, 8, and 9 and inhibited poly(ADP-ribose)polymerase 1 cleavage and DNA fragmentation in different extrinsic and intrinsic models of apoptosis in vitro. Furthermore, GRI977143 promoted carcinoma cell invasion of human umbilical vein endothelial cell monolayers and fibroblast proliferation. The antiapoptotic cellular signaling responses were present selectively in mouse embryonic fibroblast cells derived from LPA1&2 double-knockout mice reconstituted with the LPA2 receptor and were absent in vector-transduced control cells. GRI977143 was an effective stimulator of extracellular signal-regulated kinase 1/2 activation and promoted the assembly of a macromolecular signaling complex consisting of LPA2, Na+-H+ exchange regulatory factor 2, and thyroid receptor interacting protein 6, which has been shown previously to be a required step in LPA-induced antiapoptotic signaling. The present findings indicate that nonlipid LPA2-specific agonists represent an excellent starting point for development of lead compounds with potential therapeutic utility for preventing the programmed cell death involved in many types of degenerative and inflammatory diseases.

Kiss, Gyongyi N.; Fells, James I.; Gupte, Renuka; Lee, Sue-Chin; Liu, Jianxiong; Nusser, Nora; Lim, Keng G.; Ray, Ramesh M.; Lin, Fang-Tsyr; Parrill, Abby L.; Sumegi, Balazs; Miller, Duane D.

2012-01-01

46

Characterization of odor-active compounds in guava wine.  

PubMed

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

Pino, Jorge A; Queris, Oscar

2011-05-11

47

Isolation and biological activity of compounds from Garcinia preussii.  

PubMed

Abstract Context: Plants of the genus Garcinia (Clusiaceae) are traditionally used to relieve stomachaches, toothaches, and as a chew stick. Objective: In order to determine which compounds were responsible for these activities, a phytochemical investigation of the fruits and leaves of Garcinia preussii Engl. was pursued. Materials and methods: Plants were extracted by solvents of various polarities. Compounds isolation was then carried out using chromatography methods (medium- and high-pressure liquid chromatography, open column and thin-layer chromatography). The isolated compounds were identified and characterized by using 1D and 2D NMR spectroscopies. The antioxidant activity was evaluated using DPPH(•), ABTS(•-), ALP, and ORAC assays. The antimicrobial activity was assayed against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis by determining the minimum inhibitory concentration (MIC) value. The cytotoxic activity of most of the isolated compounds was evaluated on a small panel of human cancer cell lines (DU145, HeLa, HT-29, and A431) using the XTT method. Results: The phytochemical investigation of G. preussii led to the isolation of eight known compounds, six benzophenones and two flavonoids. These compounds were tested for their biological activities. 1, 2, 3, 4, 7 and 8 demonstrated a high free radical scavenging activity with ER50 ranging from 0.1 to 0.7. The antimicrobial activity was shown only against Gram-positive bacteria for 1, 4, and 5. A moderate cytotoxic activity with IC50 ranging from 7 to 50?µM was observed, except for 6 which was not active. Conclusion: These results appear to support some of the properties reported for Garcinia species. PMID:24824323

Biloa Messi, Bernadette; Ho, Raimana; Meli Lannang, Alain; Cressend, Delphine; Perron, Karl; Nkengfack, Augustin Ephrem; Carrupt, Pierre-Alain; Hostettmann, Kurt; Cuendet, Muriel

2014-06-01

48

Application of Micro Arrayed Compound Screening (pcARCS) to Identify Inhibitors of Caspase3  

Microsoft Academic Search

Micro Arrayed Compound Screening (pARCS) is a miniaturized ultra-high-throughput screening platform developed at Abbott Laboratories. In this format, 8640 discrete compounds are spotted and dried onto a polystyrene sheet, which has the same footprint as a 96-well plate. A homogeneous time-resolved fluorescence assay format (LANCE) was applied to identify the inhibitors of caspase-3 using a peptide substrate labeled with a

Sujatha M. Gopalakrishnan; Jarkko Karvinen; James L. Kofron; David J. Burns; Usha Warrior

2002-01-01

49

Identifying inhibitory compounds in lignocellulosic biomass hydrolysates using an exometabolomics approach  

PubMed Central

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

2014-01-01

50

Identifying Diverse Means for Assessing Physical Activity  

ERIC Educational Resources Information Center

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

Perlman, Dana J.; Pearson, Phil

2012-01-01

51

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

2007-11-01

52

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

53

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

54

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

PubMed

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

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

2012-11-15

55

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...

56

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...

57

Aroma-active compounds of miniature beefsteakplant (Mosla dianthera Maxim).  

PubMed

Volatile flavor compounds of miniature beefsteakplant (Mosla dianthera Maxim.) from Vietnam were analyzed through gas chromatography-mass spectrometry-olfactometry (GC-MS-O). Sixty-two compounds were identified by GC-MS. Of these, (+/-)-carvone and (+/-)-limonene were the most abundant, followed by (Z)-limonene oxide, beta-caryophyllene, and alpha-humulene. Twenty aroma-active compounds were detected by aroma extract dilution analysis conducted on two GC columns of different polarities (DB-5MS and DB-Wax). The most intense aroma-active compounds were linalool (floral/sweet/lemon), (-)-carvone (spearminty), and 1-octen-3-one (mushroom/earthy). Other predominant aroma-active compounds included (Z)-3-hexenol (grassy/leafy/metallic), (Z)-limonene oxide (lemon/floral), myrcene (plastic/sweet), (+)-limonene (orange/lemon), alpha-thujene (soy sauce/grassy), and (Z)-dihydrocarvone (spearminty/pepperminty). On the basis of the aroma characteristics and intensity, it was concluded that (-)-carvone was responsible for the characteristic aroma of miniature beefsteakplant. PMID:10898640

Kim, T H; Thuy, N T; Shin, J H; Baek, H H; Lee, H J

2000-07-01

58

Web server to identify similarity of amino acid motifs to compounds (SAAMCO).  

PubMed

Protein-protein interactions are fundamental in mediating biological processes including metabolism, cell growth, and signaling. To be able to selectively inhibit or induce protein activity or complex formation is a key feature in controlling disease. For those situations in which protein-protein interactions derive substantial affinity from short linear peptide sequences, or motifs, we can develop search algorithms for peptidomimetic compounds that resemble the short peptide's structure but are not compromised by poor pharmacological properties. SAAMCO is a Web service ( http://bioware.ucd.ie/ approximately saamco) that facilitates the screening of motifs with known structures against bioactive compound databases. It is built on an algorithm that defines compound similarity based on the presence of appropriate amino acid side chain fragments and a favorable Root Mean Squared Deviation (RMSD) between compound and motif structure. The methodology is efficient as the available compound databases are preprocessed and fast regular expression searches filter potential matches before time-intensive 3D superposition is performed. The required input information is minimal, and the compound databases have been selected to maximize the availability of information on biological activity. "Hits" are accompanied with a visualization window and links to source database entries. Motif matching can be defined on partial or full similarity which will increase or reduce respectively the number of potential mimetic compounds. The Web server provides the functionality for rapid screening of known or putative interaction motifs against prepared compound libraries using a novel search algorithm. The tabulated results can be analyzed by linking to appropriate databases and by visualization. PMID:18570372

Casey, Fergal P; Davey, Norman E; Baran, Ivan; Varekova, Radka Svobodova; Shields, Denis C

2008-07-01

59

Systems biology approaches in identifying the targets of natural compounds for cancer therapy.  

PubMed

Natural compounds have been known to exert inhibitory effects on the development and progression of human cancers. However, the targets of these naturally occurring agents are largely elusive. Recently, systems biology approaches based on high-throughput technologies such as DNA microarrays have begun to be utilized for investigating the targets of drugs including natural compounds. Therefore, in this review article, we will briefly introduce the several systems biology approaches, and will discuss the application of these new technologies for identifying the therapeutic targets of natural compounds for supporting their roles in the prevention and/or treatment of human cancers. Furthermore, identification of the novel targets will be useful for designing more effective and targeted therapeutic strategies for achieving better treatment outcome in patients diagnosed with cancers. PMID:23237676

Tan, Yi; Wu, Qiong; Xia, Jun; Miele, Lucio; Sarkar, Fazlul H; Wang, Zhiwei

2013-06-01

60

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

PubMed

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

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

2008-06-01

61

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

2013-04-01

62

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

PubMed Central

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.

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

2012-01-01

63

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

64

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

PubMed Central

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

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

2013-01-01

65

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

2013-01-01

66

[Compounds from fraction with cardiovascular activity of Chrysanthemum indicum].  

PubMed

In order to investigate the chemical constituents from the fraction with cardiovascular activtiy of Chrysanthemum indicum, the isolation and purification of compounds from this active fraction were performed, and the chemical structures were elucidated by spectral analysis and comparison of the spectral data with those reported in the literature. As a result, twelve compounds were obtained and identified as (2S) -eriodictyol-7-O-beta-D-glucuronide (1), (2S) -eriodictyol-7-O-beta-D-glucoside (2), (2S) -hesperetin-7-O-beta-D-glucuronide (3), luteolin-7-O-beta-D-glucoside (4), luteolin-7-O-beta-D-glucuronide (5), diosmetin-7-O-beta-D-glucuronide (6), quercetin -7-O-beta-D-glucoside (7), (2S)-eriodict-dicaffeoylquinate (8), 3, 5-dicaffeoylquinic acid(9), 3, 5-cis-dicaffeoylquinic acid (10), 1, 5-dicaffeoylquinic acid (11), and 1, 3-dicaffeoylquinic acid (12). The above result indicated that flavonoids were the ma-dicaffeoylquinate (8), 3, 5-dicaffeoylquinic acid (9), 3, 5-cis-dicaffeoylquinic acid (10), 1, 5-dicaffeoylquinic acid (11), and 1, 3-dicaffeoylquinic acid (12). The above result indicated that flavonoids were the major components of the active fraction. Compounds 2, 3, 7, 8 and 10 were obtained from this genus for the first time, and compounds 5, 6, 9, 11, and 12 were first isolated from C. indicum. PMID:22741463

Sun, Yu; Ma, Xiaobin; Liu, Jianxun

2012-01-01

67

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

68

Alarm responses caused by newly identified compounds derived from the honeybee sting.  

PubMed

Twelve compounds identified from honeybee,Apis mellifera L., sting extracts were evaluated in a standardized laboratory test for their effectiveness in eliciting an alarm response from caged worker honeybees. Two-1-decanol and phenol-were judged ineffective as alarm pheromones. The other ten-1-butanol, isopentyl acetate, isopentyl alcohol, 1-hexanol, 2-heptyl acetate, 2-heptanol, 1-octanol, 1-acetoxy-2-octene, 2-nonyl acetate, and 1-acetoxy-2-nonene-produced alarm responses of similar speed and intensity. Three non-sting-derived compounds-?-ionone, methyl benzoate, andtrans-cinnamaldehyde-caused weak or no responses, indicating that the responses were not simply a reaction to concentrated odoriferous substances. PMID:24408619

Collins, A M; Blum, M S

1983-01-01

69

Unbiased compound screening identifies unexpected drug sensitivities and novel treatment options for gastrointestinal stromal tumors.  

PubMed

Most gastrointestinal stromal tumors (GIST) are caused by oncogenic KIT or platelet-derived growth factor receptor activation, and the small molecule kinase inhibitor imatinib mesylate is an effective first-line therapy for metastatic or unresectable GIST. However, complete remissions are rare and most patients ultimately develop resistance, mostly because of secondary mutations in the driver oncogenic kinase. Hence, there is a need for novel treatment options to delay failure of primary treatment and restore tumor control in patients who progress under therapy with targeted agents. Historic data suggest that GISTs do not respond to classical chemotherapy, but systematic unbiased screening has not been performed. In screening a compound library enriched for U.S. Food and Drug Administration (FDA)-approved chemotherapeutic agents (NCI Approved Oncology Drugs Set II), we discovered that GIST cells display high sensitivity to transcriptional inhibitors and topoisomerase II inhibitors. Mechanistically, these compounds exploited the cells' dependency on continuous KIT expression and/or intrinsic DNA damage response defects, explaining their activity in GIST. Mithramycin A, an indirect inhibitor of the SP1 transcription factor, and mitoxantrone, a topoisomerase II inhibitor, exerted significant antitumor effects in mouse xenograft models of human GIST. Moreover, these compounds were active in patient-derived imatinib-resistant primary GIST cells, achieving efficacy at clinically relevant concentrations. Taken together, our findings reveal that GIST cells have an unexpectedly high and specific sensitivity to certain types of FDA-approved chemotherapeutic agents, with immediate implications for encouraging their clinical exploration. PMID:24385214

Boichuk, Sergei; Lee, Derek J; Mehalek, Keith R; Makielski, Kathleen R; Wozniak, Agnieszka; Seneviratne, Danushka S; Korzeniewski, Nina; Cuevas, Rolando; Parry, Joshua A; Brown, Matthew F; Zewe, James; Taguchi, Takahiro; Kuan, Shin-Fan; Schöffski, Patrick; Debiec-Rychter, Maria; Duensing, Anette

2014-02-15

70

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

71

Yeast as a biosensor of detoxification: a tool for identifying new compounds that revert multidrug resistance.  

PubMed

During tumour progression, cells accumulate secondary mutations and/or chromosomal aberrations that generate genetic diversity within the tumour cell population. This may result in the acquisition of new properties that increase tumour malignancy, such as invasiveness or resistance to chemotherapy. One of the important mechanisms of chemotherapy resistance is overexpression or biochemical activation of ABC family transporters. ABC transporters remove anti tumour drugs from the cell, reducing their intracellular concentration and producing resistance against a wide range of chemically unrelated drugs, known as multidrug resistant phenotype (MDR). During recent decades, much effort has been devoted to the isolation of compounds able to inhibit the activity of these transporters. However, few such compounds have reached clinical practice and MDR remains a serious complication in cancer therapy. In an innovative approach to finding new ABC inhibitors, we propose using fission yeast Schizosaccharomyces pombe as a biosensor of detoxification that would enable cost-efficient screening of natural compounds and chemical libraries for molecules that revert the MDR phenotype. Existing fission yeast tools provide genetic, biochemical and cell biological analysis, thereby facilitating identification of drug targets. Putative inhibitors and modulators of ABC transporters could be used in combination with chemotherapeutic drugs for the treatment of multidrug resistant tumours. PMID:23614676

Martín-Cordero, Carmen; Sanchez-Pico, Angeles; Leon-Gonzalez, Antonio J; Perez-Pulido, Antonio J; Daga, Rafael R

2013-08-01

72

A 1536-well quantitative high-throughput screen to identify compounds targeting cancer stem cells.  

PubMed

Tumor cell subpopulations called cancer stem cells (CSCs) or tumor-initiating cells (TICs) have self-renewal potential and are thought to drive metastasis and tumor formation. Data suggest that these cells are resistant to current chemotherapy and radiation therapy treatments, leading to cancer recurrence. Therefore, finding new drugs and/or drug combinations that cause death of both the differentiated tumor cells as well as CSC populations is a critical unmet medical need. Here, we describe how cancer-derived CSCs are generated from cancer cell lines using stem cell growth media and nonadherent conditions in quantities that enable high-throughput screening (HTS). A cell growth assay in a 1536-well microplate format was developed with these CSCs and used to screen a focused collection of oncology drugs and clinical candidates to find compounds that are cytotoxic against these highly aggressive cells. A hit selection process that included potency and efficacy measurements during the primary screen allowed us to efficiently identify compounds with potent cytotoxic effects against spheroid-derived CSCs. Overall, this research demonstrates one of the first miniaturized HTS assays using CSCs. The procedures described here should enable further testing of the effect of compounds on CSCs and help determine which pathways need to be targeted to kill them. PMID:22927676

Mathews, Lesley A; Keller, Jonathan M; Goodwin, Bonnie L; Guha, Rajarshi; Shinn, Paul; Mull, Rebecca; Thomas, Craig J; de Kluyver, Rachel L; Sayers, Thomas J; Ferrer, Marc

2012-10-01

73

Gene Expression Profiling Identifies Important Genes Affected by R2 Compound Disrupting FAK and P53 Complex  

PubMed Central

Focal Adhesion Kinase (FAK) is a non-receptor kinase that plays an important role in many cellular processes: adhesion, proliferation, invasion, angiogenesis, metastasis and survival. Recently, we have shown that Roslin 2 or R2 (1-benzyl-15,3,5,7-tetraazatricyclo[3.3.1.1~3,7~]decane) compound disrupts FAK and p53 proteins, activates p53 transcriptional activity, and blocks tumor growth. In this report we performed a microarray gene expression analysis of R2-treated HCT116 p53+/+ and p53?/? cells and detected 1484 genes that were significantly up- or down-regulated (p < 0.05) in HCT116 p53+/+ cells but not in p53?/? cells. Among up-regulated genes in HCT p53+/+ cells we detected critical p53 targets: Mdm-2, Noxa-1, and RIP1. Among down-regulated genes, Met, PLK2, KIF14, BIRC2 and other genes were identified. In addition, a combination of R2 compound with M13 compound that disrupts FAK and Mmd-2 complex or R2 and Nutlin-1 that disrupts Mdm-2 and p53 decreased clonogenicity of HCT116 p53+/+ colon cancer cells more significantly than each agent alone in a p53-dependent manner. Thus, the report detects gene expression profile in response to R2 treatment and demonstrates that the combination of drugs targeting FAK, Mdm-2, and p53 can be a novel therapy approach.

Golubovskaya, Vita M.; Ho, Baotran; Conroy, Jeffrey; Liu, Song; Wang, Dan; Cance, William G.

2014-01-01

74

Gene Expression Profiling Identifies Important Genes Affected by R2 Compound Disrupting FAK and P53 Complex.  

PubMed

Focal Adhesion Kinase (FAK) is a non-receptor kinase that plays an important role in many cellular processes: adhesion, proliferation, invasion, angiogenesis, metastasis and survival. Recently, we have shown that Roslin 2 or R2 (1-benzyl-15,3,5,7-tetraazatricyclo[3.3.1.1~3,7~]decane) compound disrupts FAK and p53 proteins, activates p53 transcriptional activity, and blocks tumor growth. In this report we performed a microarray gene expression analysis of R2-treated HCT116 p53+/+ and p53-/- cells and detected 1484 genes that were significantly up- or down-regulated (p < 0.05) in HCT116 p53+/+ cells but not in p53-/- cells. Among up-regulated genes in HCT p53+/+ cells we detected critical p53 targets: Mdm-2, Noxa-1, and RIP1. Among down-regulated genes, Met, PLK2, KIF14, BIRC2 and other genes were identified. In addition, a combination of R2 compound with M13 compound that disrupts FAK and Mmd-2 complex or R2 and Nutlin-1 that disrupts Mdm-2 and p53 decreased clonogenicity of HCT116 p53+/+ colon cancer cells more significantly than each agent alone in a p53-dependent manner. Thus, the report detects gene expression profile in response to R2 treatment and demonstrates that the combination of drugs targeting FAK, Mdm-2, and p53 can be a novel therapy approach. PMID:24452144

Golubovskaya, Vita M; Ho, Baotran; Conroy, Jeffrey; Liu, Song; Wang, Dan; Cance, William G

2014-01-01

75

Compounds from Ageratum conyzoides: isolation, structural elucidation and insecticidal activity.  

PubMed

This work aimed at identifying plant compounds with insecticidal activity against Diaphania hyalinata (L.) (Lepidoptera: Pyralidae), Musca domestica (L.) (Diptera: Muscidae), Periplaneta americana (L.) (Blattodea: Blattidae) and Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae). The plant species used were: basil (Ocimum selloi Benth.), rue (Ruta graveolens L.), lion's ear (Leonotis nepetaefolia L.), Jimson weed (Datura stramonium L.), 'baleeira' herb (Cordia verbenaceae L.), mint (Mentha piperita L.), wild balsam apple (Mormodica charantia L.) and billy goat weed (Ageratum conyzoides L.). Firstly, the insecticidal activities of hexane and ethanol plant extracts were evaluated against adults of R. dominica. Among them, only the hexane extract of A. conyzoides showed insecticidal activity. The hexane extract of this plant species was therefore fractionated by silica gel column chromatography to isolate and purify its bioactive chemical constituents. Three compounds were identified using IR spectra, (1)H NMR, (13)C NMR, HMBC and NOE after gel chromatography: 5,6,7,8,3', 4', 5'-heptamethoxyflavone, 5,6,7,8,3'-pentamethoxy-4', 5'-methylenedioxyflavone and coumarin. The complete assignment of (13)C NMR to 5,6,7,8,3'-pentamethoxy-4', 5'-methylenedioxyflavone was successfully made for the first time. 5,6,7,8,3'-Pentamethoxy-4', 5'-methylenedioxyflavone did not show any insecticidal activity against the four insect species tested. 5,6,7,8,3', 4', 5'-Heptamethoxyflavone showed low activity against D. hyalinata and R. dominica and was not toxic to M. domestica or P. americana. In contrast, coumarin showed insecticidal activity against all four insect pest species tested, with the following order of susceptibility: R. dominica < P. americana < D. hyalinata < M. domestica after 24 h exposure. PMID:17469080

Moreira, Márcio D; Picanço, Marcelo C; Barbosa, Luiz Cláudio A; Guedes, Raul Narciso C; Barros, Emerson C; Campos, Mateus R

2007-06-01

76

Larvicidal activity of lignans identified in Phryma leptostachya Var. asiatica roots against three mosquito species.  

PubMed

The insecticidal activity of phytochemicals isolated from the roots of Phryma leptostachya var. asiatica against third instar larvae of Culex pipiens pallens, Aedes aegypti, and Ocheratatos togoi was examined. The two constituents of P. leptostachya var. asiatica roots were identified as the leptostachyol acetate (I) and 8'-acetoxy-2,2',6-trimethoxy-3,4,4',5'-dimethylenedioxyphenyl-7,7'-dioxabicyclo[3.3.0]octane (II) by spectroscopic analysis. Compound I was lethal to C. pipiens pallens, A. aegypti, and O. togoi at 10 ppm. Compound II showed weak or no insecticidal activity against three mosquito species at 10 ppm. The LC(50) values of I against C. pipiens pallens, A. aegypti, and O. togoi were 0.41, 2.1, and 2.3 ppm, respectively. Naturally occurring P. leptostachya var. asiatica root-derived compounds merit further study as potential mosquito larval control agents or lead compounds. PMID:15713007

Park, Il-Kwon; Shin, Sang-Chul; Kim, Chul-Su; Lee, Hak-Ju; Choi, Won-Sil; Ahn, Young-Joon

2005-02-23

77

Antioxidant activity of Magnolol, honokiol, and related phenolic compounds  

Microsoft Academic Search

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

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

1997-01-01

78

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

PubMed

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

Stumpfe, Dagmar; Dimova, Dilyana; Bajorath, Jürgen

2014-02-24

79

Identifying the nonpoint source of perfluorinated compounds using a geographic information system based approach.  

PubMed

Perfluorinated compounds (PFCs) have been detected in a wide range of places. They have also been reported to come from nonpoint sources, but the origin of these sources has not been identified. In the present study, we attempted to characterize the nonpoint source of PFCs in the Hayabuchi River, Japan, which runs through an urban area, using a geographic information system (GIS) and statistical analysis. We also estimated annual PFC loads from nonpoint sources in Japan as a whole, determining a magnitude comparable to that from sewage treatment plants (STPs); the range was a few tons per year for each PFC. Perfluorinated compound pollution in river water was found to increase when the river received drainage from an area with a high proportion of commercial and/or transportation land use. It was also found that more PFCs were discharged from the watersheds where train stations are located. This result could be interpreted as the use of land for commercial and transportation purposes is prevalent in close proximity to train stations, and that the effluents from those areas contain high concentrations of PFCs. These findings suggested that train stations could be indicators of nonpoint sources of PFCs. PMID:19159126

Zushi, Yasuyuki; Masunaga, Shigeki

2009-04-01

80

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

PubMed

The volatile compounds and the most odor-active compounds of dry-cured Iberian ham were investigated by extracting them using a solid phase microextraction technique with a 2?cm Carboxen/PDMS/DVB fiber. The detection frequency method was applied to estimate the potential contribution of each compound to the odor of hams. Twenty-one volatile compounds were tentatively identified for the first time in dry-cured ham by gas chromatography-mass spectrometry, and eight in dry-cured Iberian ham. Gas chromatography-olfactometry allowed the identification for the first time of six compounds not previously reported as odorants of Iberian ham, and also two odorants were newly identified in dry-cured ham. According to the detection frequency method, the most odor active compounds found were 3-methylbutanoic acid (dirty sock-like smelling), hexanal (cut grass-like odor), 3-methylbutanal (sweaty and bitter almond-like odor), 2-methyl-3-furanthiol (toasted nuts-like odor) and 1-octen-3-one (mushroom-like odor). PMID:23685564

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

2013-06-01

81

Synthesis and anti-norovirus activity of pyranobenzopyrone compounds.  

PubMed

During the last decade, noroviruses have gained media attention as the cause of large scale outbreaks of gastroenteritis on cruise ships, dormitories, nursing homes, etc. Although noroviruses do not multiply in food or water, they can cause large outbreaks because approximately 10-100 virions are sufficient to cause illness in a healthy adult. Recently, it was shown that the activity of acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1) enzyme may be important in norovirus infection. In search of anti-noroviral agents based on the inhibition of ACAT1, we synthesized and evaluated the inhibitory activities of a class of pyranobenzopyrone molecules containing amino, pyridine, substituted quinolines, or 7,8-benzoquinoline nucleus. Three of the sixteen evaluated compounds possess ED(50) values in the low micrometer range. 2-Quinolylmethyl derivative 3A and 4-quinolylmethyl derivative 4A showed ED(50) values of 3.4 and 2.4 ?M and TD(50) values of >200 and 96.4 ?M, respectively. The identified active compounds are suitable for further modification for the development of anti-norovirus agents. PMID:22513282

Pokhrel, Laxman; Kim, Yunjeong; Nguyen, Thi D T; Prior, Allan M; Lu, Jianyu; Chang, Kyeong-Ok; Hua, Duy H

2012-05-15

82

Activity profile relationships between structurally similar promiscuous compounds.  

PubMed

Compound promiscuity results from specific interactions of a small molecule with multiple biological targets and is an emerging concept in medicinal chemistry and drug discovery as it provides the basis for polypharmacology. Recent studies have assessed the degree of promiscuity among drugs and bioactive compounds. On the basis of currently available data, many drugs and bioactive compounds have been found to interact with more than one target. Herein, we further extend the study of promiscuity by focusing on structurally similar promiscuous compounds, comparing their activity profiles, and determining multi-target activity patterns. The analysis revealed that most structurally similar promiscuous compounds have identical or similar activity profiles but also detected different types of structure-activity pattern relationships. In addition, the propensity of activity cliff formation among promiscuous compounds was determined. Activity cliffs were formed at a high rate among promiscuous compounds indicating that many structurally similar promiscuous compounds have greatly varying activity against one or more targets they share. Taken together, these findings show that compound promiscuity and target selectivity are not mutually exclusive and further refine current views of promiscuity. PMID:24077530

Hu, Ye; Bajorath, Jürgen

2013-11-01

83

Microalgae as sources of pharmaceuticals and other biologically active compounds  

Microsoft Academic Search

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

Michael A. Borowitzka

1995-01-01

84

Identifying Emotions on the Basis of Neural Activation  

PubMed Central

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

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

2013-01-01

85

SURVEY OF INDUSTRIAL APPLICATIONS OF VAPOR-PHASE ACTIVATED-CARBON ADSORPTION FOR CONTROL OF POLLUTANT COMPOUNDS FROM MANUFACTURE OF ORGANIC COMPOUNDS  

EPA Science Inventory

This study covers industrial use of activated carbon for vapor-phase applications. A listing of over 700 applications of vapor-phase carbon systems is made available for use in identifying sites where a given compound is being removed....

86

Thin-layer chromatographic (TLC) separations and bioassays of plant extracts to identify antimicrobial compounds.  

PubMed

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

Kagan, Isabelle A; Flythe, Michael D

2014-01-01

87

Sorption of Alkyl Benzyl Dimethyl Ammonium Compounds by Activated Sludge  

Microsoft Academic Search

The adsorption isotherms on activated sludge from wastewater treatment plants and the surface properties in aqueous solution of alkyl benzyl dimethyl ammonium compounds have been investigated. Langmuir and Freundlich adsorption isotherms described satisfactorily the equilibrium adsorption of these cationic surfactants on activated sludge. Adsorption on sludge as well as the affinity of these compounds to be adsorbed in the liquid\\/gas

M. Teresa García; Encarna Campos; Francesc Comelles

2006-01-01

88

Antioxidant activity relationship of phenolic compounds in Hypericum perforatum L.  

PubMed Central

Background The St John's Wort (Hypericum perforatum; Clusiaceae) has been used in traditional and modern medicine for a long time due to its high content of biologically active phenolics. The purpose of this work was to develop a method for their fractionation and identification, and to determine the most active antioxidant compounds in plant extract. Results An LC-MS method which enables fast qualitative and semiquantitative analysis was developed. The composition determined is in agreement with the previous results, where 6 flavonoids, 4 naphthodianthrones and 4 phloroglucinols have been identified. Significant antioxidant activity was determined for most of the fractions by DPPH assay (the lowest IC50 of 0.52 ?g/ml), NO scavenging (6.11 ?g/ml), superoxide scavenging (1.86 ?g/ml), lipid peroxidation (0.0079 ?g/ml) and FRAP (the highest reduction capacity of 104 mg Fe equivalents/g) assays. Conclusion LC-MS technique has been successfully applied for a quick separation and identification of the major components of H. perforatum fractions. Majority of the fractions analyzed have expressed a very high antioxidative activity when compared to synthetic antioxidants. The antioxidant activity could be attributed to flavonoids and phenolic acids, while phloroglucinols and naphthodianthrones showed no significant activity. It is demonstrated that it is possible to obtain, by fractionation, H. perforatum preparations with significantly increased phloroglucinols-to-naphthodianthrones ratio (up to 95:5).

2011-01-01

89

Targeting the Wnt pathway in zebrafish as a screening method to identify novel therapeutic compounds.  

PubMed

Activating mutations in the Wnt signaling pathway account for the initiation of greater than 90% of all colorectal cancers and this pathway has been implicated in numerous other diseases. Therefore, identifying small molecule inhibitors of this pathway is of critical importance towards identifying clinically relevant drugs. Numerous screens have been employed to identify therapeutic reagents, but none have made it to advanced clinical trials, suggesting that traditional screening methods are ineffective at identifying clinically relevant targets. Here, we describe a novel in vivo screen to identify small molecule inhibitors of the Wnt pathway. Specifically, treatment of zebrafish embryos with LiCl inhibits GSK3 kinase function, resulting in hyperactivation of the signaling pathway and an eyeless phenotype at 1 day post fertilization. Using the small molecule XAV939, a known inhibitor of Wnt signaling, we rescued the LiCl induced eyeless phenotype, confirming efficacy of the screen. We next tested our assay with 400 known small molecule kinase inhibitors, none of which should inhibit Wnt signaling below the level of GSK3 based on their known targets. Accordingly, none of these small molecules rescued the eyeless phenotype, which demonstrates the stringency of the assay. However, several of these small molecule kinase inhibitors did generate a non-Wnt phenotype in accordance with the kinase they targeted. Therefore, combining the efficacy, sensitivity, and stringency of this preliminary screen, this model will provide an alternative to the traditional in vitro screen, generating potentially clinical relevant drugs in a rapid and cost-effective way. PMID:24414478

Robertson, Joshua K; Danzmann, Kestral; Charles, Sherise; Blake, Katherine; Olivares, Annia; Bamikole, Solape; Olson, Meghan; Van Raay, Terence J

2014-02-01

90

Cell-Based Small-Molecule Compound Screen Identifies Fenretinide as Potential Therapeutic for Translocation-Positive Rhabdomyosarcoma  

PubMed Central

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.

Herrero Martin, David; Boro, Aleksandar; Schafer, Beat W.

2013-01-01

91

Orally Active Antischistosomal Early Leads Identified from the Open Access Malaria Box  

PubMed Central

Background Worldwide hundreds of millions of schistosomiasis patients rely on treatment with a single drug, praziquantel. Therapeutic limitations and the threat of praziquantel resistance underline the need to discover and develop next generation drugs. Methodology We studied the antischistosomal properties of the Medicines for Malaria Venture (MMV) malaria box containing 200 diverse drug-like and 200 probe-like compounds with confirmed in vitro activity against Plasmodium falciparum. Compounds were tested against schistosomula and adult Schistosoma mansoni in vitro. Based on in vitro performance, available pharmacokinetic profiles and toxicity data, selected compounds were investigated in vivo. Principal Findings Promising antischistosomal activity (IC50: 1.4–9.5 µM) was observed for 34 compounds against schistosomula. Three compounds presented IC50 values between 0.8 and 1.3 µM against adult S. mansoni. Two promising early leads were identified, namely a N,N?-diarylurea and a 2,3-dianilinoquinoxaline. Treatment of S. mansoni infected mice with a single oral 400 mg/kg dose of these drugs resulted in significant worm burden reductions of 52.5% and 40.8%, respectively. Conclusions/Significance The two candidates identified by investigating the MMV malaria box are characterized by good pharmacokinetic profiles, low cytotoxic potential and easy chemistry and therefore offer an excellent starting point for antischistosomal drug discovery and development.

Ingram-Sieber, Katrin; Cowan, Noemi; Panic, Gordana; Vargas, Mireille; Mansour, Nuha R.; Bickle, Quentin D.; Wells, Timothy N. C.; Spangenberg, Thomas; Keiser, Jennifer

2014-01-01

92

Identifying Associations between Student Achievement and Parental Involvement Activities  

ERIC Educational Resources Information Center

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

Waddle, Ann R.

2011-01-01

93

Phenolic compounds from Brazilian propolis with pharmacological activities  

Microsoft Academic Search

Four compounds were isolated from Brazilian propolis. They are identified as: (1) 3-prenyl-4-hydroxycinnamic acid (PHCA), (2) 2,2-dimethyl-6-carboxyethenyl-2H-1-benzopyrane (DCBEN), (3) 3,5-diprenyl-4-hydroxycinnamic acid (DHCA), and (4) 2,2-dimethyl-6-carboxyethenyl-8-prenyl-2H-1-benzopyran (DPB). The structures of the compounds were determined by MS and NMR techniques. All compounds were assayed against Trypanosoma cruzi and the bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus faecalis. Compounds (1) to

M. C. Marcucci; F. Ferreres; C. Garc??a-Viguera; V. S. Bankova; S. L. De Castro; A. P. Dantas; P. H. M. Valente; N. Paulino

2001-01-01

94

Active compounds and medicinal properties of Myrciaria genus.  

PubMed

The genus Myrciaria occurs in various Brazilian biomes. Its species contains several active components, including phenolic compounds, such as tannins, flavonoids, ellagic acid and anthocyanins. Biological activities reported for Myrciaria fruits and leaf and bark extracts include antioxidant, antibacterial and antifungal effects. This work aims to provide an overview of the active compounds of Myrciaria, highlighting its secondary metabolites and medicinal properties for stimulating new studies regarding this genus. PMID:24491724

Borges, Leonardo Luiz; Conceiçăo, Edemilson Cardoso; Silveira, Dâmaris

2014-06-15

95

Antioxidant activity and effective compounds of immature calamondin peel.  

PubMed

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

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

2013-02-15

96

Towards Antitumor Active trans-Platinum Compounds  

PubMed Central

Substitution of NH3 by a range of amines in trans-[PtCl2(NH3)2] produces compounds with cytotoxicity significantly improved over the parent transplatin and in many cases equivalent to that of cisplatin. This microreview summarizes the chemistry and biology of trans-platinum compounds containing principally planar amines and succinctly reviews the current status of anticancer relevance of the trans-platinum geometry. The nature of bifunctional DNA adducts (intrastrand, interstrand) is remarkably dependent on the nature of the amine. Further, the stability of monofunctional adducts allows for competitive production of DNA-protein crosslinks and overall the results suggest that the trans-platinum chemotype may offer significant potential for design of selective DNA-protein crosslinking agents. A subset of proteins known to bind to DNA modified by trans-platinum is that comprised of zinc fingers – model studies show the potential for formation of heteronuclear thiolate-bridged species as precedent for zinc displacement from the biomolecule.

Aris, Sheena M.; Farrell, Nicholas P.

2010-01-01

97

Phytotoxicity of vulpia residues: III. Biological activity of identified allelochemicals from Vulpia myuros.  

PubMed

Twenty compounds identified in vulpia (Vulpia myuros) residues as allelochemicals were individually and collectively tested for biological activity. Each exhibited characteristic allelochemical behavior toward the test plant, i.e., inhibition at high concentrations and stimulation or no effect at low concentrations, but individual activities varied. Allelopathins present in large quantities, such as syringic, vanillic, and succinic acids, possessed low activity, while those present in small quantities, such as catechol and hydrocinnamic acid, possessed strong inhibitory activity. The concept of a phytotoxic strength index was developed for quantifying the biological properties of each individual allelopathin in a concise, comprehensive, and meaningful format. The individual contribution of each allelopathin, assessed by comparing the phytotoxic strength index to the overall toxicity of vulpia residues, was variable according to structure and was influenced by its relative proportion in the residue. The majority of compounds possessed low or medium biological activity and contributed most of the vulpia phytotoxicity, while compounds with high biological activity were in the minority and only present at low concentration. Artificial mixtures of these pure allelochemicals also produced phytotoxicity. There were additive/synergistic effects evident in the properties of these mixtures. One such mixture, formulated from allelochemicals found in the same proportions as occur in vulpia extract, produced stronger activity than another formulated from the same set of compounds but in equal proportions. These results suggest that the exploration of the relative composition of a cluster of allelopathins may be more important than simply focusing on the identification of one or two compounds with strong biological activity and that synergism is fundamental to the understanding of allelopathy. PMID:14768822

An, M; Pratley, J E; Haig, T

2001-02-01

98

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

99

Compound screening platform using human induced pluripotent stem cells to identify small molecules that promote chondrogenesis.  

PubMed

Articular cartilage, which is mainly composed of collagen II, enables smooth skeletal movement. Degeneration of collagen II can be caused by various events, such as injury, but degeneration especially increases over the course of normal aging. Unfortunately, the body does not fully repair itself from this type of degeneration, resulting in impaired movement. Microfracture, an articular cartilage repair surgical technique, has been commonly used in the clinic to induce the repair of tissue at damage sites. Mesenchymal stem cells (MSC) have also been used as cell therapy to repair degenerated cartilage. However, the therapeutic outcomes of all these techniques vary in different patients depending on their age, health, lesion size and the extent of damage to the cartilage. The repairing tissues either form fibrocartilage or go into a hypertrophic stage, both of which do not reproduce the equivalent functionality of endogenous hyaline cartilage. One of the reasons for this is inefficient chondrogenesis by endogenous and exogenous MSC. Drugs that promote chondrogenesis could be used to induce self-repair of damaged cartilage as a non-invasive approach alone, or combined with other techniques to greatly assist the therapeutic outcomes. The recent development of human induced pluripotent stem cell (iPSCs), which are able to self-renew and differentiate into multiple cell types, provides a potentially valuable cell resource for drug screening in a "more relevant" cell type. Here we report a screening platform using human iPSCs in a multi-well plate format to identify compounds that could promote chondrogenesis. PMID:23161332

Yang, Sheng-Lian; Harnish, Erica; Leeuw, Thomas; Dietz, Uwe; Batchelder, Erika; Wright, Paul S; Peppard, Jane; August, Paul; Volle-Challier, Cecile; Bono, Francoise; Herbert, Jean-Marc; Izpisua Belmonte, Juan Carlos

2012-12-01

100

Pyrazolone compounds and thrombopoietin receptor activator  

US Patent & Trademark Office Database

A preventive, therapeutic or improving agent for diseases against which activation of the thrombopoietin receptor is effective or a platelet increasing agent, which contains a thrombopoietin receptor activator represented by the formula (1): wherein A is a C?2-14#191 aryl group, B is a hydrogen atom, a C?1-6#191 alkyl group, a C?1-3#191 alkyl group substituted with one or more fluorine atoms or a C?2-14#191 aryl group, D is a hydrogen atom, a C?1-6#191 alkyl group, a C?1-3#191 alkyl group substituted with one or more fluorine atoms or a C?2-14#191 aryl group, and E is a C?2-14#191 aryl group, a tautomer, prodrug or pharmaceutically acceptable salt of the activator or a solvate thereof, as an active ingredient. ##STR00001##

2011-11-08

101

ACTIVATED CARBON ADSORPTION OF TRACE ORGANIC COMPOUNDS  

EPA Science Inventory

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

102

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

PubMed Central

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

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

2014-01-01

103

Steroid hormone activity of flavonoids and related compounds  

Microsoft Academic Search

Soy isoflavones have been studied extensively for estrogenic and antiestrogenic properties. Other flavonoids, found in fruits, vegetables, tea and wine, have been much less tested for steroid hormone activity. We therefore assessed the estrogenic, androgenic and progestational activities of 72 flavonoids and structurally-related compounds. These compounds were tested on BT-474 human breast cancer cells at concentrations of 108–10-5?M, with estradiol

Rachel S. Rosenberg Zand; David J. A. Jenkins; Eleftherios P. Diamandis

2000-01-01

104

Activation of shallow dopants in II-VI compounds  

SciTech Connect

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

Walukiewicz, W.

1995-08-01

105

Studies identify problems and strengths of collector seals and sealing compounds  

SciTech Connect

Results of an extensive literature search and accelerated testing of elastomers used for preformed seals and sealing compounds in solar collectors are summarized. Data include compression set thermal aging data, sealant outgassing test results, and the effect of glaze deposits on relative light transmittance. The preformd seals and sealing compounds recommended are fluorocarbons for high temperature, and silicones, acrylics, acrylic copolymers and EPDMs for intermediate temperature. (LEW)

Not Available

1981-08-01

106

Biologically active polysaccharides as possible lead compounds  

Microsoft Academic Search

Various carbohydrate polymers have during the last decades been shown to be responsible for biological effects, either by\\u000a exhibiting the effect themselves or by inducing effects via complex reaction cascades. These are e.g. anti-inflammatory, immunostimulating,\\u000a complement activation, antithrombotic, antidiabetic and infection protectant. Modern pharmaceutical industry has extensive\\u000a research programs where the aim is to obtain information on traditional use of

Berit Smestad Paulsen

2002-01-01

107

Antibacterial activity of a virgatusin-related compound.  

PubMed

The relationship between antibacterial activity of tetra-substituted tetrahydrofuran lignans (1-4) and their absolute configurations was tested. Only compound 4 among two virgatusins and two related compounds exhibited growth inhibitory activity against the Gram-positive bacteria Bacillus subtilis, Staphylococcus aureus and Listeria denitrificans. Compound 4 affected the growth of B. subtilis in a bactericidic manner, and its ability to dissipate the cytoplasmic membrane potential was investigated using the fluorescence probe 3,3'-dipropylthiadicarbocyanine iodide. These results suggested that compound 4 damages cells by causing the loss of the proton motive force and disruption of the cellular integrity of the membrane, leading to cell death. In addition, it was shown that the antibacterial activity of a lignan was closely related to its absolute configuration and functional groups. PMID:17341839

Maruyama, Masafumi; Yamauchi, Satoshi; Akiyama, Koichi; Sugahara, Takuya; Kishida, Taro; Koba, Yojiro

2007-03-01

108

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

PubMed

The distribution of pharmaceutically active compounds in the environment has been reported in several works in which wastewater treatment plants have been identified as the main source of these compounds to the environment. The concentrations of these compounds in influent wastewater can vary widely not only during the day but also along the year, because of the seasonal-consumption patterns of some pharmaceuticals. However, only few studies have attempted to assess the hourly variability of the concentrations of pharmaceutically active compounds in wastewater. In this work, the distribution and seasonal and hourly variability of twenty-one pharmaceuticals, belonging to seven therapeutic groups, have been investigated in urban and industrial wastewater. The highest concentrations of pharmaceutically active compounds, except salicylic acid, were found in urban wastewater, especially in the case of anti-inflammatory drugs and caffeine. The highest concentrations of salicylic acid were measured in industrial wastewater, reaching concentration levels up to 3295?gL(-)(1). The studied pharmaceutically active compounds showed different distribution patterns during winter and summer periods. Temporal variability of pharmaceutically active compounds during a 24-h period showed a distribution in concordance with their consumption and excretion patterns, in the case of urban wastewater, and with the schedule of industrial activities, in the case of industrial wastewater. PMID:24997902

Camacho-Muńoz, Dolores; Martín, Julia; Santos, Juan Luis; Aparicio, Irene; Alonso, Esteban

2014-09-01

109

Target Fishing for Chemical Compounds using Target-Ligand Activity data and Ranking based Methods  

PubMed Central

In recent years the development of computational techniques that identify all the likely targets for a given chemical compound, also termed as the problem of Target Fishing, has been an active area of research. Identification of likely targets of a chemical compound helps to understand problems such as toxicity, lack of efficacy in humans, and poor physical properties associated with that compound in the early stages of drug discovery. In this paper we present a set of techniques whose goal is to rank or prioritize targets in the context of a given chemical compound such that most targets that this compound may show activity against appear higher in the ranked list. These methods are based on our extensions to the SVM and Ranking Perceptron algorithms for this problem. Our extensive experimental study shows that the methods developed in this work outperform previous approaches by 2% to 60% under different evaluation criterions.

Wale, Nikil; Karypis, George

2009-01-01

110

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

Microsoft Academic Search

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

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

2010-01-01

111

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

112

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

113

Vanadium compounds. Their action on alkaline phosphatase activity.  

PubMed

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

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

1994-06-01

114

Antimicrobial Activity of Extractable Conifer Heartwood Compounds Toward Phytophthora ramorum  

Microsoft Academic Search

Ethyl acetate extracts from heartwood of seven western conifer trees and individual volatile compounds in the extracts were\\u000a tested for antimicrobial activity against Phytophthora ramorum. Extracts from incense and western redcedar exhibited the strongest activity, followed by yellow-cedar, western juniper,\\u000a and Port-Orford-cedar with moderate activity, and no activity for Douglas-fir and redwood extracts. Chemical composition of\\u000a the extracts varied both

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

2007-01-01

115

Potential therapeutic effects of functionally active compounds isolated from garlic.  

PubMed

The medicinal properties of functionally active organosulfur compounds such as allin, diallyl disulfide, S-allylmercaptocysteine, and S-trityl-L-cysteine isolated from garlic have received great attention from a large number of investigators who have studied their pharmacological effects for the treatment of various diseases. These organosulfur compounds are able to prevent for development of cancer, cardiovascular, neurological, and liver diseases as well as allergy and arthritis. There have been also many reports on toxicities and pharmacokinetics of these compounds. The aim of this study is to review a variety of experimental and clinical reports, and describe the effectiveness, toxicities and pharmacokinetics, and possible mechanisms of pharmaceutical actions of functionally active compounds isolated from garlic. PMID:24333688

Yun, Hyung-Mun; Ban, Jung Ok; Park, Kyung-Ran; Lee, Chong Kil; Jeong, Heon-Sang; Han, Sang Bae; Hong, Jin Tae

2014-05-01

116

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

EPA Science Inventory

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

117

Dose–Response Assessment Strategies for Endocrine-Active Compounds  

Microsoft Academic Search

Hazard identification provides evidence for the potential of compounds to cause effects in exposed people. Dose–response assessments define the range of exposure conditions associated with minimal risks of adverse effects. With endocrine-active compounds (EACs), the vast majority of resources are presently being applied to hazard identification. In the past, dose–response assessments have been based on empirical analysis of these relationships.

Hugh A. Barton; Melvin E. Andersen

1997-01-01

118

Cytotoxic activity of new phenolic compounds from Vietnamese Caesalpinia sappan.  

PubMed

Two new phenolic compounds, caesalpiniaphenols G-H (1 and 2), were isolated from Vietnamese Caesalpinia sappan heartwood. The chemical structures were established mainly by extensive spectroscopic studies and chemical evidence. Compounds 1 and 2 showed potent inhibitory activity against HL-60 cancer cell lines with respective IC50 values of 16.7 and 22.5 µg/mL. Treating HL-60 cells with various concentrations of 1 resulted in growth inhibition and the induction of apoptosis. PMID:24317049

Hung, Tran Manh; Hai, Nguyen Xuan; Nhan, Nguyen Trung; Quang, Ton That; Quan, Tran Le; Cuong, To Dao; Dang, Nguyen Hai; Dat, Nguyen Tien

2013-01-01

119

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

PubMed

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

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

2003-08-01

120

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

PubMed Central

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

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

2007-01-01

121

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

PubMed

The nematicidal activity of two cassia, Cinnamomum cassia, oils (Especial and true), four cinnamon, Cinnamomum zey-lanicum, oils (technical, #500, bark and green leaf), and their compounds (e.g., trans-cinnamaldehyde and trans-cinnamic acid) toward adult Bursaphelenchus xylophilus was examined by a direct contact bioassay. Results were compared with those of 34 related compounds. As judged by 24-hour LC(50) values, two cassia oils (0.084-0.085 mg/ml) and four cinnamon oils (0.064-0.113 mg/ml) were toxic toward adult B. xylophilus. Of 45 test compounds, trans-cinnamaldehyde (0.061 mg/ml) was the most active nematicide, followed by ethyl cinnamate, alpha-methyl-trans-cinnamaldehyde, methyl cinnamate and allyl cinnamate (0.114-0.195 mg/ml). Potent nematicidal activity was also observed with 4-methoxycinnamonitrile, trans-4-methoxycinnamaldehyde, trans-2-methoxy-cinnamaldehyde, ethyl alpha-cyanocinnamate, cinnamonitrile and cinnamyl bromide (0.224-0.502 mg/ml). Structure-activity relationships indicate that structural characteristics, such as types of functional groups, saturation and carbon skeleton, appear to play a role in determining the toxicities to adult B. xylophilus. Cassia and cinnamon oils and test compounds described merit further study as potential nematicides or leads for the control of pine wilt disease caused by B. xylophilus. PMID:19259472

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

2007-03-01

122

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

2012-12-01

123

Biological Activities of Phenolic Compounds Present in Virgin Olive Oil  

PubMed Central

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

Cicerale, Sara; Lucas, Lisa; Keast, Russell

2010-01-01

124

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

125

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

126

A yeast chemical genetics approach identifies the compound 3,4,5-trimethoxybenzyl isothiocyanate as a calcineurin inhibitor.  

PubMed

The phosphatase enzyme calcineurin controls gene expression in a variety of biological contexts however few potent inhibitors are currently available. A screen of 360 plant extracts for inhibition of calcineurin-dependent gene expression in the model organism Saccharomyces cerevisiae identified the compound 3,4,5-trimethoxybenzyl isothiocyanate as an inhibitor. The compound was subsequently shown to inhibit human calcineurin via a mixed inhibition mechanism. To gain further mechanistic insight a yeast haploinsufficiency screen of 1152 deletion strains was carried out using a novel liquid medium screening method. The resulting haploinsufficiency profile is similar to that reported for the known calcineurin inhibitor FK506. PMID:24374339

Prescott, Thomas A K; Panaretou, Barry; Veitch, Nigel C; Simmonds, Monique S J

2014-01-31

127

Trypanothione Reductase High-Throughput Screening Campaign Identifies Novel Classes of Inhibitors with Antiparasitic Activity ? †  

PubMed Central

High-throughput screening of 100,000 lead-like compounds led to the identification of nine novel chemical classes of trypanothione reductase (TR) inhibitors worthy of further investigation. Hits from five of these chemical classes have been developed further through different combinations of preliminary structure-activity relationship rate probing and assessment of antiparasitic activity, cytotoxicity, and chemical and in vitro metabolic properties. This has led to the identification of novel TR inhibitor chemotypes that are drug-like and display antiparasitic activity. For one class, a series of analogues have displayed a correlation between TR inhibition and antiparasitic activity. This paper explores the process of identifying, investigating, and evaluating a series of hits from a high-throughput screening campaign.

Holloway, Georgina A.; Charman, William N.; Fairlamb, Alan H.; Brun, Reto; Kaiser, Marcel; Kostewicz, Edmund; Novello, Patrizia M.; Parisot, John P.; Richardson, John; Street, Ian P.; Watson, Keith G.; Baell, Jonathan B.

2009-01-01

128

Anti-Human Rhinoviral Activity of Polybromocatechol Compounds Isolated from the Rhodophyta, Neorhodomela aculeata  

PubMed Central

An extract of the red alga, Neorhodomela aculeata, exhibited antiviral activity against human rhinoviruses. Bioassay-guided purification was performed to yield six compounds, which were subsequently identified as lanosol (1) and five polybromocatechols (2–6) by spectroscopic methods, including 1D and 2D NMR and mass spectrometric analyses. Structurally, all of these compounds, except compound 5, contain one or two 2,3-dibromo-4,5-dihydroxyphenyl moieties. In a biological activity assay, compound 1 was found to possess antiviral activity with a 50% inhibitory concentration (IC50) of 2.50 ?g/mL against HRV2. Compound 3 showed anti-HRV2 activity, with an IC50 of 7.11 ?g/mL, and anti-HRV3 activity, with an IC50 of 4.69 ?g/mL, without demonstrable cytotoxicity at a concentration of 20 ?g/mL. Collectively, the results suggest that compounds 1 and 3 are candidates for novel therapeutics against two different groups of human rhinovirus.

Park, Soon-Hye; Song, Jae-Hyoung; Kim, Taejung; Shin, Woon-Seob; Park, Gab Man; Lee, Seokjoon; Kim, Young-Joo; Choi, Pilju; Kim, Heejin; Kim, Hui-Seong; Kwon, Dur-Han; Choi, Hwa Jung; Ham, Jungyeob

2012-01-01

129

Effect of vanadium compounds on acid phosphatase activity.  

PubMed

The direct effect of different vanadium compounds on acid phosphatase (ACP) activity was investigated. Vanadate and vanadyl but not pervanadate inhibited the wheat germ ACP activity. These vanadium derivatives did not alter the fibroblast Swiss 3T3 soluble fraction ACP activity. Using inhibitors of tyrosine phosphatases (PTPases), the wheat germ ACP was partially characterized as a PTPase. This study suggests that the inhibitory ability of different vanadium derivatives to modulate ACP activity seems to depend on the geometry around the vanadium atom more than on the oxidation state. Our results indicate a correlation between the PTPase activity and the sensitivity to vanadate and vanadyl cation. PMID:8862747

Vescina, C M; Sálice, V C; Cortizo, A M; Etcheverry, S B

1996-01-01

130

IAP Binding Peptides and Assay for Identifying Compounds that Bind IAP.  

National Technical Information Service (NTIS)

The present invention relates to the field of drug design and development for prevention and treatment of cell proliferative disease. Specifically, the invention features an assay for identifying peptides and peptidomimetics for promoting apotosis in cell...

G. McLendon R. A. Kipp M. Case Y. Shi

2002-01-01

131

[Synthesis of pyronaridine related compounds and comparison of antimalarial activities].  

PubMed

The paper reports the synthesis of pyronaridine (I) related compounds II-V for exploring whether the antimalarial activity of pyronaridine is by virtue of a nitrogen atom at position 1 in the ring and a pair of pyrrolidinyl Mannich base side chains in its structure. The condensation of 2-methoxy-6,9-dichloroacridine or 4,7-dichloro-1,5-naphthyridine with 4-hydroxy-3,5-bis-(pyrrolidinyl-1'-methyl) aniline yielded the related compound II, 1-deazapyronaridine, or V, 5-azabispyroquine, respectively. 2-Methoxy-7,10-dichlorobenzo (b) 1,5-naphthyridine or 4,7-dichloro-1,5-naphthyridine was condensed with 4-diethylamino-1-methylbutylamine to obtain the related compound III, azacrin, or IV, 5-azachloroquine, respectively. The results of in vivo tests against Plasmodium berghei chloroquine-resistant ANKA strain, drug-sensitive P. berghei N line and drug-resistant P. yoelii nigeriensis line showed that all the related compounds II-V were less effective than pyronaridine (I). It suggests that the nitrogen atom at position 1 and pyrrolidinyl Mannich base side chains on the structure of pyronaridine play an important and indispensable role for antimalarial activity of pyronaridine. The pyrrolidinyl Mannich bases impart increased activity to the corresponding compounds. PMID:8285067

Chen, C; Zheng, X Y; Guo, H Z

1993-01-01

132

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

133

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

2013-01-01

134

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

PubMed Central

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

2013-01-01

135

A Ligand-Based Approach To Identify Quantitative Structure-Activity Relationships for the Androgen Receptor  

PubMed Central

We examined the three-dimensional quantitative structure–activity relationship (QSAR) of a group of endogenous and synthetic compounds for the androgen receptor (AR) using comparative molecular field analysis (CoMFA). The goal of these studies was to identify structural features necessary for high binding affinity and optimization of selective androgen receptor modulators (SARMs). A homology model of the AR was used as a scaffold to align six lead compounds that served as templates for alignment of the remaining 116 structures prior to CoMFA modeling. The conventional r2 and cross-validated q2 relating observed and predicted relative binding affinity (RBA) were 0.949 and 0.593, respectively. Comparison of predicted and observed RBA for a test set of 10 compounds resulted in an r2 of 0.954, demonstrating the excellent predictive ability of the model. These integrated homology modeling and CoMFA studies identified critical amino acids for SARM interactions and provided QSAR data as the basis for mechanistic studies of AR structure, function, and design of optimized SARMs.

Bohl, Casey E.; Chang, Cheng; Mohler, Michael L.; Chen, Jiyun; Miller, Duane D.; Swaan, Peter W.; Dalton, James T.

2007-01-01

136

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

137

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

PubMed

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. PMID:19995961

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

2010-01-01

138

An overview of NMR-based metabolomics to identify secondary plant compounds involved in host plant resistance.  

PubMed

Secondary metabolites provide a potential source for the generation of host plant resistance and development of biopesticides. This is especially important in view of the rapid and vast spread of agricultural and horticultural pests worldwide. Multiple pests control tactics in the framework of an integrated pest management (IPM) programme are necessary. One important strategy of IPM is the use of chemical host plant resistance. Up to now the study of chemical host plant resistance has, for technical reasons, been restricted to the identification of single compounds applying specific chemical analyses adapted to the compound in question. In biological processes however, usually more than one compound is involved. Metabolomics allows the simultaneous detection of a wide range of compounds, providing an immediate image of the metabolome of a plant. One of the most universally used metabolomic approaches comprises nuclear magnetic resonance spectroscopy (NMR). It has been NMR which has been applied as a proof of principle to show that metabolomics can constitute a major advancement in the study of host plant resistance. Here we give an overview on the application of NMR to identify candidate compounds for host plant resistance. We focus on host plant resistance to western flower thrips (Frankliniella occidentalis) which has been used as a model for different plant species. PMID:21765818

Leiss, Kirsten A; Choi, Young H; Verpoorte, Robert; Klinkhamer, Peter G L

2011-06-01

139

The synthesis and surface active properties of certain amphoteric compounds  

Microsoft Academic Search

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

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

1963-01-01

140

Antimicrobial activities of polyether compounds of dinoflagellate origins  

Microsoft Academic Search

Twelve polyether compounds originating from dinoflagellates were tested for growth-inhibiting activities againstAspergillus niger, Penicillium funiculosum, Candida rugosa, Escherichia coli, Bacillus megaterium andStaphylococcus aureus by a paper disc method. These polyethers represent six groups of different skeletons and originate from three species;Prorocentrum lima, Dinophysis fortii andGambierdiscus toxicus. Potent antifungal activities were observed with okadaic acid and its two congeners, desulfated yessotoxin,

Hiroshi Nagai; Masayuki Satake; Takeshi Yasumoto

1990-01-01

141

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

142

Exploring Compound Promiscuity Patterns and Multi-Target Activity Spaces  

PubMed Central

Compound promiscuity is rationalized as the specific interaction of a small molecule with multiple biological targets (as opposed to non-specific binding events) and represents the molecular basis of polypharmacology, an emerging theme in drug discovery and chemical biology. This concise review focuses on recent studies that have provided a detailed picture of the degree of promiscuity among different categories of small molecules. In addition, an exemplary computational approach is discussed that is designed to navigate multi-target activity spaces populated with various compounds.

Hu, Ye; Gupta-Ostermann, Disha; Bajorath, Jurgen

2014-01-01

143

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

PubMed Central

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

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

2012-01-01

144

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

145

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

2013-01-01

146

Electrochemical screening of biomembrane-active compounds in water.  

PubMed

Interactions of biomembrane-active compounds with phospholipid monolayers on microfabricated Pt/Hg electrodes in an on-line high throughput flow system are demonstrated by recording capacitance current peak changes as rapid cyclic voltammograms (RCV). Detection limits of the compounds' effects on the layer have been estimated from the data. Compounds studied include steroids, polycyclic aromatic hydrocarbons, tricyclic antidepressants and tricyclic phenothiazines. The results show that the extent and type of interaction depends on the-(a) presence and number of aromatic rings and substituents, (b) presence and composition of side chains and, (c) molecular shape. Interaction is only indirectly related to compound hydrophobicity. For a selection of tricyclic antidepressants and tricyclic phenothiazines the detection limit in water is related to their therapeutic normal threshold. The sensing assay has been tested in the presence of humic acid as a potential interferent and in a tap water matrix. The system can be applied to the screening of putative hazardous substances and pharmaceuticals allowing for early detection thereof in the water supply. The measurements are made in real time which means that potentially toxic compounds are detected rapidly within <10 min per assay. This technology will contribute greatly to environment safety and health. PMID:24528664

Mohamadi, Shahrzad; Tate, Daniel J; Vakurov, Alexander; Nelson, Andrew

2014-02-27

147

Novel curcumin- and emodin-related compounds identified by in silico 2D/3D conformer screening induce apoptosis in tumor cells  

PubMed Central

Background Inhibition of the COP9 signalosome (CSN) associated kinases CK2 and PKD by curcumin causes stabilization of the tumor suppressor p53. It has been shown that curcumin induces tumor cell death and apoptosis. Curcumin and emodin block the CSN-directed c-Jun signaling pathway, which results in diminished c-Jun steady state levels in HeLa cells. The aim of this work was to search for new CSN kinase inhibitors analogue to curcumin and emodin by means of an in silico screening method. Methods Here we present a novel method to identify efficient inhibitors of CSN-associated kinases. Using curcumin and emodin as lead structures an in silico screening with our in-house database containing more than 106 structures was carried out. Thirty-five compounds were identified and further evaluated by the Lipinski's rule-of-five. Two groups of compounds can be clearly discriminated according to their structures: the curcumin-group and the emodin-group. The compounds were evaluated in in vitro kinase assays and in cell culture experiments. Results The data revealed 3 compounds of the curcumin-group (e.g. piceatannol) and 4 of the emodin-group (e.g. anthrachinone) as potent inhibitors of CSN-associated kinases. Identified agents increased p53 levels and induced apoptosis in tumor cells as determined by annexin V-FITC binding, DNA fragmentation and caspase activity assays. Conclusion Our data demonstrate that the new in silico screening method is highly efficient for identifying potential anti-tumor drugs.

Fullbeck, Melanie; Huang, Xiaohua; Dumdey, Renate; Frommel, Cornelius; Dubiel, Wolfgang; Preissner, Robert

2005-01-01

148

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

PubMed Central

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.

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

2012-01-01

149

Degradation of volatile organic compounds with thermally activated persulfate oxidation  

Microsoft Academic Search

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

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

2005-01-01

150

Small-Molecule Activators of Insulin-Degrading Enzyme Discovered through High-Throughput Compound Screening  

PubMed Central

Background Hypocatabolism 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 Findings Based on the finding that ATP and other nucleotide polyphosphates modulate IDE activity at physiological concentrations, we conducted parallel high-throughput screening campaigns in the absence or presence of ATP and identified two compounds—designated Ia1 and Ia2—that significantly stimulate IDE proteolytic activity. Both compounds were found to interfere with the crosslinking of a photoaffinity ATP analogue to IDE, suggesting that they interact with a bona fide ATP-binding domain within IDE. Unexpectedly, we observed highly synergistic activation effects when the activity of Ia1 or Ia2 was tested in the presence of ATP, a finding that has implications for the mechanisms underlying ATP-mediated activation of IDE. Notably, Ia1 and Ia2 activated the degradation of A? by ?700% and ?400%, respectively, albeit only when A? was presented in a mixture also containing shorter substrates. Conclusions/Significance This study describes the first examples of synthetic small-molecule activators of IDE, showing that pharmacological activation of this important protease with drug-like compounds is achievable. These novel activators help to establish the putative ATP-binding domain as a key modulator of IDE proteolytic activity and offer new insights into the modulatory action of ATP. Several larger lessons abstracted from this screen will help inform the design of future screening campaigns and facilitate the eventual development of IDE activators with therapeutic utility.

Cabrol, Christelle; Huzarska, Malwina A.; Dinolfo, Christopher; Rodriguez, Maria C.; Reinstatler, Lael; Ni, Jake; Yeh, Li-An; Cuny, Gregory D.; Stein, Ross L.; Selkoe, Dennis J.; Leissring, Malcolm A.

2009-01-01

151

Antioxidant activity and phenolic compounds in selected herbs.  

PubMed

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

Zheng, W; Wang, S Y

2001-11-01

152

Antioxidant activity relationship of phenolic compounds in Hypericum perforatum L  

Microsoft Academic Search

Background  The St John's Wort (Hypericum perforatum; Clusiaceae) has been used in traditional and modern medicine for a long time due to its high content of biologically active\\u000a phenolics. The purpose of this work was to develop a method for their fractionation and identification, and to determine the\\u000a most active antioxidant compounds in plant extract.\\u000a \\u000a \\u000a \\u000a \\u000a Results  An LC-MS method which enables fast

Dejan Z Or?i?; Neda M Mimica-Duki?; Marina M Franciškovi?; Slobodan S Petrovi?; Emilija ? Jovin

2011-01-01

153

Orally active opioid compounds from a non-poppy source.  

PubMed

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

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

2013-06-27

154

Cholinergic activity of acetylenic imidazoles and related compounds.  

PubMed

A series of acetylenic imidazoles related to oxotremorine (1a) were prepared and evaluated as cholinergic agents with in vitro binding assays and in vivo pharmacological tests in mice. 1-[4-(1H-Imidazol-1-yl)-2-butynyl]-2-pyrrolidinone (1b) was a cholinergic agonist with one-half the potency of oxotremorine. Analogues of 1b with a 5- or 2-methyl substituent in the imidazole ring (compounds 1c and 1g) were cholinergic partial agonists. Analogues of 1b with a methyl substituent at the 5-position in the pyrrolidinone ring (7b) or at the alpha-position in the acetylenic chain (8b) were antagonists. Various analogues of these imidazole acetylenes where the pyrrolidinone ring was replaced by an amide, carbamate, or urea residue were prepared. Several compounds which contained 5-methylimidazole as the amine substituent were partial agonists. The activities of the imidazole compounds are compared with those of the related pyrrolidine and dimethylamine analogues. Agonist and antagonist conformations for these compounds at muscarinic receptors are proposed. PMID:1875333

Moon, M W; Chidester, C G; Heier, R F; Morris, J K; Collins, R J; Russell, R R; Francis, J W; Sage, G P; Sethy, V H

1991-08-01

155

Antibiofilm activity, compound characterization, and acute toxicity of extract from a novel bacterial species of paenibacillus.  

PubMed

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

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

2014-01-01

156

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

PubMed Central

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

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

2014-01-01

157

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

Microsoft Academic Search

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

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

2008-01-01

158

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

PubMed Central

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

2010-01-01

159

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

2011-09-01

160

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

2013-05-24

161

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

PubMed Central

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

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

2014-01-01

162

Flavor-active compounds potentially implicated in cooked cauliflower acceptance.  

PubMed

The aim of the present study was to determine the flavor-active compounds responsible for the "sulfur" and "bitter" flavors of cooked cauliflower potentially implicated in cauliflower rejection by consumers. Eleven varieties of cauliflower were cooked and assessed by a trained sensory panel for flavor profile determination. Among the 13 attributes, the varieties differed mainly according to their "cauliflower odor note" and their "bitterness". Various glucosinolates were quantified by HPLC and correlated with bitterness intensity. The results showed that neoglucobrassicin and sinigrin were responsible for the bitterness of cooked cauliflower. Application of Dynamic Headspace GC-Olfactometry and DH-GC-MS showed that allyl isothiocyanate (AITC), dimethyl trisulfide (DMTS), dimethyl sulfide (DMS), and methanethiol (MT) were the key odorants of cooked cauliflower "sulfur" odors. Moreover, these volatile compounds corresponded to the main compositional differences observed between varieties. Finally, AITC, DMTS, DMS, MT, sinigrin, and neoglucobrassicin were shown to be potential physicochemical determinants of cooked cauliflower acceptance. PMID:12381134

Engel, Erwan; Baty, Céline; Le Corre, Daniel; Souchon, Isabelle; Martin, Nathalie

2002-10-23

163

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

164

Screening for antiviral activities of isolated compounds from essential oils.  

PubMed

Essential oil of star anise as well as phenylpropanoids and sesquiterpenes, for example, trans-anethole, eugenol, ?-eudesmol, farnesol, ?-caryophyllene and ?-caryophyllene oxide, which are present in many essential oils, were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro. Antiviral activity was analyzed by plaque reduction assays and mode of antiviral action was determined by addition of the drugs to uninfected cells, to the virus prior to infection or to herpesvirus-infected cells. Star anise oil reduced viral infectivity by >99%, phenylpropanoids inhibited HSV infectivity by about 60-80% and sesquiterpenes suppressed herpes virus infection by 40-98%. Both, star anise essential oil and all isolated compounds exhibited anti-HSV-1 activity by direct inactivation of free virus particles in viral suspension assays. All tested drugs interacted in a dose-dependent manner with herpesvirus particles, thereby inactivating viral infectivity. Star anise oil, rich in trans-anethole, revealed a high selectivity index of 160 against HSV, whereas among the isolated compounds only ?-caryophyllene displayed a high selectivity index of 140. The presence of ?-caryophyllene in many essential oils might contribute strongly to their antiviral ability. These results indicate that phenylpropanoids and sesquiterpenes present in essential oils contribute to their antiviral activity against HSV. PMID:20008902

Astani, Akram; Reichling, Jürgen; Schnitzler, Paul

2011-01-01

165

MEG identifies dorsal medial brain activations during sleep.  

PubMed

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 in precuneus during light sleep (stages 1/2) and in the left dorso-medial prefrontal cortex (L-DMPFC) during deep sleep (stages 3/4). The L-DMPFC activated area expands laterally during rapid eye movement (REM) sleep, into a volume of about 5 cm(3) bounded by regions attributed to Theory of Mind (ToM) and default systems, both involved in introspection. Gamma band activity in this area was higher during REM sleep than other sleep stages and active wakefulness. There is a tantalizing correspondence between increased wide-band activity (dominated by low frequencies) in early non-REM (NREM) sleep stages and increases in gamma-band activity in late NREM and REM periods that we attribute to a lateral disinhibition mechanism. The results provide a description of regional electrophysiological changes in awake state, light and deep sleep, and REM sleep. These changes are most pronounced in the L-DMPFC and the other areas around the dorsal midline that are close to, but do not overlap with areas of the default and ToM systems, suggesting that the DMPFC, particularly in the left hemisphere, plays an important role in late NREM stages, in REM and possibly in dreaming. PMID:18950718

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

2009-01-15

166

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

PubMed

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

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

2003-09-01

167

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

168

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

PubMed Central

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

2014-01-01

169

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

170

Antiestrogenic Activity of Hydroxylated Polychlorinated Biphenyl Congeners Identified in Human Serum  

Microsoft Academic Search

Several hydroxylated polychlorinated biphenyls (PCBs) identified in human serum have been synthesized and these include 2,2?,3,4?,5,5?-hexachloro-4-biphenylol; 2,3,3?,4?,5-pentachloro-4-biphenylol; 2?,3,3?,4?,5-pentachloro-4-biphenylol; 2,2?,3,3?,4?,5-hexachloro-4-biphenylol; 2,2?,3,3?,4?,5,5?-heptachloro-4-biphenylol; 2,2?,3,4?,5,5?,6-heptachloro-4-biphenylol; and 2,2?,3?,4,4?,5,5?-heptachloro-3-biphenylol. The hydroxy-PCBs exhibited minimal binding to the rat uterine cytosolic estrogen receptor (ER) and did not induce proliferation of estrogen-responsive MCF-7 human breast cancer cells at concentrations ranging from 10?5to 10?8m. The estrogenic activity of these compounds

M. Moore; M. Mustain; K. Daniel; I. Chen; S. Safe; T. Zacharewski; B. Gillesby; A. Joyeux; P. Balaguer

1997-01-01

171

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

2010-03-01

172

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

2011-08-01

173

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

PubMed

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

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

2007-12-01

174

Aminobenzoic Acid Compounds as HOCl Traps for Activated Neutrophils  

Microsoft Academic Search

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

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

1997-01-01

175

Laccase Catalyzed Synthesis of Iodinated Phenolic Compounds with Antifungal Activity  

PubMed Central

Iodine is a well known antimicrobial compound. Laccase, an oxidoreductase which couples the one electron oxidation of diverse phenolic and non-phenolic substrates to the reduction of oxygen to water, is capable of oxidizing unreactive iodide to reactive iodine. We have shown previously that laccase-iodide treatment of spruce wood results in a wash-out resistant antimicrobial surface. In this study, we investigated whether phenolic compounds such as vanillin, which resembles sub-structures of softwood lignin, can be directly iodinated by reacting with laccase and iodide, resulting in compounds with antifungal activity. HPLC-MS analysis showed that vanillin was converted to iodovanillin by laccase catalysis at an excess of potassium iodide. No conversion of vanillin occurred in the absence of enzyme. The addition of redox mediators in catalytic concentrations increased the rate of iodide oxidation ten-fold and the yield of iodovanillin by 50%. Iodinated phenolic products were also detected when o-vanillin, ethyl vanillin, acetovanillone and methyl vanillate were incubated with laccase and iodide. At an increased educt concentration of 0.1 M an almost one to one molar ratio of iodide to vanillin could be used without compromising conversion rate, and the insoluble iodovanillin product could be recovered by simple centrifugation. The novel enzymatic synthesis procedure fulfills key criteria of green chemistry. Biocatalytically produced iodovanillin and iodo-ethyl vanillin had significant growth inhibitory effects on several wood degrading fungal species. For Trametes versicolor, a species causing white rot of wood, almost complete growth inhibition and a partial biocidal effect was observed on agar plates. Enzymatic tests indicated that the iodinated compounds acted as enzyme responsive, antimicrobial materials.

Ihssen, Julian; Schubert, Mark; Thony-Meyer, Linda; Richter, Michael

2014-01-01

176

Laccase catalyzed synthesis of iodinated phenolic compounds with antifungal activity.  

PubMed

Iodine is a well known antimicrobial compound. Laccase, an oxidoreductase which couples the one electron oxidation of diverse phenolic and non-phenolic substrates to the reduction of oxygen to water, is capable of oxidizing unreactive iodide to reactive iodine. We have shown previously that laccase-iodide treatment of spruce wood results in a wash-out resistant antimicrobial surface. In this study, we investigated whether phenolic compounds such as vanillin, which resembles sub-structures of softwood lignin, can be directly iodinated by reacting with laccase and iodide, resulting in compounds with antifungal activity. HPLC-MS analysis showed that vanillin was converted to iodovanillin by laccase catalysis at an excess of potassium iodide. No conversion of vanillin occurred in the absence of enzyme. The addition of redox mediators in catalytic concentrations increased the rate of iodide oxidation ten-fold and the yield of iodovanillin by 50%. Iodinated phenolic products were also detected when o-vanillin, ethyl vanillin, acetovanillone and methyl vanillate were incubated with laccase and iodide. At an increased educt concentration of 0.1 M an almost one to one molar ratio of iodide to vanillin could be used without compromising conversion rate, and the insoluble iodovanillin product could be recovered by simple centrifugation. The novel enzymatic synthesis procedure fulfills key criteria of green chemistry. Biocatalytically produced iodovanillin and iodo-ethyl vanillin had significant growth inhibitory effects on several wood degrading fungal species. For Trametes versicolor, a species causing white rot of wood, almost complete growth inhibition and a partial biocidal effect was observed on agar plates. Enzymatic tests indicated that the iodinated compounds acted as enzyme responsive, antimicrobial materials. PMID:24594755

Ihssen, Julian; Schubert, Mark; Thöny-Meyer, Linda; Richter, Michael

2014-01-01

177

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

PubMed

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

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

2014-04-01

178

Activation of the TCR complex by small chemical compounds.  

PubMed

Small chemical compounds and certain metal ions can activate T cells, resulting in drug hypersensitivity reactions that are a main problem in pharmacology. Mostly, the drugs generate new antigenic epitopes on peptide-major histocompatibility complex (MHC) molecules that are recognized by the T-cell antigen receptor (TCR). In this review we discuss the molecular mechanisms of how the drugs alter self-peptide-MHC, so that neo-antigens are produced. This includes (1) haptens covalently bound to peptides presented by MHC, (2) metal ions and drugs that non-covalently bridge self-pMHC to the TCR, and (3) drugs that allow self-peptides to be presented by MHCs that otherwise are not presented. We also briefly discuss how a second signal-next to the TCR-that naďve T cells require to become activated is generated in the drug hypersensitivity reactions. PMID:24214616

Louis-Dit-Sully, Christine; Schamel, Wolfgang W A

2014-01-01

179

Characterisation of the most odour-active compounds of bone tainted dry-cured Iberian ham.  

PubMed

The most odour-active compounds of different bone tainted dry-cured Iberian hams were researched using the detection frequency method. Most of the odourants identified were found in all the Iberian hams (spoiled and unspoiled). Some compounds (ethyl butanoate, dimethyl disulfide, phenylacetaldehyde, acetic, propanoic, butanoic, 3-methylbutanoic and pentanoic acids) were identified in the spoiled hams as Iberian ham odourants for the first time. The detection frequency (DF) values for the spoiled and the unspoiled hams were markedly different. The main differences were found for 2-methylpropanal, ethyl-2-methylpropanoate, ethyl-2-methylbutanoate, phenylacetaldehyde and methional (the lowest DF values were found in the unspoiled ham) and hexanal (the largest DF value was found in the unspoiled ham). Spoiled hams with a different global odour had different DF values. PMID:20374864

Carrapiso, Ana I; Martín, Lourdes; Jurado, Angela; García, Carmen

2010-05-01

180

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

181

Prediction of individual compounds forming activity cliffs using emerging chemical patterns.  

PubMed

Activity cliffs are formed by structurally similar or analogous compounds having large potency differences. In medicinal chemistry, pairs or groups of compounds forming activity cliffs are of interest for structure-activity relationship (SAR) analysis and compound optimization. Thus far, activity cliff assessment has mostly been descriptive, i.e., compound data sets and activity landscape representations have been searched for activity cliffs in the context of SAR analysis. Only recently, first attempts have also been made to depart from descriptive analysis and predict activity cliffs. This has been done by building computational models that distinguish compound pairs forming activity cliffs from non-cliff pairs. However, it is principally more challenging to predict single compounds that participate in activity cliffs. Here, we show that individual compounds having high or low potency can be accurately predicted to form activity cliffs on the basis of emerging chemical patterns. PMID:24304008

Namasivayam, Vigneshwaran; Iyer, Preeti; Bajorath, Jürgen

2013-12-23

182

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

PubMed

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

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

2013-12-01

183

Identifying active methane-oxidizers in thawed Arctic permafrost by proteomics  

NASA Astrophysics Data System (ADS)

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

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

2012-12-01

184

Anti-leishmanial activities of extracts and isolated compounds from Drechslera rostrata and Eurotium tonpholium.  

PubMed

The fungal extract of Drechslera rostrata and Eurotium tonpholium showed a significant anti-leishmanial activity against Leishmania major; IC50 was 28.8 and 28.2??g/mL, respectively. Seven compounds, five from D. rostrata (H1-H5) and two from E. tonpholium (H6 and H7), were isolated and identified using different spectroscopic analysis including (1) HNMR, (13) CNMR, Hetero-nuclear multiple bond connectivity (HMBC), Hetero-nuclear Multiple Quantum Correlation (HMQC), and EI-MS. The isolated compounds are: di-2-ethylhexyl phthalate (1), (22E)-5?,8?-epidioxyergosta-6,22-diene-3?-ol (2),1,3,8-trihydroxy-6-methyl-nthraquinone (3), aloe-emodine 8-O-glucopyranoside(4), 2R, 3R,4R,5R hexane 1, 2, 3, 4, 5, 6 hexole (Mannitol) (5), 1,8-dihydroxy-3-methoxy-6-methyl-anthraquinone (6) and 1, 4, 5-trihydroxy-7-methoxy-2-methyl-anthraquinone (7). However, compounds (1) and (6) showed activity against L. major with IC50 of 3.2 and 10.38?µg/mL, respectively. On the other hand, oral administration of the two extracts (100?mg/kg) and compounds 1 and 6 (50?mg/kg) showed very good activity when compared with the anti-leishmanial drug Pentostam (125?mg/kg). Interestingly, the complete heeling activity of the extracts and compounds (1) and (6) was obtained after 13-17?days of treatment, while complete healing activity of Pentostam was obtained after 28?days. No alteration on liver and kidney functions was recorded on animals treated with the two extracts for 15 consecutive days. PMID:24375822

Awaad, Amani S; Al-Zaylaee, Haifa M; Alqasoumi, Saleh I; Zain, Mohamed E; Aloyan, Ebtesam M; Alafeefy, Ahmed M; Awad, Elham S H; El-Meligy, Reham M

2014-05-01

185

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

186

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

PubMed

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

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

2006-11-01

187

Development of a QPatch automated electrophysiology assay for identifying KCa3.1 inhibitors and activators.  

PubMed

The intermediate-conductance Ca(2+)-activated K(+) channel KCa3.1 (also known as KCNN4, IK1, or the Gárdos channel) plays an important role in the activation of T and B cells, mast cells, macrophages, and microglia by regulating membrane potential, cellular volume, and calcium signaling. KCa3.1 is further involved in the proliferation of dedifferentiated vascular smooth muscle cells and fibroblast and endothelium-derived hyperpolarization responses in the vascular endothelium. Accordingly, KCa3.1 inhibitors are therapeutically interesting as immunosuppressants and for the treatment of a wide range of fibroproliferative disorders, whereas KCa3.1 activators constitute a potential new class of endothelial function preserving antihypertensives. Here, we report the development of QPatch assays for both KCa3.1 inhibitors and activators. During assay optimization, the Ca(2+) sensitivity of KCa3.1 was studied using varying intracellular Ca(2+) concentrations. A free Ca(2+) concentration of 1??M was chosen to optimally test inhibitors. To identify activators, which generally act as positive gating modulators, a lower Ca(2+) concentration (?200?nM) was used. The QPatch results were benchmarked against manual patch-clamp electrophysiology by determining the potency of several commonly used KCa3.1 inhibitors (TRAM-34, NS6180, ChTX) and activators (EBIO, riluzole, SKA-31). Collectively, our results demonstrate that the QPatch provides a comparable but much faster approach to study compound interactions with KCa3.1 channels in a robust and reliable assay. PMID:24351043

Jenkins, David Paul; Yu, Weifeng; Brown, Brandon M; Lřjkner, Lars Damgaard; Wulff, Heike

2013-01-01

188

Exome Sequencing Identifies Compound Heterozygous Mutations in CYP4V2 in a Pedigree with Retinitis Pigmentosa  

PubMed Central

Retinitis pigmentosa (RP) is a heterogeneous group of progressive retinal degenerations characterized by pigmentation and atrophy in the mid-periphery of the retina. Twenty two subjects from a four-generation Chinese family with RP and thin cornea, congenital cataract and high myopia is reported in this study. All family members underwent complete ophthalmologic examinations. Patients of the family presented with bone spicule-shaped pigment deposits in retina, retinal vascular attenuation, retinal and choroidal dystrophy, as well as punctate opacity of the lens, reduced cornea thickness and high myopia. Peripheral venous blood was obtained from all patients and their family members for genetic analysis. After mutation analysis in a few known RP candidate genes, exome sequencing was used to analyze the exomes of 3 patients III2, III4, III6 and the unaffected mother II2. A total of 34,693 variations shared by 3 patients were subjected to several filtering steps against existing variation databases. Identified variations were verified in the rest family members by PCR and Sanger sequencing. Compound heterozygous c.802-8_810del17insGC and c.1091-2A>G mutations of the CYP4V2 gene, known as genetic defects for Bietti crystalline corneoretinal dystrophy, were identified as causative mutations for RP of this family.

Yang, Qiaona; Yu, Wenhan; Yan, Naihong; Zhou, Xiaomin; Fu, Jin; Guo, Xinwu; Han, Pengfei; Wang, Jun; Liu, Xuyang

2012-01-01

189

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

PubMed Central

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

Weidner, Stanislaw; Powalka, Anna; Karamac, Magdalena; Amarowicz, Ryszard

2012-01-01

190

Estradiol-antagonistic activity of phenolic compounds from leguminous plants.  

PubMed

Natural flavonoids are currently receiving much attention because of their estrogenic and antiestrogenic properties. Six isoflavones (isoprunetin, isoprunetin 7-O-beta-D-glucopyranoside, isoprunetin 4',7-di-O-beta-D-glucopyranoside, genistein, genistein 7-O-beta-D-glucopyranoside, daidzein), four flavones (luteolin, luteolin 7-O-beta-D-glucopyranoside, luteolin 4'-O-beta-D-glucopyranoside, licoflavone C), isolated from Genista morisii and G. ephedroides (two Leguminosae plants of the Mediterranean area) together with two structurally related pterocarpans, bitucarpin A and erybraedyn C, isolated from Bituminaria bituminosa (Leguminosae), were tested for the antagonist activity by a yeast based estrogen receptor assay (Saccharomyces cerevisiae RMY326 ER-ERE). Most compounds inhibited the estradiol-induced transcriptional activity in a concentration dependent manner. In particular, for the flavone luteolin 77% inhibition of the induced beta-galactosidase activity was observed. Interestingly, licoflavone C exhibited a dose-dependent antagonistic activity at concentrations up to 10(-4) M, but stimulated beta-galactosidase expression at higher concentrations resulting in a U-shaped-like dose-response curve. PMID:18167044

Pinto, B; Bertoli, A; Noccioli, C; Garritano, S; Reali, D; Pistelli, L

2008-03-01

191

Identification of polycyclic aromatic compounds containing two heteroatoms in coal liquids and shale oils. Technical progress report, March 1, 1983-October 31, 1985. [More tran 200 compounds identified and synthesized; ring structure given  

SciTech Connect

The methodology has been developed for isolating and identifying components of five new classes of PAC in coal liquids. The methods have been applied to one coal liquid (and a coal tar for comparison). The major contributions of this work to DOE health and environmental science issues are as follows: (a) A superior sulfur heterocycle isolation method, based on ligand exchange chromatography, has been developed. (b) Methods have been developed using adsorption chromatography and gas chromatographic selective detection to isolate, detect, identify, and quantify the amino sulfur heterocycles, the amino nitrogen heterocycles, the hydroxy sulfur heterocycles, the hydroxy nitrogen heterocycles, and the azathiophenic compounds in coal-derived materials. (c) A large number of standard reference compounds have been synthesized. (d) Two new gas chromatographic stationary phases have been applied to the resolution of these isomeric PAC. (e) The aminodibenzothiophenes have been found to possess significant mutagenic activity in the Ames Assay. (f) A fractionation method for PAC based on the number of aromatic rings using supercritical carbon dioxide has been developed. Recommendations for future work in this area are given. 68 refs.

Lee, M.L.; Castle, R.N.

1985-01-01

192

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

193

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

194

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

EPA Science Inventory

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

195

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

PubMed

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

Bankova, Vassya; Popova, Milena; Trusheva, Boryana

2014-01-01

196

Wogonin, an active compound in Scutellaria baicalensis, induces apoptosis and reduces telomerase activity in the HL-60 leukemia cells.  

PubMed

Crude extract of Scutellaria baicalensis (S. baicalensis) has cytotoxic effect on human myelogenous leukemia cells (HL-60). We invesigated which compound from the crude extract is responsible for the cytotoxic effect on HL-60 cells. We identified 29 compounds from the crude extract using high performance liquid chromatography mass spectrometry (HPLC/MS). Two of the compounds, baicalin and wogonoside, are converted to baicalein and wogonin, respectively, after treatment with beta-glucuronidase. We observed a dose-dependent reduction in cell viability when cells with either wogonin or aqueous extract of S. baicalensis. Several of the apoptotic features including deoxyribonucleic acid (DNA) fragmentation and increased caspase-3 activity were found in cells treated with wogonin and aqueous extract. The changes were associated with down-regulation of Bcl-2, and not Bax. Furthermore, treatment of HL-60 cells with wogonin or S. baicalensis led to the inhibition of human telomerase reverse transcriptase (hTERT), human telomerase-associated protein 1 (hTP1) and c-myc messenger ribonucleic acid (m-RNA) expression. Wogonin and S. baicaleisis down-regulated the telomerase activity. Our findings suggest that wogonin may be the major compound in S. baicalensis responsible for HL-60 growth inhibition in vitro. The inhibition of HL-60 cell growth is mediated partly through the induction of Bax/Bcl-2 apoptosis and by telomerase inhibition through suppression of c-myc, which is a promoter of hTERT. PMID:19577445

Huang, Sheng-Teng; Wang, Chen-Yu; Yang, Rong-Chi; Chu, Chih-Ju; Wu, Hsiao-Ting; Pang, Jong-Hwei S

2010-01-01

197

Use of natural chrysanthone compounds having antiangiogenic activity  

US Patent & Trademark Office Database

A series of compounds of natural origin are described, as useful agents for the treatment of diseases characterised by abnormal angiogenesis. These compounds are: chrysanthone A having formula (I); chrysanthone B having formula (II); and chrysanthone C having formula (III).

2005-05-03

198

Antitumor Platinum Compounds: Synthesis, Structure and Biological Activity.  

National Technical Information Service (NTIS)

Contents: General introduction--(Survey of the development of platinum coordination compounds in the chemotherapy of cancer; and introduction to the work described in this thesis.); Synthesis and characterization of platinum and palladium compounds with n...

C. G. van Kralingen

1979-01-01

199

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

2008-04-01

200

Development of a screen to identify selective small molecules active against patient-derived metastatic and chemoresistant breast cancer cells  

PubMed Central

Introduction High failure rates of new investigational drugs have impaired the development of breast cancer therapies. One challenge is that excellent activity in preclinical models, such as established cancer cell lines, does not always translate into improved clinical outcomes for patients. New preclinical models, which better replicate clinically-relevant attributes of cancer, such as chemoresistance, metastasis and cellular heterogeneity, may identify novel anti-cancer mechanisms and increase the success of drug development. Methods Metastatic breast cancer cells were obtained from pleural effusions of consented patients whose disease had progressed. Normal primary human breast cells were collected from a reduction mammoplasty and immortalized with human telomerase. The patient-derived cells were characterized to determine their cellular heterogeneity and proliferation rate by flow cytometry, while dose response curves were performed for chemotherapies to assess resistance. A screen was developed to measure the differential activity of small molecules on the growth and survival of patient-derived normal breast and metastatic, chemoresistant tumor cells to identify selective anti-cancer compounds. Several hits were identified and validated in dose response assays. One compound, C-6, was further characterized for its effect on cell cycle and cell death in cancer cells. Results Patient-derived cells were found to be more heterogeneous, with reduced proliferation rates and enhanced resistance to chemotherapy compared to established cell lines. A screen was subsequently developed that utilized both tumor and normal patient-derived cells. Several compounds were identified, which selectively targeted tumor cells, but not normal cells. Compound C-6 was found to inhibit proliferation and induce cell death in tumor cells via a caspase-independent mechanism. Conclusions Short-term culture of patient-derived cells retained more clinically relevant features of breast cancer compared to established cell lines. The low proliferation rate and chemoresistance make patient-derived cells an excellent tool in preclinical drug development.

2013-01-01

201

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

PubMed

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

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

2014-12-15

202

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

PubMed

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

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

2011-08-01

203

Pomegranate Fruit as a Rich Source of Biologically Active Compounds  

PubMed Central

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

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

2014-01-01

204

Formation of activity cliffs is accompanied by systematic increases in ligand efficiency from lowly to highly potent compounds.  

PubMed

Activity cliffs (ACs) are defined as pairs of structurally similar compounds sharing the same biological activity but having a large difference in potency. Therefore, ACs are often studied to rationalize structure-activity relationships (SARs) and aid in lead optimization. Hence, the AC concept plays an important role in compound development. For compound optimization, ligand efficiency (LE) represents another key concept. LE accounts for the relation between compound potency and mass. A major goal of lead optimization is to increase potency and also LE. Despite their high relevance for drug development, the AC and LE concepts have thus far not been considered in combination. It is currently unknown how compounds forming ACs might be related in terms of LE. To explore this question, ACs were systematically identified on the basis of high-confidence activity data and LE values for cliff partners were determined. Surprisingly, a significant increase in LE was generally detected for highly potent cliff partners compared to their lowly potent counterparts, regardless of the compound classes and their targets. Hence, ACs reveal chemical modifications that determine SARs and improve LE. These findings further increase the attractiveness of AC information for compound optimization and development. PMID:24477941

de la Vega de León, Antonio; Bajorath, Jürgen

2014-03-01

205

Discovery and Preliminary Structure-Activity Relationship of Arylpiperazines as Novel, Brain-Penetrant Antiprion Compounds  

PubMed Central

Creutzfeldt-Jakob disease and kuru in humans, BSE in cattle, and scrapie in sheep are fatal neurodegenerative disorders. Such illnesses are caused by the conversion and accumulation of a misfolded pathogenic isoform (termed PrPSc) of a normally benign, host cellular protein, denoted PrPC. We employed high-throughput screening enzyme-linked immunosorbent assays to evaluate compounds for their ability to reduce the level of PrPSc in Rocky Mountain Laboratory prion-infected mouse neuroblastoma cells (ScN2a-cl3). Arylpiperazines were among the active compounds identified, but the initial hits suffered from low potency and poor drug-likeness. The best of those hits, such as 1, 7, 13, and 19, displayed moderate antiprion activity with EC50 values in the micromolar range. Key analogues were designed and synthesized on the basis of the structure–activity relationship, with analogues 41, 44, 46, and 47 found to have submicromolar potency. Analogues 41 and 44 were able to penetrate the blood–brain barrier and achieved excellent drug concentrations in the brains of mice after oral dosing. These compounds represent good starting points for further lead optimization in our pursuit of potential drug candidates for the treatment of prion diseases.

2013-01-01

206

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

207

Acaricidal Activity of Eugenol Based Compounds against Scabies Mites  

PubMed Central

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

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

2010-01-01

208

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

NASA Astrophysics Data System (ADS)

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

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

2008-12-01

209

Compound  

NASA Astrophysics Data System (ADS)

We have prepared Ce-doped polycrystalline AgSbTe2.01 compounds from high-purity elements by a melt-quench technique followed by spark plasma sintering, and their thermoelectric transport properties have been investigated in the temperature range of 300 K to 625 K. The actual concentration of Ce was much less than the initial composition, but roughly proportional to it. Small additions of Ce shifted the composition of the homogeneity range from the nearly ideal atomic ratio Ag:Sb:Te = 0.98:1.02:2.01 toward Sb rich (Ag poor), and led to the reemergence of Ag2Te impurity in AgSbTe2 compound. The Ce-doped samples possessed lower electrical conductivity compared with the undoped AgSbTe2.01 compound at room temperature, but the carrier mobility and effective mass were essentially constant, indicating intact band structure near the covalent band maximum upon Ce substitution for Sb. Due to the decrease of lattice vibration anharmonicity resulting from Ce substitution for Sb, the lattice conductivity of the Ce-doped samples was about 0.1 W m-1 K-1 higher than that of the AgSbTe2.01 sample, and the magnitude spanned the range from 0.30 W m-1 K-1 to 0.55 W m-1 K-1. A ZT of 1.20 was achieved at about 615 K for the AgSb0.99Ce0.01Te2.01 sample.

Du, B.; Li, H.; Tang, X.

2014-06-01

210

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

211

Plant- and Microbe-Derived Compounds Affect the Expression of Genes Encoding Antifungal Compounds in a Pseudomonad with Biocontrol Activity?  

PubMed Central

We have investigated the impacts of 63 different low-molecular-weight compounds, most of them plant derived, on the in vitro expression of two antifungal biosynthetic genes by the plant-protecting rhizobacterium Pseudomonas fluorescens CHA0. The majority of the compounds tested affected the expression of one or both antifungal genes. This suggests that biocontrol activity in plant-beneficial pseudomonads is modulated by plant-bacterium signaling.

de Werra, Patrice; Huser, Aurelie; Tabacchi, Raphael; Keel, Christoph; Maurhofer, Monika

2011-01-01

212

Recent studies on the chemistry and biological activities of the organosulfur compounds of garlic (allium sativum)  

Microsoft Academic Search

Garlic, Allium sativum, is known to contain a wide range of biologically active compounds. The organosulfur compounds are mainly the biologically active components of garlic. Many health benefits has been ascribed to them, possessing biological activities including antibacterial, antifungal, antiatherosclerotic, antihypertensive, lipid and cholesterol lowering effects, inhibition of carcinogenesis, enhancing the immune system and other biological activities. The chemistry of

A. Kamel; M. Saleh

2000-01-01

213

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

PubMed Central

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

Rudel, R

1997-01-01

214

Compound  

NASA Astrophysics Data System (ADS)

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

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

2014-06-01

215

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

PubMed

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

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

2015-01-01

216

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

PubMed Central

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

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

2014-01-01

217

The novel antibacterial compound walrycin A induces human PXR transcriptional activity  

PubMed Central

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

Berthier, Alexandre; Oger, Frederik; Gheeraert, Celine; Boulahtouf, Abdel; Le Guevel, Remy; Balaguer, Patrick; Staels, Bart; Salbert, Gilles; Lefebvre, Philippe

2012-01-01

218

Combining Cheminformatics Methods and Pathway Analysis To Identify Molecules With Whole-Cell Activity Against Mycobacterium tuberculosis  

PubMed Central

Purpose New strategies for developing inhibitors of Mycobacterium tuberculosis (Mtb) are required in order to identify the next generation of tuberculosis (TB) drugs. Our approach leverages the integration of intensive data mining and curation and computational approaches, including cheminformatics combined with bioinformatics, to suggest biological targets and their small molecule modulators. Knowledge of which biological targets are essential for Mtb viability, under a given set of in vitro or in vivo assay conditions, and absent in the human host is a crucial input. We draw on the mimicry of the associated “essential metabolites” to suggest small molecule inhibitors of the essential protein target. Empirical studies are then utilized to delineate the effect of the small molecule putative mimic on cultured Mtb growth. Methods We now describe a combined cheminformatics and bioinformatics approach that uses the TBCyc pathway and genome database, the Collaborative Drug Discovery database of molecules with activity against Mtb and their associated targets, a 3D pharmacophore approach and Bayesian models of TB activity in order to select pathways and metabolites and ultimately prioritize molecules that may be acting as metabolite mimics and exhibit activity against TB. Results In this study we combined the TB cheminformatics and pathways databases that enabled us to computationally search >80,000 vendor available molecules and ultimately test 23 compounds in vitro that resulted in two compounds (N-(2-furylmethyl)-N?-[(5-nitro-3-thienyl)carbonyl]thioureaand N-[(5-nitro-3-thienyl)carbonyl]-N?-(2-thienylmethyl)thiourea) proposed as mimics of D-fructose 1,6 bisphosphate, (MIC of 20 and 40?g/ml, respectively). Conclusion This is a simple yet novel approach that has the potential to identify inhibitors of bacterial growth as illustrated by compounds identified in this study that have activity against Mtb.

Sarker, Malabika; Talcott, Carolyn; Madrid, Peter; Chopra, Sidharth; Bunin, Barry A.; Lamichhane, Gyanu; Freundlich, Joel S.; Ekins, Sean

2013-01-01

219

Marine bacteria produce compounds that modulate multixenobiotic transport activity in Urechis caupo embryos  

Microsoft Academic Search

Marine bacteria isolated from the intestine of the sediment-dwelling worm, Urechis caupo, produce compounds that are potential substrates of the multixenobiotic transport protein in Urechis embryos. Three strains isolated from the intestines of two worms were identified as Vibrio harveyi, Vibrio vulnificus and Shewanella putrefaciens. A fourth strain was not identified. Compounds extracted from V. harveyi were most effective at

Barbara Holland Toomey; Melissa R. Kaufman; David Epel

1996-01-01

220

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

2012-05-01

221

Selective growth-inhibiting effects of compounds identified in Tabebuia impetiginosa inner bark on human intestinal bacteria.  

PubMed

The growth-inhibiting activity of anthraquinone-2-carboxylic acid and lapachol identified in the inner bark of taheebo, Tabebuia impetiginosa, toward 10 human intestinal bacteria was evaluated by using a paper disk diffusion bioassay and compared to those of seven lapachol congeners (1,4-naphthoquinone, naphthazarin, menadione, lawsone, plumbagin, juglone, and dichlone) as well as two commercially available antibiotics, chloramphenicol and tetracycline. Anthraquinone-2-carboxylic acid exhibited very strong growth inhibition of Clostridium paraputrificum at 1 microg/disk while 100 microg/disk of lapachol was needed for moderate growth inhibition of the same organism. These two isolates exhibited weak inhibition of Clostridium perfringens and Escherichia coli at 100 microg/disk while no adverse effects were observed on the growth of Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium infantis, Lactobacillus acidophilus, and Lactobacillus casei at 1000 microg/disk. Structure-activity relationships indicate that a methyl group in the C-2 position of 1,4-naphthoquinone derivatives might play an important role in antibacterial activity. PMID:15713033

Park, Byeoung-Soo; Kim, Jun-Ran; Lee, Sung-Eun; Kim, Kyoung Soon; Takeoka, Gary R; Ahn, Young-Joon; Kim, Jeong-Han

2005-02-23

222

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

223

New active media based on bifluorophormic compounds for dye lasers  

NASA Astrophysics Data System (ADS)

The photophysical properties (photostability, spectral-luminescent and generation properties) of eight new organic compounds have been studied, in which the molecular composition of two flurophores -- 1,3,5-triphenylpyrazoline and 2,5-diphenylzoxazole-1,3 (or 2,5- diphenyloxazole-1,3,4) -- were included. The effect of the structure of the investigated molecules and the polar properties of solvents on the spectral position of absorption and fluorescence bands was analyzed. The dyes have been found to have a fluorescence quantum efficiency (gamma) between 0.40 and 0.82 in these solvents. The dye laser performance using these dyes has also been investigated using the same solvents under nitrogen-laser pumping to compare them with the commercially available standard dye POPOP, which generates radiation in the violet spectrum region and allows the extension of the range of the active media used in liquid lasers in this spectrum region. A tuning range of nearly 60 nm was obtained in the blue region with efficiency up to 85% in comparison to the standard dye POPOP.

Neyra Bueno, O. L.; Gruzinskiy, V. V.; Seniuk, M. A.; Afanasiady, L. S.

1996-02-01

224

Prediction of compounds with closely related activity profiles using weighted support vector machine linear combinations.  

PubMed

Using support vector machine (SVM) ranking, a complex multi-class prediction task has been investigated involving sets of compounds that were active against related targets and represented all possible combinations of single-, dual-, and triple-target activities. Standard SVM models were not capable of differentiating compounds with overlapping yet distinct activity profiles. To address this problem, we designed differentially weighted SVM linear combinations that were found to preferentially detect compounds with desired activity profiles and deprioritize others. Hence, combining independently derived SVM models using negative and positive linear weighting factors balanced relative contributions from individual reference sets and successfully distinguished between compounds with overlapping activity profiles. PMID:23517241

Heikamp, Kathrin; Bajorath, Jürgen

2013-04-22

225

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

PubMed

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

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

2014-02-01

226

Screening method to identify preclinical liquid and semi-solid formulations for low solubility compounds: miniaturization and automation of solvent casting and dissolution testing.  

PubMed

We have developed an efficient screening method to identify liquid and semisolid formulations for low-solubility compounds. The method is most suitable for identifying dosing vehicles for compounds in lead optimization, where compound supply is limited and long-term stability is not a requirement. Dilute compound and excipient stock solutions are prepared in organic solvent and then dispensed and mixed in 96-well plates. The solvent is removed in a vacuum centrifuge evaporator, leaving neat formulation (e.g., 10-40 microg compound, 0.4 mg excipient) at the bottom of each well. After an aging step, an aqueous dilution medium is added and the plates are incubated (agitation by orbital shaking). The diluted formulations are then filtered and analyzed by ultraviolet (UV) absorbance or high-performance liquid chromatography (HPLC). To illustrate the method, two compounds (aqueous solubility compound/surfactant/oil formulations is also presented. PMID:17094139

Mansky, Paul; Dai, Wei-Guo; Li, Shu; Pollock-Dove, Crystal; Daehne, Klaus; Dong, Liang; Eichenbaum, Gary

2007-06-01

227

Use of Computerized Data Listings and Activity Profiles of Genetic and Related Effects in the Review of 195 Compounds (Journal Version).  

National Technical Information Service (NTIS)

Computer-generated listings of data from short-term tests for genetic and related effects (activity profile listings) were prepared for 195 compounds that included for each compound: the test system (identified by a three-letter code word); qualitative re...

M. D. Waters H. F. Stack A. L. Brady P. H. M. Lohman L. Haroun

1988-01-01

228

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

229

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...

230

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

PubMed

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

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

2014-01-01

231

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

PubMed Central

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

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

2014-01-01

232

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

PubMed

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

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

2014-05-01

233

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

PubMed

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

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

2009-09-01

234

Structural alerts for predicting clastogenic activity of pro-oxidant flavonoid compounds: quantitative structure-activity relationship study.  

PubMed

Flavonoids have been reported to exert multiple biological effects that include acting as pro-oxidants at very high doses. The authors determined a structural alert to identify the clastogenic activity of a series of flavonoids with pro-oxidant activity. The methodology was based on a quantitative structure-activity relationship (QSAR) study. Specifically, the authors developed a virtual screening method for a clastogenic model using the topological substructural molecular design (TOPS-MODE) approach. It represents a useful platform for the automatic generation of structural alerts, based on the calculation of spectral moments of molecular bond matrices appropriately weighted, taking into account the hydrophobic, electronic, and steric molecular features. Therefore, it was possible to establish the structural criteria for maximal clastogenicity of pro-oxidant flavonoids: the presence of a 3-hydroxyl group and a 4-carbonyl group in ring C, the maximal number of hydroxyl groups in ring B, the presence of methoxyl and phenyl groups, the absence of a 2,3-double bond in ring C, and the presence of 5,7 hydroxyl groups in ring A. The presented clastogenic model may be useful for screening new pro-oxidant compounds. This alert could help in the design of new and efficient flavonoids, which could be used as bioactive compounds in nutraceuticals and functional food. PMID:21940715

Yordi, Estela Guardado; Pérez, Enrique Molina; Matos, Maria Joao; Villares, Eugenio Uriarte

2012-02-01

235

Identification of aroma-active compounds in Jiashi muskmelon juice by GC-O-MS and OAV calculation.  

PubMed

To identify aromatic compounds in Jiashi melon juice, gas chromatography-mass spectrometry-olfactometry (GC-MS-O) analysis was used. Odor activity values (OAVs) were also calculated on the basis of the qualitative and quantitative analysis of volatile compounds. Results showed that 42 volatiles were identified, among which 4 compounds, namely, diethyl carbonate, isophorone, 2-butoxyethyl acetate, and menthol, were identified or tentatively identified for the first time as volatiles in melon fruit. Twelve compounds, namely, (2E,6Z)-nona-2,6-dienal, (3Z,6Z)-nona-3,6-dien-1-ol, ethyl butanoate, ethyl 2-methylbutyrate, ethyl 2-methylpropanoate, (Z)-non-6-enal, (E)-2-nonenal, heptanal, methyl 2-methylbutyrate, nonanal, hexanal, and 2-methylpropyl acetate, were identified as the potent odorants of Jiashi melon juice by both OAV and detection frequency analysis (DFA). In addition, seven odorants were detected by all of the panelists and showed higher OAVs, indicating that DFA and OAV resulted in relatively similar "Jiashi" melon aroma patterns. PMID:22497266

Pang, Xueli; Guo, Xingfeng; Qin, Zihan; Yao, Yubo; Hu, Xiaosong; Wu, Jihong

2012-05-01

236

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

PubMed

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

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

2014-03-01

237

The influence of interactions among phenolic compounds on the antiradical activity of chokeberries (Aronia melanocarpa).  

PubMed

In the present work, interactions between phenolic compounds from chokeberries and their influence on the antiradical activity was studied. Three fractions were isolated from chokeberries containing different classes of phenolic compounds. The first fraction contained a major part of phenolic acids and flavonols, the second anthocyanins, and the third insoluble phenols and proanthocyanidins. The phenolic compound content was determined using high-performance liquid chromatography, and the antiradical activity using the DPPH test. In order to evaluate the effects of interactions between phenolic compounds on the antiradical activity, the antiradical activity of individual phenolic fractions was compared with that obtained by mixing phenolic fractions. Phenolic mixtures showed the decrease in the antiradical activity in comparison with the individual phenolic fractions. These results suggest the existence of complex interactions among phenolic compounds that caused the decrease of the antiradical activity. Interactions among chokeberry phenols promoted a negative synergism. PMID:21214419

Jakobek, Lidija; Seruga, Marijan; Krivak, Petra

2011-06-01

238

Repellent activity of constituents identified in Foeniculum vulgare fruit against Aedes aegypti (Diptera: Culicidae).  

PubMed

The repellent activity of materials derived from the methanol extract of fruits from Foeniculum vulgareagainst hungry Aedes aegypti females was examined using skin and patch tests and compared with that of the commercial N,N-diethyl-m-toluamide (deet) and (Z)-9-octadecenoic acid. The biologically active constituents of the Foeniculum fruits were characterized as (+)-fenchone and (E)-9-octadecenoic acid by spectroscopic analyses. Responses varied according to compound, dose, and exposure time. In a skin test with female mosquitoes, at a dose of 0.4 mg/cm(2), (+)-fenchone and (Z)-9-octadecenoic acid exhibited moderate repellent activity at 30 min after treatment, whereas deet provided >1 h of protection against adult mosquitoes at 0.2 mg/cm(2). (Z)-9-Octadecenoic acid was a more potent repellent agent than (E)-9-octadecenoic acid. (+)-Fenchone and (E)-9-octadecenoic acid merit further study as potential mosquito repellent agents or as lead compounds. PMID:12428949

Kim, Do-Hyoung; Kim, Soon-Il; Chang, Kyu-Sik; Ahn, Young-Joon

2002-11-20

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

2013-08-01

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

Activated Carbon Adsorption of Some Phenolic Compounds Present in Agroindustrial Wastewater  

Microsoft Academic Search

Single solute and simultaneous experimental adsorption isotherms of three phenolic compounds: gallic acid, p-hydroxybenzoic acid and syringic acid, have been investigated at 20, 30 and 40°C, using a bituminous coal based activated carbon. Regardless of temperature, the capacity of the activated carbon used to adsorb these compounds presented the following order: syringic acid > p-hydroxybenzoic acid > gallic acid. The

J. F. García-Araya; F. J. Beltrán; P. Álvarez; F. J. Masa

2003-01-01

242

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

243

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

PubMed

Excess dietary intake may induce metabolic inflammation which is associated with insulin resistance and cardiovascular disease. Recent evidence indicates that dietary bioactive compounds may diminish metabolic inflammation. To identify anti-inflammatory bioactives, we developed a screening assay using the human H293-NF-?B-RE-luc2P reporter cell line. Under optimised conditions we determined the anti-inflammatory activity of vegetables and purified bioactives, by monitoring their potency to inhibit TNF-?-induced NF-?B activity, as assessed by sensitive chemiluminescence detection in a 96-well assay format. Minced broccoli seedlings reduced NF-?B activity by 16%, while sulphoraphane, the dominant bioactive in broccoli seedlings, inhibited NF-?B activity with an IC50 of 5.11?mol/l. Short-chain fatty acids also reduced NF-?B activity in the order butyrate>propionate?acetate with IC50 of 51, 223, and 1300?mol/l, respectively. The H293-NF-?B-RE-luc2P reporter cell line is a sensitive tool for rapid high-throughput screening for bioactives with anti-inflammatory activity. PMID:25053041

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

2015-01-01

244

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

245

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

246

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

PubMed Central

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

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

2011-01-01

247

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

PubMed

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

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

2014-12-01

248

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

PubMed

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

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

2014-09-15

249

A structure-activity relationship study of compounds with antihistamine activity.  

PubMed

A structure-activity relationship (SAR) analysis of H(1)-, H(2)- and H(3)-antihistamine activity was carried out and chromatographic data of 2-[2-(phenylamino)thiazol-4-yl]ethanamine, 2-(2-benzyl-4-thiazolyl)ethanamine, 2-(2-benzhydrylthiazol4-yl)ethanamine, 2-(1-piperazinyl- and 2-(hexahydro-1H-1,4-diazepin-1-yl)benzothiazole, 2-(1-piperazinyl)benzothiazole, 2-[4-(1-alkyl)piperidinyl]benzothiazole, 2-(N,N',N'-dimethylalkyl-1,2-ethanediamino)benzothiazole, 2[1-(4-aminopiperidinyl)]benzothiazole, 2-[2-phenyl-4-thiazolyl]ethanamine derivatives and selected H(1)- and H(2)-antihistamine drugs were obtained. NP TLC and RP2 TLC plates (silica gel NP 60F(254) and silica gel RP2 60F(254) silanized precoated), impregnated with a solution of aspartic acid (L-Asp) and a solution of an analogue of aspartic acid (propionic acid), were used in two developing solvents as H(1)-, H(2)- and H(3)-antihistaminic interaction models. The lipophilicity data of the examined compounds were obtained and used in the SAR assay. Biochromatographic tests using TLC plates impregnated with solutions of asparic acid or propionic acid were found to be a source of useful data for the qualitative analysis of compounds with different structures, demonstrating activity to histamine H(1)-, H(2)- and H(3)-receptors. The four presented discriminant models based on biochromatographic studies are an efficient tool in the SAR analysis for initial prediction of compound activity direction within histamine receptors. PMID:16506293

Brzezi?ska, Elzbieta; Ko?ka, Grazyna

2006-10-01

250

Development of a mouse model to determine the systemic activity of potential flea-control compounds.  

PubMed

Probe studies were performed to determine if the cat flea (Ctenocephalides felis), the most common ectoparasite of companion animals, will feed on laboratory mice and, if so, to incorporate this into a small animal assay to detect systemically active compounds. Consequently, a protocol was developed which incorporated acepromazine maleate to temporarily sedate various strains of mice and allow fleas a window of time to feed undisturbed. For validation of the model, CD-1 mice were dosed per os with seven known insecticides at 30, 10 and 1mg/kg. Mice were sedated with 0.0125 ml acepromazine maleate intraperitoneally, and infested with fleas. After 2h, fleas were removed, one-third were examined immediately to confirm the occurrence of feeding, and 77% were found to have ingested a blood meal. The remaining fleas were incubated for 24h to determine mortality. Nitenpyram, the active ingredient in Capstar, was highly active (>94%) at 1mg/kg. Selamectin, the active ingredient in Revolution, was very active (86%) at 10mg/kg, but inactive at 1mg/kg. Fipronil, the active ingredient of Frontline Topspot, was very active (83%) at 30 mg/kg, moderately active (54%) at 10mg/kg and inactive at 1mg/kg. Cythioate, the active ingredient in Proban, and nodulisporic acid, a recently discovered oral insecticide, were moderately active (64 and 55%, respectively) at 10mg/kg, but both were inactive at 1mg/kg. Lufenuron and ivermectin exhibited no efficacy at any level tested. These findings suggest that this mouse model can effectively identify systemic flea-control leads and, subsequently, reduce the use of large animals in research. PMID:11812623

Santora, Karen A; Zakson-Aiken, Michelle; Rasa, Cordelia; Shoop, Wes

2002-03-20

251

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

2013-07-17

252

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

PubMed Central

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

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

2014-01-01

253

Anti-inflammatory and anticancer activities of extracts and compounds from the mushroom Inonotus obliquus.  

PubMed

Mushroom Inonotus obliquus (I. obliquus) has been used as functional food and traditional Chinese herbs for long time. An efficient method for bioassay-guided preparative isolation was used for identifying the anti-inflammatory and anticancer constituents in I. obliquus. The petroleum ether and ethyl acetate fractions were found to have significant inhibition effects on NO production and NF-?B luciferase activity in macrophage RAW 264.7 cells and cytotoxicity against human prostatic carcinoma cell PC3 and breast carcinoma cell MDA-MB-231. Six main constituents were isolated from these two fractions and they were identified as lanosterol (1), 3?-hydroxy-8,24-dien-21-al (2), ergosterol (3), inotodiol (4), ergosterol peroxide (5) and trametenolic acid (6). Compound ergosterol, ergosterol peroxide and trametenolic acid showed anti-inflammatory activities and ergosterol peroxide and trametenolic acid showed obviously cytotoxicity on human prostatic carcinoma cell PC3 and breast carcinoma MDA-MB-231 cell. The results obtained in this work might contribute to understanding the biological activity of mushroom I. obliquus for food and drug application. PMID:23561137

Ma, Lishuai; Chen, Haixia; Dong, Peng; Lu, Xueming

2013-08-15

254

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

PubMed

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

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

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

256

Theoretical study of some nitrososulfamide compounds with antitumor activity.  

PubMed

The lowest-energy conformations of four 2-chloroethylnitrososulfamides were determined using the MM+ molecular mechanics method as implemented in Hyperchem 6.0. Some of the calculated structural parameters, angles and bonds lengths were compared with the crystal structure data of N-nitroso-N-(2-chloroethyl)-N'-sulfamoyl- proline. Using MM+, AM1 and PM3 the anti conformation was predicted to be more stable than the syn conformation in each of these compounds. With these methods we found that the relative energy of the transition state (TS) was considerably higher, but with the ab initio method using RHF with minimal basic function STO-3G we found that the syn conformation is predicted to be slightly more stable. The determination of some atomic charges of a selection of atoms on the syn, anti and TS structures of the various compounds provided some details about the nature of the transition state. PMID:18007489

Djameleddine, Khatmi; Soumeya, Seridi; Fatiha, Madi

2004-01-01

257

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

NASA Astrophysics Data System (ADS)

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

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

2004-09-01

258

A Causal Discovery Approach to Identifying Active Components of Herbal Medicine  

Microsoft Academic Search

In the present study, a stepwise causal adjacent relationship discovery (STEPCARD) method has been developed to identify active components of herbal medicine. The combination of two active components had been successfully recognized from a typical Chinese formulation. Animal experiments validated the computational result. It indicates current work might be helpful to accelerate the process of new drug discovery from herbal

Yi Wang; Xuewei Wang; Yiyu Cheng

2005-01-01

259

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

260

Establishment and validation of whole-cell based fluorescence assays to identify anti-mycobacterial compounds using the Acanthamoeba castellanii-Mycobacterium marinum host-pathogen system.  

PubMed

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

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

2014-01-01

261

Antimicrobial, antimalarial and antileishmanial activities of mono- and bisquaternary pyridinium compounds  

PubMed Central

Pyridinium-based oxime compounds have been utilized worldwide as antidotes following exposure to anticholinesterase agents. In the event of combined chemical and biological incident, it is of vital importance to know the ability of antidotes to provide additional protection against biological threats. This paper reports results of in vitro antimicrobial and antiprotozoal activities of a series of quaternary pyridinium oximes against a number of lower pathogenicity BSL-1 and 2 agents. In general, our compound panel had little to no antimicrobial action except for thiophene- and benzothiophene-substituted monoquaternary pyridinium compounds 21 and 24 that showed moderate antibacterial activity against Staphylococus aureus and methicillin resistant S. aureus with IC50 values ranging from 12.2–17.7 µg/mL. Compounds 21 and 24 also exhibited antileishmanial activity against Leishmania donovani with IC50 values of 19 and 18 µg/mL, respectively. Another monoquaternary pyridinium compound with a bromobutyl side chain 17 showed antimalarial activity against both a chloroquine sensitive and resistant strains of Plasmodium falciparum with IC50 values of 3.7 and 4.0 µg/mL, respectively. None of the bisquaternary pyridinium compounds showed antimicrobial, or antiprotozoal activity. None of the compounds showed cytotoxic effects towards mammalian kidney fibroblasts. Results of this study indicate that the pyridinium compounds, some of which are already in use as antidotes, do not have significant antimicrobial and antiprotozoal activities and cannot be relied upon for additional protection in the event of combined chemical-biological incident.

Bharate, Sandip B.; Thompson, Charles M.

2010-01-01

262

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

PubMed

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

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

2014-05-01

263

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

264

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

2007-08-01

265

Activation Tagging in Tomato Identifies a Transcriptional Regulator of Anthocyanin Biosynthesis, Modification, and Transport  

Microsoft Academic Search

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

Helena Mathews; Stephanie K. Clendennen; Colby G. Caldwell; Xing Liang Liu; Karin Connors; Nikolaus Matheis; Debra K. Schuster; D. J. Menasco; Wendy Wagoner; Jonathan Lightner; D. Ry

2003-01-01

266

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

PubMed Central

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

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

2012-01-01

267

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

268

Synthesis, molecular structure, DNA-binding, cytotoxicity, apoptosis and antioxidant activity of compounds containing aryloxazole.  

PubMed

Three novel aryloxazole compounds 1-3 were synthesized and characterized. The crystal structures of compounds 2 and 3 show that N atom locates at ?-position and O atom at ?-position in naphthalene cycle. The DNA binding constants for compounds 1-3 are 4.44 × 10(3), 5.31 × 10(3) and 2.64 × 10(3) M(-1), respectively. The viscosity measurements indicate that these compounds intercalate between the DNA base pairs. Upon irradiation, compounds 1-3 can effectively cleave pBR322 DNA. The cytotoxicity of the compounds against BEL-7402, A549, MG-63 and SKBR-3 were assayed by MTT method. The apoptosis and cell cycle arrest were investigated towards A549 cells. The antioxidant activities of the compounds against hydroxyl radicals were also explored. PMID:24780596

Wang, Xiu-Zhen; Jiang, Guang-Bin; Lin, Gan-Jian; Huang, Hong-Liang; Xie, Yang-Yin; Liu, Yun-Jun

2014-06-10

269

Antiasthmatic activity of phenolic compounds from the roots of Gastrodia elata Bl  

Microsoft Academic Search

We previously reported that 4-hydroxy-3-methoxybenzaldehyde has the most potent anti-inflammatory and analgesic activity of eight phenolic compounds obtained from the dried roots of Gastrodiaelata (GE) Blume (Orchidaceae); its activity may be related to inhibition of cyclooxygenase activities and oxidation. In the present study, the effects of nine phenolic compounds from GE on immediate-phase (IAR) and late-phase (LAR) asthmatic responses after

Young Woon Jang; Ji Yun Lee; Chang Jong Kim

2010-01-01

270

Low-Molecular-Weight, Biologically Active Compounds from Marine Pseudoalteromonas Species  

Microsoft Academic Search

We have examined the ability of marine Proteobacteria from the Pseudoalteromonas genus and Alteromonas macleodii to produce low-molecular-weight, biologically active compounds with antimicrobial and surface-active properties. A new marine bacterium, Pseudoalteromonas issachenkonii, exhibited a high level of biological activity and produced antifungal and hemolytic compounds. A detailed spectroscopic investigation based on UV, IR, high-resolution mass spectrometry, and 2D 1H and

Nataliya I. Kalinovskaya; Elena P. Ivanova; Yulia V. Alexeeva; Nataliya M. Gorshkova; Tatyana A. Kuznetsova; Andrey S. Dmitrenok; Dan V. Nicolau

2004-01-01

271

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

272

Review on natural coumarin lead compounds for their pharmacological activity.  

PubMed

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

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

2013-01-01

273

A new iridoid glycoside and NO production inhibitory activity of compounds isolated from Russelia equisetiformis.  

PubMed

From the 1-BuOH-soluble fraction of a MeOH extract of the leaves of Russelia equisetiformis, one new iridoid glucoside was isolated along with 24 known compounds, comprising iridoids and iridoid glucosides, phenyl propane glucosides, phenyl ethanoids, lignan glucosides, and flavonoid glucosides. The structure of the new compound was elucidated to be 10-O-cinnamoyl sinuatol. Of the 25 compounds isolated, rehmaglutin B exhibited moderate inhibitory activity toward NO production, which was not associated with cytotoxicity. PMID:21822607

Ochi, Madoka; Matsunami, Katsuyoshi; Otsuka, Hideaki; Takeda, Yoshio

2012-01-01

274

Compounds for delivering amino acids or peptides with antioxidant activity into mitochondria and use thereof  

US Patent & Trademark Office Database

Disclosed are hydrophilic choline/N-heterocycle ester compounds containing single amino acids, peptides, or derivatives thereof which have the potential to express anti-oxidant activity capable of reducing reactive oxygen species in cells. These compounds may be used to inhibit oxidative stress-induced cell injury or death both in vivo and ex vivo. In addition, methods for the synthesis of these compounds are disclosed.

2009-09-08

275

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

2012-12-28

276

Human kinome profiling identifies a requirement for AMP-activated protein kinase during human cytomegalovirus infection  

PubMed Central

Human cytomegalovirus (HCMV) modulates numerous cellular signaling pathways. Alterations in signaling are evident from the broad changes in cellular phosphorylation that occur during HCMV infection and from the altered activity of multiple kinases. Here we report a comprehensive RNAi screen, which predicts that 106 cellular kinases influence growth of the virus, most of which were not previously linked to HCMV replication. Multiple elements of the AMP-activated protein kinase (AMPK) pathway scored in the screen. As a regulator of carbon and nucleotide metabolism, AMPK is poised to activate many of the metabolic pathways induced by HCMV infection. An AMPK inhibitor, compound C, blocked a substantial portion of HCMV-induced metabolic changes, inhibited the accumulation of all HCMV proteins tested, and markedly reduced the production of infectious progeny. We propose that HCMV requires AMPK or related activity for viral replication and reprogramming of cellular metabolism.

Terry, Laura J.; Vastag, Livia; Rabinowitz, Joshua D.; Shenk, Thomas

2012-01-01

277

Molluscicidal and antischistosomal activities of methanol extracts and isolated compounds from Eucalyptus globulus and Melaleuca styphelioides.  

PubMed

Abstract Context: Schistosomiasis is a parasitic disease that results in severe organ damage. Snail control is the best measure to control schistosomiasis. Plant-derived molluscicides have gained increasing attention for the control of schistosomiasis because they have low toxicity towards non-target organisms. Tannins are particularly suitable for snail control because they are less toxic than saponins to non-target organisms. Objective: To identify the most toxic components of two plants belonging to the family Myrtaceae, namely Eucalyptus globulus Labill. and Melaleuca styphelioides Sm against the different developmental stages of Schistosoma mansoni and its snail host. Materials and methods: The 80% MeOH leaf extracts of the tested plants and their isolated compounds were screened for their molluscicidal activity (expressed as LC50 and LC90 after 24?h exposure) against the snail Biomphalaria alexandrina. The anti-schistosomal activity of the tested samples was determined at 20?ppm (after 1 or 2?h exposure) against the different developmental stages of S. mansoni, including the miracidia, cercariae and worms. Biochemical parameters were measured to determine the toxicity mechanisms of the treated snails. The structures of the isolated compounds were elucidated based on NMR, UV and HRESI-MS/MS data. Results: Potent molluscicidal activity was observed for the ellagitannin dimer eucalbanin B (12), with an LC50 value of 55?ppm. Treatment of the snails with the LC25 of eucalbanin B (30.8?ppm) resulted in a significant decrease in the protein level by 22.7% and 25.8% in the snail tissues and hemolymph, respectively. The decreased protein content was attributed to destruction of the snail tissue and impairment in protein synthesis under stress conditions of intoxication with eucalbanin B. Alterations in the activities of the transaminases and phosphatases in the treated snails indicated destruction and intoxication of the snail tissues. A significant increase in the levels of the transaminases alanine aminotransferase (ALT) (57.8%) and aspartate aminotransferase (AST) (113.2%) in the snail hemolymph and a significant decrease in their tissue levels to 7.4 and 48.6%, respectively, were attributed to their release from the damaged tissue into the hemolymph. Alkaline phosphatase (ALP) was significantly increased by 38.5 and 181.4% in the hemolymph and tissues, respectively. Acid phosphatase (ACP) was also significantly increased by 48.4 and 21.2% in the hemolymph and tissues, respectively. The 80% MeOH extract of E. globulus together with mallophenol B (3), 2,2,8-trimethyl-6-formyl-chrom-3-ene-7-O-?-d-glucopyranoside (5) and benzyl alcohol 7-O-(3',4',6'-tri-O-galloyl)-?-d-glucopyranoside (10) exhibited miracidicidal activity with almost 100% toxicity at 20?ppm for the three compounds and 80% toxicity for the extract. Moreover, E. globulus extract showed cercaricidal and schistosomicidal activity with 100 and 40% mortality, respectively. Conclusion: E. globulus is a potential source for biocidal compounds against S. mansoni and its snail host. This is the first study to test the biocidal activity of the isolated compounds. PMID:24824322

Al-Sayed, Eman; Hamid, Hoda Abdel; Abu El Einin, Hanaa M

2014-06-01

278

NF-kappaB Activation by compounds found in Platycodon grandiflorum extract.  

PubMed

Compounds extracted from Platycodon grandiflorum were evaluated for an activation effect on nuclear factor-kappa B (NF-kappaB). In its active state, NF-kappaB turns on the expression of genes related to cell proliferation or death. NF-kappaB activators promote growth of neuron cells and can be used to control neurodegenerative diseases. The biological activity of P. grandiflorum extracts toward NF-kappaB had not yet been studied. Although the biological activity of several compounds extracted from P. grandiflorum was evaluated, only three exhibited any significant activation effect on NF-kappaB. PMID:19597312

Hong, Sungwon; Yong, Yeonjoong; Kang, Kyungrai; Shin, Soon Young; Lee, Young Han; Lim, Yoongho

2009-06-01

279

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

280

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

PubMed

Although ubiquitination plays a critical role in virtually all cellular processes, mechanistic details of ubiquitin (Ub) transfer are still being defined. To identify the molecular determinants within E3 ligases that modulate activity, we scored each member of a library of nearly 100,000 protein variants of the murine ubiquitination factor E4B (Ube4b) U-box domain for auto-ubiquitination activity in the presence of the E2 UbcH5c. This assay identified mutations that enhance activity both in vitro and in cellular p53 degradation assays. The activity-enhancing mutations fall into two distinct mechanistic classes: One increases the U-box:E2-binding affinity, and the other allosterically stimulates the formation of catalytically active conformations of the E2?Ub conjugate. The same mutations enhance E3 activity in the presence of another E2, Ube2w, implying a common allosteric mechanism, and therefore the general applicability of our observations to other E3s. A comparison of the E3 activity with the two different E2s identified an additional variant that exhibits E3:E2 specificity. Our results highlight the general utility of high-throughput mutagenesis in delineating the molecular basis of enzyme activity. PMID:23509263

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

2013-04-01

281

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

PubMed

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

Bottone, Frank G; Alston-Mills, Brenda

2011-06-01

282

NF-kappaB inhibitory activity of compounds isolated from Cantharellus cibarius.  

PubMed

The inhibitory activities of the extracts of Cantharellus cibarius and isolated compounds were investigated in an enzyme-based ELISA NF-kappaB assay. Of the tested compounds, ergosterol, ergosterol peroxide and cerevisterol were noted to have the most potent inhibition of NF-kappaB activation. The ability of the active metabolites to inhibit the NF-kappaB translocation from the cytoplasm to the nucleus was assessed using a cell-based NF-kappaB assay. The isolated compounds were elucidated through the analysis of various spectroscopic methods. PMID:18570270

Kim, Jeong Ah; Tay, David; de Blanco, Esperanza Carcache

2008-08-01

283

Application of modified in vitro screening procedure for identifying herbals possessing sulfonylurea-like activity  

Microsoft Academic Search

We describe here the application of a modified in vitro procedure for identifying herbs potentially possessing sulfonylurea-like activity. The procedure consists of the combination of an SUR1 receptor binding assay and an insulin secretion assay in cultures of HIT-T15 cells. This procedure could be used as an initial step in identifying new safe and efficacious agents for the management of

Y Rotshteyn; S. W Zito

2004-01-01

284

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

285

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

PubMed Central

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

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

2014-01-01

286

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

2010-03-01

287

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

288

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

PubMed

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

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

2013-03-20

289

Extensive Mutagenesis of a Transcriptional Activation Domain Identifies Single Hydrophobic and Acidic Amino Acids Important for Activation In Vivo  

Microsoft Academic Search

C1 is a transcriptional activator of genes encoding biosynthetic enzymes of the maize anthocyanin pigment pathway. C1 has an amino terminus homologous to Myb DNA-binding domains and an acidic carboxyl terminus that is a transcriptional activation domain in maize and yeast cells. To identify amino acids critical for transcriptional activation, an extensive random mutagenesis of the C1 carboxyl terminus was

MANUEL B. SAINZ; STEPHEN A. GOFF; ANDVICKI L. CHANDLER

290

Antiproliferative activity of Saponaria vaccaria constituents and related compounds.  

PubMed

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

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

2012-01-01

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

Artificial Neural Network Based Analysis of High Throughput Screening Data for Improved Prediction of Active Compounds  

PubMed Central

Artificial Neural Networks (ANNs) are trained using High Throughput Screening (HTS) data to recover active compounds from a large data set. Improved classification performance was obtained on combining predictions made by multiple ANNs. The HTS data, acquired from a Methionine Aminopeptidases Inhibition study, consisted of a library of 43,347 compounds, and the ratio of active to non-active compounds, RA/N, was 0.0321. Back-propagation ANNs were trained and validated using Principal Components derived from the physico-chemical features of the compounds. On selecting the training parameters carefully, an ANN recovers one-third of all active compounds from the validation set with a three-fold gain in RA/N value. Further gains in RA/N values were obtained upon combining the predictions made by a number of ANNs. The generalization property of the back-propagation ANNs was utilized to train those ANNs with the same training samples, after being initialized with different sets of random weights. As a result, only 10% of all available compounds were needed for training and validation, and the rest of the data set was screened with more than a ten-fold gain of the original RA/N value. Thus, ANNs trained with limited HTS data might become useful in recovering active compounds from large data sets.

Chakrabarti, Swapan; Svojanovsky, Stan R.; Slavik, Romana; Georg, Gunda I.; Wilson, George S.; Smith, Peter G.

2014-01-01

293

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

294

Advances in the Biochemistry, Biophysics, and Chemistry of Physiologically Active Compounds During the past Fifty Years.  

National Technical Information Service (NTIS)

This article reports the meeting of the Department of Biochemistry, Biophysics, and Chemistry of Physiologically Active Compounds, Academy of Sciences USSR, which at its anniversary meeting summed up the results of the progress made to date and the outloo...

V. G. Kocherezhkin T. N. Shcherbinovskaya

1968-01-01

295

Agents that stabilize mutated von Hippel-Lindau (VHL) protein: results of a high-throughput screen to identify compounds that modulate VHL proteostasis.  

PubMed

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that affects multiple organs. Treatment is mainly surgical, and effective systemic therapies are needed. We developed a cell-based screening tool to identify compounds that stabilize or upregulate full-length, point-mutated VHL protein. The 786-0 cell line was infected with full-length W117A-mutated VHL linked to a C-terminal Venus fluorescent protein. This VHL-W117A-Venus line was used to screen the Prestwick drug library and was tested against proteasome inhibitors MG132 and bortezomib. Western blot validation and evaluation of functional readouts, including hypoxia-inducible factor 2? (HIF2?) and glucose transporter 1 (Glut1) levels, were performed. We found that bortezomib, MG132, and the Prestwick compounds 8-azaguanine, thiostrepton, and thioguanosine upregulated VHL-W117A-Venus in 786-0 cells. 8-Azaguanine downregulated HIF2? levels and was augmented by the presence of VHL W117A. VHL p30 band intensities varied as a function of compound used, suggesting alternate posttranslational processing. Nuclear-cytoplasmic localization of VHL-W117A-Venus varied among the different compounds. In conclusion, a 786-0 cell line containing VHL-W117A-Venus was successfully used to identify compounds that upregulate VHL levels, with differential effect on VHL intracellular localization and posttranslational processing. Further screening efforts will broaden the number of pharmacophores available to develop therapeutic agents that will upregulate and refunctionalize mutated VHL. PMID:22357874

Ding, Zhiyong; German, Peter; Bai, Shanshan; Feng, Zhehui; Gao, Meng; Si, Wendy; Sobieski, Mary M; Stephan, Clifford C; Mills, Gordon B; Jonasch, Eric

2012-06-01

296

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

297

Acaricidal activity of constituents identified in Foeniculum vulgare fruit oil against Dermatophagoides spp. (Acari: Pyroglyphidae).  

PubMed

Acaricidal activities of components derived from Foeniculum vulgare fruit oil against Dermatophagoides farinae and Dermatophagoides pteronyssinus were examined using direct contact application and compared with that of the commercial repellent benzyl benzoate. The major biologically active constituent of Foeniculum fruit oil was characterized as (+)-fenchone by spectroscopic analyses. On the basis of LD(50) values, the compound most toxic to D. farinae was p-anisaldehyde (11.3 mg/m(2)) followed by (+)-fenchone (38.9 mg/m(2)), (-)-fenchone (41.8 mg/m(2)), benzyl benzoate (89.2 mg/m(2)), thymol (90.3 mg/m(2)), and estragol (413.3 mg/m(2)). Against D. pteronyssinus, p-anisaldehyde (10.1 mg/m(2)) was much more effective than benzyl benzoate (67.5 mg/m(2)), thymol (68.5 mg/m(2)), and estragol (389.9 mg/m(2)). These results indicate that the acaricidal activity of F. vulgare fruit oil likely results from (+)-fenchone and p-anisaldehyde. (+)-Fenchone was 20.3 times more abundant in the oil than p-anisaldehyde. (+)-Fenchone and p-anisaldehyde merit further study as potential house dust mite control agents or as lead compounds. PMID:15137830

Lee, Hoi-Seon

2004-05-19

298

Isolation and evaluation of the enantiospecific antitubercular activity of a novel triazole compound.  

PubMed

Cyclohex-3-enyl(5-phenyl-4H-1,2,4-triazol-3-yl)methanol (MSDRT 12) is a novel triazole-based antitubercular compound with two chiral centers. To evaluate the enantiospecific antitubercular activity, the four stereoisomers were isolated using preparative chiral chromatography and the individual stereoisomers were evaluated using the resazurin microtiter assay method (REMA) and a microbroth dilution technique against the Mycobacterium tuberculosis H37Rv strain. Isomer III of MSDRT 12 was found to be the most potent with a minimum inhibitory concentration (MIC) of 0.78 ?g/mL, Isomer II had a MIC of 12.5 ?g/mL, and isomers I and IV showed no activity. The diastereomeric mixture of MSDRT 12 showed a MIC of 3.125 ?g/mL and isoniazid, used as the standard drug, showed a MIC of 0.4 ?g/mL. This confirms the necessity of screening individual enantiomers for their pharmacological activity early in the discovery phase to identify the most potent isomer for further development efforts. PMID:24634844

Shekar, Radha; Sinha, Barij Nayan; Mukhopadhya, Arindam; Degani, Mariam S

2014-03-01

299

Removal of inhibitory phenolic compounds by biological activated carbon coupled membrane bioreactor  

Microsoft Academic Search

Phenolic compounds cause problem for conventional treatments due to their toxic and inhibitory properties. This work investigated the treatability of phenolic compounds by using two membrane-bioreactor systems namely: activated sludge coupled with MBR (AS-MBR) and biological granular activated carbon coupled with MBR (BAC-MBR). Initially, the system was fed with phenol (500 mg\\/L) followed by adding 2, 4- Dichlorophenol (2,4-DCP). Phenol,

Q. T. T. Thuy; C. Visvanathan

2006-01-01

300

An artificial neural network to estimate physical activity energy expenditure and identify physical activity type from an accelerometer.  

PubMed

The aim of this investigation was to develop and test two artificial neural networks (ANN) to apply to physical activity data collected with a commonly used uniaxial accelerometer. The first ANN model estimated physical activity metabolic equivalents (METs), and the second ANN identified activity type. Subjects (n = 24 men and 24 women, mean age = 35 yr) completed a menu of activities that included sedentary, light, moderate, and vigorous intensities, and each activity was performed for 10 min. There were three different activity menus, and 20 participants completed each menu. Oxygen consumption (in ml x kg(-1) x min(-1)) was measured continuously, and the average of minutes 4-9 was used to represent the oxygen cost of each activity. To calculate METs, activity oxygen consumption was divided by 3.5 ml x kg(-1) x min(-1) (1 MET). Accelerometer data were collected second by second using the Actigraph model 7164. For the analysis, we used the distribution of counts (10th, 25th, 50th, 75th, and 90th percentiles of a minute's second-by-second counts) and temporal dynamics of counts (lag, one autocorrelation) as the accelerometer feature inputs to the ANN. To examine model performance, we used the leave-one-out cross-validation technique. The ANN prediction of METs root-mean-squared error was 1.22 METs (confidence interval: 1.14-1.30). For the prediction of activity type, the ANN correctly classified activity type 88.8% of the time (confidence interval: 86.4-91.2%). Activity types were low-level activities, locomotion, vigorous sports, and household activities/other activities. This novel approach of applying ANNs for processing Actigraph accelerometer data is promising and shows that we can successfully estimate activity METs and identify activity type using ANN analytic procedures. PMID:19644028

Staudenmayer, John; Pober, David; Crouter, Scott; Bassett, David; Freedson, Patty

2009-10-01

301

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

302

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

2013-10-25

303

Structural determinants of glutathione transferases with azathioprine activity identified by DNA shuffling of alpha class members.  

PubMed

A library of alpha class glutathione transferases (GSTs), composed of chimeric enzymes derived from human (A1-1, A2-2 and A3-3), bovine (A1-1) and rat (A2-2 and A3-3) cDNA sequences was constructed by the method of DNA shuffling. The GST variants were screened in bacterial lysates for activity with the immunosuppressive agent azathioprine, a prodrug that is transformed into its active form, 6-mercaptopurine, by reaction with the tripeptide glutathione catalyzed by GSTs. Important structural determinants for activity with azathioprine were recognized by means of primary structure analysis and activities of purified enzymes chosen from the screening. The amino acid sequences could be divided into 23 exchangeable segments on the basis of the primary structures of 45 chosen clones. Segments 2, 20, 21, and 22 were identified as primary determinants of the azathioprine activity representing two of the regions forming the substrate-binding H-site. Segments 21 and 22 are situated in the C-terminal helix characterizing alpha class GSTs, which is instrumental in their catalytic function. The study demonstrates the power of DNA shuffling in identifying segments of primary structure that are important for catalytic activity with a targeted substrate. GSTs in combination with azathioprine have potential as selectable markers for use in gene therapy. Knowledge of activity-determining segments in the structure is valuable in the protein engineering of glutathione transferase for enhanced or suppressed activity. PMID:18155239

Kurtovic, Sanela; Modén, Olof; Shokeer, Abeer; Mannervik, Bengt

2008-02-01

304

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

Microsoft Academic Search

In the present study, we investigated the inducibility of the drug conjugate transporter genes MRP1 and MRP2 by redox-active compounds such as tertiary butylated hydroquinone (tBHQ) and quercetin and by chemicals known to activate the pregnane X receptor (PXR) such as rifampicin and clotrimazol and by the metalloid compound arsenite. The human MRP2 gene was found to be inducible in

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

2002-01-01

305

Sorption of quaternary ammonium compounds in soils: Implications to the soil microbial activities  

Microsoft Academic Search

Despite their widespread use in household activities and various industries, information on the toxicity of quaternary ammonium compounds (QACs) to microbial activities in soil is scant. This study investigated the effect of three commonly used QACs namely hexadecyltrimethyl ammonium bromide (HDTMA), octadecyltrimethyl ammonium bromide (ODTMA) and Arquad on dehydrogenase and potential nitrification activities in three different soils. The toxicity of

Binoy Sarkar; Mallavarapu Megharaj; Yunfei Xi; G. S. R. Krishnamurti; Ravi Naidu

2010-01-01

306

Using macromolecules as osmotically active compounds in osmosis followed by filtration (OF) system  

Microsoft Academic Search

Finding a suitable osmostically active solute is the most important problem in forward osmosis (FO). Even though there are a number of osmotically active compounds that exist, the major problem occurs during the separation of product water from the solute. Osmotically active macromolecules (polyethylene glycol [PEG] and humic acid [HA]) were investigated in this research as possible draw solutes for

S. Sarp; S. Lee; J. H. Kim; J. Cho

2012-01-01

307

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

308

Ecological Congruence Assessment for Classroom Activities and Routines: Identifying Goals and Intervention Practices in Childcare.  

ERIC Educational Resources Information Center

This article explains how educators can use the ecological congruence assessment process for identifying functional goals for young children with disabilities. Process steps include: teacher collects information about functioning in usual classroom activities, routines, and transitions; summarizes the collected information; and shares the…

Wolery, Mark; Brashers, Margaret Sigalove; Neitzel, Jennifer C.

2002-01-01

309

Does Art Therapy Work? Identifying the Active Ingredients of Art Therapy Efficacy  

Microsoft Academic Search

Art therapy research is beginning to identify more precisely the active ingredients that produce change in treatment and to test commonly held assumptions about efficacy. This editorial discusses the progression from clinical observation to single-case research and randomized controlled trials in building an evidence-based model of art therapy.

Lynn Kapitan

2012-01-01

310

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

ERIC Educational Resources Information Center

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

Chamberlin, Scott A.; Moon, Sidney M.

2005-01-01

311

Antioxidant activity of olive pulp and olive oil phenolic compounds of the arbequina cultivar.  

PubMed

The aim of this study was to characterize antioxidant activities of phenolic compounds that appear in olive pulp and olive oils using both radical scavenging and antioxidant activity tests. Antiradical and antioxidant activities of olive pulp and olive oil phenolic compounds were due mainly to the presence of a 3,4-dihydroxy moiety linked to an aromatic ring, and the effect depended on the polarity of the phenolic compound. Glucosides and more complex phenolics exhibited higher antioxidant activities toward oxidation of liposomes, whereas in bulk lipids aglycons were more potent antioxidants with the exception of oleuropein. Lignans acted as antioxidants only in liposomes, which could partly be due to their chelating activity, because liposome oxidation was initiated by cupric acetate. The antioxidant activity of virgin olive oil is principally due to the dialdehydic form of elenolic acid linked to hydroxytyrosol (3,4-DHPEA-EDA), a secoiridoid derivative (peak RT 36, structure unidentified), and luteolin. PMID:15769127

Morelló, José-Ramón; Vuorela, Satu; Romero, Maria-Paz; Motilva, Maria-José; Heinonen, Marina

2005-03-23

312

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

313

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

PubMed

Dactylogyrus intermedius is a significant monogenean parasite on the gills of cyprinid fishes and can cause serious problem in fish aquaculture. In the present study, bioassay-guided fractionation was employed to identify the active compounds from Fructus Arctii against D. intermedius. Five solvents (petroleum ether, chloroform, ethyl acetate, ethanol, and water) were applied for the extraction of Fructus Arctii. Among them, only the chloroform extract exhibited promising anthelmintic efficacy and therefore, subjected to the further isolation and purification using various chromatographic techniques. Two compounds showing potent activity were obtained and identified by spectral data (infrared, nuclear magnetic resonance, and mass spectrometry) as: arctigenin (1) and arctiin (2). They were found to be significantly effective against D. intermedius with median effective concentration (EC(50)) values of 0.62 and 3.55 mg L(-1), respectively. Arctigenin exhibited higher activity as compared with the positive control mebendazole with an EC(50) value of 1.25 mg L(-1). The 48-h acute toxicity tests (LC(50)) of arctigenin and arctiin were found to be 8.47 and 14.14 mg L(-1) for goldfish, respectively. These results provided evidence that the studied plant extract, as well as the isolated compounds, might be potential sources of new antiparasitic drug for the control of Dactylogyrus. PMID:19859737

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

2009-12-01

314

Antioxidant Activity of Plant Extracts Containing Phenolic Compounds  

Microsoft Academic Search

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

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

1999-01-01

315

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

316

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

317

Activation of a carbonyl compound by halogen bonding.  

PubMed

Using a prototypical Diels-Alder reaction as benchmark, we show that dicationic halogen-bond donors are capable of activating a neutral organic substrate. By various comparison experiments, the action of traces of acid or of other structural features of the halogen-bond donor not related to halogen bonding are excluded with high certainty. PMID:24796408

Jungbauer, Stefan H; Walter, Sebastian M; Schindler, Severin; Rout, Laxmidhar; Kniep, Florian; Huber, Stefan M

2014-06-14

318

Antioxidant activity of plant extracts containing phenolic compounds.  

PubMed

The antioxidative activity of a total of 92 phenolic extracts from edible and nonedible plant materials (berries, fruits, vegetables, herbs, cereals, tree materials, plant sprouts, and seeds) was examined by autoxidation of methyl linoleate. The content of total phenolics in the extracts was determined spectrometrically according to the Folin-Ciocalteu procedure and calculated as gallic acid equivalents (GAE). Among edible plant materials, remarkable high antioxidant activity and high total phenolic content (GAE > 20 mg/g) were found in berries, especially aronia and crowberry. Apple extracts (two varieties) showed also strong antioxidant activity even though the total phenolic contents were low (GAE < 12.1 mg/g). Among nonedible plant materials, high activities were found in tree materials, especially in willow bark, spruce needles, pine bark and cork, and birch phloem, and in some medicinal plants including heather, bog-rosemary, willow herb, and meadowsweet. In addition, potato peel and beetroot peel extracts showed strong antioxidant effects. To utilize these significant sources of natural antioxidants, further characterization of the phenolic composition is needed. PMID:10552749

Kähkönen, M P; Hopia, A I; Vuorela, H J; Rauha, J P; Pihlaja, K; Kujala, T S; Heinonen, M

1999-10-01

319

Antiprotozoal and Antimycobacterial Activities of Pure Compounds from Aristolochia elegans Rhizomes  

PubMed Central

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

Jimenez-Arellanes, Adelina; Leon-Diaz, Rosalba; Meckes, Mariana; Tapia, Amparo; Molina-Salinas, Gloria Maria; Luna-Herrera, Julieta; Yepez-Mulia, Lilian

2012-01-01

320

The Mast Cell Degranulator Compound 48/80 Directly Activates Neurons  

PubMed Central

Background Compound 48/80 is widely used in animal and tissue models as a “selective” mast cell activator. With this study we demonstrate that compound 48/80 also directly activates enteric neurons and visceral afferents. Methodology/Principal Findings We used in vivo recordings from extrinsic intestinal afferents together with Ca++ imaging from primary cultures of DRG and nodose neurons. Enteric neuronal activation was examined by Ca++ and voltage sensitive dye imaging in isolated gut preparations and primary cultures of enteric neurons. Intraluminal application of compound 48/80 evoked marked afferent firing which desensitized on subsequent administration. In egg albumen-sensitized animals, intraluminal antigen evoked a similar pattern of afferent activation which also desensitized on subsequent exposure to antigen. In cross-desensitization experiments prior administration of compound 48/80 failed to influence the mast cell mediated response. Application of 1 and 10 µg/ml compound 48/80 evoked spike discharge and Ca++ transients in enteric neurons. The same nerve activating effect was observed in primary cultures of DRG and nodose ganglion cells. Enteric neuron cultures were devoid of mast cells confirmed by negative staining for c-kit or toluidine blue. In addition, in cultured enteric neurons the excitatory action of compound 48/80 was preserved in the presence of histamine H1 and H2 antagonists. The mast cell stabilizer cromolyn attenuated compound 48/80 and nicotine evoked Ca++ transients in mast cell-free enteric neuron cultures. Conclusions/Significance The results showed direct excitatory action of compound 48/80 on enteric neurons and visceral afferents. Therefore, functional changes measured in tissue or animal models may involve a mast cell independent effect of compound 48/80 and cromolyn.

Schemann, Michael; Kugler, Eva Maria; Buhner, Sabine; Eastwood, Christopher; Donovan, Jemma; Jiang, Wen; Grundy, David

2012-01-01

321

Persistence of biologically active compounds in soil: Final report  

SciTech Connect

This document describes the long-term effects of soil-applied oil shale process water on the VA fungi and Rhizobium bacteria in a native soil. Techniques include assessing the VA fungal activity at field treatment plots and using treated field soils in a bioassay to determine VA infection and Rhizobium-nodulation potentials four years after process water application. 52 refs., 32 figs., 2 tabs.

Williams, S.E.

1987-02-01

322

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

323

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

PubMed

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

Rumiyati; Jayasena, Vijay; James, Anthony P

2013-12-01

324

Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds from Allanblackia monticola and Symphonia globulifera.  

PubMed

In a preliminary antiprotozoal screening of several Clusiaceae species, the methanolic extracts of Allanblackia monticola and Symphonia globulifera showed high in vitro leishmanicidal activity. Further bioguided phytochemical investigation led to the isolation of four benzophenones: guttiferone A (1), garcinol (2), cambogin (3) and guttiferone F (4), along with three xanthones: allanxanthone A (5), xanthone V1 (6) and globulixanthone C (7) as active constituents. Compounds 1 and 6 were isolated from S. globulifera leaves, while compounds 2-5 were obtained from A. monticola fruits. Guttiferone A (1) and F (4) showed particulary strong leishmanicidal activity in vitro, with IC50 values (0.2 microM and 0.16 microM, respectively) comparable to that of the reference compound, miltefosine (0.46 microM). Although the leishmanicidal activity is promising, the cytotoxicity profile of these compounds prevent at this state further in vivo biological evaluation. In addition, all the isolated compounds were tested in vitro for their anticholinesterase properties. The four benzophenones showed potent anticholinesterase properties towards acetylcholinesterase (AChE) and butylcholinesterase (AChE). For AChE, the IC50 value (0.66 microM) of garcinol (2) was almost equal to that of the reference compound galanthamine (0.50 microM). Furthermore, guttiferone A (1) and guttiferone F (4) (IC50 = 2.77 and 3.50 microM, respectively) were more active than galanthamine (IC50 = 8.5) against BChE. PMID:17960072

Lenta, Bruno Ndjakou; Vonthron-Sénécheau, Catherine; Weniger, Bernard; Devkota, Krishna Prasad; Ngoupayo, Joseph; Kaiser, Marcel; Naz, Qamar; Choudhary, Muhammad Iqbal; Tsamo, Etienne; Sewald, Norbert

2007-01-01

325

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

PubMed Central

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

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

1996-01-01

326

Synthesis, fungicidal activity, and structure-activity relationship of spiro-compounds containing macrolactam (macrolactone) and thiadiazoline rings.  

PubMed

Two series of novel spiro-compounds containing macrolactam or macrolactone and thiadiazoline rings, 1-thia-2-alkylimino-3,4,9-triaza-10-oxospiro[4.15]eicosyl-3-ene (4F) and 1-thia-2-alkylimino-3,4-diaza-9-oxa-10-oxospiro[4.15]eicosyl-3-ene (4G), were synthesized from 12-oxo-1,15-pentadecanlactam and 12-oxo-1,15-pentadecanlactone, respectively. Their structures were confirmed by elemental analysis, (1)H NMR, and (13)C NMR. The conformation of compounds 4F was determined via the crystal structure of a representative compound (4F(6)). The bioassay showed that compounds 4F have much better fungicidal activity against five fungi ( Botrytis cinerea Pers., Sclerotinia sclerotiorum , Rhizoctonia solani Kuhn., Phomopsis asparagi Sacc., and Pyricularia oryzae Cav.) than compounds 4G. The fact above showed that the presence of a hydrogen-bonding donor for the fungicidal activity of macrocyclic compounds is very important. 4F(6) showed excellent fungicidal activity against P. oryzae, which is much better than the commercial fungicide isoprothiolane, and 4F(13) showed excellent fungicidal activity against P. oryzae and good fungicidal activity against P. asparagi. PMID:20041703

Li, Jian-Jun; Liang, Xiao-Mei; Jin, Shu-Hui; Zhang, Jian-Jun; Yuan, Hui-Zhu; Qi, Shu-Hua; Chen, Fu-Heng; Wang, Dao-Quan

2010-03-10

327

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

Microsoft Academic Search

Phenolic compounds, related to antioxidative and antifungal properties of ethanolic extracts from five commercial grape cultivars (three red and two white) grown in Turkey were determined. A reversed-phase high performance liquid chromatography (RP-HPLC) procedure was developed, and a total 18 different phenolic compounds were identified. Total phenolic contents of the extracts were determined using Folin–Ciocalteau method. Antioxidant activities of the

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

2011-01-01

328

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

PubMed

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

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

2014-02-01

329

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

PubMed

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

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

2009-04-01

330

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

PubMed Central

The prion protein (PrP) is implicated in the Transmissible Spongiform Encephalopathies (TSEs), which comprise a group of fatal neurodegenerative diseases affecting humans and other mammals. Conversion of cellular PrP (PrPC) into the scrapie form (PrPSc) is the hallmark of TSEs. Once formed, PrPSc aggregates and catalyzes PrPC misfolding into new PrPSc molecules. Although many compounds have been shown to inhibit the conversion process, so far there is no effective therapy for TSEs. Besides, most of the previously evaluated compounds failed in vivo due to poor pharmacokinetic profiles. In this work we propose a combined in vitro/in silico approach to screen for active anti-prion compounds presenting acceptable drugability and pharmacokinetic parameters. A diverse panel of aromatic compounds was screened in neuroblastoma cells persistently infected with PrPSc (ScN2a) for their ability to inhibit PK-resistant PrP (PrPRes) accumulation. From ?200 compounds, 47 were effective in decreasing the accumulation of PrPRes in ScN2a cells. Pharmacokinetic and physicochemical properties were predicted in silico, allowing us to obtain estimates of relative blood brain barrier permeation and mutagenicity. MTT reduction assays showed that most of the active compounds were non cytotoxic. Compounds that cleared PrPRes from ScN2a cells, were non-toxic in the MTT assay, and presented a good pharmacokinetic profile were investigated for their ability to inhibit aggregation of an amyloidogenic PrP peptide fragment (PrP109–149). Molecular docking results provided structural models and binding affinities for the interaction between PrP and the most promising compounds. In summary, using this combined in vitro/in silico approach we have identified new small organic anti-scrapie compounds that decrease the accumulation of PrPRes in ScN2a cells, inhibit the aggregation of a PrP peptide, and possess pharmacokinetic characteristics that support their drugability. These compounds are attractive candidates for prion disease therapy.

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

2014-01-01

331

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

332

Identifying Functionally Important Conformational Changes in Proteins: Activation of the Yeast ?-factor Receptor Ste2p  

PubMed Central

We have developed a procedure in which disulfide crosslinks are used to identify regions of proteins that undergo functionally important intramolecular motion. The approach was applied to the identification of disulfide bonds that stabilize the active state of the yeast ?-mating pheromone receptor Ste2p, a member of the superfamily of G Protein Coupled Receptors. Cysteine residues were introduced at random positions in targeted regions of a starting allele of Ste2p that completely lacks cysteines. Libraries of mutated receptors were then screened for alleles that exhibit constitutive signaling. Two strongly activated alleles were recovered containing cysteine residues in transmembrane segments 5 and 6. Constitutive activity of these alleles was dependent on the presence of both introduced cysteines and was sensitive to reducing agent. Crosslinked peptides derived from the mutant receptors were detected by immunoblotting. Additional sites of crosslinking between transmembrane segments 5 and 6 that did not lead to constitutive activation were also identified. These results indicate that relative motion of the transmembrane segments 5 and 6 in the extracellular half of the membrane is sufficient to activate the receptor and that transmembrane segment 6, but not transmembrane segment 5, exhibits rotational mobility that is not associated with receptor activation.

Taslimi, Amir; Mathew, Elizabeth; Celic, Andjelka; Wessel, Sarah; Dumont, Mark E.

2012-01-01

333

Oxidation of pharmaceutically active compounds by a ligninolytic fungal peroxidase.  

PubMed

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

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

2011-06-01

334

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

PubMed

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

Lage, Paula Sousa; de Andrade, Pedro Henrique Rocha; Lopes, Amanda de Santana; Chávez Fumagalli, Miguel Angel; Valadares, Diogo Garcia; Duarte, Mariana Costa; Pagliara Lage, Daniela; Costa, Lourena Emanuele; Martins, Vivian Tamietti; Ribeiro, Tatiana Gomes; Filho, José Dias de Souza; Tavares, Carlos Alberto Pereira; de Pádua, Rodrigo Maia; Leite, Joăo Paulo Viana; Coelho, Eduardo Antonio Ferraz

2013-01-01

335

Modifiers of notch transcriptional activity identified by genome-wide RNAi  

PubMed Central

Background The Notch signaling pathway regulates a diverse array of developmental processes, and aberrant Notch signaling can lead to diseases, including cancer. To obtain a more comprehensive understanding of the genetic network that integrates into Notch signaling, we performed a genome-wide RNAi screen in Drosophila cell culture to identify genes that modify Notch-dependent transcription. Results Employing complementary data analyses, we found 399 putative modifiers: 189 promoting and 210 antagonizing Notch activated transcription. These modifiers included several known Notch interactors, validating the robustness of the assay. Many novel modifiers were also identified, covering a range of cellular localizations from the extracellular matrix to the nucleus, as well as a large number of proteins with unknown function. Chromatin-modifying proteins represent a major class of genes identified, including histone deacetylase and demethylase complex components and other chromatin modifying, remodeling and replacement factors. A protein-protein interaction map of the Notch-dependent transcription modifiers revealed that a large number of the identified proteins interact physically with these core chromatin components. Conclusions The genome-wide RNAi screen identified many genes that can modulate Notch transcriptional output. A protein interaction map of the identified genes highlighted a network of chromatin-modifying enzymes and remodelers that regulate Notch transcription. Our results open new avenues to explore the mechanisms of Notch signal regulation and the integration of this pathway into diverse cellular processes.

2010-01-01

336

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

PubMed

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

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

2014-07-01

337

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

PubMed

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

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

2014-01-01

338

Potent inhibition of NFAT activation and T cell cytokine production by novel low molecular weight pyrazole compounds.  

PubMed

NFAT (nuclear factor of activated T cell) proteins are expressed in most immune system cells and regulate the transcription of cytokine genes critical for the immune response. The activity of NFAT proteins is tightly regulated by the Ca(2+)/calmodulin-dependent protein phosphatase 2B/calcineurin (CaN). Dephosphorylation of NFAT by CaN is required for NFAT nuclear localization. Current immunosuppressive drugs such as cyclosporin A and FK506 block CaN activity thus inhibiting nuclear translocation of NFAT and consequent cytokine gene transcription. The inhibition of CaN in cells outside of the immune system may contribute to the toxicities associated with cyclosporin A therapy. In a search for safer immunosuppressive drugs, we identified a series of 3,5-bistrifluoromethyl pyrazole (BTP) derivatives that block Th1 and Th2 cytokine gene transcription. The BTP compounds block the activation-dependent nuclear localization of NFAT as determined by electrophoretic mobility shift assays. Confocal microscopy of cells expressing fluorescent-tagged NFAT confirmed that the BTP compounds block calcium-induced movement of NFAT from the cytosol to the nucleus. Inhibition of NFAT was selective because the BTP compounds did not affect the activation of NF-kappaB and AP-1 transcription factors. Treatment of intact T cells with the BTP compounds prior to calcium ionophore-induced activation of CaN caused NFAT to remain in a highly phosphorylated state. However, the BTP compounds did not directly inhibit the dephosphorylation of NFAT by CaN in vitro, nor did the drugs block the dephosphorylation of other CaN substrates including the type II regulatory subunit of protein kinase A and the transcription factor Elk-1. The data suggest that the BTP compounds cause NFAT to be maintained in the cytosol in a phosphorylated state and block the nuclear import of NFAT and, hence, NFAT-dependent cytokine gene transcription by a mechanism other than direct inhibition of CaN phosphatase activity. The novel inhibitors described herein will be useful in better defining the cellular regulation of NFAT activation and may lead to identification of new therapeutic targets for the treatment of autoimmune disease and transplant rejection. PMID:11592964

Trevillyan, J M; Chiou, X G; Chen, Y W; Ballaron, S J; Sheets, M P; Smith, M L; Wiedeman, P E; Warrior, U; Wilkins, J; Gubbins, E J; Gagne, G D; Fagerland, J; Carter, G W; Luly, J R; Mollison, K W; Djuric, S W

2001-12-21

339

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

Microsoft Academic Search

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

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

1997-01-01

340

[Assessment of antioxidant activity of natural compound by water- and lipid-soluble antioxidant factor].  

PubMed

We evaluated the antioxidant activity of natural compounds in water-soluble and lipid-soluble phases and found that ferulic acid, quercetin and caffeic acid showed stronger activity in the water-soluble phase. Various fractions isolated from Bidens pilosa showed this activity mainly in the water-soluble phase. Antioxidant activity in the lipid-soluble phase of propolis depended on the lipophilic extraction. PMID:15516812

Usami, Eiji; Kusano, Genjiro; Katayose, Takanori; Wachi, Hiroshi; Seyama, Yoshiyuki

2004-11-01

341

Antihypertensive activity of peptides identified in the in vitro gastrointestinal digest of pork meat.  

PubMed

This study investigated the in vivo antihypertensive activity of three novel peptides identified in the in vitro digest of pork meat. These peptides were RPR, KAPVA and PTPVP and all of them showed significant antihypertensive activity after oral administration to spontaneously hypertensive rats, RPR being the peptide with the greatest in vivo activity. To our knowledge, this is the first report showing the in vivo antihypertensive action of the three peptides from nebulin (RPR) and titin (KAPVA and PTPVP), thus confirming their reported in vitro angiotensin I-converting enzyme (ACE) inhibitory activity. These findings suggest that pork meat could constitute a source of bioactive constituents that could be utilized in functional foods or nutraceuticals. PMID:22405912

Escudero, Elizabeth; Toldrá, Fidel; Sentandreu, Miguel Angel; Nishimura, Hitoshi; Arihara, Keizo

2012-07-01

342

Zoosporicidal activity of polyflavonoid tannin identified in Lannea coromandelica stem bark against phytopathogenic oomycete Aphanomyces cochlioides.  

PubMed

In a survey of nonhost plant secondary metabolites regulating motility and viability of zoospores of the Aphanomyces cochlioides, we found that stem bark extracts of Lannea coromandelica remarkably inhibited motility of zoospores followed by lysis. Bioassay-guided fractionation and chemical characterization of Lannea extracts by MALDI-TOF-MS revealed that the active constituents were angular type polyflavonoid tannins. Commercial polyflavonoid tannins, Quebracho and Mimosa, also showed identical zoosporicidal activity. Against zoospores, the motility-inhibiting and lytic activities were more pronounced in Lannea extracts (MIC 0.1 microg/mL) than in Quebracho (MIC 0.5 microg/mL) and Mimosa (MIC 0.5 microg/mL). Scanning electron microscopic observation visualized that both Lannea and commercial tannins caused lysis of cell membrane followed by fragmentation of cellular materials. Naturally occurring polyflavonoid tannin merits further study as potential zoospore regulating agent or as lead compound. To the best of our knowledge, this is the first report of zoosporicidal activity of natural polyflavonoid tannins against an oomycete phytopathogen. PMID:12405764

Islam, Md Tofazzal; Ito, Toshiaki; Sakasai, Mitsuyoshi; Tahara, Satoshi

2002-11-01

343

In silico identification of novel lead compounds with AT1 receptor antagonist activity: successful application of chemical database screening protocol  

PubMed Central

Background AT1 receptor antagonists are clinically effective drugs for the treatment of hypertension, cardiovascular, and related disorders. In an attempt to identify new AT1 receptor antagonists, a pharmacophore-based virtual screening protocol was applied. The pharmacophore models were generated from 30 training set compounds. The best model was chosen on the basis of squared correlation coefficient of training set and internal test set. The validity of the developed model was also ensured using catScramble validation method and external test set prediction. Results The final model highlighted the importance of hydrogen bond acceptor, hydrophobic aliphatic, hydrophobic, and ring aromatic features. The model satisfied all the statistical criteria such as cost function analysis and correlation coefficient. The result of estimated activity for internal and external test set compounds reveals that the generated model has high prediction capability. The validated pharmacophore model was further used for mining of 56000 compound database (MiniMaybridge). Total 141 hits were obtained and all the hits were checked for druggability, this led to the identification of two active druggable AT1 receptor antagonists with diverse structure. Conclusion A highly validated pharmacophore model generated in this study identified two novel druggable AT1 receptor antagonists. The developed model can also be further used for mining of other virtual database.

2012-01-01

344

Volatile Compounds of Viola odorata Absolutes: Identification of Odorant Active Markers to Distinguish Plants Originating from France and Egypt.  

PubMed

Absolutes isolated from Viola odorata leaves, valuable materials for the flavor and fragrance industry, were studied. Violets are mainly cultivated in France and Egypt and extracted locally. The absolutes of the two origins showed different olfactory profiles both in top and heart notes, as evidenced by sensory analysis. The aims of this study were i) to characterize the volatile compounds, ii) to determine the odorant-active ones, and iii) to identify some markers of the plant origin. Two complementary analytical methods were used for these purposes, i.e., headspace solid-phase microextraction (HS-SPME) using different fiber coatings followed by GC/MS analysis and gas chromatography - olfactometry/mass spectrometry (GC-O/MS) applied to violet leaf extracts. From a total of 70 identified compounds, 61 have never been reported so far for this species, 17 compounds were characterized by both techniques (with seven among them known from the literature), 23 compounds were solely identified by HS-SPME GC/MS (among them only two being already mentioned as components of violet absolutes in the literature), and, finally, 30 compounds were only identified by GC-O/MS. According to the HS-SPME GC/MS analyses, ethyl hexanoate and (2E,6Z)-nona-2,6-dienol were specific volatile compounds of the sample with French origin, while (E,E)-hepta-2,4-dienal, hexanoic acid, limonene, tridecane, and eugenol were specific of the samples with Egyptian origin. Additional compounds that were not detected by HS-SPME GC/MS analysis were revealed by GC-O analyses, some of them being markers of origin. Pent-1-en-3-ol, 3-methylbut-2-enal, 2-methoxy-3-(1-methylethyl)pyrazine, 4-ethylbenzaldehyde, ?-phenethyl formate, and 2-methoxy-3-(2-methylpropyl)pyrazine revealed to be odorant markers of the French sample, whereas cis-rose oxide, trans-rose oxide, and 3,5,5-trimethylcyclohex-2-enone were odorant markers of the Egyptian samples. PMID:24934671

Saint-Lary, Laure; Roy, Céline; Paris, Jean-Philippe; Tournayre, Pascal; Berdagué, Jean-Louis; Thomas, Olivier P; Fernandez, Xavier

2014-06-01

345

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

PubMed Central

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

2013-01-01

346

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

PubMed Central

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

2013-01-01

347

A novel dicyclodextrinyl diselenide compound with glutathione peroxidase activity.  

PubMed

A 6A,6A'-dicyclohexylamine-6B,6B'-diselenide-bis-beta-cyclodextrin (6-CySeCD) was designed and synthesized to imitate the antioxidant enzyme glutathione peroxidase (GPX). In this novel GPX model, beta-cyclodextrin provided a hydrophobic environment for substrate binding within its cavity, and a cyclohexylamine group was incorporated into cyclodextrin in proximity to the catalytic selenium in order to increase the stability of the nucleophilic intermediate selenolate. 6-CySeCD exhibits better GPX activity than 6,6'-diselenide-bis-cyclodextrin (6-SeCD) and 2-phenyl-1,2-benzoisoselenazol-3(2H)-one (Ebselen) in the reduction of H(2)O(2), tert-butyl hydroperoxide and cumenyl hydroperoxide by glutathione, respectively. A ping-pong mechanism was observed in steady-state kinetic studies on 6-CySeCD-catalyzed reactions. The enzymatic properties showed that there are two major factors for improving the catalytic efficiency of GPX mimics. First, the substrate-binding site should match the size and shape of the substrate and second, incorporation of an imido-group increases the stability of selenolate in the catalytic cycle. More efficient antioxidant ability compared with 6-SeCD and Ebselen was also seen in the ferrous sulfate/ascorbate-induced mitochondria damage system, and this implies its prospective therapeutic application. PMID:17617230

Lv, Shao-Wu; Wang, Xiao-Guang; Mu, Ying; Zang, Tian-Zhu; Ji, Yue-Tong; Liu, Jun-Qiu; Shen, Jia-Cong; Luo, Gui-Min

2007-08-01

348

SYNTHESIS AND BIOLOGICAL ACTIVITIES OF CERTAIN MESOIONIC SYDNONE COMPOUNDS CONTAINING CHALCONE MOIETY  

PubMed Central

In order to have antibacterial, analgesic and anti-inflammatory activity in the same molecule, 4-[1-oxo-3- (substituted aryl)-2-propenyl]-3-(4-chlorophenyl) sydnones were synthesized by condensing 4-acetyl-3-(4-chlorophenyl)sydnone with various substituted aryl aldehydes and characterized by spectral studies; 4-acetyl-3-(4-chlorophenyl)sydnone itself, was prepared by acetylation of 3-(4-chlorophenyl) sydnone. The newly synthesized compounds were evaluated for antibacterial and anti-inflammatory activities by cup plate and carrageenan induced rat paw edema methods respectively. Some of the compounds showed promising antibacterial and anti-inflammatory activities

Deshpande, Shreenivas R.; Pai, K. Vasantakumar

2010-01-01

349

Virtual Screening against Highly Charged Active Sites:  Identifying Substrates of Alpha?Beta Barrel Enzymes †  

Microsoft Academic Search

We have developed a virtual ligand screening method designed to help assign enzymatic function for alpha-beta barrel proteins. We dock a library of 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-

Chakrapani Kalyanaraman; Katarzyna Bernacki; Matthew P. Jacobson

2005-01-01

350

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

PubMed

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

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

2008-09-15

351

Isolation and identification of acaricidal compounds in Eupatorium adenophorum petroleum ether extract and determination of their acaricidal activity against Psoroptes cuniculi.  

PubMed

We used multiple silica gel column chromatography and thin-layer chromatography coupled with (1)H nuclear magnetic resonance (NMR) and (13)C NMR to separate and identify the active acaricidal ingredients in Eupatorium adenophorum petroleum ether extract. The acaricidal activity of each compound was tested against Psoroptes cuniculi in vitro. Three compounds had strong acaricidal activity against P. cuniculi in vitro. The insecticidal effect of 0.5% compound 9?-hydroxy-ageraphorone was better than the insecticidal effect of fenvalerate, and compounds 9-oxo-ageraphorone and 9-oxo-10,11-dehydro-ageraphorone exhibited higher insecticidal effects than 9?-hydroxy-ageraphorone. Thus, the E. adenophorum petroleum ether extract contains an effective composition of acaricides that could potentially be developed as a promising plant-origin acaricide. PMID:24569033

Nong, Xiang; Li, Shu-Hua; Chen, Feng-Zheng; Wang, Jia-Hai; Xie, Yue; Fang, Chun-Lin; Liu, Tian-Fei; He, Ran; Gu, Xiao-Bin; Peng, Xue-Rong; Yang, Guang-You

2014-06-16

352

Pharmacophore based virtual screening, molecular docking and biological evaluation to identify novel PDE5 inhibitors with vasodilatory activity.  

PubMed

Prompted by the role of PDE5 and its closely associated cAMP and cGMP in hypertension, we have attempted to discover novel PDE5 inhibitors through ligand based virtual screening. Rigorously validated model comprising of one HBA, one HY and one RA was used as a query to search the NCI database leading to retrieval of many compounds which were screened on the basis of estimated activity, fit value and Lipinski's violation. Selected compounds were subjected to docking studies which resulted into visualization of potential interaction capabilities of NCI compounds in line to pharmacophoric features. Finally three compounds were subjected to in vitro evaluation using the isolated rat aortic model. The results showed that all three compounds are potent and novel PDE5 inhibitors with vasodilatory activity range from 10(-2) to 10(-5)M. PMID:24856068

Mittal, Anupama; Paliwal, Sarvesh; Sharma, Mukta; Singh, Aarti; Sharma, Swapnil; Yadav, Divya

2014-07-15

353

Adsorption and Regeneration on Activated Carbon Fiber Cloth for Volatile Organic Compounds at Indoor Concentration Levels  

Microsoft Academic Search

There are increasing concerns about indoor volatile organic compounds (VOCs) regarding their health effects and frequent occurrence. Adsorption using granular activated carbon (GAC) is a safe methodology for removing VOCs from indoor air. Although GAC has been widely used to remove VOCs from indoor air, the use of activated carbon fiber cloth (ACFC) is a promising substitute to the conventional

Meng Yao; Qiong Zhang; David W. Hand; David Perram; Roy Taylor; Mridul Gautam; Nigel Clark; Thomas Spencer; Daniel Carder; Thomas Balon; Paul Moynihan; Joshua Fu; David Streets; Carey Jang; Jiming Hao; Kebin He; Litao Wang; Qiang Zhang; Jan Paca; Martin Halecky; Mark Fitch; David Williams; William Potter; William Clarkson; Dee Sanders; John Stevens; Hazem El-Zanan; Barbara Zielinska; Lynn Mazzoleni; D. Hansen; Hyun-Sun Kim; Seung-Muk Yi; Eric Edgerton; Gary Casuccio; Rick Saylor; Traci Lersch; Benjamin Hartsell; John Jansen; Roger Wayson; Gregg Fleming; Ralph Iovinelli; Hans Grimm; Delbert Eatough

2009-01-01

354

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

PubMed Central

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

Klancnik, Anja; Mozina, Sonja Smole; Zhang, Qijing

2012-01-01

355

Assay development for identifying inhibitors of the mycobacterial FadD32 activity.  

PubMed

FadD32, a fatty acyl-AMP ligase (FAAL32) involved in the biosynthesis of mycolic acids, major and specific lipid components of the mycobacterial cell envelope, is essential for the survival of Mycobacterium tuberculosis, the causative agent of tuberculosis. The protein catalyzes the conversion of fatty acid to acyl-adenylate (acyl-AMP) in the presence of adenosine triphosphate and is conserved in all the mycobacterial species sequenced so far, thus representing a promising target for the development of novel antituberculous drugs. Here, we describe the optimization of the protein purification procedure and the development of a high-throughput screening assay for FadD32 activity. This spectrophotometric assay measuring the release of inorganic phosphate was optimized using the Mycobacterium smegmatis FadD32 as a surrogate enzyme. We describe the use of T m (melting temperature) shift assay, which measures the modulation of FadD32 thermal stability, as a tool for the identification of potential ligands and for validation of compounds as inhibitors. Screening of a selected library of compounds led to the identification of five novel classes of inhibitors. PMID:23364516

Galandrin, Ségolčne; Guillet, Valérie; Rane, Rajendra S; Léger, Mathieu; N, Radha; Eynard, Nathalie; Das, Kaveri; Balganesh, Tanjore S; Mourey, Lionel; Daffé, Mamadou; Marrakchi, Hedia

2013-06-01

356

A Phosphotyrosine Proteomic Screen Identifies Multiple Tyrosine Kinase Signaling Pathways Aberrantly Activated in Malignant Mesothelioma  

PubMed Central

Malignant mesothelioma (MM) is a highly aggressive cancer that is refractory to all current chemotherapeutic regimens. Therefore, uncovering new rational therapeutic targets is imperative in the field. Tyrosine kinase signaling pathways are aberrantly activated in many human cancers and are currently being targeted for chemotherapeutic intervention. Thus, we sought to identify tyrosine kinases hyperactivated in MM. An unbiased phosphotyrosine proteomic screen was employed to identify tyrosine kinases activated in human MM cell lines. From this screen, we have identified novel signaling molecules, such as JAK1, STAT1, cortactin (CTTN), FER, p130Cas (BCAR1), SRC, and FYN as tyrosine phosphorylated in human MM cell lines. Additionally, STAT1 and SRC family kinases (SFK) were confirmed to be active in primary MM specimens. We also confirmed that known signal transduction pathways previously implicated in MM, such as EGFR and MET signaling axes, are coactivated in the majority of human MM specimens and cell lines tested. EGFR, MET, and SFK appear to be coactivated in a significant proportion of MM cell lines, and dual inhibition of these kinases was demonstrated to be more efficacious for inhibiting MM cell viability and downstream effector signaling than inhibition of a single tyrosine kinase. Consequently, these data suggest that tyrosine kinase inhibitor monotherapy may not represent an efficacious strategy for the treatment of MM due to multiple tyrosine kinases potentially signaling redundantly to cellular pathways involved in tumor cell survival and proliferation.

Menges, Craig W.; Chen, Yibai; Mossman, Brooke T.; Chernoff, Jonathan; Yeung, Anthony T.; Testa, Joseph R.

2010-01-01

357

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 figures.

Tuan Vodinh.

1993-12-21

358

Dinuclear alkyldiamine platinum antitumor compounds: a structure-activity relationship study.  

PubMed

Six related dinuclear trans-platinum complexes, with the formula [[trans-PtCl(2)(NH(3))(L)](2)(mu-H(2)N(CH(2))(n)NH(2))](2+) (L = pyridine, 2-picoline, 4-picoline; n = 4, 6) and chloride or nitrate anions, are compared with known cytotoxic dinuclear compounds (L = NH(3); n = 4, 6) that overcome cisplatin resistance. The cytotoxicity of the compounds was determined in L1210 murine leukemia and L1210/2, a cisplatin-resistant derivative. Unlike the L = NH(3) compounds, the substituted n = 4 compounds are more susceptible toward the resistance mechanisms in L1201/2. The n = 6 compounds, however, have comparable IC(50) values in both cell lines. In general, the substituted compounds are less cytotoxic than their NH(3) counterparts. After incubation with equimolar concentrations, the amount of platinum bound to cellular DNA was determined. The compounds show comparable binding, except for the sterically hindered 2-picoline compounds that bind significantly less. The amounts of platinum bound to DNA do not correlate with the cytotoxicity data. As DNA is considered to be the cellular target of platinum antitumor drugs, structural details of the DNA adducts probably account for the differences in cytotoxic activity. PMID:11170634

Jansen, B A; van der Zwan, J; den Dulk, H; Brouwer, J; Reedijk, J

2001-01-18

359

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

2013-01-01

360

Antioxidant activity of commercial wild rice and identification of flavonoid compounds in active fractions.  

PubMed

The health benefits of whole grain consumption have been attributed to their content of complex carbohydrates, vitamins, minerals, and other phytochemical constituents. Wild rice is a whole grain finding applications in gourmet foods due to its nutritional value and unique taste. However, little is known about its antioxidant properties and phytochemical components. The objectives of this study were to evaluate the antioxidant properties of wild rice. Eleven commercial wild rice samples (raw, mixed, and processed) were extracted with acetone and fractionated using a Sephadex LH-20 column. 2,2-Diphenyl-1-picrylhydrazyl radical (DPPH(*)) scavenging activity, oxygen radical absorbance capacity (ORAC), and total phenolic content were evaluated to determine the antioxidant properties of wild rice. The antioxidant activity of wild rice was found to be 30 times greater than that of the control white rice. Significant differences (p < 0.05) in antioxidant activities were found among raw, mixed, and processed samples. For raw samples, DPPH(*) radical scavenging activities and ORAC values ranged from 611 to 917 micromol of Trolox equivalent (TE)/100 g and from 4069 to 6064 micromol of TE/100 g, respectively. For mixed and processed wild rice, DPPH(*) radical scavenging activities were 373 and 441 micromol of TE/100 g, respectively. The corresponding ORAC values were 2284 and 2557 micromol of TE/100 g. Total phenolic content (TPC) of raw wild rice varied from 2472 to 4072 mg of ferulic acid equivalent (FAE)/kg, higher than that of the mixed sample (1460 mg of FAE/kg) and processed sample (2076 mg of FAE/kg). TPC was highly correlated with total antioxidant activity of wild rice (r = 0.92). Tandem mass spectrometric techniques revealed the antioxidants identified in wild rice to be flavonoid glycosides (diglucosyl apigenin, glucosyl-arabinosyl apigenin, and diarabinosyl apigenin) in factions 2 and 3 and flavan-3-ols (catechin, epicatechin, and oligomeric procyanidin) in fractions 4 and 5. PMID:19630388

Qiu, Yang; Liu, Qin; Beta, Trust

2009-08-26

361

Cost Analysis of Activated Carbon Versus Photocatalytic Oxidation for Removing Organic Compounds from Indoor Air  

Microsoft Academic Search

A cost comparison has been conducted of 1 m\\/sec indoor air cleaners using granular activated carbon (GAC) versus photocatalytic oxidation (PCO) for treating a steady-state inlet volatile organic compound (VOC) concentration of 0.27 mg\\/m. The commercial GAC unit was costed assuming that the inlet VOCs had a reasonable carbon sorption affinity, representative of compounds having four or more atoms (exclusive

D. Bruce Henschel

1998-01-01

362

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

363

Pupicidal and repellent activities of Pogostemon cablin essential oil chemical compounds against medically important human vector mosquitoes  

PubMed Central

Objective To determine the repellent and pupicidal activities of Pogostemon cablin (P. cablin) chemical compositions were assayed for their toxicity against selected important vector mosquitoes, viz., Aedes aegypti (Ae. aegypti), Anopheles stephensi (An. stephensi) and Culex quinquefasciatus (Cx. quinquefasciatus) (Diptera: Culicidae). Methods The plants dry aerial parts were subjected to hydrodistillation using a modified Clevenger-type apparatus. The composition of the essential oil was analyzed by Gas Chromatography (GC) and GC mass spectrophotometry. Evaluation was carried out in a net cage (45 cm×30 cm×45 cm) containing 100 blood starved female mosquitoes and were assayed in the laboratory condition by using the protocol of WHO 2010. The repellent activity of P. cablin chemical compositions at concentration of 2mg/cm2were applied on skin of fore arm in man and exposed against adult female mosquitoes. The pupicidal activity was determined against selected important vector mosquitoes to concentration of 100 mg/L and mortality of each pupa was recorded after 24 h of exposure to the compounds. Results Chemical constituents of 15 compounds were identified in the oil of P.cablin compounds representing to 98.96%. The major components in essential oil were â-patchoulene, á-guaiene, ă-patchoulene, á-bulnesene and patchouli alcohol. The repellent activity of patchouli alcohol compound was found to be most effective for repellent activity and 2 mg/cm2 concentration provided 100% protection up to 280 min against Ae. aegypti, An. stephensi and Cx. quinquefasciatus, respectively. Similarly, pupae exposed to 100 mg/L concentrations of P. cablin chemical compositions. Among five compounds tested patchouli alcoholwas found to be most effective for pupicidal activity provided 28.44, 26.28 and 25.36 against Ae.aegypti, An.stephensi and Cx. quinquefasciatus, respectively. The percent adult emergence was inversely proportional to the concentration of compounds and directly proportional to the pupal mortality. Conclusion These results suggest that the P. cablin chemical compositions have the potential to be used as an ideal eco-friendly approach for the control of mosquitoes. This is the first report on the mosquito repellent and pupicidal activities of the reported P. cablin chemical compositions.

Gokulakrishnan, J; Kuppusamy, Elumalai; Shanmugam, Dhanasekaran; Appavu, Anandan; Kaliyamoorthi, Krishnappa

2013-01-01

364

Carcinogenic potential of phthalic acid esters and related compounds: structure-activity relationships.  

PubMed Central

Chronic toxicity and carcinogenicity studies of several phthalic acid esters (PAEs) and compounds containing a 2-ethylhexyl moiety were conducted in Fischer 344 rats and B6C3F1 (hybrid) mice. The compounds studied were phthalic anhydride, di(2-ethylhexyl) phthalate, butyl benzyl phthalate, diallyl phthalate, di(2-ethylhexyl) adipate, tris(2-ethylhexyl) phosphate, and 2-ethylhexyl sulfate (sodium salt). Estimated maximum tolerable doses and fractionally lower doses of each compound were administered to groups of 50 male and 50 female rats and mice for 2 years, followed by sacrifice, necropsy, and histopathological examination of major organs and tissues. The low toxic potencies of most of the compounds allowed for relatively high doses to be given during the chronic studies. In general, the toxic manifestations of the PAEs were closely correlated with their ester substituents. Although many of the PAEs possessed some carcinogenic activity, target sites for such effects were dissimilar, suggesting the absence of a common mode of action. In contrast, all of the 2-ethylhexyl-containing compounds studied possessed some hepatocarcinogenic activity, indicating that this moiety may have a propensity for causing hepatocarcinogenesis in mice, particularly those of the female sex. The 2-ethylhexyl compound that caused the greatest hepatocarcinogenic response in mice, di(2-ethylhexyl) phthalate, was also hepatocarcinogenic in rats. Similarly, those with a relatively greater effect in female mice were also active in male mice. Thus, sex and species differences in 2-ethylhexyl-induced hepatocarcinogenesis in rodents are probably quantitative rather than qualitative in nature.

Kluwe, W M

1986-01-01

365

Fate of toxic organic compounds in activated sludge and integrated activated sludge/carbon treatment systems. Volumes I and II  

SciTech Connect

Results from steady-state bioreactor studies indicated that 70 to 90% of the influent fluxes of benzene, toluene, ethylbenzene, o-xylene, chlorobenzene, and nitrobenzene and approximately 35% of the influent flux of 1,2-dichlorobenzene were biodegraded by acclimated activated sludges. Biodegradation effected approximately equal percent reductions in effluent and off-gas concentrations of the volatile, biodegradable compounds. Acclimation periods for all biodegradable compounds ranged from 14 to 21 days. Lindane and 1,2,4-trichlorobenzene were found to be nonbiodegradable in the experimental system. Results from steady-state bioreactor studies showed that the addition of less than 100 mg/l powdered activated carbon did not enhance the removal of the biodegradable compounds benzene, toluene, ethylbenzene, o-xylene, chlorobenzene, and nitrobenzene. Significantly improved removals of the poorly and non-biodegradable compounds, 1,2-dichlorobenzene, 1,2,4-trichlorobenzene, and lindane, occurred at influent powdered carbon concentrations in the 12.5 to 25 mg/l range. Influent PAC concentrations of 100 mg/l effected overall removals greater than 90%. The addition of powdered activated carbon not only reduced effluent concentration, but also reduced amounts of the volatile compounds stripped to the atmosphere. PAC-bioreactor studies demonstrated that the influent PAC concentration rather than the mixed liquor PAC concentration controlled the amounts of the compounds removed during steady-state operating periods.

Jones, B.E.

1985-01-01

366

Significant Centers of Tectonic Activity as Identified by Wrinkle Ridges for the Western Hemisphere of Mars  

NASA Technical Reports Server (NTRS)

The western hemisphere region of Mars has been the site of numerous scientific investigations regarding its tectonic evolution. For this region of Mars, the dominant tectonic region is the Tharsis province. Tharsis is characterized by an enormous system of radiating grabens and a circumferential system of wrinkle ridges. Past investigations of grabens associated with Tharsis have identified specific centers of tectonic activity. A recent structural analysis of the western hemisphere region of Mars which includes the Tharsis region, utilized 25,000 structures to determine the history of local and regional centers of tectonic activity based primarily on the spatial and temporal relationships of extensional features. This investigation revealed that Tharsis is more structurally complex (heterogeneous) than has been previously identified: it consists of numerous regional and local centers of tectonic activity (some are more dominant and/or more long lived than others). Here we use the same approach as Anderson et al. to determine whether the centers of tectonic activity that formed the extensional features also contributed to wrinkle ridge (compressional) formation.

Anderson, R.C.; Haldemann, A. F. C.; Golombek, M. P.; Franklin, B. J.; Dohm, J. M.; Lias, J.

2000-01-01

367

Low-molecular-weight, biologically active compounds from marine Pseudoalteromonas species.  

PubMed

We have examined the ability of marine Proteobacteria from the Pseudoalteromonas genus and Alteromonas macleodii to produce low-molecular-weight, biologically active compounds with antimicrobial and surface-active properties. A new marine bacterium, Pseudoalteromonas issachenkonii, exhibited a high level of biological activity and produced antifungal and hemolytic compounds. A detailed spectroscopic investigation based on UV, IR, high-resolution mass spectrometry, and 2D 1H and 13C nuclear magnetic resonance revealed that the former was indole-2,3-dione (isatin). The chemical structure of red-brown pigment (C9H7N3OS3) responsible for hemolytic activity remained unclear. Four of the 15 strains studied (P. luteoviolacea, P. rubra, P. undina, and P. issachenkonii) produced cell-bound, two (P. elaykovii and P. carrageenovora) produced extracellular, and one strain (P. citrea) produced cell-bound and extracellular fatty acids and phospholipids with surface activity. Neither peptides nor glycolipids with surface activity were detected. PMID:15170241

Kalinovskaya, Nataliya I; Ivanova, Elena P; Alexeeva, Yulia V; Gorshkova, Nataliya M; Kuznetsova, Tatyana A; Dmitrenok, Andrey S; Nicolau, Dan V

2004-06-01

368

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

2011-06-01

369

Accelerometer tags: detecting and identifying activities in fish and the effect of sampling frequency.  

PubMed

Monitoring and measuring the behaviour and movement of aquatic animals in the wild is typically challenging, though micro-accelerometer (archival or telemetry) tags now provide the means to remotely identify and quantify behavioural states and rates such as resting, swimming and migrating, and to estimate activity and energy budgets. Most studies use low-frequency (?32 Hz) accelerometer sampling because of battery and data-archiving constraints. In this study we assessed the effect of sampling frequency (aliasing) on activity detection probability using the great sculpin (Myoxocephalus polyacanthoceaphalus) as a model species. Feeding strikes and escape responses (fast-start activities) and spontaneous movements among seven different great sculpin were triggered, observed and recorded using video records and a tri-axial accelerometer sampling at 100 Hz. We demonstrate that multiple parameters in the time and probability domains can statistically differentiate between activities with high detection (90%) and identification (80%) probabilities. Detection probability for feeding and escape activities decreased by 50% when sampling at <10 Hz. Our analyses illustrate additional problems associated with aliasing and how activity and energy-budget estimates can be compromised and misinterpreted. We recommend that high-frequency (>30 Hz) accelerometer sampling be used in similar laboratory and field studies. If battery and/or data storage is limited, we also recommend archiving the events via an on-board algorithm that determines the highest likelihood and subsequent archiving of the various event classes of interest. PMID:23197088

Broell, Franziska; Noda, Takuji; Wright, Serena; Domenici, Paolo; Steffensen, John Fleng; Auclair, Jean-Pierre; Taggart, Christopher T

2013-04-01

370

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

PubMed

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 Ni(3)(shi)(2)(Hpko)(2)(py)(2)(1), two metal ions show a square planar geometry while the third one is in an octahedral environment. The compounds with four and five nickel atoms construct metallacrown cores with two distinct connectivities. The tetranuclear vacant metallacrown [12-MC(Ni(II)N(Hshi)2(pko)2)-4](2+) shows the connectivity pattern [-O-Ni-O-N-Ni-N-](2), while the pentanuclear ([Ni(II)][12-MC(Ni(II)N(shi)2(pko)2)-4])(2+) follows the pattern [-Ni-O-N-](4). Two distinct arrangements of the chelates around the ring metal ions were observed; a 6-5-6-5-6-5-6-5 arrangement for the [12-MC(Ni(II)N(Hshi)2(pko)2)-4] core and a 6-6-5-5-6-6-5-5 arrangement for the [12-MC(Ni(II)N(shi)2(pko)2)-4] core. Magnetic variable temperature susceptibility study of the trinuclear compound revealed the presence of one paramagnetic nickel(II) ion with strong crystal field dependence, with D=5.0(4) cm(-1), g(xy)=2.7(3) and g(z)=2.3(3). The effect of the synthesized Ni(II) complexes on the integrity and electrophoretic mobility of nucleic acids was examined. Only compounds 2, 3 and 4 altered the mobility of pDNA, forming high molecular weight concatamers at low concentrations or precipitates at higher concentrations. Antibacterial activity screening of the above compounds suggests that nickel compounds 2, 3 and 4 were the most active and can act as potent antibacterial agents. PMID:12576289

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

2003-01-15

371

Adsorption kinetics of aromatic compounds on carbon nanotubes and activated carbons.  

PubMed

Adsorption kinetics of two organic compounds on four types of carbonaceous adsorbents (a granular activated carbon [HD4000], an activated carbon fiber [ACF10], a single-walled carbon nanotube [SWNT], and a multiwalled carbon nanotube [MWNT]) was examined in aqueous solutions. The times needed for the adsorption to reach apparent equilibrium on the four carbons followed the order of ACF10?>?HD4000?>?SWNT?>?MWNT. Ultrasonication of the carbon nanotubes (CNTs) accelerated their adsorption kinetics but had no effect on their equilibrium adsorption capacities. The pseudo-second order model (PSOM) provided good fitting for the kinetic data. The fitting of kinetic data with the intraparticle diffusion model indicated that external mass transfer controls the sorption process in the organic compound-CNT systems, whereas intraparticle diffusion dominates in the sorption of organic compounds onto activated carbons. PMID:22021047

Zhang, Shujuan; Shao, Ting; Kose, H Selcen; Karanfil, Tanju

2012-01-01

372

Identifying Barriers to Patient Acceptance of Active Surveillance: Content Analysis of Online Patient Communications  

PubMed Central

Objectives Qualitative research aimed at identifying patient acceptance of active surveillance (AS) has been identified as a public health research priority. The primary objective of this study was to determine if analysis of a large-sample of anonymous internet conversations (ICs) could be utilized to identify unmet public needs regarding AS. Methods English-language ICs regarding prostate cancer (PC) treatment with AS from 2002–12 were identified using a novel internet search methodology. Web spiders were developed to mine, aggregate, and analyze content from the world-wide-web for ICs centered on AS. Collection of ICs was not restricted to any specific geographic region of origin. NLP was used to evaluate content and perform a sentiment analysis. Conversations were scored as positive, negative, or neutral. A sentiment index (SI) was subsequently calculated according to the following formula to compare temporal trends in public sentiment towards AS: [(# Positive IC/#Total IC) - (#Negative IC/#Total IC) x 100]. Results A total of 464 ICs were identified. Sentiment increased from -13 to +2 over the study period. The increase sentiment has been driven by increased patient emphasis on quality-of-life factors and endorsement of AS by national medical organizations. Unmet needs identified in these ICs include: a gap between quantitative data regarding long-term outcomes with AS vs. conventional treatments, desire for treatment information from an unbiased specialist, and absence of public role models managed with AS. Conclusions This study demonstrates the potential utility of online patient communications to provide insight into patient preferences and decision-making. Based on our findings, we recommend that multidisciplinary clinics consider including an unbiased specialist to present treatment options and that future decision tools for AS include quantitative data regarding outcomes after AS.

Mishra, Mark V.; Bennett, Michele; Vincent, Armon; Lee, Olivia T.; Lallas, Costas D.; Trabulsi, Edouard J.; Gomella, Leonard G.; Dicker, Adam P.; Showalter, Timothy N.

2013-01-01

373

Antioxidant, ?-glucosidase and xanthine oxidase inhibitory activity of bioactive compounds from maize (Zea mays L.).  

PubMed

Chemical investigations into maize (Zea mays L.) kernels yielded phenolic compounds, which were structurally established using chromatographic and spectroscopic methods. The isolated phenolic compounds from maize kernel were examined in vitro for their antioxidant abilities by DPPH (2,2-diphenyl-1-picryl hydrazine) radical, OH radical scavenging activity, and reducing ability, along with ?-glucosidase and xanthine oxidase (XO) inhibition. The isolated maize phenolics revealed significant xanthine oxidase and ?-glucosidase inhibitory activity to that of allopurinol and acarbose in vitro and in vivo, respectively. The kinetics study with xanthine oxidase revealed competitive type of inhibition by isolated maize vanillic acid (M2), ferulic acid (M5), 3'-methoxyhirsutrin (M7), and peonidin-3-glucoside (M10) as compared to control allopurinol. Overall, with few exceptions, all the phenolic compounds from maize kernel revealed significant biological activities with all parameters examined. Also, the phenolic compounds from maize were found to be more reactive toward DPPH radical and had considerable reducing ability and OH radical scavenging activity. These findings suggest that maize kernel phenolic compounds can be considered as potential antioxidant, ?-glucosidase, and XO inhibitory agents those might be further explored for the design of lead antioxidant, antidiabetic and antigout drug candidates using in vivo trials. PMID:23957301

Nile, Shivraj H; Park, Se W

2014-01-01

374

Synthesis and evaluation of diaryl sulfides and diaryl selenide compounds for antitubulin and cytotoxic activity.  

PubMed

We have devised a procedure for the synthesis of analogs of combretastatin A-4 (CA-4) containing sulfur and selenium atoms as spacer groups between the aromatic rings. CA-4 is well known for its potent activity as an inhibitor of tubulin polymerization, and its prodrugs combretastatin A-4 phosphate (CA-4P) and combretastatin A-1 phosphate (CA-1P) are being investigated as antitumor agents that cause tumor vascular collapse in addition to their activity as cytotoxic compounds. Here we report the preparation of two sulfur analogs and one selenium analog of CA-4. All synthesized compounds, as well as several synthetic intermediates, were evaluated for inhibition of tubulin polymerization and for cytotoxic activity in human cancer cells. Compounds 3 and 4 were active at nM concentration against MCF-7 breast cancer cells. As inhibitors of tubulin polymerization, both 3 and 4 were more active than CA-4 itself. In addition, 4 was the most active of these agents against 786, HT-29 and PC-3 cancer cells. Molecular modeling binding studies are also reported for compounds 1, 3, 4 and CA-4 to tubulin within the colchicine site. PMID:23810282

dos Santos, Edson dos A; Hamel, Ernest; Bai, Ruoli; Burnett, James C; Tozatti, Camila Santos Suniga; Bogo, Danielle; Perdomo, Renata T; Antunes, Alexandra M M; Marques, M Matilde; Matos, Maria de F C; de Lima, Dęnis P

2013-08-15

375

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

NASA Astrophysics Data System (ADS)

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

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

2009-06-01

376

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; Castańo, A; Montero, J C; Criado-Alvarez, J J; Mirón, I J; Catalá, M

2013-03-01

377

Antibacterial activities of naturally occurring compounds against Mycobacterium avium subsp. paratuberculosis.  

PubMed

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