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1

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

PubMed

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

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

2005-02-01

2

Conserved valproic-acid-induced lipid droplet formation in Dictyostelium and human hepatocytes identifies structurally active compounds  

PubMed Central

SUMMARY Lipid droplet formation and subsequent steatosis (the abnormal retention of lipids within a cell) has been reported to contribute to hepatotoxicity and is an adverse effect of many pharmacological agents including the antiepileptic drug valproic acid (VPA). In this study, we have developed a simple model system (Dictyostelium discoideum) to investigate the effects of VPA and related compounds in lipid droplet formation. In mammalian hepatocytes, VPA increases lipid droplet accumulation over a 24-hour period, giving rise to liver cell damage, and we show a similar effect in Dictyostelium following 30 minutes of VPA treatment. Using 3H-labelled polyunsaturated (arachidonic) or saturated (palmitic) fatty acids, we shown that VPA treatment of Dictyostelium gives rise to an increased accumulation of both types of fatty acids in phosphatidylcholine, phosphatidylethanolamine and non-polar lipids in this time period, with a similar trend observed in human hepatocytes (Huh7 cells) labelled with [3H]arachidonic acid. In addition, pharmacological inhibition of ?-oxidation in Dictyostelium phenocopies fatty acid accumulation, in agreement with data reported in mammalian systems. Using Dictyostelium, we then screened a range of VPA-related compounds to identify those with high and low lipid-accumulation potential, and validated these activities for effects on lipid droplet formation by using human hepatocytes. Structure-activity relationships for these VPA-related compounds suggest that lipid accumulation is independent of VPA-catalysed teratogenicity and inositol depletion. These results suggest that Dictyostelium could provide both a novel model system for the analysis of lipid droplet formation in human hepatocytes and a rapid method for identifying VPA-related compounds that show liver toxicology. PMID:22003123

Elphick, Lucy M.; Pawolleck, Nadine; Guschina, Irina A.; Chaieb, Leila; Eikel, Daniel; Nau, Heinz; Harwood, John L.; Plant, Nick J.; Williams, Robin S. B.

2012-01-01

3

Chemistry & Biology Synthetic Lethal Screening Identifies Compounds  

E-print Network

Chemistry & Biology Article Synthetic Lethal Screening Identifies Compounds Activating IronDepartment of Biological Sciences 2Department of Chemistry Columbia University, Fairchild Center, MC2406, 1212 Amsterdam Avenue, New York, NY 10027, USA *Correspondence: stockwell@biology.columbia.edu DOI 10

Stockwell, Brent R.

4

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.

5

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. PMID:23454872

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

2013-01-01

6

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

PubMed Central

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

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

2012-01-01

7

Screening with a Novel Cell-Based Assay for TAZ Activators Identifies a Compound That Enhances Myogenesis in C2C12 Cells and Facilitates Muscle Repair in a Muscle Injury Model  

PubMed Central

The transcriptional coactivator with a PDZ-binding motif (TAZ) cooperates with various transcriptional factors and plays various roles. Immortalized human mammalian epithelial MCF10A cells form spheres when TAZ is overexpressed and activated. We developed a cell-based assay using sphere formation by TAZ-expressing MCF10A cells as a readout to screen 18,458 chemical compounds for TAZ activators. Fifty compounds were obtained, and 47 were confirmed to activate the TAZ-dependent TEAD-responsive reporter activity in HEK293 cells. We used the derived subset of compounds as a TAZ activator candidate minilibrary and searched for compounds that promote myogenesis in mouse C2C12 myoblast cells. In this study, we focused on one compound, IBS008738. IBS008738 stabilizes TAZ, increases the unphosphorylated TAZ level, enhances the association of MyoD with the myogenin promoter, upregulates MyoD-dependent gene transcription, and competes with myostatin in C2C12 cells. TAZ knockdown verifies that the effect of IBS008738 depends on endogenous TAZ in C2C12 cells. IBS008738 facilitates muscle repair in cardiotoxin-induced muscle injury and prevents dexamethasone-induced muscle atrophy. Thus, this cell-based assay is useful to identify TAZ activators with a variety of cellular outputs. Our findings also support the idea that TAZ is a potential therapeutic target for muscle atrophy. PMID:24550007

Yang, Zeyu; Nakagawa, Kentaro; Sarkar, Aradhan; Maruyama, Junichi; Iwasa, Hiroaki; Bao, Yijun; Ishigami-Yuasa, Mari; Ito, Shigeru; Kagechika, Hiroyuki; Hata, Shoji; Nishina, Hiroshi; Abe, Shinya; Kitagawa, Masanobu

2014-01-01

8

Microfluidic in vivo screen identifies compounds enhancing neuronal  

E-print Network

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

Haggarty, Stephen

9

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

EPA Science Inventory

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

10

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...

11

A staining protocol for identifying secondary compounds in Myrtaceae1  

PubMed Central

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

Retamales, Hernan A.; Scharaschkin, Tanya

2014-01-01

12

Zebrafish screen identifies novel compound with selective toxicity against leukemia  

PubMed Central

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

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

2012-01-01

13

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

PubMed 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. PMID:22286231

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

14

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

PubMed Central

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

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

2014-01-01

15

Antiapicoplast and gametocytocidal screening to identify the mechanisms of action of compounds within the malaria box.  

PubMed

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

Bowman, Jessica D; Merino, Emilio F; Brooks, Carrie F; Striepen, Boris; Carlier, Paul R; Cassera, Maria B

2014-01-01

16

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

17

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

18

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

EPA Science Inventory

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

19

Identifying Sexual Harassment: A Classroom Activity  

ERIC Educational Resources Information Center

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

Madson, Laura; Shoda, Jennifer

2002-01-01

20

Nematicidal activities of acetylene compounds from Coreopsis lanceolata L.  

PubMed

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

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

2008-01-01

21

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

PubMed Central

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

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

2013-01-01

22

A new active compound from Centaurea species.  

PubMed

The extract containing sesquiterpene lactones of Centaurea iberica (Asteraceae) isolated was separated and a steroidal compound, which is stigmast-1,5-dien-3beta-ol, was purified. The chemical structure was established based on spectroscopic data (UV, IR, MS, 1H NMR, 13C NMR). Both the extract and the compound showed significant antioxidant and antimicrobial activities. PMID:16610215

Dumlu, Melek U; Gürkan, Elcin

2006-01-01

23

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

24

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. PMID:24945358

Doloc-Mihu, Anca; Calabrese, Ronald L.

2014-01-01

25

Antifungal Activity of Isothiocyanates and Related Compounds  

PubMed Central

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

Drobnica, L.; Zemanova, M.; Nemec, P.; Antos, K.; Kristian, P.; Stullerova, A.; Knoppova, V.; Nemec, P.

1967-01-01

26

Antifungal Activity of Isothiocyanates and Related Compounds  

PubMed Central

This paper presents the results of a study on the antifungal activity of isothiocyanates—derivatives of biphenyl (group “A”), of stilbene (“B”), of azobenzene and benzeneazonaphthalene (“C”), of naphthalene (“D”), and of further polycondensed aromatic hydrocarbons (“E”). From a total of 48 investigated compounds, antifungal activity was observed only in A and D group compounds. B, C, and E group derivatives are extremely insoluble in water, and the molecules are very large; as a result, they probably cannot pass into spores or mycelium of fungi. Thus, the —NCS group cannot manifest its reactivity. PMID:5647516

Drobnica, L.; Zemanova, M.; Nemec, P.; Antos, K.; Kristian, P.; Martvon, A.; Zavodska, E.

1968-01-01

27

Identifying Promising Compounds in Drug Discovery: Genetic Algorithms and Some New Statistical Techniques  

E-print Network

Identifying Promising Compounds in Drug Discovery: Genetic Algorithms and Some New Statistical, Michigan 48105 Received December 14, 2006 Throughout the drug discovery process, discovery teams are asked to prioritize compounds for subsequent stages of the drug discovery process, given results from

Wu, Jeff

28

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

EPA Science Inventory

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

29

A high throughput pharmaceutical screen identifies compounds with specific toxicity against BRCA2-deficient tumors  

PubMed Central

Purpose: Hereditary breast cancer is partly explained by germline mutations in BRCA1 and BRCA2. While patients carry heterozygous mutations, their tumors have typically lost the remaining wild-type allele. Selectively targeting BRCA-deficiency may therefore constitute an important therapeutic approach. Clinical trials applying this principle are underway, but it is unknown whether the compounds tested are optimal. It is therefore important to identify alternative compounds that specifically target BRCA-deficiency and to test new combination therapies to establish optimal treatment strategies. Experimental Design: We performed a high-throughput pharmaceutical screen on BRCA2-deficient mouse mammary tumor cells and isogenic controls with restored BRCA2 function. Subsequently, we validated positive hits in vitro and in vivo using mice carrying BRCA2-deficient mammary tumors. Results: Three alkylators – chlorambucil, melphalan and nimustine – displayed strong and specific toxicity against BRCA2-deficient cells. In vivo, these showed heterogeneous but generally strong BRCA2-deficient antitumor activity, with melphalan and nimustine outperforming cisplatin and the poly-(ADP-ribose)-polymerase (PARP) inhibitor olaparib (AZD2281) in this small study. In vitro drug combination experiments showed synergistic interactions between the alkylators and olaparib. Tumor intervention studies combining nimustine and olaparib resulted in recurrence-free survival exceeding 330 days in 3 out of 5 animals tested. Conclusions: We generated and validated a platform for identification of compounds with specific activity against BRCA2-deficient cells that translates well to the preclinical setting. Our data call for the re-evaluation of alkylators – especially melphalan and nimustine – alone or in combination with PARP inhibitors for the treatment of breast cancers with a defective BRCA pathway. PMID:20008842

Evers, Bastiaan; Schut, Eva; van der Burg, Eline; Braumuller, Tanya M.; Egan, David A.; Holstege, Henne; Edser, Pauline; Adams, David J.; Wade-Martins, Richard; Bouwman, Peter; Jonkers, Jos

2009-01-01

30

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

PubMed Central

Cellular senescence is a persistently growth-arrested phenotype in normal and transformed cells induced by non-cytotoxic stress. Cytostasis as a method of cancer treatment has recently generated significant interest. Research into the induction of cellular senescence as cancer therapy has been hindered by a lack of compounds that efficiently induce this response. We describe a semiautomated high-throughput method to identify library compounds that induce senescence using prostate cancer cells cultured in 96 well plates. Primary hits are identified by low cell numbers after 3 days in culture, measured by Hoechst 33342 fluorescence. A secondary visual assessment of senescence-associated ?-galactosidase staining and cellular morphology in the same wells distinguishes senescence from quiescence, apoptosis and other false-positives. This method was used to screen a 4160 compound library of known bioactive compounds and natural products at a 10?M dose. Candidate compounds were further selected based on persistent growth arrest after drug removal and increased expression of previously described senescence marker genes. Four lead compounds not previously associated with senescence were identified for further investigation. This is the first successful assay to identify novel agents from compound libraries based on senescence-induction in cancer cells. PMID:19641224

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

2010-01-01

31

Identifying uncertainty in epicardial activation maps  

Microsoft Academic Search

Epicardial activation maps in surviving infarct regions are derived by: (1) choosing a specific activation time at each recording site and (2) interpolating the data so that contours can be drawn representing the activation wavefronts. Concentrating on the latter problem, the spatial autocorrelation function (SAF) was calculated to evaluate the smoothness or regional correlation of activation times obtained at neighboring

Edward J. Berbari; Dinendra Ramachandran; Paul Lander; David Geselowitz

1992-01-01

32

Antifungal Activity of Isothiocyanates and Related Compounds  

PubMed Central

Antifungal activity on Aspergillus niger, Penicillium cyclopium, and Rhizopus oryzae, as well as on additional saprophytic and parasitic fungi, was determined in 57 substituted derivatives of phenylisothiocyanate. Most of the investigated compounds displayed rather equal activity against the three mentioned fungi, in contradistinction to the analogues of natural benzyl- and ?-phenylethylisothiocyanate with their characteristic low activity against R. oryzae. Differences occurred in the type of activity of compounds in which the —NCS group is directly bound on the aromatic moiety, as compared with those compounds in which this group is bound to the aliphatic radical or to the aromatic moiety indirectly by means of the methyl group or by a longer aliphatic chain. The results obtained confirm the negative influence of ionized substituents on the aromatic moiety, i.e., of —COOH, —CH2— COOH, and —SO3H groups, as well as of substituents which cause an extreme increase in reactivity of the —NCS group resulting in a high instability of the entire isothiocyanate molecule. PMID:6049295

Drobnica, L.; Zemanova, M.; Nemec, P.; Kristian, P.; Antos, K.; Hulka, A.

1967-01-01

33

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. PMID:22968304

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

34

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

35

Compounds active against cell walls of medically important fungi.  

PubMed Central

A number of substances that directly or indirectly affect the cell walls of fungi have been identified. Those that actively interfere with the synthesis or degradation of polysaccharide components share the property of being produced by soil microbes as secondary metabolites. Compounds specifically interfering with chitin or beta-glucan synthesis have proven effective in studies of preclinical models of mycoses, though they appear to have a restricted spectrum of coverage. Semisynthetic derivatives of some of the natural products have offered improvements in activity, toxicology, or pharmacokinetic behavior. Compounds which act on the cell wall indirectly or by a secondary mechanism of action, such as the azoles, act against diverse fungi but are usually fungistatic in nature. Overall, these compounds are attractive candidates for further development. PMID:8457977

Hector, R F

1993-01-01

36

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. PMID:24655423

2014-01-01

37

Identifying Creative Activities in Preschool Children.  

ERIC Educational Resources Information Center

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

Keily, Margaret Mary

38

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

39

Natural products as a resource for biologically active compounds  

SciTech Connect

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

Hanke, F.J.

1986-01-01

40

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...

41

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

EPA Science Inventory

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

42

Bacteriostatic, Fungistatic, and Algistatic Activity of Fatty Nitrogen Compounds  

PubMed Central

A total of 164 fatty nitrogen compounds, consisting of quaternary ammonium compounds, alkylamines, N-alkyl-1, 3-propylene diamines, substituted amino hydroxystearonitriles, substituted amino hydroxystearyl amines, and nitrogen-containing surfactants, were screened for bacteriostatic, fungistatic, and algistatic activity. The most active compounds were dodecylamine and dodecylamine acetate. A number of compounds were very active against gram-negative bacteria. Most of the surfactants were virtually nontoxic to all of the test organisms. Images Fig. 1 PMID:5970815

Hueck, Hendrik J.; Adema, Dorothea M. M.; Wiegmann, John R.

1966-01-01

43

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

44

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

45

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. 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

46

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

47

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

48

Optimisation and characterisation of various extraction conditions of phenolic compounds and antioxidant activity in olive seeds  

Microsoft Academic Search

This study was conducted to optimise the extraction conditions of phenolic compounds to evaluate antioxidant extraction parameters and to identify the major free and bound phenolic compounds in olive seeds. The results obtained using methanol as an extraction solvent for olive seeds indicated that the optimised total phenolic content and antioxidant activity were obtained at an extraction time of 12?h,

Muhammad H. Alu’datt; Inteaz Alli; Khalil Ereifej; Mohammad N. Alhamad; Ahmad Alsaad; Taha Rababeh

2011-01-01

49

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

50

Aroma-active compounds in jinhua ham produced with different fermentation periods.  

PubMed

The aroma-active compounds in Jinhua ham processed and stored for 9, 12, 15 and 18 months were extracted by dynamic headspace sampling (DHS) and solvent-assisted flavor evaporation (SAFE) and analyzed by gas chromatography-olfactometry-mass spectrometry (GC-O-MS). In GC-O-MS, volatile compounds were identified based on their mass spectrum, linear retention index (LRI), odor properties, or reference compound comparisons. The results showed that a total number of 81 aroma-active compounds were identified by GC-O-MS. Among them, acids (such as acetic acid, butanoic acid and 3-methylbutanoic acid), saturated aldehydes (such as hexanal, heptanal, octanal and 3-methylbutanal), benzene derivatives (such as benzeneacetic acid), ester and lactone (such as ?-nonalactone and ?-decalactone) were identified as critical compounds in Jinhua ham aroma. The results also indicated that the type and content of the odorants increased significantly with the duration of the fermentation period. PMID:25415474

Liu, Xiao-Sheng; Liu, Jian-Bin; Yang, Zheng-Mao; Song, Huan-Lu; Liu, Ye; Zou, Ting-Ting

2014-01-01

51

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

PubMed

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

Cho, Ji Young

2012-01-01

52

E-prescribing errors identified in a compounding pharmacy: a quality-improvement project.  

PubMed

Errors during the prescribing process can cause problems for patients. When the pharmacist intercepts a prescribing error, it can cause a delay, as the patient may not receive the medication until the problem is resolved. Electronic prescriptions are purported to reduce prescribing errors. However, studies have shown that electronic prescriptions can be prone to certain types of errors. Compounding pharmacies may present an additional obstacle for e-prescribing, as the prescribed medications are not commercially available and may not be listed in the e-prescribing software. The objectives of this study were to estimate the electronic prescription error rate in a compounding pharmacy, determine the most common error types, list the most common interventions pharmacists made, and estimate how long it took to resolve these errors. The study design was quality improvement with descriptive data. During the four weeks of data collection, the pharmacists were trained to complete a standardized data collection form when they identified an electronic prescription error. Percentages were calculated for new prescriptions, electronic prescriptions with errors, error types, and error resolution methods. In the four-week period of the study, there were 982 new prescriptions, 111 of which were electronic prescriptions. Of those 111 electronic prescriptions, 70 had errors. The electronic prescriptions error rate was 63%. The most common type of error was wrong entry field (70.3%). For this project, wrong entry field was defined to mean that the drug name was in the wrong field (81%) or that multiple entries were in the wrong field (7%). Pharmacists usually used their own judgment to resolve an error (67%). Many e-prescription errors were identified in this compounding pharmacy. When prescription errors happen, workflow and patient care are disrupted. Our goal is to discuss these findings with Surescripts and e-prescribing software companies to seek systems-based solutions. PMID:24881345

Reed-Kane, Dana; Kittell, Katrina; Adkins, Jacquelyn; Flocks, Sarah; Nguyen, Thu

2014-01-01

53

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

54

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

55

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

PubMed Central

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

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

2014-01-01

56

Profiling file repository access patterns for identifying data exfiltration activities  

Microsoft Academic Search

Studies show that a significant number of employees steal data when changing jobs. Insider attackers who have the authorization to access the best-kept secrets of organizations pose a great challenge for organizational security. Although increasing efforts have been spent on identifying insider attacks, little research concentrates on detecting data exfiltration activities. This paper proposes a model for identifying data exfiltration

Yi Hu; Charles Frank; James Walden; Emily Crawford; Dhanuja Kasturiratna

2011-01-01

57

Biologically active compounds of semi-metals.  

PubMed

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

Rezanka, Tomás; Sigler, Karel

2008-02-01

58

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

PubMed

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

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

2011-09-01

59

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

PubMed

We have here investigated the activities of Slovenian propolis extracts in the yeast Saccharomyces cerevisiae, and identified the phenolic compounds that appear to contribute to these activities. We correlated changes in intracellular oxidation and cellular metabolic energy in these yeasts with the individual fractions of the propolis extracts obtained following solid-phase extraction. The most effective fraction was further investigated according to its phenolic compounds. PMID:23409133

Petelinc, Tanja; Polak, Tomaž; Demšar, Lea; Jamnik, Polona

2013-01-01

60

Fractionation of Phenolic Compounds Extracted from Propolis and Their Activity in the Yeast Saccharomyces cerevisiae  

PubMed Central

We have here investigated the activities of Slovenian propolis extracts in the yeast Saccharomyces cerevisiae, and identified the phenolic compounds that appear to contribute to these activities. We correlated changes in intracellular oxidation and cellular metabolic energy in these yeasts with the individual fractions of the propolis extracts obtained following solid-phase extraction. The most effective fraction was further investigated according to its phenolic compounds. PMID:23409133

Petelinc, Tanja; Polak, Tomaz; Demsar, Lea; Jamnik, Polona

2013-01-01

61

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

62

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; Conceição, Edemilson Cardoso; Silveira, Dâmaris

2014-06-15

63

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 Naïve Bayes pooled variance classifier, we demonstrate the ability to identify specific emotions experienced by an individual at well over chance accuracy on the basis of: 1) neural activation of the same individual in other trials, 2) neural activation of other individuals who experienced similar trials, and 3) neural activation of the same individual to a qualitatively different type of emotion induction. Factor analysis identified valence, arousal, sociality, and lust as dimensions underlying the activation patterns. These results suggest a structure for neural representations of emotion and inform theories of emotional processing. PMID:23840392

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

2013-01-01

64

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

65

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. PMID:24416463

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

66

Effects of Compounds Found in Propolis on Streptococcus mutans Growth and on Glucosyltransferase Activity  

Microsoft Academic Search

Propolis, a resinous bee product, has been shown to inhibit the growth of oral microorganisms and the activity of bacterium-derived glucosyltransferases (GTFs). Several compounds, mainly polyphenolics, have been identified in this natural product. The present study evaluated the effects of distinct chemical groups found in propolis on the activity of GTF enzymes in solution and on the surface of saliva-coated

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

2002-01-01

67

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

NASA Astrophysics Data System (ADS)

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

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

2001-04-01

68

Cytotoxicity and antiviral activity of the compounds from Euphorbia kansui.  

PubMed

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

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

1998-12-01

69

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 ...

70

Identifying critical activities in stochastic resource constrained networks  

Microsoft Academic Search

The analysis of the stochastic project network can provide indications of both the magnitude of temporal risk and the sources of that risk. In a project dominated by technological dependencies rather than resource constraints, the sources of risk can be identified by examining the probabilities of each activity lying on a critical path. Similar criticality probabilities can also be derived

J. Bowers

1996-01-01

71

Identifying environmental antigens that activate myelin-specific T cells.  

PubMed

Human genetic and environmental factors underlie susceptibility to the T cell-mediated autoimmune disease, multiple sclerosis (MS). How the environment influences the pathogenesis of MS has been difficult to parse. A recent paper in Cell shows that environmental antigens that activate myelin-specific T cells can be identified with unprecedented accuracy. PMID:24820694

Stadinski, Brian D; Huseby, Eric S

2014-06-01

72

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

73

Antimicrobial Activities of Synthetic Bismuth Compounds against Clostridium difficile  

PubMed Central

Clostridium difficile is a major nosocomial pathogen responsible for pseudomembranous colitis and many cases of antibiotic-associated diarrhea. Because of potential relapse of disease with current antimicrobial therapy protocols, there is a need for additional and/or alternative antimicrobial agents for the treatment of disease caused by C. difficile. We have synthesized a systematic series of 14 structurally simple bismuth compounds and assessed their biological activities against C. difficile and four other gastrointestinal species, including Helicobacter pylori. Here, we report on the activities of six compounds that exhibit antibacterial activities against C. difficile, and some of the compounds have MICs of less than 1 ?g/ml. Also tested, for comparison, were the activities of bismuth subcitrate and ranitidine bismuth citrate obtained from commercial sources. C. difficile and H. pylori were more sensitive both to the synthetic bismuth compounds and to the commercial products than were Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis, and the last three species were markedly resistant to the commercial bismuth salts. Testing with human foreskin fibroblast cells revealed that some of the synthetic compounds were more cytotoxic than others. Killing curves for C. difficile treated with the more active compounds revealed rapid death, and electron microscopy showed that the bismuth of these compounds was rapidly incorporated by C. difficile. Energy dispersive spectroscopy X-ray microanalysis of C. difficile cells containing electron-dense material confirmed the presence of internalized bismuth. Internalized bismuth was not observed in C. difficile treated with synthetic bismuth compounds that lacked antimicrobial activity, which suggests that the uptake of the metal is required for killing activity. The nature of the carrier would seem to determine whether bismuth is transported into susceptible bacteria like C. difficile. PMID:10049270

Mahony, D. E.; Lim-Morrison, S.; Bryden, L.; Faulkner, G.; Hoffman, P. S.; Agocs, L.; Briand, G. G.; Burford, N.; Maguire, H.

1999-01-01

74

Synthesis, antibacterial and antifungal activities of electron-rich olefins derived benzimidazole compounds  

Microsoft Academic Search

New benzimidazole derivatives were synthesised by electron-rich olefines (7, 8 and 9) with appropriate reagents. The compounds synthesised were identified by 1H NMR, 13C NMR, FT-IR spectroscopic techniques and elemental analysis. All compounds studied in this work were screened for their in vitro antimicrobial activities against the standard strains: Enterococcus faecalis (ATCC 29212), Staphylococcus aureus (ATCC 29213), Escherichia coli (ATCC

Hasan Küçükbay; Riza Durmaz; Ersin Orhan; Selami Günal

2003-01-01

75

ANTIMICROBIAL ACTIVITY OF SOME BIGINELLI COMPOUNDS  

Microsoft Academic Search

3,4-Dihydropyrimidin-2(1H)-ones(thiones) and their derivatives have attracted great interest due to their promising biological effects, including antibacterial, antiviral, antitumor, antiinflammatory, antihypertensive, calcium channel blocker, ?-1a-antagonist and neuropeptide Y (NPY) antagonist activities (1). In our previous study, we have reported the preparation of some 5-acetyl-3,4-dihydro-6-methyl-4- (substituted phenyl)-2(1H)-pyrimidinone derivatives by using the Biginelli three-component cyclocondensation reaction of substituted benzaldehyde, acetylacetone and thiourea (2).

Ekrem KILIÇ; Meral ÖZALP; Selma SARAÇ

76

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

PubMed

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

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

2014-10-17

77

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

PubMed

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

Miyazawa, Mitsuo; Tamura, Naotaka

2007-03-01

78

Antioxidant activity of some foods containing phenolic compounds  

Microsoft Academic Search

This study was designed to determine the total phenols (TP) and total antioxidant activity (TAA) of some liquid and solid plant foods that are commonly consumed in Turkey. Total phenols were analysed according to the Folin- Ciocalteu method and antioxidant activities of these compounds in aqueous phase were assessed by measuring their direct ABTSï- radical scavenging abilities. Total phenols varied

S. Karakaya; S. N. El; A. A. Taç

2001-01-01

79

Antibacterial Activity of Phenolic Compounds Against the Phytopathogen Xylella fastidiosa  

Microsoft Academic Search

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

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

2010-01-01

80

Synthesis and Radioprotective Activity of New Organosilicon and Germanium Compounds  

PubMed Central

Silathiazolidine and metalladithioacetals (M = Si, Ge) have been prepared by the interaction of dialkyldichloro- or bis(diethylamino)dialkylsilanes and -germanes with 3-[N-(2- thioethyl)]amino-propanamide (WR-2529) and [1-thioethyl-2-(1-naphtylmethyl)]-2- imidazoline. The study of these compounds in the field of chemical radioprotection has shown a notable decrease in the toxicity and a rather large increase in the radioprotective activity of these new derivatives in comparison with the starting organic compounds. PMID:18475835

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

1998-01-01

81

Odour active aroma compounds of sea fig ( Microcosmus sulcatus)  

Microsoft Academic Search

Sea fig is an original shellfish appreciated for its powerful “marine, iodized” flavour. Different methods of analysis by gas chromatography, coupled with olfactometry (GC–O), were studied and compared. Subsequently, odour-active aroma compounds of sea fig extract were analyzed by OSME and CHARM analysis. Twenty-nine olfactive areas were observed by OSME, and 18 by CHARM analysis. Volatile compounds of the extract

Perrine Senger-Emonnot; Sophie Rochard; Florent Pellegrin; Gérard George; Xavier Fernandez; Louisette Lizzani-Cuvelier

2006-01-01

82

Identifying new small molecule anti-invasive compounds for glioma treatment  

PubMed Central

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

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

2013-01-01

83

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

SciTech Connect

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

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

2010-09-20

84

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. PMID:19259472

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

2007-01-01

85

Chemotherapeutically active nitro compounds. 4.5-Nitroimidazoles (Part II).  

PubMed

More than 170 1-methyl-5-nitroimidazoles substituted in the 2-position via an aminomethyl, thiomethyl, sulphinylmethyl or sulphonylmethyl group were synthesized and tested for their effect against various protozoa. In the NMRI mouse which had been i.p. infected with Trichomonas fetus 2 compounds showed an effect superior to that of tinidazole and 31 showed similarly good efficacy as that compound. In comparison with metronidazole 54 preparations proved to be distinctly more active, while 34 others lay in the range of efficacy of the standard compound. A large majority of the most active derivatives is substituted in the 2-position via a C--S bridge with heterocyclics, particularly with a pyridyl radical. An effect against Entamoeba histolytica in the intrahepatically infected golden hamster was observed much less often. Only 14 preparations developed a systemic effect comparable with that of metronidazole. In the NMRI mouse infected i.p. with Trypanosoma brucei or s.c. with T. cruzi parasitemia was clearly influenced by 11 compounds. With a few exceptions a trypanocidal effect against T. brucei occurred only at high doses. Only 3 compounds showed pronounced suppressive activity against blood forms of T. cruzi and only after prolonged treatment. The structure-activity relationship of the new 5-nitroimidazoles is discussed. PMID:350230

Winkelmann, E; Raether, W; Sinharay, A

1978-01-01

86

Enzyme activities in single electrophysiologically identified crab muscle fibres.  

PubMed

The superficial muscle fibres in the proximal part of the closer muscle in the crab Eriphia can be separated into four fibre groups (I-IV) on the basis of electrophysiological and histochemical characteristics. The activity levels of glyceraldehydephosphate dehydrogenase (GAPDH), lactate dehydrogenase (LDH), citrate synthase (CS), NADP-isocitrate dehydrogenase (IDH) and 3-hydroxyacyl-CoA dehydrogenase (HAD), determined in single electrophysiologically identified fibres, differed significantly among the different fibre groups. In addition, fibres belonging to the same group, with similar electrophysiological characteristics, demonstrated variability with regard to metabolic enzyme activities. Nevertheless, comparison of absolute enzyme activities and enzyme activity ratios permitted the discrimination of at least three groups. These groups corresponded with those defined according to electrophysiological and histochemical characteristics. The group I fibres (tonic fibres) are intermediate in oxidative potential and show the lowest values of glycolytic enzymes. The group II and group III fibres can be regarded as fast oxidative fibres. The high ratio between activity levels of enzymes for glycolytic and oxidative metabolism found for group IV fibres (fast fibres) demonstrated that this group depends strongly on anaerobic metabolism. PMID:3701650

Maier, L; Pette, D; Rathmayer, W

1986-02-01

87

Enzyme activities in single electrophysiologically identified crab muscle fibres.  

PubMed Central

The superficial muscle fibres in the proximal part of the closer muscle in the crab Eriphia can be separated into four fibre groups (I-IV) on the basis of electrophysiological and histochemical characteristics. The activity levels of glyceraldehydephosphate dehydrogenase (GAPDH), lactate dehydrogenase (LDH), citrate synthase (CS), NADP-isocitrate dehydrogenase (IDH) and 3-hydroxyacyl-CoA dehydrogenase (HAD), determined in single electrophysiologically identified fibres, differed significantly among the different fibre groups. In addition, fibres belonging to the same group, with similar electrophysiological characteristics, demonstrated variability with regard to metabolic enzyme activities. Nevertheless, comparison of absolute enzyme activities and enzyme activity ratios permitted the discrimination of at least three groups. These groups corresponded with those defined according to electrophysiological and histochemical characteristics. The group I fibres (tonic fibres) are intermediate in oxidative potential and show the lowest values of glycolytic enzymes. The group II and group III fibres can be regarded as fast oxidative fibres. The high ratio between activity levels of enzymes for glycolytic and oxidative metabolism found for group IV fibres (fast fibres) demonstrated that this group depends strongly on anaerobic metabolism. PMID:3701650

Maier, L; Pette, D; Rathmayer, W

1986-01-01

88

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

PubMed

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

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

2006-07-01

89

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...

90

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. PMID:23170079

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

91

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

PubMed Central

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

2014-01-01

92

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

USGS Publications Warehouse

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

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

1997-01-01

93

Infinite dilution activity coefficients of apple juice aroma compounds  

Microsoft Academic Search

An apparatus based on the inert gas stripping method was assembled for measuring infinite dilution activity coefficients, ??, of 15 apple juice aroma compounds in aqueous solutions. Values were estimated using the UNIFAC model and compared with experimental results; differences ranged from ?80 to 118% with an average of 48% for the absolute values of the differences. Values predicted with

Martin F. Sancho; M. A. Rao; D. L. Downing

1997-01-01

94

Antibacterial activity of phenolic compounds against the phytopathogen Xylella fastidiosa.  

PubMed

Xylella fastidiosa is a pathogenic bacterium that causes diseases in many crop species, which leads to considerable economic loss. Phenolic compounds (a group of secondary metabolites) are widely distributed in plants and have shown to possess antimicrobial properties. The anti-Xylella activity of 12 phenolic compounds, representing phenolic acid, coumarin, stilbene and flavonoid, was evaluated using an in vitro agar dilution assay. Overall, these phenolic compounds were effective in inhibiting X. fastidiosa growth, as indicated by low minimum inhibitory concentrations (MICs). In addition, phenolic compounds with different structural features exhibited different anti-Xylella capacities. Particularly, catechol, caffeic acid and resveratrol showed strong anti-Xylella activities. Differential response to phenolic compounds was observed among X. fastidiosa strains isolated from grape and almond. Elucidation of secondary metabolite-based host resistance to X. fastidiosa will have broad implication in combating X. fastidiosa-caused plant diseases. It will facilitate future production of plants with improved disease resistance properties through genetic engineering or traditional breeding approaches and will significantly improve crop yield. PMID:19813054

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

2010-01-01

95

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

PubMed

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

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

2014-09-01

96

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

97

Identification of compounds that inhibit the kinase activity of leucine-rich repeat kinase 2  

Microsoft Academic Search

Mutations in leucine-repeat rich kinase 2 (LRRK2) are the most common known cause of late-onset Parkinson’s disease. In this study, a novel system to purify active recombinant LRRK2 expressed in mammalian cells was generated. This recombinant enzyme was used to characterize the specificity of LRRK2 and identify small compounds that can inhibit the kinase activity. Recombinant LRRK2 was shown to

Jason P. Covy; Benoit I. Giasson

2009-01-01

98

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. PMID:19364854

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

99

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

Microsoft Academic Search

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

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

2008-01-01

100

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

PubMed

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

Drouet, Christophe

2013-01-01

101

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.” PMID:23984373

2013-01-01

102

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. PMID:19995961

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

2009-01-01

103

Aldose Reductase Inhibitory Activity of Compounds from Zea mays L.  

PubMed Central

Aldose reductase (AR) inhibitors have a considerable therapeutic potential against diabetes complications and do not increase the risk of hypoglycemia. Through bioassay-guided fractionation of an EtOH extract of the kernel from purple corn (Zea mays L.), 7 nonanthocyanin phenolic compounds (compound 1–7) and 5 anthocyanins (compound 8–12) were isolated. These compounds were investigated by rat lens aldose reductase (RLAR) inhibitory assays. Kinetic analyses of recombinant human aldose reductase (rhAR) were performed, and intracellular galactitol levels were measured. Hirsutrin, one of 12 isolated compounds, showed the most potent RLAR inhibitory activity (IC50, 4.78??M). In the kinetic analyses using Lineweaver-Burk plots of 1/velocity and 1/substrate concentration, hirsutrin showed competitive inhibition against rhAR. Furthermore, hirsutrin inhibited galactitol formation in rat lens and erythrocytes sample incubated with a high concentration of galactose; this finding indicates that hirsutrin may effectively prevent osmotic stress in hyperglycemia. Therefore, hirsutrin derived from Zea mays L. may be a potential therapeutic agent against diabetes complications. PMID:23586057

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

2013-01-01

104

Oviposition stimulants for the black swallowtail butterfly: Identification of electrophysiologically active compounds in carrot volatiles.  

PubMed

Headspace volatiles were collected from undamaged foliage of carrot,Daucus carota, a host-plant species of the black swallowtail butterfly,Papilio polyxenes. The volatiles were fractionated over silica on an open column, and the fractions were tested in behavioral assays withP. polyxenes females in laboratory experiments. The polar fractions, as well as the total mixture of volatiles, increased the landing frequency and the number of eggs laid on model plants with leaves bearing contact-oviposition stimulants. The nonpolar fraction, containing the most abundant compounds in carrot odor, was not stimulatory. Gas Chromatographic (GC) separation of the fractions was coupled with electroantennogram (EAG) recordings to identify the compounds perceived byP. polyxenes females. The EAG activity corresponded to the behavioral activity of the fractions. None of the nonpolar compounds, identified as various monoterpenes, evoked a major EAG response, but several constituents of the polar fractions elicited high EAG responses. Sabinene hydrate (both stereoisomers), 4-terpineol, bomyl acetate, and (Z)-3-hexenyl acetate were identified by GC-MS as active compounds. PMID:24249074

Baur, R; Feeny, P; Städler, E

1993-05-01

105

Smooth muscle relaxant activity of pterosin Z and related compounds.  

PubMed

The natural products pterosin Z, acetylpterosin Z, originally from the fern Pteridium aquilinum, and their isopterosin analogues have been synthesized and their smooth muscle relaxation activity has been measured. All of the test compounds show activity with pterosin Z being the most active (EC50 = 1.3 +/- 0.1 x 10(-6) M), exhibiting 100 times the activity reported for the related fern metabolites onitin (EC50 = 1 x 10(-4) M), onotisin (EC50 = 2 x 10(-3) M) and otninoside (EC50 = 7 x 10(-4) M). The smooth muscle relaxant activity of pterosin Z is approximately equipotent with that of the related fungal pterosin (EC50 of 2.9 +/- 1.6 x 10(-6) M). These results suggest that smooth muscle relaxant activity is reduced when a phenol group is present in the pterosin nucleus and when one of the dimethyl groups is derivatized. PMID:10232079

Sheridan, H; Frankish, N; Farrell, R

1999-04-01

106

High-Content Imaging Assays for Identifying Compounds that Generate Superoxide and Impair Mitochondrial Membrane Potential in Adherent Eukaryotic Cells.  

PubMed

Reactive oxygen species (ROS) are constantly produced in cells as a result of aerobic metabolism. When there is an excessive production of ROS and the cell's antioxidant defenses are overwhelmed, oxidative stress occurs. The superoxide anion is a type of ROS that is produced primarily in mitochondria but is also generated in other regions of the cell including peroxisomes, endoplasmic reticulum, plasma membrane, and cytosol. Here, a high-content imaging assay using the dye dihydroethidium is described for identifying compounds that generate superoxide in eukaryotic cells. A high-content imaging assay using the fluorescent dye tetramethylrhodamine methyl ester is also described to identify compounds that impair mitochondrial membrane potential in eukaryotic cells. The purpose of performing both assays is to identify compounds that (1) generate superoxide at lower concentrations than they impair mitochondrial membrane potential, (2) impair mitochondrial membrane potential at lower concentrations than they generate superoxide, (3) generate superoxide and impair mitochondrial function at similar concentrations, and (4) do not generate superoxide or impair mitochondrial membrane potential during the duration of the assays. Curr. Protoc. Toxicol. 59:25.1.1-25.1.14. © 2014 by John Wiley & Sons, Inc. PMID:24789364

Billis, Puja; Will, Yvonne; Nadanaciva, Sashi

2014-01-01

107

How can we identify ictal and interictal abnormal activity?  

PubMed

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

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

2014-01-01

108

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

PubMed Central

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

Thi, Nhuan Do; Hwang, Eun-Sun

2014-01-01

109

Biological activity of 3-formylchromones and related compounds.  

PubMed

Several 3-formylchromone derivatives were examined for their tumor cell-cytotoxic, anti-Helicobacter pylori, urease inhibitory and anti-HIV activity. Comparing their relative cytotoxicity against four human tumor cell lines and three normal human cells, tumor cell-specific cytotoxicity was detected in some 3-formylchromone derivatives. There was no clear-cut relationship between the cytotoxicity and the chemical structures of the compounds. 6,8-Dichloro-3-formylchromone (FC10) showed comparable anti-H. pylori activity with metronidazole and potent urease inhibition against jack bean urease. On the other hand, 6,8-dibromo-3-formylchromone (FC11) exhibited potent inhibitory activity against the urease, but had no anti-H. pylori activity. No chromones (FC1-16) exhibited anti-HIV activity. PMID:18019419

Kawase, Masami; Tanaka, Toru; Kan, Hiroyuki; Tani, Satoru; Nakashima, Hideki; Sakagami, Hiroshi

2007-01-01

110

Simple aromatic compounds containing propenone moiety show considerable dual COX/5-LOX inhibitory activities.  

PubMed

For the development of safer anti-inflammatory agents, simple aromatic compounds containing propenone moiety were prepared and evaluated for their dual COX/5-LOX inhibitory activities. Among the 17 prepared compounds, most of the compounds exhibited considerable COX/5-LOX inhibitory activities. Especially compound C(15) showed the most significant dual COX/5-LOX inhibitory activity. PMID:15109651

Jahng, Yurngdong; Zhao, Long-Xuan; Moon, Yoon-Soo; Basnet, Arjun; Kim, Eun-kyung; Chang, Hyeun Wook; Ju, Hye Kyung; Jeong, Tae Cheon; Lee, Eung-Seok

2004-05-17

111

A bayesian analysis for identifying DNA copy number variations using a compound poisson process.  

PubMed

To study chromosomal aberrations that may lead to cancer formation or genetic diseases, the array-based Comparative Genomic Hybridization (aCGH) technique is often used for detecting DNA copy number variants (CNVs). Various methods have been developed for gaining CNVs information based on aCGH data. However, most of these methods make use of the log-intensity ratios in aCGH data without taking advantage of other information such as the DNA probe (e.g., biomarker) positions/distances contained in the data. Motivated by the specific features of aCGH data, we developed a novel method that takes into account the estimation of a change point or locus of the CNV in aCGH data with its associated biomarker position on the chromosome using a compound Poisson process. We used a Bayesian approach to derive the posterior probability for the estimation of the CNV locus. To detect loci of multiple CNVs in the data, a sliding window process combined with our derived Bayesian posterior probability was proposed. To evaluate the performance of the method in the estimation of the CNV locus, we first performed simulation studies. Finally, we applied our approach to real data from aCGH experiments, demonstrating its applicability. PMID:20976296

Chen, Jie; Yi?iter, Ayten; Wang, Yu-Ping; Deng, Hong-Wen

2010-01-01

112

Characterization of phenolic compounds and antinociceptive activity of Sempervivum tectorum L. leaf juice.  

PubMed

Sempervivum tectorum L. (houseleek) leaf juice has been known as a traditional herbal remedy. The aim of the present study was the chemical characterization of its phenolic compounds and to develop quantitation methods for its main flavonol glycoside, as well as to evaluate its antinociceptive activity. Lyophilized houseleek leaf juice was studied by HPLC-DAD coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) to identify flavonol glycosides, hydroxy-benzoic and hydroxy-cinnamic acids. Ten flavonol glycosides and sixteen phenolic acid compounds were identified or tentatively characterized. Structure of the main flavonol compound was identified by nuclear magnetic resonance spectroscopy. Three characteristic kaempferol glycosides were isolated and determined by LC-ESI-MS/MS with external calibration method, using the isolated compounds as standard. The main flavonol glycoside was also determined by HPLC-DAD. Validated HPLC-DAD and LC-ESI-MS/MS methods were developed to quantify kaempferol-3-O-rhamnosyl-glucoside-7-O-rhamnoside and two other kaempferol glycosides. Antinociceptive activity of houseleek leaf juice was investigated by writhing test of mice. Sempervivum extract significantly reduced pain in the mouse writhing test. PMID:22785376

Alberti, Ágnes; Béni, Szabolcs; Lackó, Erzsébet; Riba, Pál; Al-Khrasani, Mahmoud; Kéry, Ágnes

2012-11-01

113

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

114

Laboratory Infrared Spectroscopy to Identify New Compounds on Icy Moon Surfaces  

NASA Astrophysics Data System (ADS)

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

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

2014-11-01

115

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

PubMed Central

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

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

2014-01-01

116

Problems for risk assessment of endocrine-active estrogenic compounds.  

PubMed Central

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

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

2002-01-01

117

Imidazolium compounds are active against all stages of Trypanosoma cruzi.  

PubMed

Imidazolium salts are best known for their applications in organic synthesis as room-temperature ionic liquids, or as precursors of stable carbenes, but they also show important biological properties such as anti-oxidative effects, induction of mitochondrial membrane permeabilisation and inhibition of the infection cycle of Plasmodium falciparum. For these reasons, and since chemotherapy for Chagas disease is inefficient, the aim of this study was to test the use of imidazolium compounds against the kinetoplastid haemoflagellate aetiological agent for this disease, namely Trypanosoma cruzi. The results show that five of the tested compounds are more effective than the reference drug benznidazole against the epimastigote and trypomastigote forms of T. cruzi. Moreover, intracellular amastigotes were also affected by the compounds, which showed lower toxicity in host cells. Transmission electron microscopy analysis demonstrated that the tested agents induced alterations of the kinetoplast and particularly of the mitochondria, leading to extraordinary swelling of the organelle. These results further demonstrate that the test agents with the best profile are those bearing symmetrical bulky substituents at N(1) and N(3), displaying promising activity against all forms of T. cruzi, interesting selectivity indexes and exceptional activity at low doses. Accordingly, these agents represent promising candidates for the treatment of Chagas disease. PMID:24359836

Faral-Tello, Paula; Liang, Mary; Mahler, Graciela; Wipf, Peter; Robello, Carlos

2014-03-01

118

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. PMID:24772387

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

119

Natural Product Compounds with Aromatase Inhibitory Activity: An Update  

PubMed Central

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

Balunas, Marcy J.; Kinghorn, A. Douglas

2010-01-01

120

Identifying user values for an activating game for children  

Microsoft Academic Search

Psychological values describe what is important to a person in life and values are also essential in persuading users. In this paper, we provide a sentence completion tool for identifying user values and demonstrate its use in a case study. The goal of the case study was to identify parents' values related to children's exercise to get first ideas for

Sari Kujala; Piia Nurkka

2009-01-01

121

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

122

Studies on the antioxidant activities of some new chromone compounds.  

PubMed

Recent reviews evidence that the naturally occurring compounds containing the chromone skeleton exhibit antiradical activities, providing protection against oxidative stress. The antioxidant activities of 13 new synthesized chromonyl-2,4-thiazolidinediones, chromonyl-2,4-imidazolidinediones and chromonyl-2-thioxoimidzolidine-4-ones were evaluated using in vitro antioxidant assays, including superoxide anion radical (O2-•), hydroxyl radical (HO•), 2,2-diphenyl-1-picryl-hydrazyl free radical (DPPH(•) ) scavenging capacity and total antioxidant capacity ferric ion reducing activity. Superoxide anion radical was produced using potassium superoxide/18-crown-6-ether dissolved in dimethylsulfoxide, and the Fenton-like reaction (Fe(II)?+?H2 O2 ) was a generator of hydroxyl radicals. Chemiluminescence, spectrophotometry, electron paramagnetic resonance (EPR) and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as the spin trap were the measurement techniques. The results showed that the majority of the chromone derivatives tested showed a strong scavenging effect towards free radicals, similar to the chemiluminescence reaction with superoxide anion radical with a high activity, inhibition of the DMPO-OOH radical EPR signal (24-58%), the DMPO-OH radical EPR signal (4-75%) and DPPH radical EPR signal (6-100%) at 1?mmol/L. Several of the examined compounds exhibited the high reduction potentials. The results obtained show that the new synthesized chromone derivatives may directly scavenger reactive oxygen species and thus may play a protective role against oxidative damage. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24482260

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

2014-11-01

123

Synthesis and in vitro anti-leukemic activity of structural analogues of JS-K, an anti-cancer lead compound  

Microsoft Academic Search

Structural analogues of JS-K, an anti-cancer lead compound, were prepared and their in vitro anti-leukemic activity was determined. The rate of nitric oxide release from the corresponding diazeniumdiolate anions did not appear to affect the anti-leukemic activity of the prodrug forms. Two compounds with potent inhibitory activity and a potentially favorable toxicological profile were identified.

Harinath Chakrapani; Michael M. Goodblatt; Vidya Udupi; Swati Malaviya; Paul J. Shami; Larry K. Keefer; Joseph E. Saavedra

2008-01-01

124

compounds  

NASA Astrophysics Data System (ADS)

Size is the key factor of nanostructured materials, since all the structural, transport, electrical, magnetic and other physical properties can be tuned by this factor of materials. Only the condition is to choose appropriate inexpensive scale-processing method for material synthesis which offers good control over the stoichiometry, morphology and particle size distribution. Present communication deals with the studies on the sol-gel grown Y0.95Ca0.05MnO3 (YCMO) nanostructured compounds for their size-induced tuning of dielectric behavior. Structural studies reveal the single phasic nature with improved crystallite size with sintering temperature. Dielectric constant (real and imaginary) is found to increase with temperature and crystallite size/sintering temperature. High dielectric loss has been observed in the present system. Size dependent activation energy ( E a), obtained from modulus measurement, showing the increase in E a with crystallite size. The variation in various dielectric parameters and E a has been discussed in the light of crystallite size, crystallite boundaries, oxygen vacancies and charge carrier hopping.

Shah, N. A.

2014-10-01

125

Novel antiproliferative chimeric compounds with marked histone deacetylase inhibitory activity.  

PubMed

Given our interest in finding potential antitumor agents and in view of the multifactorial mechanistic nature of cancer, in the present work, taking advantage of the multifunctional ligands approach, new chimeric molecules were designed and synthesized by combining in single chemical entities structural features of SAHA, targeting histone deacetylases (HDACs), with substituted stilbene or terphenyl derivatives previously obtained by us and endowed with antiproliferative and pro-apoptotic activity. The new chimeric derivatives were characterized with respect to their cytotoxic activity and their effects on cell cycle progression on different tumor cell lines, as well as their HDACs inhibition. Among the other, trans -6 showed the most interesting biological profile, as it exhibited a strong pro-apoptotic activity in tumor cell lines in comparison with both of its parent compounds and a marked HDAC inhibition. PMID:25221651

Giacomini, Elisa; Nebbioso, Angela; Ciotta, Alfonso; Ianni, Cristina; Falchi, Federico; Roberti, Marinella; Tolomeo, Manlio; Grimaudo, Stefania; Cristina, Antonietta Di; Pipitone, Rosaria Maria; Altucci, Lucia; Recanatini, Maurizio

2014-09-11

126

Activity of several molybdenum compounds for the methanation of CO  

SciTech Connect

The initial specific activities of the unsupported catalysts tested for the reaction of 3:1 hydrogen/carbon monoxide at 350/sup 0/C decreased in the order nickel > molybdenum carbide > molybdenum > molybdenum nitride > molybdenum dioxide > molybdenum disulfide > molybdenum trioxide. The molybdenum carbide, which apparently acted as a catalyst and not an intermediate, was more stable than the other catalysts. The molybdenum metal produced more C/sub 2/-C/sub 3/ hydrocarbons than the sulfide or oxide. The molybdenum compounds except the sulfide and trioxide had higher activities for the water gas shift than nickel or iron and were as active in 1:1 as in 3:1 hydrogen/carbon monoxide conversion. The product distributions suggested that hydrogenation of carbon monoxide proceeds by different mechanisms on molybdenum and Group VIII metal catalyst.

Saito, M.; Anderson, R.B.

1980-06-01

127

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

128

Anti-inflammatory activity of different agave plants and the compound cantalasaponin-1.  

PubMed

Species of the agave genus, such as Agave tequilana, Agave angustifolia and Agave americana are used in Mexican traditional medicine to treat inflammation-associated conditions. These plants' leaves contain saponin compounds which show anti-inflammatory properties in different models. The goal of this investigation was to evaluate the anti-inflammatory capacity of these plants, identify which is the most active, and isolate the active compound by a bio-directed fractionation using the ear edema induced in mice with 12-O-tetradecanoylphorbol-13-acetate (TPA) technique. A dose of 6 mg/ear of acetone extract from the three agave species induced anti-inflammatory effects, however, the one from A. americana proved to be the most active. Different fractions of this species showed biological activity. Finally the F5 fraction at 2.0 mg/ear induced an inhibition of 85.6%. We identified one compound in this fraction as (25R)-5?-spirostan-3?,6?,23?-triol-3,6-di-O-?-D-glucopyranoside (cantalasaponin-1) through 1H- and 13C-NMR spectral analysis and two dimensional experiments like DEPT NMR, COSY, HSQC and HMBC. This steroidal glycoside showed a dose dependent effect of up to 90% of ear edema inhibition at the highest dose of 1.5 mg/ear. PMID:23846754

Monterrosas-Brisson, Nayeli; Ocampo, Martha L Arenas; Jiménez-Ferrer, Enrique; Jiménez-Aparicio, Antonio R; Zamilpa, Alejandro; Gonzalez-Cortazar, Manases; Tortoriello, Jaime; Herrera-Ruiz, Maribel

2013-01-01

129

Large-scale assessment of activity landscape feature probabilities of bioactive compounds.  

PubMed

Activity landscape representations integrate pairwise compound similarity and potency relationships and provide direct access to characteristic structure-activity relationship features in compound data sets. Because pairwise compound comparisons provide the foundation of activity landscape design, the assessment of specific landscape features such as activity cliffs has generally been confined to the level of compound pairs. A conditional probability-based approach has been applied herein to assign most probable activity landscape features to individual compounds. For example, for a given data set compound, it was determined if it would preferentially engage in the formation of activity cliffs or other landscape features. In a large-scale effort, we have determined conditional activity landscape feature probabilities for more than 160,000 compounds with well-defined activity annotations contained in 427 different target-based data sets. These landscape feature probabilities provide a detailed view of how different activity landscape features are distributed over currently available bioactive compounds. PMID:24410456

Kayastha, Shilva; Dimova, Dilyana; Iyer, Preeti; Vogt, Martin; Bajorath, Jürgen

2014-02-24

130

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

PubMed

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

Banerjee, Debapriya; Sanyal, Suparna

2014-10-01

131

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

PubMed Central

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

Banerjee, Debapriya; Sanyal, Suparna

2014-01-01

132

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

PubMed

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

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

2008-01-01

133

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

134

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

Microsoft Academic Search

The toxicity of cinnamon, Cinnamomum zeylanicum, bark essential oil compounds against eggs and adult females of human head louse, Pediculus humanus capitis, was examined using direct contact and vapour phase toxicity bioassays and compared with the lethal activity of their related compounds, benzyl alcohol, cinnamic acid, cinnamyl acetate, 4-hydroxybenzaldehyde and salicylaldehyde, as well as two widely used pediculicides, d-phenothrin and

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

2005-01-01

135

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. PMID:23593196

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

2013-01-01

136

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. PMID:23109858

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

2012-01-01

137

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

PubMed

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

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

2012-01-01

138

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

139

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

PubMed

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

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

2014-05-01

140

Developing a Schoolwide Enrichment Activity Program for Identified Gifted Students.  

ERIC Educational Resources Information Center

A needs assessment was conducted of 32 middle school gifted students. Analysis of a parent survey, teacher survey, and meetings with students revealed 10 primary need areas (including opportunities for advanced skills, independent thinking, expression of creativity and originality, and acceptance from grade level peers). Four enrichment activities

Perlini, Ernest L.

141

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

PubMed Central

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

Majchrzak, Kinga; Hartman, Mariusz; Czyz, Malgorzata

2014-01-01

142

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

PubMed

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

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

2014-08-01

143

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. PMID:24812573

2014-01-01

144

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

SciTech Connect

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

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

1993-02-15

145

Antioxidative Activities and Active Compounds of Extracts from Catalpa Plant Leaves  

PubMed Central

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

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

2014-01-01

146

Identifying criminal activities at the operating system level  

NASA Astrophysics Data System (ADS)

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

Hussain, Khaled; Sapre, Sampada; Hajgude, Poonam

2005-05-01

147

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

148

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

149

Exome Sequencing Analysis Identifies Compound Heterozygous Mutation in ABCA4 in a Chinese Family with Stargardt Disease  

PubMed Central

Stargardt disease is the most common cause of juvenile macular dystrophy. Five subjects from a two-generation Chinese family with Stargardt disease are reported in this study. All family members underwent complete ophthalmologic examinations. Patients of the family initiated the disease during childhood, developing progressively impaired central vision and bilateral atrophic macular lesions in the retinal pigmental epithelium (RPE) that resembled a “beaten-bronze” appearance. Peripheral venous blood was obtained from all patients and their family members for genetic analysis. Exome sequencing was used to analyze the exome of two patients II1, II2. A total of 50709 variations shared by the two patients were subjected to several filtering steps against existing variation databases. Identified variations were verified in all family members by PCR and Sanger sequencing. Compound heterozygous variants p.Y808X and p.G607R of the ATP-binding cassette, sub-family A (ABC1), member 4 (ABCA4) gene, which encodes the ABCA4 protein, a member of the ATP-binding cassette (ABC) transport superfamily, were identified as causative mutations for Stargardt disease of this family. Our findings provide one novel ABCA4 mutation in Chinese patients with Stargardt disease. PMID:24632595

Chen, Hui; Huang, Lulin; Zhu, Xiong; Li, Youping; Wang, Zhili; Lin, He; Hao, Fang; Yang, Zhenglin; Wang, Liya; Zhu, Xianjun

2014-01-01

150

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; Løjkner, Lars Damgaard; Wulff, Heike

2013-01-01

151

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

PubMed Central

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

Jenkins, David Paul; Yu, Weifeng; Brown, Brandon M.; L?jkner, Lars Damgaard

2013-01-01

152

[The effect of selected tannery chemical compounds on selected bacteria of activated sludge].  

PubMed

Influence of tannery chemical compounds on the selected bacteria of the activated sludge was investigated. The chromium compounds must be diluted to 1:15-1:20 to loss its activity on the bacteria. Other compounds like: natrium chloratum, natrium formate and greased oils have any influence on the growth of the selected bacteria. PMID:11286092

Mendrycka, M; Mierzejewski, J; Lidacki, A; Smiechowski, K

2000-01-01

153

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

SciTech Connect

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

Steven B. Hawthorne

2007-04-15

154

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. PMID:24818149

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

2014-01-01

155

Evaluation of Biologically Active Compounds from Calendula officinalis Flowers using Spectrophotometry  

PubMed Central

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

2012-01-01

156

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. PMID:20711455

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

2010-01-01

157

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

158

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 ...

159

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

160

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

E-print Network

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

Hale, Anna Louise

2005-02-17

161

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

Microsoft Academic Search

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

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

2005-01-01

162

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

PubMed

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

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

2015-03-15

163

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

164

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

SciTech Connect

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

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

1995-06-01

165

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

EPA Science Inventory

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

166

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 890.19-970.01 mg of vitamin C/100 g DW, and 1579.04-1680.90 ?M Trolox/100 g DW or 340.18-362.18 mg of vitamin C/100 g DW, respectively. Six phenolic compounds were identified in the peel from the tropical fruits studied: ferulic, caffeic, sinapic, gallic, ellagic and myricetin. This study demonstrated that freeze-dried peels from purple star apple, yellow cashew and red cashew, could serve as potential sources of antioxidants for use in food and pharmaceutical industries. PMID:25053022

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

167

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

NASA Astrophysics Data System (ADS)

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

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

2009-12-01

168

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

PubMed Central

Background Influenza viruses are a major cause of morbidity and mortality around the world. More recently, a swine-origin influenza A (H1N1) virus that is spreading via human-to-human transmission has become a serious public concern. Although vaccination is the primary strategy for preventing infections, influenza antiviral drugs play an important role in a comprehensive approach to controlling illness and transmission. In addition, a search for influenza-inhibiting drugs is particularly important in the face of high rate of emergence of influenza strains resistant to several existing influenza antivirals. Methods We searched for novel anti-influenza inhibitors using a cell-based neutralization (inhibition of virus-induced cytopathic effect) assay. After screening 20,800 randomly selected compounds from a library from ChemDiv, Inc., we found that BPR1P0034 has sub-micromolar antiviral activity. The compound was resynthesized in five steps by conventional chemical techniques. Lead optimization and a structure-activity analysis were used to improve potency. Time-of-addition assay was performed to target an event in the virus life cycle. Results The 50% effective inhibitory concentration (IC50) of BPR1P0034 was 0.42 ± 0.11 ?M, when measured with a plaque reduction assay. Viral protein and RNA synthesis of A/WSN/33 (H1N1) was inhibited by BPR1P0034 and the virus-induced cytopathic effects were thus significantly reduced. BPR1P0034 exhibited broad inhibition spectrum for influenza viruses but showed no antiviral effect for enteroviruses and echovirus 9. In a time-of-addition assay, in which the compound was added at different stages along the viral replication cycle (such as at adsorption or after adsorption), its antiviral activity was more efficient in cells treated with the test compound between 0 and 2 h, right after viral infection, implying that an early step of viral replication might be the target of the compound. These results suggest that BPR1P0034 targets the virus during viral uncoating or viral RNA importation into the nucleus. Conclusions To the best of our knowledge, BPR1P0034 is the first pyrazole-based anti-influenza compound ever identified and characterized from high throughput screening to show potent (sub-?M) antiviral activity. We conclude that BPR1P0034 has potential antiviral activity, which offers an opportunity for the development of a new anti-influenza virus agent. PMID:20178582

2010-01-01

169

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. PMID:23879992

2013-01-01

170

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. PMID:22314385

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

2012-01-01

171

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

172

Discovery of a novel activator of 5-lipoxygenase from an anacardic acid derived compound collection.  

PubMed

Lipoxygenases (LOXs) and cyclooxygenases (COXs) metabolize poly-unsaturated fatty acids into inflammatory signaling molecules. Modulation of the activity of these enzymes may provide new approaches for therapy of inflammatory diseases. In this study, we screened novel anacardic acid derivatives as modulators of human 5-LOX and COX-2 activity. Interestingly, a novel salicylate derivative 23a was identified as a surprisingly potent activator of human 5-LOX. This compound showed both non-competitive activation towards the human 5-LOX activator adenosine triphosphate (ATP) and non-essential mixed type activation against the substrate linoleic acid, while having no effect on the conversion of the substrate arachidonic acid. The kinetic analysis demonstrated a non-essential activation of the linoleic acid conversion with a KA of 8.65 ?M, ?KA of 0.38?M and a ? value of 1.76. It is also of interest that a comparable derivative 23d showed a mixed type inhibition for linoleic acid conversion. These observations indicate the presence of an allosteric binding site in human 5-LOX distinct from the ATP binding site. The activatory and inhibitory behavior of 23a and 23d on the conversion of linoleic compared to arachidonic acid are rationalized by docking studies, which suggest that the activator 23a stabilizes linoleic acid binding, whereas the larger inhibitor 23d blocks the enzyme active site. PMID:24231650

Wisastra, Rosalina; Kok, Petra A M; Eleftheriadis, Nikolaos; Baumgartner, Matthew P; Camacho, Carlos J; Haisma, Hidde J; Dekker, Frank J

2013-12-15

173

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

PubMed Central

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

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

2013-01-01

174

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

Microsoft Academic Search

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

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

2005-01-01

175

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...

176

Antioxidant activity of compounds from the medicinal herb Aster tataricus  

Microsoft Academic Search

A number of compounds were isolated from the medicinal plant Aster tataricus including shionone, epifriedelinol, quercetin, kaempferol, scopoletin, emodin, aurantiamide acetate and 1,7-dihydroxy-6-methyl-anthraquinone. The compounds were compared with regard to their ability in inhibiting hemolysis of rat erythrocytes induced by 2?-2? azobis (2-amidinopropane) dihydrochloride, lipid peroxidation using the FeSO4-ascorbic acid system, and generation of superoxide radicals using a phenazine methosulfate-nicotinamide

T. B. Ng; Fang Liu; Yanhua Lu; C. H. K. Cheng; Zhengtao Wang

2003-01-01

177

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

PubMed Central

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

2012-01-01

178

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. PMID:24754012

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

2014-01-01

179

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

PubMed Central

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

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

2012-01-01

180

Activity of and initial mechanistic studies on a novel antileishmanial agent identified through in silico pharmacophore development and database searching.  

PubMed

A 3D pharmacophore was generated to describe the antileishmanial activity of dinitroaniline sulfonamides by CATALYST 3D-QSAR methodology, and this pharmacophore was used to search the Maybridge database. Two compounds identified in this search, BTB 06237 and BTB 06256, were highly active with IC(50) values against L. donovani amastigotes of 0.5 +/- 0.2 and 2.3 +/- 0.8 microM, respectively. BTB 06237 also reduced parasite burdens in L. mexicana-infected J774 macrophages at low micromolar concentrations. Unlike the dinitroaniline sulfonamides, the active compounds did not display antimitotic effects against Leishmania. Transmission electron microscopy showed that the single parasite mitochondrion becomes dilated following incubation with BTB 06237, and fluorescence microscopy demonstrated that this organelle fragments into intensely staining spheres when treated with a mitochondrion-specific dye. The mitochondrial membrane potential was also dissipated in BTB 06237-treated parasites. These results indicate that BTB 06237 is an intriguing antileishmanial lead compound that likely interferes with mitochondrial function. PMID:16821779

Delfín, Dawn A; Bhattacharjee, Apurba K; Yakovich, Adam J; Werbovetz, Karl A

2006-07-13

181

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

182

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

183

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

NASA Technical Reports Server (NTRS)

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

Kyte, F. T.

1976-01-01

184

Identification of Compounds that Inhibit the Kinase Activity of Leucine-rich Repeat Kinase 2  

PubMed Central

Mutations in leucine-repeat rich kinase-2 (LRRK2) are the most common known cause of late-onset Parkinson's disease. In this study, a novel system to purify active recombinant LRRK2 expressed in mammalian cells was generated. This recombinant enzyme was used to characterize the specificity of LRRK2 and identify small compounds that can inhibit the kinase activity. Recombinant LRRK2 was shown to autophosphorylate and phosphorylate MBP and a peptide (LRRKtide) corresponding to the T688 site in moesin. A series of well-characterized kinase peptide substrates was not modified by LRRK2 demonstrating remarkable specificity. G2019S, the most common disease-causing mutation in LRRK2, increased kinase activity more dramatically than previously appreciated (?10-fold). Several small molecules sharing a basic indolocarbazole structure (Gö6976, K252a and staurosporine) where identified as potent inhibitors of LRRK2 kinase activity. These findings provide important insights and tools to study the mechanisms of LRRK2 pathobiology, and could lead to therapeutic applications. PMID:19027715

Covy, Jason P.; Giasson, Benoit I.

2009-01-01

185

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

186

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

DOEpatents

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

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

2007-04-03

187

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

188

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

NASA Astrophysics Data System (ADS)

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

Peterson, B.; Wheeler, R.

189

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

190

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

PubMed

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

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

2015-03-15

191

Reactivity studies of antitumor active dirhodium compounds with DNA oligonucleotides  

E-print Network

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

Kang, Mijeong

2007-04-25

192

Nanopharmacy: Inorganic nanoscale devices as vectors and active compounds  

Microsoft Academic Search

In this review we would like to aim at pharmaceuticals engineered on the nanoscale, i.e. pharmaceuticals where the nanomaterial plays the pivotal therapeutic role or adds additional functionality to the previous compound. Those cases would be considered as nanopharmaceuticals. The development of inorganic systems is opening the pharmaceutical nanotechnology novel horizons for diagnosis, imaging and therapy mainly because of their

Pilar Rivera Gil; Dominik Hühn; Loretta L. del Mercato; Daniel Sasse; Wolfgang J. Parak

2010-01-01

193

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

PubMed Central

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

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

1986-01-01

194

Activity artifacts in drug discovery and different facets of compound promiscuity  

PubMed Central

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

Bajorath, Jurgen

2014-01-01

195

Synthesis, molecular structure, DNA interaction and antioxidant activity of novel naphthoxazole compound  

NASA Astrophysics Data System (ADS)

A novel naphthoxazole compound 1 was synthesized and characterized. The crystal structure of the compound shows that N atom locates at ?-position and oxygen atom at ?-position in naphthalene cycle. The DNA binding was studied by absorption spectroscopy, viscosity and luminescence spectra. The DNA binding constant was determined to be 6.16 × 103. The stoichiometry of compound/DNA is 1:1. The pBR322 DNA cleavage induced by the compound was investigated. The antioxidant activity of the compound against hydroxyl radical was also explored.

Wang, Xiu-Zhen; Jiang, Guan-Bin; Xie, Yang-Yin; Liu, Yun-Jun

2014-01-01

196

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

PubMed

The toxicity of cinnamon, Cinnamomum zeylanicum, bark essential oil compounds against eggs and adult females of human head louse, Pediculus humanus capitis, was examined using direct contact and vapour phase toxicity bioassays and compared with the lethal activity of their related compounds, benzyl alcohol, cinnamic acid, cinnamyl acetate, 4-hydroxybenzaldehyde and salicylaldehyde, as well as two widely used pediculicides, d-phenothrin and pyrethrum. In a filter-paper contact toxicity bioassay with female lice at 0.25 mg/cm(2), benzaldehyde was 29- and 27-fold more toxic than pyrethrum and d-phenothrin, respectively, as judged by median lethal time (LT(50)) values. Salicylaldehyde was nine and eight times more active than pyrethrum and d-phenothrin, respectively. Pediculicidal activity of linalool was comparable with that of d-phenothrin and pyrethrum. Cinnamomum bark essential oil was slightly less effective than either d-phenothrin or pyrethrum. Benzyl alcohol and (E)-cinnamaldehyde exhibited moderate pediculicidal activity. After 24h of exposure, no hatching was observed with 0.063 mg/cm(2) salicylaldehyde, 0.125 mg/cm(2) benzaldehyde, 0.5mg/cm(2)Cinnamomum bark essential oil, 1.0 mg/cm(2) (E)-cinnamaldehyde, and 1.0 mg/cm(2) benzyl cinnamate. Little or no ovicidal activity was observed with d-phenothrin or pyrethrum. In vapour phase toxicity tests with female lice, benzaldehyde and salicylaldehyde were much more effective in closed containers than in open ones, indicating that the mode of delivery of these compounds was largely due to action in the vapour phase. Neither d-phenothrin nor pyrethrum exhibited fumigant toxicity. Cinnamomum bark essential oil and test compounds described merit further study as potential pediculicides or ovicides for the control of P. h. capitis. PMID:16188263

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

2005-12-01

197

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

198

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

PubMed Central

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

Revathi, S.; Malathy, N. S.

2013-01-01

199

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

200

Antitumor activity of extracts and compounds from the skin of the toad Bufo bufo gargarizans Cantor.  

PubMed

The skin of the toad Bufo bufo gargarizans Cantor is known to be rich in bufadienolides, peptides and alkaloids. It has been found to be a source of some extracts and biologically active compounds with antitumor activity. Cinobufacini (Huachansu), a Chinese medicine prepared from the dried toad skin, has been widely used in clinical therapy for various cancers in China. Bufadienolides, such as bufalin, cinobufagin, resibufogenin, and telocinobufagin, are the major active compounds derived from the toad skin. They are the maker biologically active compounds of cinobufagin while the antitumor activity of cinobufagin may be due to this kind of components. Experimental research has suggested that cinobufacini and its active compounds (e.g. bufalin and cinobufagin) exhibit significant antitumor activity, including inhibition of cell proliferation, induction of cell differentiation, induction of apoptosis, disruption of the cell cycle, inhibition of cancer angiogenesis, reversal of multi-drug resistance, and regulation of the immune response. Clinical data have indicated that cinobufacini may have effective anticancer activity with low toxicity and few side effects. Data to date suggest it may also enhance quality of life for patients with cancer. Thus, this review briefly summarizes recent studies on the anticancer activity of cinobufacini and some of its active compounds from the skin of the toad Bufo bufo gargarizans Cantor. This might provide additional evidence for further study of the extracts and active compounds from the toad skin in cancer treatment. PMID:21185919

Qi, Fanghua; Li, Anyuan; Inagaki, Yoshinori; Kokudo, Norihiro; Tamura, Sumihito; Nakata, Munehiro; Tang, Wei

2011-03-01

201

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. PMID:21151471

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

2010-01-01

202

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

Microsoft Academic Search

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

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

2003-01-01

203

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. PMID:21931717

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

2011-01-01

204

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

PubMed

Perfluorinated compounds (PFCs) have been shown to disrupt lipid metabolism and even induce cancer in rodents through activation of peroxisome proliferator-activated receptors (PPARs). Lines of evidence showed that PPAR? was activated by PFCs. However, the information on the binding interactions between PPAR? and PFCs and subsequent alteration of PPAR? activity is still limited and sometimes inconsistent. In the present study, in vitro binding of 16 PFCs to human PPAR? ligand binding domain (hPPAR?-LBD) and their activity on the receptor in cells were investigated. The results showed that the binding affinity was strongly dependent on their carbon number and functional group. For the eleven perfluorinated carboxylic acids (PFCAs), the binding affinity increased with their carbon number from 4 to 11, and then decreased slightly. The binding affinity of the three perfluorinated sulfonic acids (PFSAs) was stronger than their PFCA counterparts. No binding was detected for the two fluorotelomer alcohols (FTOHs). Circular dichroim spectroscopy showed that PFC binding induced distinctive structural change of the receptor. In dual luciferase reporter assays using transiently transfected Hep G2 cells, PFCs acted as hPPAR? agonists, and their potency correlated with their binding affinity with hPPAR?-LBD. Molecular docking showed that PFCs with different chain length bind with the receptor in different geometry, which may contribute to their differences in binding affinity and transcriptional activity. PMID:24998974

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

2014-09-15

205

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

SciTech Connect

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

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

1982-04-01

206

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

PubMed Central

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

2013-01-01

207

Multiple microbial activities for volatile organic compounds reduction by biofiltration.  

PubMed

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

Civilini, Marcello

2006-07-01

208

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

209

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. PMID:25001223

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

2014-01-01

210

[Influence of natural complex compounds with hipolipidemic activity on expression of bacteria virulence factors].  

PubMed

Natural complex compounds with hipolipidemic activity, having considerable inhibitory effect on expression of bacteria virulence factors were isolated. Inhibitory properties of the compounds with respect to pyocyanine and protease formation, as well as their influence on the quorum sensing mechanism in Chromobacterium violacium were shown. PMID:22359861

Gotovtseva, V Iu; Grammatikova, N É; Bibikova, M V; Katlinski?, A V

2011-01-01

211

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

Microsoft Academic Search

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

Begum Demir; Francesca Bovolo; Lorenzo Bruzzone

2011-01-01

212

Salmonella Locus Affecting Phosphoenolpyruvate Synthase Activity Identified by a Deletion Analysis  

PubMed Central

Strain leu-4017, derived from Salmonella typhimurium LT2, cannot utilize acetate, pyruvate, or citric acid cycle intermediates as sole sources of carbon. The mutation in this strain extends from the A cistron of the leucine operon to some point between leu and azi, presumably deleting one or more loci involved in the utilization of these compounds. One of these loci is required for phosphoenolpyruvate synthase activity. PMID:4928014

Calvo, J. M.; Goodman, M.; Salgo, M.; Capes, N.

1971-01-01

213

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

PubMed

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

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

2001-08-01

214

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. PMID:23843877

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

2013-01-01

215

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. PMID:23935933

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

216

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

PubMed

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

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

2013-01-01

217

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

ERIC Educational Resources Information Center

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

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

2010-01-01

218

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

PubMed

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

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

2013-11-01

219

A Review on the Radioprotective Activity of organogermanium and Organosilicon Compounds  

PubMed Central

The present review describes the work carried out during the last 20 years in the field of the radioprotective activity and toxicity of several classes of organosilicon and organogermanium compounds (i.e. metallathiazolidines, metalladithioacetals, metallatranes and germathianes). PMID:18475880

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

1999-01-01

220

Adsorption of aromatic compounds from the biodegradation of azo dyes on activated carbon  

NASA Astrophysics Data System (ADS)

The adsorption of three selected aromatic compounds (aniline, sulfanilic acid and benzenesulfonic acid) on activated carbons with different surface chemical properties was investigated at different solution pH. A fairly basic commercial activated carbon was modified by means of chemical treatment with HNO 3, yielding an acid activated carbon. The textural properties of this sample were not significantly changed after the oxidation treatment. Equilibrium isotherms of the selected compounds on the mentioned samples were obtained and the results were discussed in relation to their surface chemistry. The influence of electrostatic and dispersive interactions involved in the uptake of the compounds studied was evaluated. The Freundlich model was used to fit the experimental data. Higher uptakes are attained when the compounds are present in their molecular form. In general, adsorption was disfavoured by the introduction of oxygen-containing groups on the surface of the activated carbon.

Faria, P. C. C.; Órfão, J. J. M.; Figueiredo, J. L.; Pereira, M. F. R.

2008-03-01

221

In vitro activity of thienyl-2-nitropropene compounds against Trypanosoma cruzi.  

PubMed

The in vitro activity of four 2-nitropropene derivatives, 1-(3-benzothienyl)-2-nitropropene (N1), 1-(3-thienyl)-2-nitropropene (N2), 1-(5-bromo-2-thienyl)-2-nitropropene (N3) and 1-(4-bromo-2-thienyl)-2-nitropropene (N4), were tested against cultures of the parasite Trypanosoma cruzi. Cytotoxicity studies were performed using Vero cells. The blood trypomastigotes, amastigotes and epimastigotes showed differential degrees of sensitivity towards the four tested compounds; the highest activity against the epimastigotes and blood tripomastigotes was exhibited by N1, followed by N3, N4 and finally N2. In contrast, whereas the compounds N1, N3 and N4 exerted similar magnitudes of activity against amastigotes, N2 was found to be a much less potent compound. According to our results, the compound N1 had the highest level of activity (IC50: 0.6 microM) against epimastigotes. PMID:20027464

Herrera, Cristina; Vallejos, Gabriel A; Loaiza, Randall; Zeledón, Rodrigo; Urbina, Andrea; Sepúlveda-Boza, Silvia

2009-11-01

222

Effects of ammonium compounds on the foliar activity of acifluorfen  

E-print Network

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

Schaffers, William Clemens

2012-06-07

223

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

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

2014-07-01

224

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

Code of Federal Regulations, 2011 CFR

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

2011-07-01

225

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

Code of Federal Regulations, 2010 CFR

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

2010-07-01

226

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

Code of Federal Regulations, 2012 CFR

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

2012-07-01

227

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

Code of Federal Regulations, 2013 CFR

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

2013-07-01

228

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

Code of Federal Regulations, 2012 CFR

...2012-01-01 false Where hazardous substance activity has been identified on property...Disposal Provisions Relating to Hazardous Substance Activity § 102-75.340 Where hazardous substance activity has been identified on...

2012-01-01

229

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

Code of Federal Regulations, 2011 CFR

...2011-01-01 false Where hazardous substance activity has been identified on property...Disposal Provisions Relating to Hazardous Substance Activity § 102-75.340 Where hazardous substance activity has been identified on...

2011-01-01

230

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

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Where hazardous substance activity has been identified on property...Disposal Provisions Relating to Hazardous Substance Activity § 102-75.340 Where hazardous substance activity has been identified on...

2013-07-01

231

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

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Where hazardous substance activity has been identified on property...Disposal Provisions Relating to Hazardous Substance Activity § 102-75.340 Where hazardous substance activity has been identified on...

2010-07-01

232

AhR-active compounds in sediments of the Haihe and Dagu Rivers, China  

Microsoft Academic Search

Total concentrations of compounds that can cause activation of the aryl hydrocarbon receptor (AhR) in extracts of river sediments from various locations in the Haihe and Dagu Rivers, Tianjin, China were determined by use of the in vitro H4IIE-luc cell line. AhR-active compounds were isolated from sediments by Soxhlet extraction, and the crude extracts were fractionated using a Florisil column

Maoyong Song; Qinting Jiang; Yan Xu; Hanxia Liu; Paul K. S. Lam; Desmond K. O’Toole; Qinghua Zhang; John P. Giesy; Guibin Jiang

2006-01-01

233

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. PMID:19877647

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

2009-01-01

234

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

235

Compositions comprising benzyl alcohol derivatives and further antimicrobial active compounds  

US Patent & Trademark Office Database

The present invention relates to a composition comprising or consisting of: (a) one, two or more compounds selected from the group consisting of benzyl alcohol derivatives of the formula (I) ##STR00001## wherein each of the substituents R.sup.1, R.sup.2, and R.sup.3 has a position at the aromatic ring, and wherein the substituents R.sup.1, R.sup.2, and R.sup.3 independently of one another are selected from the group consisting of: H; OH; OCH.sub.3; COON; linear or branched, saturated aliphatic hydrocarbon radical having 1 to 8 carbon atoms; linear or branched, unsaturated aliphatic hydrocarbon radical having 2 to 8 carbon atoms; COOR.sup.4, wherein R.sup.4 is a linear or branched alkyl radical having 1 to 8 carbon atoms; wherein the total number of carbon atoms in substituents R.sup.1, R.sup.2 and R.sup.3 is 1 to 12, and (b) one, two or more compounds selected from the group consisting of: (i) branched or unbranched 1,2-alkanediols having 3 to 14 carbon atoms, (ii) benzoic acid (INCI: Benzoic Acid) and its esters and salts, (iii) 4-hydroxybenzoic acid and its esters (INCI: Parabens) and salts, (iv) 2,4-hexadienoic acid (INCI: Sorbic Acid) and its salts, (v) 2-phenoxyethanol (INCI: Phenoxyethanol) (vi) 3-iodo-2-propinyl-butylcarbamate (INCI: Iodopropynyl Butylcarbamate), (vii) 3-(4-chlorphenoxy)-1,2-propane-1,2-diol (INCI: Chlorphenesin), (viii) urea (INCI: Urea) and derivatives thereof, in particular 1,1'-methylen-bis(3-(1-hydroxymethyl-2,4-dioximidazolidin-5-yl))urea (INCI: Imidazolidinyl urea), N-hydroxymethyl-N-(1,3-di(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl)-N'-h- ydroxy-methylurea (INCI: Diazolidinyl Urea) and N-(4-chlorophenyl)-N'-(3,4-dichlorophenyl)-urea (INCI: Triclocarban), (ix) 1,3-bis-(hydroxymethyl)-5,5-dimethyl-2,4-imidazolidindione (INCI: DMDM hydantoin), (x) 1,2-propanediol, 3-(2-ethylhexyloxy) (INCI: Octoxyglycerin), (xi) isothiazolinones and mixtures thereof (e.g. a mixture of 5-chloro-2-methyl-3(2H)-isothiazolinone and 2-methyl-3(2H)-isothiazolinone with magnesium chloride and magnesium nitrate; INCI: Methylchloroisothiazolinone and Methylisothiazolinone).

2014-08-05

236

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

237

A high-content, multiplexed screen in human breast cancer cells identifies profilin-1 inducers with anti-migratory activities.  

PubMed

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

Joy, Marion E; Vollmer, Laura L; Hulkower, Keren; Stern, Andrew M; Peterson, Cameron K; Boltz, R C Dutch; Roy, Partha; Vogt, Andreas

2014-01-01

238

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

PubMed

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

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

2014-05-27

239

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

E-print Network

% B. The flow rate was 1 mL/min and 10 ?L of sample were injected. The temperature of the column was kept at 35 ?C (Hale 2003). Phenolic compounds were identified by comparing the retention time and UV-visible spectral data to known previously... in diphenylamine-aniline-phosphate revealing solution. Quantification of phenolic compounds The concentration of anthocyanin glycosides was determined from standard curves prepared by injecting different volumes of stock solution of standards in the range...

Pedreschi, Romina Paola

2005-08-29

240

Activity of several molybdenum compounds for the methanation of CO  

Microsoft Academic Search

The initial specific activities of the unsupported catalysts tested for the reaction of 3:1 hydrogen\\/carbon monoxide at 350°C decreased in the order nickel > molybdenum carbide > molybdenum > molybdenum nitride > molybdenum dioxide > molybdenum disulfide > molybdenum trioxide. The molybdenum carbide, which apparently acted as a catalyst and not an intermediate, was more stable than the other catalysts.

M. Saito; R. B. Anderson

1980-01-01

241

Antioxidant activity of plants methanolic extracts containing phenolic compounds  

Microsoft Academic Search

The presence of natural antioxidant in plants is well known. This paper reports the antioxidative activities of some methanolic plant extracts namely 'ulam raja' (Cosmos caudatus), 'kesum' (Polygonum minus), 'selom' (Oenanthe javanica), 'pegaga' (Centella asiatica) and 'curry leaf' (Murraya koenigii). The analysis carried out was total phenolic content, ferric reducing power, ferric thiocyanate (FTC) and thiobarbituric acid (TBA) tests. From

A. Noriham; A. S. Norrakiah; Food Biotechnology Programme; Bandar Baru Nilai

242

In vitro antimicrobial and cytotoxic activities of ferrocene derivative compounds.  

PubMed

The aim of the present study was to investigate the biocidal activity of four new ferrocene derivative based coordination complexes, [1,2,3-trithia-/3/-ferrocenophane, C1]; [disodium-1,1'-ferrocenedithiolate, C2]; [1,1'-(ferrocene-1,1'-diyl)-diethanol, C3]; [ferrocenyl(ethyl-phenyl)-methanol, C4]; against microbes (bacteria and fungi) and brine shrimp (Artemia salina Lech.) nauplii. C2 showed modest antibacterial activity at the concentration of 200 microg disc(-1) and gave its Minimum Inhibitory Concentration values at 32-64 microg mL(-1) against the tested bacteria. These complexes gave comparatively better antibacterial activity against the Gram-positives than the Gram-negatives. C3, C1 and C4 showed moderate antifungal activity at concentration of 200 microg disc(-1). Brine shrimp eggs were hatched in artificial sea water and exposed to the complexes. Median lethal concentration (LC50) values were calculated. Both complexes showed toxicity against brine shrimp but complex C3 explored its potent cytotoxicity having LC50 values at 6.031 microg mL(-1) (ppm). PMID:19070108

Al-Bari, M Abdul Alim; Hossen, M Faruk; Khan, Alam; Islam, M Robiul; Kudrat-E-Zahan, M; Mosaddik, M Ashik; Zakaria, Choudhury M; Islam, M Anwar Ul

2007-08-01

243

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. 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.

2013-01-01

244

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. PMID:22454670

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

2012-01-01

245

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

PubMed

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

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

2008-07-01

246

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

PubMed

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

Shibata, S

2001-12-01

247

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

E-print Network

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

Phithakkitnukoon, Santi

2010-01-01

248

Novel anti-Cryptosporidium activity of known drugs identified by high-throughput screening against parasite fatty acyl-CoA binding protein (ACBP)  

PubMed Central

Background Cryptosporidium parvum causes an opportunistic infection in AIDS patients, and no effective treatments are yet available. This parasite possesses a single fatty acyl-CoA binding protein (CpACBP1) that is localized to the unique parasitophorous vacuole membrane (PVM). The major goal of this study was to identify inhibitors from known drugs against CpACBP1 as potential new anti-Cryptosporidium agents. Methods A fluorescence assay was developed to detect CpACBP1 activity and to identify inhibitors by screening known drugs. Efficacies of top CpACBP1 inhibitors against Cryptosporidium growth in vitro were evaluated using a quantitative RT–PCR assay. Results Nitrobenzoxadiazole-labelled palmitoyl-CoA significantly increased the fluorescent emission upon binding to CpACBP1 (excitation/emission 460/538 nm), which was quantified to determine the CpACBP1 activity and binding kinetics. The fluorescence assay was used to screen a collection of 1040 compounds containing mostly known drugs, and identified the 28 most active compounds that could inhibit CpACBP1 activity with sub-micromolar IC50 values. Among them, four compounds displayed efficacies against parasite growth in vitro with low micromolar IC50 values. The effective compounds were broxyquinoline (IC50 64.9 ?M), cloxyquin (IC50 25.1 ?M), cloxacillin sodium (IC50 36.2 ?M) and sodium dehydrocholate (IC50 53.2 ?M). Conclusions The fluorescence ACBP assay can be effectively used to screen known drugs or other compound libraries. Novel anti-Cryptosporidium activity was observed in four top CpACBP1 inhibitors, which may be further investigated for their potential to be repurposed to treat cryptosporidiosis and to serve as leads for drug development. PMID:22167242

Fritzler, Jason M.; Zhu, Guan

2012-01-01

249

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

250

Auraptene: a natural biologically active compound with multiple targets.  

PubMed

Auraptene is the most abundant prenyloxycoumarin that occurs in nature. It has been isolated from plants belonging to many genus of the Rutaceae family, comprising several edible fruits and vegetables. Although known for a long time, only in the last decade auraptene was seen to exert valuable pharmacological properties as orally active cancer chemopreventive, anti-bacterial, anti-protozoal, anti-fungal, anti-inflammatory, and anti-oxidant agent. The aim of this review is to examine in detail the in so far reported effects and what is known about the mechanism of action underlying the observed pharmacological activities of this secondary metabolite by means of a survey of the current literature in which auraptene has been reported as an inhibitor of key biological targets like metalloproteinases, glycoprotein P, PPARs, and several others. PMID:20955144

Genovese, Salvatore; Epifano, Francesco

2011-03-01

251

Peptidergic modulation of patterned motor activity in identified neurons of Helisoma  

PubMed Central

The neuroactive peptides SCPB (small cardioactive peptide B) and FMRFamide (Phe-Met-Arg-Phe-NH2), both originally isolated from molluscs, have potent modulatory effects upon the production of patterned motor activity in identified neurons (e.g., B5 and B19) in the buccal ganglia of the snail Helisoma. Such patterned motor activity has previously been shown to underlie feeding behavior. Micromolar concentrations of SCPB initiate patterned motor activity in quiescent ganglia and increase the rate of activity in ganglia that are spontaneously active. Micromolar concentrations of FMRFamide inhibit patterned motor activity in Helisoma buccal ganglia, and 10 ?M FMRFamide completely suppresses such activity. In addition, there are both anti-SCPB-and anti-FMRFamide-immunoreactive neurons in Helisoma buccal ganglia. Our results suggest that peptides may play a prominent role in the regulation of feeding behavior in Helisoma. Images PMID:16593621

Murphy, A. D.; Lukowiak, Ken; Stell, W. K.

1985-01-01

252

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

PubMed

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

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

2013-09-01

253

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

PubMed

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

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

2006-05-01

254

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. PMID:24400098

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

2014-01-01

255

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

PubMed

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

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

2007-05-30

256

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

PubMed Central

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; Chavez Fumagalli, Miguel Angel; Valadares, Diogo Garcia; Duarte, Mariana Costa; Costa, Lourena Emanuele; Filho, Jose Dias de Souza; Tavares, Carlos Alberto Pereira; de Padua, Rodrigo Maia; Leite, Joao Paulo Viana; Coelho, Eduardo Antonio Ferraz

2013-01-01

257

Multifractal analysis of Mt. St. Helens seismicity as a tool for identifying eruptive activity  

Microsoft Academic Search

We present a multifractal analysis of Mount St. Helens seismic activity\\u000aduring 1980-2002. The seismic time distribution is studied in relation to the\\u000aeruptive activity, mainly marked by the 1980 major explosive eruptions and by\\u000athe 1980-1986 dome building eruptions. The spectrum of the generalized fractal\\u000adimensions, i.e. Dq vs q, extracted from the data, allows us to identify two

Filippo Caruso; Sergio Vinciguerra; Vito Latora; Andrea Rapisarda; Stephen Malone

2003-01-01

258

Leishmanicidal and cytotoxic activities of extracts and naturally-occurring compounds from two Lauraceae species.  

PubMed

The in vitro leishmanicidal effects of ethanolic extracts and fifteen naturally-occurring compounds (five lignans, eight neolignans, a diterpene and a dihydrochalcone), obtained from Pleurothyrium cinereum and Ocotea macrophylla, were evaluated on promastigotes of Leishmania panamensis and L. braziliensis. In addition, in order to determine the selective action on Leishmania species as a safety principle, in vitro cytotoxicity on J774 cells was also evaluated for test compounds and extracts. One extract and seven compounds showed activity against Leishmania parasites at different levels. Dihydroflavokawin B (8) was found to be the most potent antileishmanial compound on both parasites, whilst (+)-otobaphenol (14), was found to be the most selective compound on L. panamensis. PMID:21425681

Sánchez-Suárez, Jeysson; Coy-Barrera, Ericsson; Cuca, Luis Enrique; Delgado, Gabriela

2011-02-01

259

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

PubMed

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

Zhu, Xianfeng; Zhang, Hongxun; Lo, Raymond

2004-12-01

260

[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

261

Evaluation of anxiolytic activity of compound Valeriana jatamansi Jones in mice  

PubMed Central

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

2012-01-01

262

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

SciTech Connect

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

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

2005-12-01

263

Anti-inflammatory and antioxidant activities of phenolic compounds from Desmodium caudatum leaves and stems.  

PubMed

Four flavanonols (1-4), one xanthone (5), and three flavonoid glycosides (6-8), were isolated from the leaves and stems of Desmodium caudatum. Their structures were elucidated by comparing spectroscopic data with reported values. The anti-inflammatory activity of the isolated compounds was investigated in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells. Among them, compounds 1 and 2 exhibited inhibitory effects on LPS-induced IL-6, IL-12 p40, and TNF-? production with IC50 values ranging from 6.0 to 29.4 ?M. Compound 5 exhibited 1,1-diphenyl-2-picrylhydrazyl radical and intracellular reactive oxygen species scavenging activity in human HaCaT keratinocytes. These results warrant further studies of the potential anti-inflammatory and antioxidant benefits of compounds from D. caudatum. PMID:24026429

Li, Wei; Sun, Ya Nan; Yan, Xi Tao; Yang, Seo Young; Kim, Sohyun; Chae, Doobyeong; Hyun, Jin Won; Kang, Hee Kyoung; Koh, Young-Sang; Kim, Young Ho

2014-06-01

264

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

Microsoft Academic Search

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 thinking; and (b) analyze students’ mathematical thinking when engaged in

Scott A. Chamberlin; Sidney M. Moon

2005-01-01

265

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

266

Use of Bromodeoxyuridine Immunocapture To Identify Active Bacteria Associated with Arbuscular Mycorrhizal Hyphae  

Microsoft Academic Search

Arbuscular mycorrhizae are beneficial for crops grown under low-till management systems. Increasingly, it is becoming apparent that bacteria associated with mycorrhizae can enhance the beneficial relationship between mycorrhizae and plants. However, it has been difficult to study these relationships by conventional techniques. In this study actively growing bacteria were identified in soil from an undisturbed fallow field known to contain

Veronica Artursson; Janet K. Jansson

2003-01-01

267

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. PMID:23618509

2013-01-01

268

Causal connection between detoxification enzyme activity and consumption of a toxic plant compound  

Microsoft Academic Search

Insect herbivores can increase their detoxification activities against a particular plant poison in response to prolonged ingestion of the same compound. For example, larval tobacco hornworms (Manduca sexta) experience a dramatic increase in cytochrome P450 activity against nicotine after ingesting nicotine. While it is generally assumed that this induction process permits increased consumption of toxic plant tissues, we are not

M. J. Snyder; J. I. Glendinning

1996-01-01

269

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

270

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. PMID:24308360

2013-01-01

271

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.

Vo-Dinh, Tuan (Knoxville, TN)

1993-01-01

272

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

Vo-Dinh, Tuan (Knoxville, TN)

1994-01-01

273

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

Microsoft Academic Search

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

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

2009-01-01

274

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

Cancer.gov

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

275

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

E-print Network

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...

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

2012-10-08

276

Functional brain activation differences in stuttering identified with a rapid fMRI sequence  

PubMed Central

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 motor and auditory brain activity in children who stutter closer to the age at which recovery from stuttering is documented. Rapid sequences may be preferred for individuals or populations who do not tolerate long scanning sessions. In this report, we document the application of a picture naming and phoneme monitoring task in three minute fMRI sequences with adults who stutter (AWS). If relevant brain differences are found in AWS with these approaches that conform to previous reports, then these approaches can be extended to younger populations. Pairwise contrasts of brain BOLD activity between AWS and normally fluent adults indicated the AWS showed higher BOLD activity in the right inferior frontal gyrus (IFG), right temporal lobe and sensorimotor cortices during picture naming and and higher activity in the right IFG during phoneme monitoring. The right lateralized pattern of BOLD activity together with higher activity in sensorimotor cortices is consistent with previous reports, which indicates rapid fMRI sequences can be considered for investigating stuttering in younger participants. PMID:22133409

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

2011-01-01

277

Hammerhead ribozyme activity and oligonucleotide duplex stability in mixed solutions of water and organic compounds  

PubMed Central

Nucleic acids are useful for biomedical targeting and sensing applications in which the molecular environment is different from that of a dilute aqueous solution. In this study, the influence of various types of mixed solutions of water and water-soluble organic compounds on RNA was investigated by measuring the catalytic activity of the hammerhead ribozyme and the thermodynamic stability of an oligonucleotide duplex. The compounds with a net neutral charge, such as poly(ethylene glycol), small primary alcohols, amide compounds, and aprotic solvent molecules, added at high concentrations changed the ribozyme-catalyzed RNA cleavage rate, with the magnitude of the effect dependent on the NaCl concentration. These compounds also changed the thermodynamic stability of RNA base pairs of an oligonucleotide duplex and its dependence on the NaCl concentration. Specific interactions with RNA molecules and reduced water activity could account for the inhibiting effects on the ribozyme catalysis and destabilizing effects on the duplex stability. The salt concentration dependence data correlated with the dielectric constant, but not with water activity, viscosity, and the size of organic compounds. This observation suggests the significance of the dielectric constant effects on the RNA reactions under molecular crowding conditions created by organic compounds. PMID:25161873

Nakano, Shu-ichi; Kitagawa, Yuichi; Miyoshi, Daisuke; Sugimoto, Naoki

2014-01-01

278

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

Microsoft Academic Search

Phenolic compounds in sugar cane (Saccharum officinarum L.) juice were identified and quantified by analytical high performance liquid chromatography and photodiode array detection, showing the predominance of flavones (apigenin, luteolin and tricin derivatives), among flavonoids, and of hydroxycinnamic, caffeic and sinapic acids, among phenolic acids, representing a total content of around 160 mg\\/L. A tricin derivative was present in the highest

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

2006-01-01

279

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

PubMed

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

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

2008-12-01

280

Cyclooxygenase enzyme inhibitory compounds with antioxidant activities from Piper methysticum (kava kava) roots.  

PubMed

Cyclooxygenase enzyme inhibitory assay-guided purification of ethyl acetate extract of Piper methysticum (kava kava) roots yielded six biologically active compounds (1-7), which were purified using MPLC, preparative TLC and HPLC methods. These compounds were also evaluated for antioxidant activities. Dihydrokawain (1) and yangonin (6) showed the highest COX-I and COX-II inhibitory activities at 100 microg/ml, respectively. The lipid oxidation assay did not reveal antioxidant activities for demethoxyangonin (2), dihydrokawain (1), kawain (4), dihydromethysticin (5) or methysticin (7) at 50 microg/ml. The antioxidant activities of flavokawain A (3) and yangonin (6) could not be tested in the lipid oxidation assay due to solubility problems. However, yangonin and methysticin showed moderate antioxidant activities in the free radical scavenging assay at 2.5 mg/ml. PMID:11924763

Wu, D; Yu, L; Nair, M G; DeWitt, D L; Ramsewak, R S

2002-01-01

281

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

282

Active-site iron dynamics in heme proteins and model compounds  

NASA Astrophysics Data System (ADS)

Active-site iron dynamics in heme proteins and model compounds are studied via nuclear resonance vibrational spectroscopy (NRVS) and compared with other experimental vibrational probes and theoretical calculations, yielding new insight into the vibrational dynamics of biologically significant proteins. NRVS is a novel technique that selectively probes only 57Fe; experiments provide quantitative information on the amplitude and frequency of all normal modes having significant iron vibrational motion. Data from other vibrational probes including traditional Mossbauer, resonance Raman spectroscopy, and inelastic neutron scattering provide complementary information on the vibrational dynamics of the heme-protein system as a whole. Specific iron participation is identified in resonance Raman and inelastic neutron modes when these spectroscopic modes are seen at the same frequency as NRVS vibrations. NRVS data is examined for 57Fe-containing myoglobin, cytochrome f, hemoglobin, and several heme model compounds. A template of heme normal modes is obtained from analyses of several model compound systems: phenyl-like modes or modes associated with the protein peak at very low-energies ˜30--60 cm-1, out-of-plane modes in the ˜70--130 cm-1 region, imidazole or histidine modes near 220 cm-1, in-plane modes from ˜200--500 cm-1, and ligand modes at the highest frequencies ˜460--600 cm-1. A qualitative understanding of the more complicated heme-protein dynamics is obtained by applying this template to the protein vibrational density of states (VDOS). Differences in heme-to-protein binding configurations in myoglobin and cytochrome f are reflected in the iron VDOS, suggesting a structural and dynamical correlation with their different biological functions (i.e. ligand binding versus electron transport). Hemoglobin hybrids containing 57Fe and 56Fe have been prepared for the first time and NRVS measurements show data for the selected alpha or beta subunits within a relatively unperturbed hemoglobin sample. Myoglobin and hybrid hemoglobin data show a broad range of modes with doming character, but modes near 100 cm-1 appear to have importance in the communication pathway of the hemoglobin allosteric effect.

Adams, Kristl L.

283

Highly efficient antiviral and antibacterial activities of solid-state cuprous compounds.  

PubMed

We found that several solid-state cuprous compounds, including cuprous oxide (Cu(2)O), sulfide (Cu(2)S), iodide (CuI), and chloride (CuCl), have highly efficient antiviral activities, whereas those of solid-state silver and cupric compounds are markedly lower. On a Cu(2)O-loaded glass substrate, for example, the infectious activity of bacteriophages was reduced by 5-orders of magnitude within 30 min and by 3-orders of magnitude within 1h for bacteria. In contrast, the infectious activities of both phages and bacteria were not markedly reduced on CuO-loaded substrates within a similar time frame. To determine the origin of this inhibitory activity, we investigated the effects of reactive oxygen species (ROS), leached copper ions, and the solid-state compound itself against bacteriophages, and concluded that infectious activity is lost following direct contact with the solid-state surface of cuprous compounds, but not ROS or copper ions. Furthermore, we found that Cu(2)O adsorbed and denatured more proteins than CuO, which suggests the difference of the inhibitory activity between Cu(2)O and CuO. PMID:22902129

Sunada, Kayano; Minoshima, Masafumi; Hashimoto, Kazuhito

2012-10-15

284

The Antimicrobial Activities of Extract and Compounds Isolated from Brillantaisia lamium  

PubMed Central

Background: Brillantaisia lamium is an erect branched herb, which grows to a height of 1.50 m in moist tropical areas, both in full sun and partial shade. In , the aerial part of this plant is used in the treatment of various microbial infections such as skin diseases and infections of urinary tract. The aim of this study was to evaluate the antimicrobial activities of CH2Cl2: MeOH (1:1) extract, fractions and compounds from the aerial part of B. lamium. Methods: The plant was dried and extracted by maceration in CH2Cl2: MeOH (1:1 v/v). Structures of the compounds from the CH2Cl2: MeOH (1:1) soluble fraction were determined by spectroscopic methods and compared with published data. The broth micro dilution method was used to evaluate the antimicrobial activities against bacteria and fungal species. Results: Four known compounds: aurantiamide acetate (1), lupeol (2), lespedin (3), sitosterol 3-O-?-D-glucopyranoside (4) and a mixture of sterols: campesterol (5), stigmasterol (6) and ?-sitosterol (7) were isolated from CH2Cl2: MeOH (1:1) extract of B. lamium aerial parts. The crude extract, fractions and isolated compounds exhibited both antibacterial and antifungal activities that varied with microorganism (MIC=6.25 – 1000 µg/ml). Compound 3 was the most active (MIC=6.25 – 100 µg/ml) while Staphylococcus aureus, Enterococcus faecalis, Candida tropicalis and Cryptococcus neoformans were the most sensitive to all the tested compounds. Conclusion: The overall results of this study indicate that the CH2Cl2: MeOH (1:1) extract and some of isolated compounds have interesting antimicrobial properties and can be used for the treatment of fungal and bacterial infections. PMID:23365474

Tamokou, Jean De Dieu; Kuiate, Jules Roger; Tene, Mathieu; Kenla Nwemeguela, Timothee Julbelin; Tane, Pierre

2011-01-01

285

Synthesis, characterization, investigation of biological activity and theoretical studies of hydrazone compounds containing choloroacetyl group  

NASA Astrophysics Data System (ADS)

In this study, three new hydrazide-hydrazone derivative compounds which contain choloroacetyl group have been synthesized and characterized. In the characterization, spectral techniques such as IR, 1H NMR, 13C NMR and UV-Vis spectroscopy techniques were used. Antibacterial effects of the synthesized compounds were investigated against Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853. In the theoretical calculations Gaussian 09 software was used with the DFT/6-311+(d,p) basis set. Experimental X-ray analysis of compounds has not been studied. Theoretical bond lengths of synthesized compounds were compared with experimental bond lengths of a similar compound. Theoretical and experimental bond lengths are in good agreement with R2: 0.896, 0.899 and 0.900 for compounds 1, 2, and 3, respectively. For antibacterial activity, the most effective one was found to be N?-(4-bromobenzylidene)-2-chloro-N-(4-(3-methyl-3-phenylcyclobutyl)-thiazol-2-yl) acetohydrazide against P.aeroginaosa ATTC 27853, among the studied compounds.

Cukurovali, Alaaddin; Yilmaz, Engin

2014-10-01

286

Efficient discovery of responses of proteins to compounds using active learning  

PubMed Central

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

2014-01-01

287

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

2013-06-01

288

THIAZOLIDINONE CFTR INHIBITORS WITH IMPROVED WATER SOLUBILITY IDENTIFIED BY STRUCTURE-ACTIVITY ANALYSIS  

PubMed Central

The thiazolidinone 3-[(3-trifluoromethyl)phenyl]-5-[(4-carboxyphenyl)methylene]-2-thioxo-4-thiazolidinone (CFTRinh-172) inhibits cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel conductance with submicromolar affinity and blocks cholera toxin-induced intestinal fluid secretion. Fifty-eight CFTRinh-172 analogs were synthesized to identify CFTR inhibitors with improved water solubility, exploring modifications in its two phenyl rings, thiazolidinone core, and core-phenyl connectors. Greatest CFTR inhibition potency was found for 3-CF3 and polar group-substituted-phenyl rings, and a thiazolidinone core. Two compounds with ~1 ?M CFTR inhibition potency and solubility >180 ?M (>10-fold more than CFTRinh-172) were identified: Tetrazolo-172, containing 4-tetrazolophenyl in place of 4-carboxyphenyl, and Oxo-172, containing thiazolidinedione in place of the thiazolidinone core. These water soluble thiazolidinone analogs had low cellular toxicity. The improved water solubility of Tetrazolo- and Oxo-172 make them potential lead candidates for therapy of secretory diarrheas and polycystic kidney disease. PMID:18691893

Sonawane, N.D.; Verkman, A.S.

2008-01-01

289

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

290

Isolation, characterization and activity of phytotoxic compounds from quackgrass [Agropyron repens (L.)Beauv].  

PubMed

Previous experiments showed that legumes grown in the presence of living or herbicidally treated quackgrass residues or extracts exhibited reduced seedling root and shoot growth and decreased nodulation and nitrogen fixation. Aqueous extracts of quackgrass shoots were most inhibitory to plant growth. Upon sequential partitioning of an aqueous extract of quackgrass shoots, the ether extract possessed the most activity and caused 50% reductions in radicle elongation of eight crop and weed species at concentrations of less than 240 ?g/ml (small-seeded species) and 1000 ?g/ml (large-seeded species). Snapbeans (Phaseolus vulgaris L. "Bush Blue Lake") grown aseptically in agar containing an ether extract at 100 and 200 ?g/ml exhibited severe root browning, lack of root hair formation, and a two- to three-fold reduction in root and shoot dry weights. The ether extract of quackgrass shoots had no inhibitory effect on the growth of fourRhizobium species in Petri dishes or two species in broth culture. Inhibitors present in the ether extract may influence the legumeRhizobium symbiosis indirectly by reducing legume root growth and root hair formation. The ether extract of quackgrass shoots was separated using high-pressure liquid, thin-layer, and liquid column chromatography in an attempt to isolate and identify the inhibitors responsible for the inhibition of seedling growth. Two closely related flavonoid inhibitors were isolated from the ether extract. One was identified as 5,7,4'-trihydroxy-3',5'-dimethoxyflavone (tricin). Both flavonoids caused 50% inhibition of radicle elongation in cress (Lepidium sativum L. "Burpee curly") seeds at concentrations of less than 125 ?g/ml. Both flavonoids were found in ether extracts of quackgrass shoots and rhizomes, but the largest amounts of both compounds occurred in quackgrass shoots collected from the field. PMID:24301884

Weston, L A; Burke, B A; Putnam, A R

1987-03-01

291

Performance of phenol-acclimated activated sludge in the presence of various phenolic compounds  

NASA Astrophysics Data System (ADS)

The objective of this study was to evaluate the performance of phenol-acclimated activated sludge in the presence of various phenolic compounds in the separated batch reactors. The phenol-acclimated activated sludge was observed to be capable of completely removing phenol, o-cresol, m-cresol, and 4-chlorophenol. Nevertheless, in the presence of 2-chlorophenol and 3-chlorophenol merely at 50 mg/L, incomplete removal of these phenolic compounds were noticed. The specific oxygen uptake rate patterns obtained for phenol, o-cresol, m-cresol, and 4-chlorophenol could be used to approximate the end point of these phenolic compounds removal as well as to monitor the growth of biomass. As the 2-chlorophenol and 3-chlorophenol were only partially removed in the mixed liquor, the patterns of specific oxygen uptake rate attained for these phenolic compounds were not feasible for the similar estimation. The calculated toxicity percentages show the toxicity effects of phenolic compounds on the phenol-acclimated activated sludge followed the order of 2-chlorophenol ? 3-chlorophenol > 4-chlorophenol > o-cresol ? m-cresol > phenol.

Lim, Jun-Wei; Tan, Je-Zhen; Seng, Chye-Eng

2013-06-01

292

Evaluating the antioxidative activity of diselenide containing compounds in human blood.  

PubMed

This study was designed to determine and compare the antioxidant effects of synthetic organoselenium compounds. In experimental trials three different diselenides were used: bis(2-hydroxyphenyl) diselenide, bis{[2-(4-hydroxybenzyl)imino]phenyl} diselenide and bis[2-(4-methylphenylsulfonylamino)phenyl] diselenide. The compounds were screened for antioxidant activities in human blood under oxidation stress conditions. Oxidative stress was induced in vitro in human blood platelet samples and in plasma by 0.1 mM peroxynitrite (ONOO(-)) or by Fe(2+). In experimental trials the levels of chosen oxidative stress markers (TBARS, O2(-), and protein carbonyl groups) were significantly decreased by the action of the tested compounds. The antioxidative properties and the changes in proteins and lipids in the presence of new synthesized selenoorganic compounds were studied in vitro and compared with activity of ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one)--a classical antioxidant, well known as the most important glutathione peroxidase mimetic agent. Our results indicate that the tested diselenides have distinctly protective effects against oxidative alterations of biomolecules caused by ONOO(-) and Fe(2+) in blood platelets and in plasma. Therefore it seems that not only ebselen with a wide spectrum of therapeutic actions but also other organoselenium compounds can be considered in the future as active pharmacological agents. PMID:23941993

Saluk, Joanna; Bijak, Micha?; Nowak, Pawe?; Wachowicz, Barbara

2013-10-01

293

Effects of the compounds 2-methoxynaphthoquinone, 2-propoxynaphthoquinone, and 2-isopropoxynaphthoquinone on ecdysone 20-monooxygenase activity.  

PubMed

The effects of the natural compound 2-methoxy-1,4-naphthoquinone, isolated from the leaves of Impatiens glandulifera and the synthetic compounds 2-propoxy-1,4-naphthoquinone and 2-isopropoxy-1,4-naphthoquinone on ecdysone 20-monooxygenase (E-20-M) activity were examined in three insect species. Homogenates of wandering stage third instar larvae of Drosophila melanogaster, or abdomens from adult female Aedes aegypti, or fat body or midgut from fifth instar larvae of Manduca sexta were incubated with radiolabelled ecdysone and increasing concentrations (from 1 x 10(-8) to 1 x 10(-3) M) of the three compounds. All three compounds were found to inhibit in a dose-dependent fashion the E-20-M activity in the three insect species. The concentration of these compounds required to elicit a 50% inhibition of this steroid hydroxylase activity in the three insect species examined ranged from approximately 3 x 10(-5) to 7 x 10(-4) M. PMID:17694563

Mitchell, Martin J; Brescia, Aaron I; Smith, Stan L; Morgan, E David

2007-09-01

294

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

PubMed

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

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

2013-01-01

295

Biofiltration of a mixture of volatile organic compounds on granular activated carbon.  

PubMed

The performance of a biofilter packed with Active Carbon (AC) was evaluated. The effluent (alcohol, ketones, esters, aromatic and chlorinated compounds) treated was a representative mixture of most common industrial emissions. To achieve a better knowledge of multicomponent adsorption mechanisms, and to underline the interest of inoculating AC, a control abiotic humidified filter had been operated in the same conditions as the biofilter. For a load of 110 g VOC m(-3) AC h(-1), after 55 days of operation, the removal efficiency was higher in the biotic than in the abiotic filter (85% vs 55%, respectively). Moreover, in the biofilter, at steady state, the elimination of all compounds was almost complete except for chlorinated compounds and p-xylene (removal efficiency of 25% and 64%, respectively). The microbial colonization of AC involved a decrease of the adsorption sites accessibility and enhanced the treatment of VOCs (volatile organic compounds) having a lower affinity for activated carbon. Moreover, while aromatic compounds and MIBK were eliminated along the overall height of the biofilter, pollutants with reduced affinity for AC, such as methanol, acetone, and halogenated compounds were only treated on the second half of the reactor. Thus, the affinity for activated carbon was an important parameter controlling the biodegradation process. Nevertheless, the use of AC as packing material in biofilters treating complex mixtures of VOCs is limited. Actually, similar removal efficiency could be reached, in the same conditions, for a biofilter packed with granular peat. Furthermore, for the biofilter packed with AC, the column height necessary to remove biodegradable compounds, with reduced affinity for the support, was important. PMID:12800142

Aizpuru, A; Malhautier, L; Roux, J C; Fanlo, J L

2003-08-20

296

Linking gene regulation and the exo-metabolome: A comparative transcriptomics approach to identify genes that impact on the production of volatile aroma compounds in yeast  

PubMed Central

Background 'Omics' tools provide novel opportunities for system-wide analysis of complex cellular functions. Secondary metabolism is an example of a complex network of biochemical pathways, which, although well mapped from a biochemical point of view, is not well understood with regards to its physiological roles and genetic and biochemical regulation. Many of the metabolites produced by this network such as higher alcohols and esters are significant aroma impact compounds in fermentation products, and different yeast strains are known to produce highly divergent aroma profiles. Here, we investigated whether we can predict the impact of specific genes of known or unknown function on this metabolic network by combining whole transcriptome and partial exo-metabolome analysis. Results For this purpose, the gene expression levels of five different industrial wine yeast strains that produce divergent aroma profiles were established at three different time points of alcoholic fermentation in synthetic wine must. A matrix of gene expression data was generated and integrated with the concentrations of volatile aroma compounds measured at the same time points. This relatively unbiased approach to the study of volatile aroma compounds enabled us to identify candidate genes for aroma profile modification. Five of these genes, namely YMR210W, BAT1, AAD10, AAD14 and ACS1 were selected for overexpression in commercial wine yeast, VIN13. Analysis of the data show a statistically significant correlation between the changes in the exo-metabome of the overexpressing strains and the changes that were predicted based on the unbiased alignment of transcriptomic and exo-metabolomic data. Conclusion The data suggest that a comparative transcriptomics and metabolomics approach can be used to identify the metabolic impacts of the expression of individual genes in complex systems, and the amenability of transcriptomic data to direct applications of biotechnological relevance. PMID:18990252

Rossouw, Debra; Naes, Tormod; Bauer, Florian F

2008-01-01

297

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

PubMed

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

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

2013-12-11

298

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

PubMed

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

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

2007-06-01

299

Biological activities of phenolic compounds and triterpenoids from the galls of Terminalia chebula.  

PubMed

Nine phenolic compounds, including two phenolic carboxylic acids, 1 and 2, seven hydrolyzable tannins, 3-9, eight triterpenoids, including four oleanane-type triterpene acids, 10-13, and four of their glucosides, 14-17, isolated from a MeOH extract of the gall of Terminalia chebula Retz. (myrobalan tree; Combretaceae), were evaluated for their inhibitory activities against melanogenesis in B16 melanoma cells induced by ?-melanocyte-stimulating hormone (?-MSH), against the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells, and against TPA-induced inflammation in mice. Their 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activities and cytotoxic activities against four human cancer cell lines were also evaluated. Compounds 6-9 and 12 exhibited potent inhibitory activities against melanogenesis (39.3-66.3% melanin content) with low toxicity to the cells (74.5-105.9% cell viability) at a concentration of 10 ?M. Western-blot analysis revealed that isoterchebulin (8) reduced the protein levels of MITF (=microphtalmia-associated transcription factor), tyrosinase, and TRP-1 (=tyrosine-related protein 1), mostly in a concentration-dependent manner. Eight triterpenoids, 10-17, showed potent inhibitory effects on EBV-EA induction with the IC50 values in the range of 269-363 mol ratio/32 pmol TPA, while these compounds exhibited no DPPH scavenging activities (IC50 >100 ?M). On the other hand, the nine phenolic compounds, 1-9, exhibited potent radical-scavenging activities (IC50 1.4-10.9 ?M) with weak inhibitory effects on EBV-EA induction (IC50 460-518 mol ratio/32 pmol TPA). The tannin 6 and seven triterpenoids, 10-16, have been shown to inhibit TPA-induced inflammation (1 ?g/ear) in mice with the ID50 values in the range of 0.06-0.33 ?mol/ear. Arjungenin (10) exhibited inhibitory effect on skin-tumor promotion in an in vivo two-stage mouse-skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator and with TPA as promoter. Compounds 1, 2, 4, 5, 7-9, 12, and 13, against HL60 cell line, compounds 1 and 4, against AZ521 cell line, and compounds 1, 11, and 12, against SK-BR-3 cell line, showed moderate cytotoxic activities (IC50 13.9-73.2 ?M). PMID:23939793

Manosroi, Aranya; Jantrawut, Pensak; Ogihara, Eri; Yamamoto, Ayako; Fukatsu, Makoto; Yasukawa, Ken; Tokuda, Harukuni; Suzuki, Nobutaka; Manosroi, Jiradej; Akihisa, Toshihiro

2013-08-01

300

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

301

JNK1-dependent antimitotic activity of thiazolidin compounds in human non-small-cell lung and colon cancer cells  

PubMed Central

We recently identified two thiazolidin compounds, 5-[(4-methylphenyl)methylene]-2-(phenylamino)-4(5H)-thiazolone (MMPT) and 5-(2,4-dihydroxybenzylidene)-2-(phenylimino)-1,3-thiazolidin (DBPT), that inhibit the growth of human non-small-cell lung and colon cancer cells independent of P-glycoprotein and p53 status. Here we further investigated the mechanism by which these thiazolidin compounds mediate their anticancer effects. Treatment of cancer cells with MMPT and DBPT led to a time-dependent accumulation of cells arrested in G2/M phase with modulating the protein expression such as cyclin B1, cdc25C, and phosphorylated histone H3. Moreover, treatment with MMPT and DBPT increased M-phase arrest with abnormal spindle formation. DBPT-mediated G2/M-phase arrest and phosphorylation of cdc25C and histone H3 were abrogated when JNK activation was blocked either by SP600125, a specific JNK inhibitor, or by a dominant-negative JNK1 gene. Moreover, DBPT-mediated microtubule disruption was also blocked by SP600125 treatment. Our results demonstrate that thiazolidin compounds can effectively induce G2/M arrest in cancer cells and that this G2/M arrest requires JNK activation. PMID:16179969

Teraishi, F.; Wu, S.; Sasaki, J.; Zhang, L.; Davis, J. J.; Guo, W.; Dong, F.

2005-01-01

302

People who perceive themselves as active cannot identify the intensity recommended by the international physical activity guidelines  

PubMed Central

Background Many national and international organizations recommend that adults achieve at least 150 minutes of aerobic physical activity (PA) weekly, at a minimum moderate intensity to optimize health benefits. It is unknown if people who consider themselves as active have the ability to identify what is considered moderate intensity. Methods Fifty-one participants who reported achieving a minimum 150 minutes per week at a minimum of moderate intensity PA were recruited through a local fitness facility. All participants underwent a single assessment involving questionnaires, clinical measures, and a treadmill test to measure the ability to perceive moderate intensity. Following the visit, participants’ PA level was evaluated by heart rate monitor, while exercising, for 7 consecutive days. Results Eighty percent of participants overestimated moderate intensity on the treadmill test; they were at vigorous intensity compared to what is considered moderate. Only 11.8% of participants accurately identified moderate intensity; all of them were women (P=0.03), had a high level of education (P=0.04), and knew that moderate intensity was the minimum intensity recommended by health organizations (P<0.01). Only 69.2% of participants reached the aerobic component of the International Physical Activity Guidelines with no significant advantage for those correctly identifying moderate intensity. Conclusion Most people who perceive themselves as active are exercising at vigorous intensity while believing they are at moderate intensity. In addition, in this active sample, one-third of the participants were not reaching the aerobic component of the International Physical Activity Guidelines. PMID:25378959

Prokop, Neal W; Hrubeniuk, Travis JR; Senechal, Martin; Bouchard, Danielle R

2014-01-01

303

Novel SiO2-based antioxidant compound with significantly extended life-time and activity  

E-print Network

Novel SiO2-based antioxidant compound with significantly extended life-time and activity Georgios A of Process Engineering ETH Zurich, Switzerland #12;May 15, 2013 Copyright ETH Zürich 2 Antioxidants: What 15, 2013 Copyright ETH Zürich 3 Current antioxidants Phenols are potent antioxidants Gallic acid

Daraio, Chiara

304

Laboratory Animal Science Issues in the Design and Conduct of Studies with Endocrine-active Compounds  

Microsoft Academic Search

The use of rodent models for research and testing on endo- crine-active compounds necessitates an awareness of a number of laboratory animal science issues to standardize bioassay methods and facilitate reproducibility of results between laboratories. These issues are not unique to endo- crine research but are particularly important in this field due to the complexities and interdependencies of the endocrine

Jeffrey I. Everitt; Paul M. D. Foster

2004-01-01

305

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

E-print Network

Femtosecond IR Studies of Alkane C-H Bond Activation by Organometallic Compounds: Direct alkane solution.8,9 Our recent study on this system attributes the origin of the low quantum yield-Pz3*, Pz* ) 3,5- dimethylpyrazolyl) in room temperature alkane solution. The relatively high C

Harris, Charles B.

306

Highly selective catalytic Friedel–Crafts acylation and sulfonylation of activated aromatic compounds using indium metal  

Microsoft Academic Search

The Friedel–Crafts acylation of activated benzenes with various aromatic and aliphatic acid chlorides was studied in the presence of indium metal. The reaction was accomplished in high isolated yields under solvent or solvent-less conditions. The method is also applicable for preparing diaryl sulfones from aromatic compounds and aryl sulfonyl chlorides.

Doo Ok Jang; Kyung Soo Moon; Dae Hyan Cho; Joong-Gon Kim

2006-01-01

307

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

Microsoft Academic Search

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

C. D. Nicholson

1990-01-01

308

Evolved neural networks for quantitative structure-activity relationships of anti-HIV compounds  

Microsoft Academic Search

This paper compares the utility of an evolved neural network to a linear model to describe the activity of a set of anti-HIV compounds. The results indicate that significant nonlinearity exists within the descriptors for these molecules. This nonlinearity can be captured in a neural network architecture for significantly increased predictive performance

Dana Landavazo; Gary B. Fogel

2002-01-01

309

EFFECTIVENESS OF ACTIVATED CARBON FOR REMOVAL OF TOXIC AND/OR CARCINOGENIC COMPOUNDS FROM WATER SUPPLIES  

EPA Science Inventory

This research addressed quantification of the performance of fixed-bed granular activated carbon processes for treatment of public water supplies. It included evaluation of the adsorption of selected toxic and/or carcinogenic trace compounds of man-related origin, including carbo...

310

VOLATILE ORGANIC COMPOUNDS AS BREATH BIOMARKERS FOR ACTIVE AND PASSIVE SMOKING  

EPA Science Inventory

Real-time breath measurement technology was used to investigate the suitability of some volatile organic compounds (VOCs) to serve as breath biomarkers for active and passive smoking and to measure actual exposures and resulting breath concentrations for persons exposed to toba...

311

COST ANALYSIS OF ACTIVATED CARBON VERSUS PHOTOCATALYTIC OXIDATION FOR REMOVING ORGANIC COMPOUNDS FROM INDOOR AIR  

EPA Science Inventory

A cost comparison has been conducted of 1 m3/s indoor air cleaners using granular activated carbon (GAC) vs. photocatalytic oxidation (PCO) for treating a steady-state inlet volatile organic compound (VOC) concentration of 0.3 mg/m3. The commercial GAC unit was costed assuming t...

312

Relationships between the Firing of Identified Striatal Interneurons and Spontaneous and Driven Cortical Activities In Vivo  

PubMed Central

The striatum is comprised of medium-sized spiny projection neurons (MSNs) and several types of interneuron, and receives massive glutamatergic input from the cerebral cortex. Understanding of striatal function requires definition of the electrophysiological properties of neurochemically identified interneurons sampled in the same context of ongoing cortical activity in vivo. To address this, we recorded the firing of cholinergic interneurons (expressing choline acetyltransferase; ChAT) and GABAergic interneurons expressing parvalbumin (PV) or nitric oxide synthase (NOS), as well as MSNs, in anesthetized rats during cortically defined brain states. Depending on the cortical state, these interneurons were partly distinguished from each other, and MSNs, on the basis of firing rate and/or pattern. During slow-wave activity (SWA), ChAT+ interneurons, and some PV+ and NOS+ interneurons, were tonically active; NOS+ interneurons fired prominent bursts but, contrary to investigations in vitro, these were not typical low-threshold spike bursts. Identified MSNs, and other PV+ and NOS+ interneurons, were phasically active. Contrasting with ChAT+ interneurons, whose firing showed poor brain state dependency, PV+ and NOS+ interneurons displayed robust firing increases and decreases, respectively, upon spontaneous or driven transitions from SWA to cortical activation. The firing of most neurons was phase locked to cortical slow oscillations, but only PV+ and ChAT+ interneurons also fired in time with cortical spindle and gamma oscillations. Complementing this diverse temporal coupling, each interneuron type exhibited distinct responses to cortical stimulation. Thus, these striatal interneuron types have distinct temporal signatures in vivo, including relationships to spontaneous and driven cortical activities, which likely underpin their specialized contributions to striatal microcircuit function. PMID:22993438

Sharott, Andrew; Doig, Natalie M.; Mallet, Nicolas; Magill, Peter J.

2014-01-01

313

Electrophysiological evidence for relation information activation in Chinese compound word comprehension.  

PubMed

How constituent concepts of a compound concept are put together for meaning construction is an important question in cognition. Using English noun-noun compounds with a modifier+noun structure, researchers have observed relation priming between compounds that share the same relation (snowball vs. snowman) compared with those that do not (snowball vs. snowshovel), suggesting explicit use of relation information during comprehension of compound expressions. The present study examined the temporal characteristics of relation priming with event-related potentials. Participants were presented with lists of two-character noun+noun Chinese compound words and judged whether each was semantically meaningful or not. About 260 ms following word presentation, the semantic N400 response was significantly reduced if a word was preceded by a prime with the same first character, indicating semantic processing of constituent morphemes. However, N400 was not modulated by manipulation of relation priming until around 340 ms. Results confirm the use of relation information in semantic composition, but more critically provide the first piece of evidence that compound word comprehension involves serial processing where constituent morphemes are activated in stage one and bound by their relation in stage two. PMID:23583969

Jia, Xiaofei; Wang, Suiping; Zhang, Bao; Zhang, John X

2013-06-01

314

[Correlation between antioxidant activity and bioactive compounds of açaí (Euterpe oleracea Mart) comercial pulps].  

PubMed

The purpose of this work was to analyze commercial açaí pulp and to correlate the contribution of vitamin C, total carotenoids and phenolic compounds with the antioxidant activity of there products besides the examination of the standard related to the quality of the obtained products. Analysis were made with regard to pH, acidity total, soluble solids, sugars, color, water activity, vitamin C, total anthocyanins, total carotenoids, antioxidant activity and phenolic compounds. All parameters analyzed showed significative difference among the marks not added with preservatives and sucrose. The açaí fruit can be considered a fair source of vitamin C and good source of natural antioxidants. In regard to the correlation with the antioxidant activity only the total anthocyanins and the total carotenoids presented positive and significative correlation. PMID:18833997

Santos, Gerusa Matias dos; Maia, Geraldo Arraes; Sousa, Paulo Henrique Machado de; Costa, José Maria Correia da; Figueiredo, Raimundo Wilane de; Prado, Giovana Matias do

2008-06-01

315

[Quantitative dependence of structure-antiseizure activity in a series of macrocyclic compounds].  

PubMed

In the present study we have further examined the influence of some structure parameters of macrocyclic polyethers upon their anticonvulsant activity in order to determine basic pharmacophore fragments. The anticonvulsant activity was studied experimentally for 25 new macrocyclic compounds, and their structure, physico-chemical properties, electron donor factors and atom charges were calculated using programs HyperChem-ChemPlus and HYBOT. The data about atomic properties were presented as a set functions of inter-atomic distances (Program MOLTRA). The cluster analysis revealed that studied compounds represent two independent groups which differ from chemical and pharmacological viewpoints. For first group, we have found that anticonvulsant activity of macrocycles is determined by their polarizability and spatial orientation of electron donor atoms. For another cluster the correlation was found between activity and spatial orientation of two hydrophobic fragments and electron donor atoms as well. PMID:9634722

Lukoianov, N V; Raevski?, O A

1998-01-01

316

Compounds from Sorindeia juglandifolia (Anacardiaceae) exhibit potent anti-plasmodial activities in vitro and in vivo  

PubMed Central

Background Discovering new lead compounds against malaria parasites is a crucial step to ensuring a sustainable global pipeline for effective anti-malarial drugs. As far as we know, no previous phytochemical or pharmacological investigations have been carried out on Sorindeia juglandifolia. This paper describes the results of an anti-malarial activity-driven investigation of the fruits of this Cameroonian plant. Methods Air-dried fruits were extracted by maceration using methanol. The extract was fractionated by flash chromatography followed by column chromatography over silica gel, eluting with gradients of hexane-ethyl acetate mixtures. Resulting fractions and compounds were tested in vitro against the Plasmodium falciparum chloroquine-resistant strain W2, against field isolates of P. falciparum, and against the P. falciparum recombinant cysteine protease falcipain-2. Promising fractions were assessed for acute toxicity after oral administration in mice. One of the promising isolated compounds was assessed in vivo against the rodent malaria parasite Plasmodium berghei. Results The main end-products of the activity-guided fractionation were 2,3,6-trihydroxy benzoic acid (1) and 2,3,6-trihydroxy methyl benzoate (2). Overall, nine fractions tested against P. falciparum W2 and falcipain-2 were active, with IC50 values of 2.3-11.6 ?g/ml for W2, and 1.1-21.9 ?g/ml for falcipain-2. Purified compounds (1) and (2) also showed inhibitory effects against P. falciparum W2 (IC50s 16.5 ?M and 13.0 ?M) and falcipain-2 (IC50s 35.4 and 6.1 ?M). In studies of P. falciparum isolates from Cameroon, the plant fractions demonstrated IC50 values of 0.14-19.4 ?g/ml and compounds (1) and (2) values of 6.3 and 36.1 ?M. In vivo assessment of compound (1) showed activity against P. berghei strain B, with mean parasitaemia suppressive dose and curative dose of 44.9 mg/kg and 42.2 mg/kg, respectively. Active fractions were found to be safe in mice after oral administration of 7 g/kg body weight. Conclusions Fractions of Sorindeia juglandifolia and two compounds isolated from these fractions were active against cultured malaria parasites, the P. falciparum protease falcipain-2, and in a rodent malaria model. These results suggest that further investigation of the anti-malarial activities of natural products from S. juglandifolia will be appropriate. PMID:23171238

2012-01-01

317

Therapeutic Uses and Pharmacological Properties of Garlic, Shallot, and Their Biologically Active Compounds  

PubMed Central

Objective(s): Garlic (Allium sativum L. family Liliaceae) is well known in Iran and its leaves, flowers, and cloves have been used in traditional medicine for a long time. Research in recent decades has shown widespread pharmacological effects of A. sativum and its organosulfur compounds especially Allicin. Studies carried out on the chemical composition of the plant show that the most important constituents of this plant are organosulfur compounds such as allicin, diallyl disulphide, S-allylcysteine, and diallyl trisulfide. Allicin represents one of the most studied among these naturally occurring compounds. In addition to A. sativum, these compounds are also present in A. hirtifolium (shallot) and have been used to treat various diseases. This article reviews the pharmacological effects and traditional uses of A. sativum, A. hirtifolium, and their active constituents to show whether or not they can be further used as potential natural sources for the development of novel drugs. Materials and Methods: For this purpose, the authors went through a vast number of sources and articles and all needed data was gathered. The findings were reviewed and classified on the basis of relevance to the topic and a summary of all effects were reported as tables. Conclusion: Garlic and shallots are safe and rich sources of biologically active compounds with low toxicity. Further studies are needed to confirm the safety and quality of the plants to be used by clinicians as therapeutic agents. PMID:24379960

Mikaili, Peyman; Maadirad, Surush; Moloudizargari, Milad; Aghajanshakeri, Shahin; Sarahroodi, Shadi

2013-01-01

318

Flavonoid and phenolic compounds from Salvia palaestina L. growing wild in Jordan and their antioxidant activities.  

PubMed

Investigation of the butanol fraction of Salvia palaestina Benth. from Jordanian origin resulted in the isolation and characterization of nine compounds, three of which are reported here for the first time in Nature. These compounds included the two phenolics: salpalaestinin (1), methyl 3-O-methylrosmarinate (3) and the flavonoid luteolin 7-O-(2?-p-hydroxybenzoyl)-?-glucuronide) (8). In addition, 3,4-dihydroxyphenyl caffeate (2), diosmetin (4), apigenin-7-O-(6?-butyryl-?-glucopyranoside) (5), luteolin-3'-O-methyl-7-O-(6?-butyryl-?-glucopyranoside) (6) and clinopodic acid B (7) were also obtained from the butanol fraction of the plant. The structures of the isolated compounds were elucidated by different spectroscopic methods including NMR (1D and 2D), UV, IR and MS (HRESIMS and EIMS). The DPPH radical scavenging activity for compounds 1, 3, 5, 6 &8 was evaluated. Compound 3 had the highest antioxidant activity (91.9±1.30% inhibition) with an IC?? value of 1.0±0.23(?g/mL). PMID:24472393

Al-Qudah, Mahmoud A; Al-Jaber, Hala I; Abu Zarga, Musa H; Abu Orabi, Sultan T

2014-03-01

319

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

PubMed

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

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

2010-09-01

320

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

PubMed

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

Guang, Jie; Zhao, Cong-Gui

2011-06-15

321

Occurrence of Endocrine Active Compounds and Biological Responses in the Mississippi River - Study Design and Data, June through August 2006  

USGS Publications Warehouse

Concern that selected chemicals in the environment may act as endocrine active compounds in aquatic ecosystems is widespread; however, few studies have examined the occurrence of endocrine active compounds and identified biological markers of endocrine disruption such as intersex occurrence in fish longitudinally in a river system. This report presents environmental data collected and analyzed by the U.S. Geological Survey, Minnesota Pollution Control Agency and St. Cloud State University as part of an integrated biological and chemical study of endocrine disruption in fish in the Mississippi River. Data were collected from water, bed sediment, and fish at 43 sites along the river from the headwaters at Lake Itasca to 14 miles downstream from Brownsville, Minnesota during June through August 2006. Twenty-four individual compounds were detected in water samples, with cholesterol, atrazine, N,N-diethyl-meta-toluamide, metolachlor, and hexahydrohexamethylcyclopentabenzopyran detected most frequently (in at least 10 percent of the samples). The number of compounds detected in water per site ranged from 0 to 8. Forty individual compounds were detected in bed-sediment samples. The most commonly detected compounds (in at least 50 percent of the samples) were indole, beta-sitosterol, cholesterol, beta-stigmastanol, 3-methyl-1H-indole, p-cresol, pyrene, phenol, fluoranthene, 3-beta coprostanol, benzo[a]pyrene, acetophenone, and 2,6-dimethylnaphthalene. The total number of detections in bed sediment (at a site) ranged from 3 to 31. The compounds NP1EO, NP2EO, and 4-nonylphenol were detected in greater than 10 percent of the samples. Most (80 percent) female fish collected had measurable concentrations of vitellogenin. Vitellogenin also was detected in 62, 63, and 33 percent of male carp, smallmouth bass, and redhorse, respectively. The one male walleye sample plasma sample analyzed had a vitellogenin detection. Vitellogenin concentrations were lower in male fish (not detected to 10.80 micrograms per milliliter) than female fish (0.04 to 248,079 micrograms per milliliter). Gonadosomatic Index values ranged from 0.02 to 7.49 percent among all male fish and were greater for male carp than for the other three species. No intersex (oocytes present in testes tissue) was found in any male fish sampled.

Lee, Kathy E.; Yaeger, Christine S.; Jahns, Nathan D.; Schoenfuss, Heiko L.

2008-01-01

322

Identifying induced seismicity in active tectonic regions: A case study of the San Joaquin Basin, California  

NASA Astrophysics Data System (ADS)

Understanding the connection between petroleum-industry activities, and seismic event occurrences is essential to monitor, quantify, and mitigate seismic risk. While many studies identified anthropogenically-induced seismicity in intraplate regions where background seismicity rates are generally low, little is known about how to distinguish naturally occurring from induced seismicity in active tectonic regions. Further, it is not clear how different oil and gas operational parameters impact the frequency and magnitude of the induced seismic events. Here, we examine variations in frequency-size and spatial distributions of seismicity within the Southern Joaquin basin, an area of both active petroleum production and active fault systems. We analyze a newly available, high-quality, relocated earthquake catalog (Hauksson et al. 2012). This catalog includes many seismic events with magnitudes up to M = 4.5 within the study area. We start by analyzing the overall quality and consistence of the seismic catalog, focusing on temporal variations in seismicity rates and catalog completeness which could indicate variations in network sensitivity. This catalog provides relatively homogeneous earthquake recordings after 1981, enabling us to compare seismicity rates before and after the beginning of more pervasive petroleum-industry activities, for example, hydraulic-fracturing and waste-water disposals. We conduct a limited study of waste-water disposal wells to establish a correlation between seismicity statistics (i.e. rate changes, fractal dimension, b-value) within specific regions and anthropogenic influences. We then perform a regional study, to investigate spatial variations in seismicity statistics which are then correlated to oil field locations and well densities. In order to distinguish, predominantly natural seismicity from induced seismicity, we perform a spatial mapping of b-values and fractal dimensions of earthquake hypocenters. Seismic events in the proximity to active oil fields generally show different characteristics of frequency-magnitude distributions, higher fractal dimensions and higher b-values compared to natural seismicity. The estimated b-values vary between 0.7 close to the San Andreas fault up to 1.3 within the North-western corner of the Kern County. High b-values within this particular region are likely related to active petroleum production. The spatial differences in seismicity statistics delineate earthquakes related to active faults from distributed seismicity toward the center of the basin. Our results highlight, that the analysis of spatial and temporal variations in seismicity statistics may be a promising tool to identify induced seismicity in active tectonic regions.

Aminzadeh, F.; Göbel, T.

2013-12-01

323

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

PubMed Central

During active muscle contraction, tension is generated through many simultaneous, independent interactions between the molecular motor myosin and the actin filaments. The ensemble of myosin motors displays heterogeneous conformations reflecting different kinetic steps of the ATPase pathway. We used electron tomography of actively contracting insect flight muscle fast-frozen, freeze-substituted, Araldite embedded, thin sectioned and stained, to obtain 3-D snapshots of the multiplicity of actin-attached myosin structures. We describe procedures for alignment of the repeating lattice of sub-volumes (38.7 nm cross-bridge repeats bounded by troponin) and multivariate data analysis to identify self-similar repeats for computing class averages. Improvements in alignment and classification of repeat sub-volumes reveals (for the first time in active muscle images) the helix of actin subunits in the thin filament and the troponin density with sufficient clarity that a quasiatomic model of the thin filament can be built into the class averages independent of the myosin cross-bridges. We show how quasiatomic model building can identify both strong and weak myosin attachments to actin. We evaluate the accuracy of image classification to enumerate the different types of actin-myosin attachments. PMID:19698791

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

2009-01-01

324

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

PubMed

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

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

2013-05-22

325

A c-Myc activation sensor-based high throughput drug screening identifies an anti-neoplastic effect of Nitazoxanide  

PubMed Central

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

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

2013-01-01

326

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

PubMed

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

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

2013-09-01

327

Compounds from marine-derived Verrucosispora sp. FIM06054 and their potential antitumour activities.  

PubMed

Strain FIM06054 was isolated from a marine sponge sample collected from the East China Sea and was characterised as a strain of Verrucosispora genus on the basis of its 16S rRNA gene sequence. One new compound, FW054-1 (1), together with a known aminofuran compound proximicin A (2), was isolated from the culture broth of Verrucosispora sp. FIM06054. Their structures were elucidated on the basis of spectral analysis. 1 and 2 showed antiproliferative activity against several human tumour cell lines. PMID:24938666

Yi-Lei, Nie; Yun-Dan, Wu; Chuan-Xi, Wang; Ru, Lin; Yang, Xie; Dong-Sheng, Fang; Hong, Jiang; Yun-Yang, Lian

2014-12-01

328

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

PubMed Central

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

2013-01-01

329

Kinetics and activation parameters of the reaction of organoarsenic(V) compounds with glutathione.  

PubMed

In this work the kinetics of the reaction of glutathione (GSH) with the organoarsenic(V) compounds phenylarsonic acid (PAA), 4-hydroxy-3-nitrophenylarsonic acid (HNPAA), p-aminophenylarsonic acid (p-APAA) and o-aminophenylarsonic acid (o-APAA) as well as monomethylarsonic acid (MMAA) and dimethylarsinic acid (DMAA) is investigated. The reaction progress is monitored in real time by (1)H NMR, allowing the determination of rate coefficients and half-lives as well as activation parameters. The reaction consists of two steps: redox reaction and conjugation. In all investigated systems the conjugation is fast compared to the redox reaction and, therefore, rate determining. All investigated phenylarsonic acids follow the same rate law, showing overall reaction orders of 3 and half-lives between 47.7±0.2 and 71.0±3.6min. The methylated compounds react slower, showing half-lives of 76.6±0.4 and 444±10min for DMAA and MMAA, respectively. Enthalpies of activation range from 20 to 36 (±2)kJmol(-1) and the entropies of activation are within -154 and -97(±7)Jmol(-1)K(-1). The results reveal a correlation of the toxicity of the arsenic compound and the reaction rate with GSH. This may pave the way for the estimation of the toxicity of such compounds by simple kinetic studies. PMID:25238190

Kretzschmar, Jerome; Brendler, Erica; Wagler, Jörg; Schmidt, Anne-Christine

2014-09-15

330

Phenolic compounds from Trifolium echinatum Bieb. and investigation of their tyrosinase inhibitory and antioxidant activities.  

PubMed

Two bischromones, 3,3'-dimethoxy-2'-oxychromone (1), 3,3'-dihydroxy-2,2'-oxychromone (2) and a biflavone, 5,7,4',5?,3'",4??-hexahydroxy-3?-O-?-glucosyl-3',7?-O-biflavone (3) have been isolated from whole plant of Trifolium echinatum Bieb. together with five known flavonoids. The structures of the compounds were elucidated by 1D and 2D NMR analysis as well as HRESIMS. The isolated compounds were investigated for their antioxidant activity and tyrosinase inhibitory activity. Highly potent inhibition was found for compounds 1 (IC50=0.41 mM), 5 (IC50=0.47 mM) and 8 (IC50=0.45 mM) compared to those of standard tyrosinase inhibitors kojic acid (IC50=0.67 mM) and l-mimosine (IC50=0.64 mM). The antioxidative effect of the extracts was determined by using ?-carotene-linoleic acid, DPPH scavenging, ABTS(+) scavenging, and CUPRAC assays. The experimental findings indicated that the compounds 2 and 8 were found to be active in radical scavenging and CUPRAC assays. PMID:24070617

Sabudak, Temine; Demirkiran, Ozlem; Ozturk, Mehmet; Topcu, Gulacti

2013-12-01

331

Antioxidant activity and mechanisms of action of natural compounds isolated from lichens: a systematic review.  

PubMed

Chronic diseases such as cancer, diabetes, neurodegenerative and cardiovascular diseases are characterized by an enhanced state of oxidative stress, which may result from the overproduction of reactive species and/or a decrease in antioxidant defenses. The search for new chemical entities with antioxidant profile is still thus an emerging field on ongoing interest. Due to the lack of reviews concerning the antioxidant activity of lichen-derived natural compounds, we performed a review of the antioxidant potential and mechanisms of action of natural compounds isolated from lichens. The search terms "lichens", "antioxidants" and "antioxidant response elements" were used to retrieve articles in LILACS, PubMed and Web of Science published until February 2014. From a total of 319 articles surveyed, 32 met the established inclusion and exclusion criteria. It was observed that the most common isolated compound studied was usnic acid, cited in 14 out of the 32 articles. The most often described antioxidant assays for the study of in vitro antioxidant activity were mainly DPPH, LPO and SOD. The most suggested mechanisms of action were scavenging of reactive species, enzymatic activation and inhibition of iNOS. Thus, compounds isolated from lichens are possible candidates for the management of oxidative stress, and may be useful in the treatment of chronic diseases. PMID:25221871

White, Pollyanna A S; Oliveira, Rita C M; Oliveira, Aldeidia P; Serafini, Mairim R; Araújo, Adriano A S; Gelain, Daniel P; Moreira, Jose C F; Almeida, Jackson R G S; Quintans, Jullyana S S; Quintans-Junior, Lucindo J; Santos, Marcio R V

2014-01-01

332

Application of quantitative structure-activity relationship models of 5-HT1A receptor binding to virtual screening identifies novel and potent 5-HT1A ligands.  

PubMed

The 5-hydroxytryptamine 1A (5-HT1A) serotonin receptor has been an attractive target for treating mood and anxiety disorders such as schizophrenia. We have developed binary classification quantitative structure-activity relationship (QSAR) models of 5-HT1A receptor binding activity using data retrieved from the PDSP Ki database. The prediction accuracy of these models was estimated by external 5-fold cross-validation as well as using an additional validation set comprising 66 structurally distinct compounds from the World of Molecular Bioactivity database. These validated models were then used to mine three major types of chemical screening libraries, i.e., drug-like libraries, GPCR targeted libraries, and diversity libraries, to identify novel computational hits. The five best hits from each class of libraries were chosen for further experimental testing in radioligand binding assays, and nine of the 15 hits were confirmed to be active experimentally with binding affinity better than 10 ?M. The most active compound, Lysergol, from the diversity library showed very high binding affinity (Ki) of 2.3 nM against 5-HT1A receptor. The novel 5-HT1A actives identified with the QSAR-based virtual screening approach could be potentially developed as novel anxiolytics or potential antischizophrenic drugs. PMID:24410373

Luo, Man; Wang, Xiang Simon; Roth, Bryan L; Golbraikh, Alexander; Tropsha, Alexander

2014-02-24

333

Antileishmanial, antimalarial and antimicrobial activities of the extract and isolated compounds from Austroplenckia populnea (Celastraceae).  

PubMed

Austroplenckia populnea (Celastraceae), known as "marmelinho do campo", is used in Brazilian folk medicine as antimicrobial, anti-inflammatory, and antitumoural agent. The aim of the present work was to evaluate the antimicrobial, antileishmanial and antimalarial activities of the crude hydroalcoholic extract of A. populnea (CHE) and some of its isolated compounds. The phytochemical study of the CHE was carried out affording the isolation of methyl populnoate (1), populnoic acid (2), and stigmast-5-en-3-O-beta-(D-glucopyranoside) (3). This is the first time that the presence of compound 3 in A. populnea is reported. The results showed that the CHE presents antifungal and antibacterial activities, especially against Candida glabrata and Candida albicans, for which the CHE showed IC50 values of 0.7 microg mL(-1) and 5.5 microg mL(-1), respectively, while amphotericin B showed an IC50 value of 0.1 microg mL(-1) against both microorganisms. Compounds 1-3 were inactive against all tested microorganisms. In the antileishmanial activity test against Leishmania donovani, the CHE showed an IC50 value of 52 microg mL(-1), while compounds 2 and 3 displayed an IC50 value of 18 microg mL(-1) In the antimalarial assay against Plasmodium falciparum (D6 and W2 clones), it was observed that all evaluated samples were inactive. In order to compare the effect on the parasites with the toxicity to mammalian cells, the cytotoxicity activity of the isolated compounds was evaluated against Vero cells, showing that all evaluated samples exhibited no cytotoxicity at the maximum dose tested. PMID:18810991

Andrade, Sérgio F; da Silva Filho, Ademar A; de O Resende, Dimas; Silva, Márcio L A; Cunha, Wilson R; Nanayakkara, N P Dhammika; Bastos, Jairo Kenupp

2008-01-01

334

[Manganeseporphyrin/vanadium-substituted polyoxometalate new coordination compound: synthesis, characterization and catalytic activity].  

PubMed

A new kind of manganeseporphyrin/vanadium-substituted polyoxometalate coordination compound was synthesized by meso-tetrakis(4-trimethylamidiophenyl) manganeseporphyrin and vanadium-substituted polyoxometalate H5 PMo10 V2O4 reacting in water solution at room temperature, and its structures were studied by IR spectrometry and UV-Vis spectrometry. The results show that metalloporphyrin ring structure and polyoxometalate cage structure still exist in the coordination compound, and these two parts connect with each other by chemical bond. As an excellent catalyst, its effects on benzene hydroxylation and catalytic capabilities were studied with H2O2 solution as an oxidant under mild reaction condition, meanwhile the catalytic active centre in the benzene hydroxylation reaction was discussed. The results indicated that V atom in polyoxometalate is the main centre of catalytic activity, while the presence of manganeseporphyrin could improve its catalytic activity greatly. PMID:17390657

Zhang, Zhen-cheng; An, Qing-da; Zhang, Shao-yin; Wang, Shao-jun

2007-01-01

335

Carbohydrate-active enzymes identified by metagenomic analysis of deep-sea sediment bacteria.  

PubMed

Subseafloor sediment samples derived from a sediment core of 60 m length were used to enrich psychrophilic aerobic bacteria on cellulose, xylan, chitin, and starch. A variety of species belonging to Alpha- and Gammaproteobacteria and to Flavobacteria were isolated from sediment depths between 12 and 42 mbsf. Metagenomic DNA purified from the pooled enrichments was sequenced and analyzed for phylogenetic composition and presence of genes encoding carbohydrate-active enzymes. More than 200 open reading frames coding for glycoside hydrolases were identified, and more than 60 of them relevant for enzymatic degradation of lignocellulose. Four genes encoding ?-glucosidases with less than 52 % identities to characterized enzymes were chosen for recombinant expression in Escherichia coli. In addition one endomannanase, two endoxylanases, and three ?-xylosidases were produced recombinantly. All genes could be actively expressed. Functional analysis revealed discrepancies and additional variability for the recombinant enzymes as compared to the sequence-based predictions. PMID:25108363

Klippel, Barbara; Sahm, Kerstin; Basner, Alexander; Wiebusch, Sigrid; John, Patrick; Lorenz, Ute; Peters, Anke; Abe, Fumiyoshi; Takahashi, Kyoma; Kaiser, Olaf; Goesmann, Alexander; Jaenicke, Sebastian; Grote, Ralf; Horikoshi, Koki; Antranikian, Garabed

2014-09-01

336

Identifying bacteria in human urine: current practice and the potential for rapid, near-patient diagnosis by sensing volatile organic compounds.  

PubMed

Urinary tract infection (UTI) represents a significant burden for the National Health Service. Extensive research has been directed towards rapid detection of UTI in the last thirty years. A wide range of microbiological and chemical techniques are now available to identify and quantify bacteria in urine. However, there is a clear and present need for near, rapid, sensitive, reliable analytical methods, preferably with low-running costs, that could allow early detection of UTI and other diseases in urine. Here we review the "state of the art" of current practice for the detection of bacteria in urine and describe the advantages of the recent "e-nose" technology as a potential tool for rapid, near-patient diagnosis of UTI, by sensing volatile organic compounds (VOCs). PMID:11758602

Guernion, N; Ratcliffe, N M; Spencer-Phillips, P T; Howe, R A

2001-10-01

337

Comparison of the activity of subsurface and surface microorganisms and their anaerobic transformation of heterocyclic compounds  

SciTech Connect

Our interest in this research was mainly to compare the physiological characteristics of microorganisms derived from subsurface and surface environments and their ability to transform heterocyclic aromatic chemicals. We selected essentially indole and pyridine compounds as representatives of heterocyclic compounds. The samples investigated originated from the subsurface drillings at the Savannah River Plant, from surface samples in Pennsylvania, from municipal sewage of State College, Pennsylvania, and from pyridine-contaminated sites at Indianapolis. At different physiological conditions (aerobic, denitrifying, sulfate-reducing or methanogenic), different groups of microorganisms are active. Not only the thermodynamics of microbial physiology vary, but different metabolic pathways are used by the various types of microbial processes. Therefore, it was important to determine under which physiological conditions a compound was metabolized, and to clarify the metabolic conditions under which intermediate(s) were produced. 29 refs.

Bollag, J.-M.

1991-02-01

338

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

PubMed Central

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

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

2014-01-01

339

An experimental method to identify neurogenic and myogenic active mechanical states of intestinal motility  

PubMed Central

Excitatory and inhibitory enteric neural input to intestinal muscle acting on ongoing myogenic activity determines the rich repertoire of motor patterns involved in digestive function. The enteric neural activity cannot yet be established during movement of intact intestine in vivo or in vitro. We propose the hypothesis that is possible to deduce indirectly, but reliably, the state of activation of the enteric neural input to the muscle from measurements of the mechanical state of the intestinal muscle. The fundamental biomechanical model on which our hypothesis is based is the “three-element model” proposed by Hill. Our strategy is based on simultaneous video recording of changes in diameters and intraluminal pressure with a fiber-optic manometry in isolated segments of rabbit colon. We created a composite spatiotemporal map (DPMap) from diameter (DMap) and pressure changes (PMaps). In this composite map rhythmic myogenic motor patterns can readily be distinguished from the distension induced neural peristaltic contractions. Plotting the diameter changes against corresponding pressure changes at each location of the segment, generates “orbits” that represent the state of the muscle according to its ability to contract or relax actively or undergoing passive changes. With a software developed in MatLab, we identified twelve possible discrete mechanical states and plotted them showing where the intestine actively contracted and relaxed isometrically, auxotonically or isotonically, as well as where passive changes occurred or was quiescent. Clustering all discrete active contractions and relaxations states generated for the first time a spatio-temporal map of where enteric excitatory and inhibitory neural input to the muscle occurs during physiological movements. Recording internal diameter by an impedance probe proved equivalent to measuring external diameter, making possible to further develop similar strategy in vivo and humans. PMID:23596400

Costa, Marcello; Wiklendt, Lukasz; Arkwright, John W.; Spencer, Nicholas J.; Omari, Taher; Brookes, Simon J. H.; Dinning, Phil G.

2013-01-01

340

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

PubMed Central

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

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

2014-01-01

341

On the anti-inflammatory activity of some substituted phenolic compounds  

PubMed Central

Some substituted dihydroxybenzenes have been examined for suppression of the yeast-induced inflammatory reaction in the rat paw. This anti-inflammatory activity is greatest in those compounds derived from resorcinol and in particular the halogenated 5-methylresorcinols. The significance of the internuclear distance between the hydroxyl groups in the meta-position to each other in resorcinol and the importance of the enhanced activity due to the halogen atom(s) is discussed. In this series the toxicity and activity could not be divorced. PMID:14190457

Lightowler, J. E.; Rylance, H. J.

1964-01-01

342

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

DOEpatents

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

Dinh, Tuan V. (Knoxville, TN)

1996-01-01

343

Lipopeptides, a novel protein, and volatile compounds contribute to the antifungal activity of the biocontrol agent Bacillus atrophaeus CAB-1.  

PubMed

Bacillus atrophaeus CAB-1 displays a high inhibitory activity against various fungal pathogens and suppresses cucumber powdery mildew and tomato gray mold. We extracted and identified lipopeptides and secreted proteins and volatile compounds produced by strain CAB-1 to investigate the mechanisms involved in its biocontrol performance. In vitro assays indicated all three types of products contributed to the antagonistic activity against the fungal pathogen Botrytis cinerea. Each of these components also effectively prevented the occurrence of the cucumber powdery mildew caused by Sphaerotheca fuliginea under greenhouse conditions. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry revealed that the major bioactive lipopeptide was fengycin A (C15-C17). We isolated the crude-secreted proteins of CAB-1 and purified a fraction with antifungal activity. This protein sequence shared a high identity with a putative phage-related pre-neck appendage protein, which has not been reported as an antifungal factor. The volatile compounds produced by CAB-1 were complex, including a range of alcohols, phenols, amines, and alkane amides. O-anisaldehyde represented one of the most abundant volatiles with the highest inhibition on the mycelial growth of B. cinerea. To our knowledge, this is the first report on profiling three types of antifungal substances in Bacilli and demonstrating their contributions to plant disease control. PMID:24013222

Zhang, Xiaoyun; Li, Baoqing; Wang, Ye; Guo, Qinggang; Lu, Xiuyun; Li, Shezeng; Ma, Ping

2013-11-01

344

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

PubMed Central

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

2012-01-01

345

Computer-aided identification, design and synthesis of a novel series of compounds with selective antiviral activity against chikungunya virus.  

PubMed

Chikungunya virus (CHIKV) is an Arbovirus that is transmitted to humans primarily by the mosquito species Aedes aegypti. Infection with this pathogen is often associated with fever, rash and arthralgia. Neither a vaccine nor an antiviral drug is available for the prevention or treatment of this disease. Albeit considered a tropical pathogen, adaptation of the virus to the mosquito species Aedes albopictus, which is also very common in temperate zones, has resulted in recent outbreaks in Europe and the US. In the present study, we report on the discovery of a novel series of compounds that inhibit CHIKV replication in the low ?M range. In particular, we initially performed a virtual screening simulation of ?5 million compounds on the CHIKV nsP2, the viral protease, after which we investigated and explored the Structure-Activity Relationships of the hit identified in silico. Overall, a series of 26 compounds, including the original hit, was evaluated in a virus-cell-based CPE reduction assay. The study of such selective inhibitors will contribute to a better understanding of the CHIKV replication cycle and may represents a first step towards the development of a clinical candidate drug for the treatment of this disease. PMID:23380636

Bassetto, Marcella; De Burghgraeve, Tine; Delang, Leen; Massarotti, Alberto; Coluccia, Antonio; Zonta, Nicola; Gatti, Valerio; Colombano, Giampiero; Sorba, Giovanni; Silvestri, Romano; Tron, Gian Cesare; Neyts, Johan; Leyssen, Pieter; Brancale, Andrea

2013-04-01

346

Variations in essential oil, phenolic compounds, and antioxidant activity of tunisian cultivated Salvia officinalis L.  

PubMed

The variation in the chemical composition of the essential oil of Salvia officinalis , growing in different habitats, was studied. GC-MS analysis revealed 57 compounds representing 94.68-96.80% of total oils. The major components were alpha-thujone (11.55-19.23%), viridiflorol (9.94-19.46%), 1,8-cineole (8.85-15.60%), camphor (5.08-15.06%), manool (5.52-13.06%), beta-caryophyllene (2.63-9.24%), alpha-humulene (1.93-8.94%), and beta-thujone (5.45-6.17%), showing significant differences between different collection sites. Analysis of some representative polyphenolic compounds and antioxidant activity was performed using postdistilled dry samples. Rosmarinic acid, carnosol, and carnosic acid were the prevalent compounds of S. officinalis methanolic extracts. The results revealed differences in the polyphenolic composition and also exhibited antioxidant and radical-scavenging activities at different magnitudes of potency. However, within the used methods, only the DPPH(*) assay showed significant differences (p < 0.05) in free radical scavenging activity among samples collected in different regions. Plants collected in the coastal regions Soliman and Kelibia accumulate more polyphenolic compounds, known to be responsible for the main antioxidant activity of sage (rosmarinic acid, carnosol, and carnosic acid), than those growing inland at Bou Arada and Sers. Moreover, the former presented a higher radical-scavenging activity. The methanolic extracts of postdistilled S. officinalis might be valuable antioxidant natural sources and seemed to be applicable in both the health medicine and food industries. PMID:19886685

Ben Farhat, Mouna; Jordán, María J; Chaouech-Hamada, Rym; Landoulsi, Ahmed; Sotomayor, Jose A

2009-11-11

347

Morus alba and active compound oxyresveratrol exert anti-inflammatory activity via inhibition of leukocyte migration involving MEK/ERK signaling  

PubMed Central

Background Morus alba has long been used in traditional Chinese medicine to treat inflammatory diseases; however, the scientific basis for such usage and the mechanism of action are not well understood. This study investigated the action of M. alba on leukocyte migration, one key step in inflammation. Methods Gas chromatography-mass spectrometry (GC-MS) and cluster analyses of supercritical CO2 extracts of three Morus species were performed for chemotaxonomy-aided plant authentication. Phytochemistry and CXCR4-mediated chemotaxis assays were used to characterize the chemical and biological properties of M. alba and its active compound, oxyresveratrol. fluorescence-activated cell sorting (FACS) and Western blot analyses were conducted to determine the mode of action of oxyresveratrol. Results Chemotaxonomy was used to help authenticate M. alba. Chemotaxis-based isolation identified oxyresveratrol as an active component in M. alba. Phytochemical and chemotaxis assays showed that the crude extract, ethyl acetate fraction and oxyresveratrol from M. alba suppressed cell migration of Jurkat T cells in response to SDF-1. Mechanistic study indicated that oxyresveratrol diminished CXCR4-mediated T-cell migration via inhibition of the MEK/ERK signaling cascade. Conclusions A combination of GC-MS and cluster analysis techniques are applicable for authentication of the Morus species. Anti-inflammatory benefits of M. alba and its active compound, oxyresveratrol, may involve the inhibition of CXCR-4-mediated chemotaxis and MEK/ERK pathway in T and other immune cells. PMID:23433072

2013-01-01

348

Activity of IQG-607, a new orally active compound, in a murine model of Mycobacterium tuberculosis infection.  

PubMed

We have previously demonstrated a potent in vitro inhibitory activity for two pentacyano(isoniazid)ferrate(II) compounds, namely IQG-607 and IQG-639, against the Mycobacterium tuberculosis enoyl-acyl carrier protein reductase enzyme. In this study, the activity of these compounds was evaluated using an in vivo murine model of tuberculosis. Swiss mice were infected with M. tuberculosis H37Rv strain and then IQG-607 or IQG-639 (250 mg/kg) was administered for 28 days or 56 days. In addition, a dose-response study was performed with IQG-607 at 5, 10, 25, 50, 100, 200 and 250 mg/kg. The activity of test compounds was compared with that of the positive control drug isoniazid (INH) (25 mg/kg). After 28 days or 56 days of treatment, both IQG-607 and INH significantly reduced M. tuberculosis-induced splenomegaly as well as significantly diminishing the colony-forming units in the spleen and lungs. IQG-607 and INH ameliorated the lung macroscopic aspect, reducing lung lesions to a similar extent. However, IQG-639 did not significantly modify any evaluated parameter. Experiments using early and late controls of infection revealed a bactericidal activity for IQG-607. IQG-607 might well represent a good candidate for clinical development as a new antimycobacterial agent. PMID:22748570

Rodrigues-Junior, Valnês S; Dos Santos Junior, André; Dos Santos, Anderson Jader; Schneider, Cristopher Zandoná; Calixto, João B; Sousa, Eduardo Henrique Silva; de França Lopes, Luiz Gonzaga; Souto, André Arigony; Basso, Luiz Augusto; Santos, Diógenes Santiago; Campos, Maria M

2012-08-01

349

Adenosine, a hepato-protective component in active hexose correlated compound: its identification and iNOS suppression mechanism.  

PubMed

Supplementation of active hexose correlated compound (AHCC) improved the prognosis of postoperative hepatocellular carcinoma patients. Excess production of nitric oxide (NO) by inducible NO synthase (iNOS) is an inflammatory biomarker in liver injury. AHCC suppressed iNOS induction in hepatocytes, suggesting that AHCC has a potential liver-protective effect. However, the active component in AHCC responsible for NO suppressive activities has not been identified. The objective of this study was to identify this NO suppressive component and to investigate its mechanisms of action. AHCC was subjected to fractionation by cation exchanger, size exclusion chromatography, and normal- and reversed-phase HPLC. Aliquots of the fractions were added to primary cultured rat hepatocytes stimulated with interleukin (IL)-1?, and NO production was assayed. By activity-guided fractionation and electron spray ionization mass spectrometry analysis, adenosine was identified as one of the NO suppressive components in AHCC. Adenosine inhibited NO production, and reduced the expression of iNOS protein and mRNA. It had no effects on I?B degradation, but it inhibited NF-?B activation. Adenosine also inhibited the upregulation of type I IL-1 receptor (IL-1RI). Experiments with iNOS promoter-luciferase constructs revealed that adenosine decreased the levels of iNOS mRNA at the promoter transactivation and mRNA stabilization steps. Adenosine decreased the expression of the iNOS gene antisense transcript, which is involved in iNOS mRNA stability. Adenosine in AHCC suppressed iNOS induction by blocking NF-?B activation and the upregulation of the IL-1RI pathways, resulting in the inhibition of NO production. PMID:24878381

Tanaka, Yoshito; Ohashi, Satomi; Ohtsuki, Aya; Kiyono, Tamami; Park, Eun Young; Nakamura, Yasushi; Sato, Kenji; Oishi, Masaharu; Miki, Hirokazu; Tokuhara, Katsuji; Matsui, Kosuke; Kaibori, Masaki; Nishizawa, Mikio; Okumura, Tadayoshi; Kwon, A-Hon

2014-08-31

350

Combining human periodontal ligament cell membrane chromatography with online HPLC/MS for screening osteoplastic active compounds from Coptidis Rhizoma.  

PubMed

We have developed an online analytical method that combines human periodontal ligament cell membrane chromatography (hPDLC/CMC) with high-performance liquid chromatography and mass spectrometry (LC/MS) for recognizing and identifying osteoplastic active components from Coptidis Rhizoma. Retention fractions on hPDLC/CMC were enriched onto an enrichment column and the components were directly analyzed by combining a 10-port column switcher with an LC/MS system for separation and preliminary identification. Using simvastatin (SIM) as a positive control, berberine from Coptidis Rhizoma was identified as the active component which could act on the hPDLC. The MTT colorimetric assay, alkaline phosphatase (ALP) activity, and staining tests revealed that berberine could promote hPDLC growth, increase the secretion of ALP in the culture medium, and enhance the formation of mineralized nodule, thus it is a potential osteoplastic ingredient. This hPDLC/CMC-online-LC/MS method can be applied for screening active components acting on hPDLC from traditional Chinese medicines exemplified by Coptidis Rhizoma and will be of great utility in drug discovery using natural medicinal herbs as a source of leading compounds. PMID:22884476

Liu, Jin; Yang, Jin; Wang, Sicen; Sun, Junyi; Shi, Jianfeng; Rao, Guozhou; Li, Ang; Gou, Jianzhong

2012-09-01

351

High-Throughput Screening (HTS) and Hit Validation to Identify Small Molecule Inhibitors with Activity against NS3/4A proteases from Multiple Hepatitis C Virus Genotypes  

PubMed Central

Development of drug-resistant mutations has been a major problem with all currently developed Hepatitis C Virus (HCV) NS3/4A inhibitors, including the two FDA approved drugs, significantly reducing the efficacy of these inhibitors. The high incidence of drug-resistance mutations and the limited utility of these inhibitors against only genotype 1 highlight the need for novel, broad-spectrum HCV therapies. Here we used high-throughput screening (HTS) to identify low molecular weight inhibitors against NS3/4A from multiple genotypes. A total of 40,967 compounds from four structurally diverse molecular libraries were screened by HTS using fluorescence-based enzymatic assays, followed by an orthogonal binding analysis using surface plasmon resonance (SPR) to eliminate false positives. A novel small molecule compound was identified with an IC50 value of 2.2 µM against the NS3/4A from genotype 1b. Mode of inhibition analysis subsequently confirmed this compound to be a competitive inhibitor with respect to the substrate, indicating direct binding to the protease active site, rather than to the allosteric binding pocket that was discovered to be the binding site of a few recently discovered small molecule inhibitors. This newly discovered inhibitor also showed promising inhibitory activity against the NS3/4As from three other HCV genotypes, as well as five common drug-resistant mutants of genotype 1b NS3/4A. The inhibitor was selective for NS3 from multiple HCV genotypes over two human serine proteases, and a whole cell lysate assay confirmed inhibitory activity in the cellular environment. This compound provides a lead for further development of potentially broader spectrum inhibitors. PMID:24130685

Lee, Hyun; Zhu, Tian; Patel, Kavankumar; Zhang, Yan-Yan; Truong, Lena; Hevener, Kirk E.; Gatuz, Joseph L.; Subramanya, Gitanjali; Jeong, Hyun-Young; Uprichard, Susan L.; Johnson, Michael E.

2013-01-01

352

Salt reduction in slow fermented sausages affects the generation of aroma active compounds.  

PubMed

Slow fermented sausages with different salt content were manufactured: control (2.7% NaCl, S), 16% salt reduced (2.26% NaCl, RS) and 16% replaced by KCl (2.26% NaCl and 0.43% KCl, RSK). The effect of salt reduction on microbiology and chemical parameters, sensory characteristics, texture and volatile compounds was studied. The aroma compounds were identified by GC-MS and olfactometry analyses. Small salt reduction (16%) (RS) affected sausage quality producing a reduction in the acceptance of aroma, taste, juiciness and overall quality. The substitution by KCl (RSK) produced the same acceptability by consumers as for high salt (S) treatment except for the aroma that was not improved by KCl addition. The aroma was affected due to the reduction in sulfur and acids and the increase of aldehyde compounds. Aroma compounds that characterized the high salt treatment (S) were dimethyl trisulfide, 3-methyl thiophene, 2,3-butanedione, 2-nonanone and acetic acid. PMID:23261539

Corral, Sara; Salvador, Ana; Flores, Mónica

2013-03-01

353

Novel compound heterozygous mutations in the MYO15A gene in autosomal recessive hearing loss identified by whole-exome sequencing  

PubMed Central

Background Inherited genetic defects play an important role in congenital hearing loss, contributing to about 60% of deafness occurring in infants. Hereditary nonsyndromic hearing loss is highly heterogeneous, and most patients with a presumed genetic etiology lack a specific molecular diagnosis. Methods By whole exome sequencing, we identified responsible gene of family 4794 with autosomal recessively nonsyndromic hearing loss (ARNSHL). We also used DNA from 56 Chinese familial patients with ARNSHL (autosomal recessive nonsyndromic hearing loss) and 108 ethnicity-matched negative samples to perform extended variants analysis. Results We identified MYO15A c.IVS25?+?3G?>?A and c.8375 T?>?C (p.V2792A) as the disease-causing mutations. Both mutations co-segregated with hearing loss in family 4794, but were absent in the 56 index patients and 108 ethnicity-matched controls. Conclusions Our results demonstrated that the hearing loss of family 4794 was caused by novel compound heterozygous mutations in MYO15A. PMID:24206587

2013-01-01

354

*These substances include metals, polynuclear aromatic hydrocarbons, volatile organic compounds, polychlorinated biphenyls, and petroleum. Areas on which these substances have been identified and other areas where historical releases of these substances m  

E-print Network

*These substances include metals, polynuclear aromatic hydrocarbons, volatile organic compounds, polychlorinated biphenyls, and petroleum. Areas on which these substances have been identified and other areas where historical releases of these substances may have occurred were the subject of the investigation

Netoff, Theoden

355

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

PubMed Central

We have developed a high-throughput T-DNA insertional mutagenesis program in tomato using activation tagging to identify genes that regulate metabolic pathways. One of the activation-tagged insertion lines (ant1) showed intense purple pigmentation from the very early stage of shoot formation in culture, reflecting activation of the biosynthetic pathway leading to anthocyanin accumulation. The purple coloration resulted from the overexpression of a gene that encodes a MYB transcription factor. Vegetative tissues of ant1 plants displayed intense purple color, and the fruit showed purple spotting on the epidermis and pericarp. The gene-to-trait relationship of ant1 was confirmed by the overexpression of ANT1 in transgenic tomato and in tobacco under the control of a constitutive promoter. Suppression subtractive hybridization and RNA hybridization analysis of the purple tomato plants indicated that the overexpression of ANT1 caused the upregulation of genes that encode proteins in both the early and later steps of anthocyanidin biosynthesis as well as genes involved in the glycosylation and transport of anthocyanins into the vacuole. PMID:12897245

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

2003-01-01

356

Synthesis and antibacterial activity of quinolone-based compounds containing a coumarin moiety.  

PubMed

A new series of quinolone-based compounds containing a coumarin moiety have been synthesized and studied for their antibacterial activity against a panel of gram-positive and gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The results of the antibacterial evaluation of N-[2-(coumarin-3-yl)ethyl]piperazinyl quinolone derivatives in comparison with parent quinolones (norfloxacin, ciprofloxacin, and enoxacin) indicated that N-[2-(coumarin-3-yl)-2-oxoethyl]ciprofloxacin derivative (compound 8b) showed comparable or more potent antibacterial activity with respect to the reference drugs against the test strains. Generally, in both gram-positive and gram-negative bacteria, better results are obtained with cyclopropyl at the N-1 position of the quinolone ring and 2-oxo- on the ethyl spacer of coumarin and piperazine rings. PMID:18072241

Emami, Saeed; Foroumadi, Alireza; Faramarzi, Mohammad A; Samadi, Nasrin

2008-01-01

357

Radioprotective effects of active compounds from Acanthopanax senticosus of Lesser Khingan Mountain in China  

NASA Astrophysics Data System (ADS)

Bioactive compounds including polysaccharides, flavones, syringin and eleutheroside E were extracted from wild Acanthopanax senticosus and purified by chromatography. In vitro and in vivo anti-radiation activities of the compounds were compared. In vitro radical scavenging results showed that polysaccharides and flavones were more effective than syringin and eleutheroside E in In vivo study proved that polysaccharides and flavones were effective in protecting mice from heavy ion radiation induced oxidative damages. Also, the activity of polysaccharides and flavones in repressing expression changes of radiation response proteins including heat shock protein, disulfide-isomerase and glutathione S-transferase were also found by our results. Moreover, the radioprotective effects were more significant when polysaccharides and flavones were used together.

Lu, Weihong; Sun, Yeqing; Shi, Jinming

358

Screening a mushroom extract library for activity against Acinetobacter baumannii and Burkholderia cepacia and the identification of a compound with anti-Burkholderia activity  

PubMed Central

Background Acinetobacter baumannii and species within the Burkholderia cepacia complex (BCC) are significant opportunistic bacterial pathogens of humans. These species exhibit a high degree of antibiotic resistance, and some clinical isolates are resistant to all currently available antimicrobial drugs used for treatment. Thus, new drugs are needed to treat infections by these species. Mushrooms could be a potential source for new drugs to treat A. baumannii and BCC infections. Methods The aim of this study was to screen a library of crude extracts from 330 wild mushrooms by disk diffusion assays for antibacterial activity against A. baumannii and Burkholderia cepacia in the hope of identifying a novel natural drug that could be used to treat infections caused by these species. Once positive hits were identified, the extracts were subjected to bioassay-guided separations to isolate and identify the active drug molecules. MICs were performed to gauge the in vitro activity of the purified compounds. Results Only three crude extracts (0.9%) had activity against A. baumannii and B. cepacia. Compounds from two of these extracts had MICs greater than 128 ?g/ml, and further analyses were not performed. From the third extract, prepared from Leucopaxillus albissimus, 2-aminoquinoline (2-AQ) was isolated. This compound exhibited a modest MIC in vitro against strains from nine different BCC species, including multi-drug resistant clinical isolates (MIC = 8-64 ?g/ml), and a weak MIC (128 ?g/ml) against A baumannii. The IC50 against a murine monocyte line was 1.5 mg/ml. Conclusion The small number of positive hits in this study suggests that finding a new drug from mushrooms to treat Gram-negative bacterial infections may be difficult. Although 2-AQ was identified in one mushroom, and it was shown to inhibit the growth of multi-drug resistant BCC isolates, the relatively high MICs (8-128 ?g/ml) for both A. baumannii and BCC strains suggests that 2-AQ is not suitable for further drug development in its current form. PMID:20092635

2010-01-01

359

Coordination modes of bridge carboxylates in dinuclear manganese compounds determine their catalase-like activities.  

PubMed

To explore the role of bridge carboxylate coordination modes on the catalase-like activities of dinuclear manganese compounds, [Mn(II)2(bpmapa)2(H2O)2](ClO4)2 (1), [Mn(II)2(pbpmapa)2(H2O)2](ClO4)2 (2), and [Mn(II)2(bpmaa)2(H2O)3](ClO4)2 (3) (bpmapa = [bis(2-pyridylmethyl)amino]propionic acid, pbpmapa = alpha-phenyl-beta-[bis(2-pyridylmethyl)amino]propionic acid, and bpmaa = [bis(2-pyridylmethyl)amino]acetic acid), in which Mn(II)-Mn(II) centers have a similar coordination sphere but different carboxylate-Mn bridging modes have been synthesized and structurally characterized by single X-ray diffraction, UV-visible, IR, and EPR spectroscopies, and their catalase-like activities were investigated. Studies of their catalytic activities and the influence of the nitrogenous bases on their catalytic activities indicated that the carboxylate-Mn coordination mode was crucial in H2O2 deprotonation, and eventually in H2O2 disproportionation. Compound 1 with a bidentate carboxylate bridge showed higher catalase-like activity than 2 and 3, in which the carboxylate groups have a monodentate bridging mode. The deprotonation ability of the carboxylate anion was determined by the O-C-O angle and the distance between the weakly bound oxygen of the bridging carboxylate to the manganese ion. The smaller the angle, and the shorter the distance, the stronger the basicity that the carboxylate anion exhibits. The bidentate mu-1,1 bridging coordination mode functionally mimicked the glutamate residues at the manganese catalase active site. Our results suggested that increasing the basicity of the bridging carboxylate ligand of the catalase model compounds will increase their deprotonation ability and lead to more active catalase mimics. PMID:19809747

Jiang, Xiaojun; Liu, Hui; Zheng, Bing; Zhang, Jingyan

2009-10-28

360

Analysis and determination of oestrogen-active compounds in fructus amomi by the combination of high-speed counter-current chromatography and high performance liquid chromatography.  

PubMed

Amomum longiligulare or Amomum villosum showed oestrogenic activity. In the present study, oestrogen-active components in fructus amomi, the seeds of A. longiligulare were separated by high-speed countercurrent chromatography (HSCCC) using stepwise elution of eight mobile phases with gradient polarity and advanced separation by high performance liquid chromatography (HPLC). The results yielded 17 compounds with the amount of 8-138mg and a purity of 94.3-99.8% from a 3g ethanolic extract of fructus amomi. The chemical structures of the compounds were identified by ESI-MS and NMR spectra, in which eight diarylheptanoids were demonstrated as the main oestrogen-active compounds in the fructus amomi. Determination of the diarylheptanoids in fructus amomi from various origins showed that fructus amomi contains more than 0.5% total diarylheptanoids. The results showed that fructus amomi is a diarylheptanoids-rich food resource possessing oestrogen-activity. The combination method of HSCCC and HPLC can be applied for the analysis of bioactive compounds by detecting the corresponding bioactivity in the HSCCC fractions and separating the target compounds with HPLC. PMID:24686238

Ying, Hao; Liu, Jinpeng; Du, Qizhen

2014-05-01

361

Polarimeter with linear response for measuring optical activity in organic compounds  

NASA Astrophysics Data System (ADS)

A polarimeter designed for measuring small rotation angles on the polarization plane of light is described. The experimental device employs one fixed polarizer and a rotating analyzer. The system generates a periodical intensity signal, which is then Fourier analyzed. The coefficients of Fourier Transform contain information about rotation angles produced by organic compounds that exhibited optical activity. The experimental device can be used to determine the sugar concentration in agave juice.

Flores, Jorge L.; Montoya, Marcial; Garcia-Torales, G.; Gonzalez Alvarez, Alejandro

2005-08-01

362

Thermodynamic and transport properties of some biologically active compounds in aqueous solutions at different temperatures  

Microsoft Academic Search

The experimental data of density and viscosity have been obtained for aqueous solutions of biologically active compounds like salbutamol sulphate (SS), diethylcarbamazine citrate (DEC), and chlorpheniramine maleate (CPM) in the concentration range (0 to 0.15)mol·kg?1 at three different temperatures. The derived parameters, such as apparent molar volume of solute (?V)), limiting apparent molar volume of solute (?V0), limiting apparent molar

Sudhakar S. Dhondge; Sangesh P. Zodape; Dilip V. Parwate

2011-01-01

363

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

PubMed

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

Baloch, Imam Bakhsh; Baloch, Musa Kaleem

2012-01-01

364

Characterization of volatiles and aroma-active compounds in honeybush (Cyclopia subternata) by GC-MS and GC-O analysis.  

PubMed

Volatile organic compounds (VOCs) in fermented honeybush, Cyclopia subternata, were sampled by means of a high-capacity headspace sample enrichment probe (SEP) and analyzed by gas chromatography-mass spectrometry (GC-MS). Stereochemistry was determined by means of enantioselective GC-MS with derivatized ?-cyclodextrin columns as chiral selectors. A total of 183 compounds, the majority of which are terpenoids (103; 56%), were identified by comparing their mass spectra and retention indices with those of reference compounds or tentatively identified by comparison with spectral library or literature data. Of these compounds, 37 were determined by gas chromatography-olfactometry (GC-O), using detection frequency (DF) and aroma extract dilution analysis (AEDA), to be odor-active (FD ? 2). (E)-?-Damascenone, (R/S)-linalool, (E)-?-damascone, geraniol, (E)-?-ionone, and (7E)-megastigma-5,7,9-trien-4-one were identified with the highest FD factors (?512). The odors of certain compounds, that is, (6E,8Z)-megastigma-4,6,8-trien-3-one, (6E,8E)-megastigma-4,6,8-trien-3-one, (7E)-megastigma-5,7,9-trien-4-one, 10-epi-?-eudesmol, epi-?-muurolol, and epi-?-cadinol, were perceived by GC-O assessors as typically honeybush-like. PMID:22394400

Le Roux, Maritha; Cronje, J Christel; Burger, Barend V; Joubert, Elizabeth

2012-03-14

365

Nematicidal activity of Trichoderma spp. and isolation of an active compound  

Microsoft Academic Search

Trichoderma spp. play an important role in biotic control, and several are efficacious against nematodes. To study the potential of Trichoderma species in controlling nematodes, fungal filtrates of 329 Trichoderma strains were evaluated for their nematicidal activity against Panagrellus redivivus and Caenorhabditis elegans. Fifteen strains exhibited nematicidal activity against P. redivivus, and 14 strains showed activity against C. elegans. The

Zhong-Shan Yang; Guo-Hong Li; Pei-Ji Zhao; Xi Zheng; Shao-Liu Luo; Lei Li; Xue-Mei Niu; Ke-Qin Zhang

2010-01-01

366

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

PubMed Central

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

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

2013-01-01

367

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

PubMed Central

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

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

2011-01-01

368

Growth inhibition of colon cancer cells by compounds affecting AMPK activity  

PubMed Central

AIM: To determine if other molecules reported to modulate AMP-dependent protein kinase (AMPK) activity would have effects resembling those of metformin and phenformin on colon cancer cell proliferation and metabolism. METHODS: Studies were performed with four human colon cancer cell lines, Caco-2, HCT116, HT29 and SW1116. The compounds that were studied included A-769662, 5-aminoimidazole-4-carboxamide-1-ribofuranoside, butyrate, (-)-epigallocatechin gallate (EGCG), KU-55933, quercetin, resveratrol and salicylates. The parameters that were measured were cell proliferation and viability, glucose uptake, lactate production and acidification of the incubation medium. RESULTS: Investigations with several molecules that have been reported to be associated with AMPK activation (A-769662, 5-aminoimidazole-4-carboxamide-1-b-D-ribofuranoside, EGCG, KU-55933, quercetin, resveratrol and salicylates) or AMPK inhibition (compound C) failed to reveal increased medium acidification and increased glucose uptake in colon cancer cells as previously established with metformin and phenformin. The only exception was 5-aminosalicylic acid with which there were apparently lower glucose levels in the medium after incubation for 72 h. Further study in the absence of cells revealed that the effect was an artifact due to inhibition of the enzyme-linked glucose assay. The compounds were studied at concentrations that inhibited cell proliferation. CONCLUSION: It was concluded that treatment with several agents that can affect AMPK activity resulted in the inhibition of the proliferation of colon cancer cells under conditions in which glucose metabolism is not enhanced, in contrast to the effect of biguanides. PMID:25024815

Lea, Michael A; Pourat, Jacob; Patel, Rupali; desBordes, Charles

2014-01-01

369

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

PubMed

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

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

2014-06-01

370

Specialized three-faceted information retrieval thesaurus as a means of indexing and retrieving biologically active compounds according to their biological effects  

Microsoft Academic Search

The first stage in the screening of new chemical compounds for biological activity is the 'informational analysis' of these compounds [i], which consists in the comparison of the structures of the new compounds under test with those of compounds previously tested having established biological activity. The aim of informational analysis is to predict possible types of activity for new chemical

V. V. Avidon; E. M. Mikhailovskii; L. A. Piruzyan

1977-01-01

371

ON EXTRACELLULAR AND INTRACELLULAR VENOM ACTIVATORS OF THE BLOOD, WITH ESPECIAL REFERENCE TO LECITHIN AND FATTY ACIDS AND THEIR COMPOUNDS.  

PubMed

In normal serums of the majority of mammalian and avian blood there exists certain substances capable of activating venom haemolysin. They are extractable from serum by means of ether, and are capable of conferring upon the originally non-activating serum a power to activate venom, when mixed with the latter. The ethereal extract consists of fatty acids, neutral fats and possibly also some ether soluble organic soaps. The fatty acids and soaps, especially of the oleinic series, acquire certain characteristics of complements in general, when they are mixed with serum. They are inactive without the venom in the mixture; they are inactivable with calcium chloride; they exhibit a tendency to go off in activity with age; they are inactive or only weakly active at 0 degrees C., and they are extractable by ether. In testing the serum from which the ether soluble substances are removed, it is found that no venom activating property is left. Warm alcoholic extraction of such serum yields, however, a large quantity of lecithin. In the case of non-activating serums no venom activating fats appear in the ethereal extract. Lecithin exists in such serum in no less quantity than in the activating kind. The addition of oleinic acid or its soluble soaps to a non-activating serum, in a ratio which corresponds to the percentage of fatty acids or soaps contained in some of the easily activating serums, will make the serum highly active in regard to venom. In normal serum of dog there exists, besides the group of activators already mentioned, another kind of venom activators which has been identified as a lecithin compound acting in the manner of free lecithin. A very sharp differentiation of the haemolysis produced by this activator and by the other groups of activators is obtained by means of calcium chloride, which is powerless against lecithin or lecithin compounds, but effective in removing the action of the latter. This lecithin containing proteid can be precipitated by half saturation with ammonium sulphate, but is perfectly soluble in water, and is not coagulated in neutral alkaline salt solutions upon boiling. Alcohol precipitates a proteid-like coagulum and extracts lecithin from it; ether does not extract lecithin from this compound. Non-activating serums do not contain any such lecithin compound. Lecithin contained in other serum proteids, mainly as lecithalbumin, and perhaps as contained in globulin, is not able to activate venom. This is true of all the serums with which I worked; it matters not whether these fractions (obtained with ammonium sulphate) belong to the most activating serum (dog) or to the non-activating serum (ox). The non-coagulable portion of all heated serum contains a venom activator of the nature of lecithin. This activator is contained in a non-coagulable proteid described by Howell which is identical with Chabrie's albumon. As there is no ether-extractable lecithin in this portion of the serum, the activating property of heated serum must be due to this proteid compound of lecithin. That this lecithin proteid does not pre-exist in normal serum but is produced by the action of high temperature is true of all serums except that of the dog. In venom activation we know now that lecithin becomes reactive with venom when it is transformed from other proteid compounds into the non-coagulable form, the albumon. Howell's view of the non-existence of the non-coagulable proteid in normal serum seems to receive a biological support from venom haemolysis. Ovovitellin derived from hen's egg is one of the best venom activators of the lecithin proteid type. The cause of venom susceptibility of various kinds of blood corpuscles does not depend upon the existence of lecithin in the corpuscles, but solely upon the amount of fatty acids, and perhaps, also, soaps and fats, contained in the corpuscles. The protection which calcium chloride gives against venom haemolysis is proof of the absence of lecithin activation. From the stroma of susceptible corpuscles fatty acids or some fats can be extracted with ether. After ethereal e

Noguchi, H

1907-07-17

372

A high-throughput screen identifies a new natural product with broad-spectrum antibacterial activity.  

PubMed

Due to the inexorable invasion of our hospitals and communities by drug-resistant bacteria, there is a pressing need for novel antibacterial agents. Here we report the development of a sensitive and robust but low-tech and inexpensive high-throughput metabolic screen for novel antibiotics. This screen is based on a colorimetric assay of pH that identifies inhibitors of bacterial sugar fermentation. After validation of the method, we screened over 39,000 crude extracts derived from organisms that grow in the diverse ecosystems of Costa Rica and identified 49 with reproducible antibacterial effects. An extract from an endophytic fungus was further characterized, and this led to the discovery of three novel natural products. One of these, which we named mirandamycin, has broad-spectrum antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Vibrio cholerae, methicillin-resistant Staphylococcus aureus, and Mycobacterium tuberculosis. This demonstrates the power of simple high throughput screens for rapid identification of new antibacterial agents from environmental samples. PMID:22359585

Ymele-Leki, Patrick; Cao, Shugeng; Sharp, Jared; Lambert, Kathleen G; McAdam, Alexander J; Husson, Robert N; Tamayo, Giselle; Clardy, Jon; Watnick, Paula I

2012-01-01

373

A High-Throughput Screen Identifies a New Natural Product with Broad-Spectrum Antibacterial Activity  

PubMed Central

Due to the inexorable invasion of our hospitals and communities by drug-resistant bacteria, there is a pressing need for novel antibacterial agents. Here we report the development of a sensitive and robust but low-tech and inexpensive high-throughput metabolic screen for novel antibiotics. This screen is based on a colorimetric assay of pH that identifies inhibitors of bacterial sugar fermentation. After validation of the method, we screened over 39,000 crude extracts derived from organisms that grow in the diverse ecosystems of Costa Rica and identified 49 with reproducible antibacterial effects. An extract from an endophytic fungus was further characterized, and this led to the discovery of three novel natural products. One of these, which we named mirandamycin, has broad-spectrum antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Vibrio cholerae, methicillin-resistant Staphylococcus aureus, and Mycobacterium tuberculosis. This demonstrates the power of simple high throughput screens for rapid identification of new antibacterial agents from environmental samples. PMID:22359585

Ymele-Leki, Patrick; Cao, Shugeng; Sharp, Jared; Lambert, Kathleen G.; McAdam, Alexander J.; Husson, Robert N.; Tamayo, Giselle; Clardy, Jon; Watnick, Paula I.

2012-01-01

374

NG2 expression in glioblastoma identifies an actively proliferating population with an aggressive molecular signature  

PubMed Central

Glioblastoma multiforme (GBM) is the most common type of primary brain tumor and a highly malignant and heterogeneous cancer. Current conventional therapies fail to eradicate or curb GBM cell growth. Hence, exploring the cellular and molecular basis of GBM cell growth is vital to develop novel therapeutic approaches. Neuroglia (NG)-2 is a transmembrane proteoglycan expressed by NG2+ progenitors and is strongly linked to cell proliferation in the normal brain. By using NG2 as a biomarker we identify a GBM cell population (GBM NG2+ cells) with robust proliferative, clonogenic, and tumorigenic capacity. We show that a significant proportion (mean 83%) of cells proliferating in the tumor mass express NG2 and that over 50% of GBM NG2+ cells are proliferating. Compared with the GBM NG2? cells from the same tumor, the GBM of NG2+ cells overexpress genes associated with aggressive tumorigenicity, including overexpression of Mitosis and Cell Cycling Module genes (e.g., MELK, CDC, MCM, E2F), which have been previously shown to correlate with poor survival in GBM. We also show that the coexpression pattern of NG2 with other glial progenitor markers in GBM does not recapitulate that described in the normal brain. The expression of NG2 by such an aggressive and actively cycling GBM population combined with its location on the cell surface identifies this cell population as a potential therapeutic target in a subset of patients with GBM. PMID:21798846

Al-Mayhani, M. Talal F.; Grenfell, Richard; Narita, Masashi; Piccirillo, Sara; Kenney-Herbert, Emma; Fawcett, James W.; Collins, V. Peter; Ichimura, Koichi; Watts, Colin

2011-01-01

375

Parallel RNA interference screens identify EGFR activation as an escape mechanism in FGFR3 mutant cancer  

PubMed Central

Activation of fibroblast growth factor receptors is a common oncogenic event. Little is known about the determinants of sensitivity to FGFR inhibition and how these may vary between different oncogenic FGFRs. Using parallel RNA interference genetic screens we demonstrate that EGFR limits sensitivity to FGFR inhibition in FGFR3 mutant and translocated cell lines, but not in other FGFR driven cell lines. We also identify two distinct mechanisms through which EGFR limits sensitivity. In partially FGFR3 dependent lines, inhibition of FGFR3 results in transient down-regulation of MAPK signalling that is rescued by rapid upregulation of EGFR signalling. In cell lines that are intrinsically resistant to FGFR inhibition, EGFR dominates signalling via repression of FGFR3, with EGFR inhibition rescued by delayed up-regulation of FGFR3 expression. Importantly, combinations of FGFR and EGFR inhibitors overcome these resistance mechanisms in vitro and in vivo. Our results illustrate the power of parallel RNA interference screens in identifying common resistance mechanisms to targeted therapies. PMID:23744832

Herrera-Abreu, Maria Teresa; Pearson, Alex; Campbell, James; Shnyder, Steve D; Knowles, Margaret A; Ashworth, Alan; Turner, Nicholas C

2013-01-01

376

Nematicidal activity of the essential oil of Rhododendron anthopogonoides aerial parts and its constituent compounds against Meloidogyne incognita.  

PubMed

Hydrodistilled essential oil from Rhododendron anthopogonoides Maxim. (Ericaceae) aerial parts was analysed by gas chromatography-mass spectrometry (GC-MS). A total of 42 compounds, accounting for 95.48% of the total oil, were identified. The main constituents of the essential oil were benzyl acetone (34.41%), nerolidol (10.19%), 1,4-cineole (8.41%), beta-caryophyllene (5.63%), gamma-elemene (5.10%), and spathulenol (3.06%). Four constituents were isolated from the essential oil based on fractionation. The essential oil of R. anthopogonoides possessed nematicidal activity against the root knot nematode (Meloidogyne incognita) with an LC50 value of 130.11 microg/ml. The main compound of the essential oil, benzyl acetone, exhibited nematicidal activity against M. incognita with an LC50 value of 74.17 microg/ml while 1,4-cineole, nerolidol, and beta-caryophyllene were not nematicidal at a concentration of 5 mg/ml. The essential oil of R. anthopogonoides and benzyl acetone show potential for their development as possible natural nematicides for the control of the root knot nematode. PMID:24066516

Bai, Peng Hua; Bai, Chun Qi; Liu, Qi Zhi; Du, Shu Shan; Liu, Zhi Long

2013-01-01

377

Antimicrobial activity of DU-6681a, a parent compound of novel oral carbapenem DZ-2640.  

PubMed Central

The in vitro antibacterial activity of DU-6681a, a parent compound of DZ-2640, against gram-positive and -negative bacteria was compared with those of penems and cephalosporins currently available. MICs at which 90% of the isolates are inhibited (MIC90s) of the compound for clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis, including methicillin-susceptible and -resistant strains, were 0.10, 25, and 12.5 microg/ml, respectively. DU-6681a inhibited the growth of all strains of Streptococcus pyogenes and of penicillin-susceptible and -insusceptible Streptococcus pneumoniae at 0.006, 0.025, and 0.20 microg/ml, respectively, and MIC90s of the compound were 6.25 and >100 microg/ml for Enterococcus faecalis and Enterococcus faecium, respectively. MIC90s of DU-6681a were 0.20, 0.10, and 0.025 microg/ml for Haemophilus influenzae, Moraxella catarrhalis, and Neisseria gonorrhoeae, respectively. For Pseudomonas aeruginosa, the MIC50 and MIC90 of DU-6681a were 25 and 50 microg/ml, respectively. DU-6681a activity was not affected by different media, varied inoculum size (10(4) to 10(7) CFU), or the addition of human serum but was decreased under acidic conditions against gram-negative bacteria, under alkaline conditions against gram-positive bacteria, and in human urine, as was the activity of the other antibiotics tested. The frequency of spontaneous resistance to DU-6681a was less than or equal to those of the reference compounds. Time-kill curve studies demonstrated the bactericidal action of DU-6681a against S. aureus, S. pneumoniae, Escherichia coli, and H. influenzae. PMID:9174181

Tanaka, M; Hohmura, M; Nishi, T; Sato, K; Hayakawa, I

1997-01-01

378

Antimicrobial activity of DU-6681a, a parent compound of novel oral carbapenem DZ-2640.  

PubMed

The in vitro antibacterial activity of DU-6681a, a parent compound of DZ-2640, against gram-positive and -negative bacteria was compared with those of penems and cephalosporins currently available. MICs at which 90% of the isolates are inhibited (MIC90s) of the compound for clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis, including methicillin-susceptible and -resistant strains, were 0.10, 25, and 12.5 microg/ml, respectively. DU-6681a inhibited the growth of all strains of Streptococcus pyogenes and of penicillin-susceptible and -insusceptible Streptococcus pneumoniae at 0.006, 0.025, and 0.20 microg/ml, respectively, and MIC90s of the compound were 6.25 and >100 microg/ml for Enterococcus faecalis and Enterococcus faecium, respectively. MIC90s of DU-6681a were 0.20, 0.10, and 0.025 microg/ml for Haemophilus influenzae, Moraxella catarrhalis, and Neisseria gonorrhoeae, respectively. For Pseudomonas aeruginosa, the MIC50 and MIC90 of DU-6681a were 25 and 50 microg/ml, respectively. DU-6681a activity was not affected by different media, varied inoculum size (10(4) to 10(7) CFU), or the addition of human serum but was decreased under acidic conditions against gram-negative bacteria, under alkaline conditions against gram-positive bacteria, and in human urine, as was the activity of the other antibiotics tested. The frequency of spontaneous resistance to DU-6681a was less than or equal to those of the reference compounds. Time-kill curve studies demonstrated the bactericidal action of DU-6681a against S. aureus, S. pneumoniae, Escherichia coli, and H. influenzae. PMID:9174181

Tanaka, M; Hohmura, M; Nishi, T; Sato, K; Hayakawa, I

1997-06-01

379

Primary amino acid derivatives: compounds with anticonvulsant and neuropathic pain protection activities.  

PubMed

Pharmacological management remains the primary method to treat epilepsy and neuropathic pain. We have advanced a novel class of anticonvulsants termed functionalized amino acids (FAAs). In this study, we examine FAA derivatives from which the terminal acetyl moiety was removed and termed these compounds primary amino acid derivatives (PAADs). Twenty-seven PAADs were prepared; the central C(2) R-substituent was varied, including C(2) stereochemistry, and the compounds were tested in rodent models of seizures and neuropathic pain. C(2)-Hydrocarbon N-benzylamide PAADs were potent anticonvulsants and excellent anticonvulsant activity (mice, ip; rat, po) was observed for C(2) R-substituted PAADs in which the R group was ethyl, isopropyl, or tert-butyl, and the C(2) stereochemistry conformed to the d-amino acid configuration ((R)-stereoisomer). These values surpassed the activities of several clinical antiepileptic drugs. The C(2) (R)-ethyl and C(2) (R)-isopropyl PAADs also displayed excellent activities in the mouse (ip) formalin neuropathic pain model. Significantly, unlike the FAA structure-activity relationship, PAAD anticonvulsant activity increased upon substitution of a methylene unit for a heteroatom in the R-substituent that was one atom removed from the C(2) site, suggesting that these PAADs function by a different pathway than FAAs. PMID:21639114

King, Amber M; Salomé, Christophe; Dinsmore, Jason; Salomé-Grosjean, Elise; De Ryck, Marc; Kaminski, Rafal; Valade, Anne; Kohn, Harold

2011-07-14

380

Reconstructing the Population Activity of Olfactory Output Neurons that Innervate Identifiable Processing Units  

PubMed Central

We investigated the functional organization of the moth antennal lobe (AL), the primary olfactory network, by integrating single-cell electrophysiological recording data with geometrical information. The moth AL contains about 60 processing units called glomeruli that are identifiable from one animal to another. We were able to monitor the output information of the AL by recording the activity of a population of output neurons, each of which innervated a single glomerulus. Using compiled in vivo intracellular recordings and staining data from different animals, we mapped the odor-evoked dynamics on a digital atlas of the AL and geometrically reconstructed the population activity. We examined the quantitative relationship between the similarity of olfactory responses and the anatomical distance between glomeruli. Globally, the olfactory response profile was independent of the anatomical distance, although some local features were present. Olfactory response profiles of superficial glomeruli were approximately similar, whereas those of deep glomeruli were different with each other, suggesting network architectures are different in superficial and deep glomerular networks during olfactory processing. PMID:18946541

Namiki, Shigehiro; Kanzaki, Ryohei

2008-01-01

381

Risk assessment of endocrine active chemicals: identifying chemicals of regulatory concern.  

PubMed

The European regulation on plant protection products (1107/2009) (EC, 2009a), the revisions to the biocides Directive (COM[2009]267) (EC, 2009b), and the regulation concerning chemicals (Regulation (EC) No. 1907/2006 'REACH') (EC.2006) only support the marketing and use of chemical products on the basis that they do not induce endocrine disruption in humans or wildlife species. In the absence of agreed guidance on how to identify and evaluate endocrine activity and disruption within these pieces of legislation a European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) task force was formed to provide scientific criteria that may be used within the context of these three legislative documents. The resulting ECETOC technical report (ECETOC, 2009a) and the associated workshop (ECETOC, 2009b) presented a science-based concept on how to identify endocrine activity and disrupting properties of chemicals for both human health and the environment. The synthesis of the technical report and the workshop report was published by the ECETOC task force (Bars et al., 2011a,b). Specific scientific criteria for the determination of endocrine activity and disrupting properties that integrate information from both regulatory (eco)toxicity studies and mechanistic/screening studies were proposed. These criteria combined the nature of the adverse effects detected in studies which give concern for endocrine toxicity with an understanding of the mode of action of toxicity so that adverse effects can be explained scientifically. A key element in the data evaluation is the consideration of all available information in a weight-of-evidence approach. However, to be able to discriminate chemicals with endocrine properties of low concern from those of higher concern (for regulatory purposes), the task force recognised that the concept needed further refinement. Following a discussion of the key factors at a second workshop of invited regulatory, academic and industry scientists (ECETOC, 2011), the task force developed further guidance, which is presented in this paper. For human health assessments these factors include the relevance to humans of the endocrine mechanism of toxicity, the specificity of the endocrine effects with respect to other potential toxic effects, the potency of the chemical to induce endocrine toxicity and consideration of exposure levels. For ecotoxicological assessments the key considerations include specificity and potency, but also extend to the consideration of population relevance and negligible exposure. It is intended that these complement and reinforce the approach originally described and previously published in this journal (Bars et al., 2011a,b). PMID:22735369

Bars, Remi; Fegert, Ivana; Gross, Melanie; Lewis, Dick; Weltje, Lennart; Weyers, Arnd; Wheeler, James R; Galay-Burgos, Malyka

2012-10-01

382

Anti-ice nucleating activity of polyphenol compounds against silver iodide.  

PubMed

Freeze-avoiding organisms survive sub-zero temperatures without freezing in several ways, such as removal of ice nucleating agents (INAs), production of polyols, and dehydration. Another way is production of anti-ice nucleating agents (anti-INAs), such as has been reported for several antifreeze proteins (AFPs) and polyphenols, that inhibit ice nucleation by inactivating INAs. In this study, the anti-ice nucleating activity of five polyphenol compounds, including flavonoid and tannin compounds of both biological and synthetic origin, against silver iodide (AgI) was examined by measuring the ice nucleation temperature in emulsified polyphenol solutions containing AgI particles. The emulsified solutions eliminated the influence of contamination by unidentified INAs, thus enabling examination of the anti-ice nucleating activity of the polyphenols against AgI alone. Results showed that all five polyphenol compounds used here have anti-ice nucleating activities that are unique compared with other known anti-INAs, such as fish AFPs (type I and III) and synthetic polymers (poly(vinyl alcohol), poly(vinylpyrrolidone) and poly(ethylene glycol)). All five polyphenols completely inactivated the ice nucleating activity of AgI even at relatively low temperatures, and the first ice nucleation event was observed at temperatures between -14.1 and -19.4°C, compared with between -8.6 and -11.8°C for the fish AFPs and three synthetic polymers. These anti-ice nucleating activities of the polyphenols at such low temperatures are promising properties for practical applications where freezing should be prevented. PMID:25086201

Koyama, Toshie; Inada, Takaaki; Kuwabara, Chikako; Arakawa, Keita; Fujikawa, Seizo

2014-10-01

383

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

NASA Astrophysics Data System (ADS)

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

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

2013-09-01