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Compounds Able (compound + able)
Selected AbstractsFlavonoids as RTK inhibitors and potential anticancer agentsMEDICINAL RESEARCH REVIEWS, Issue 5 2008Florence Teillet Abstract Tyrosine kinase receptors (RTKs) play a crucial role in the regulation of the cell division cycle. Currently more than 50 RTKs divided into several subfamilies have been described. The inhibition of these enzymes has emerged as an important research-area. Compounds able to inhibit the activity of these enzymes are expected to display antiproliferative properties. Flavonoids are representative of various small molecules acting as RTK inhibitors. These naturally occurring compounds are able to bind to the ATP-binding site of several kinases. The most plausible current hypothesis explaining the action of these substances on kinases is that the chromenone moiety of the flavonoid acts as a mimetic of the adenine moiety of ATP, the receptor co-factor. In this review, we report recent results on the activity of natural and synthetic derivatives of flavonoids as inhibitors of RTKs. Mechanistic aspects, the therapeutic usefulness, and the potential clinical use are discussed. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 5, 715,745, 2008 [source] Oxazoline-terminated macromonomers by the alkylation of 2-methyl-2-oxazolineJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 11 2005Olfa Glaied Abstract Well-defined macromonomers of poly(ethylene oxide) and poly(tert -butyl methacrylate) were obtained by anionic polymerization induced directly by the carbanion issued from 2-methyl-2-oxazoline. When ethylene oxide was added to this carbanion with lithium as the counterion, a new compound able to initiate the polymerization of ,-caprolactone in an anionically coordinated way was synthesized, and this led to well-defined poly(,-caprolactone) macromonomers. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 2440,2447, 2005 [source] Genistein potentiates activity of the cation channel TRPC5 independently of tyrosine kinasesBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2010Ching-On Wong Background and purpose:, TRPC5 is a Ca2+ -permeable channel with multiple modes of activation. We have explored the effects of genistein, a plant-derived isoflavone, on TRPC5 activity, and the mechanism(s) involved. Experimental approach:, Effects of genistein on TRPC5 channels were investigated in TRPC5-over-expressing human embryonic kidney 293 (HEK) cells and bovine aortic endothelial cells (BAECs) using fluorescent Ca2+ imaging and electrophysiological techniques. Key results:, In TRPC5-over-expressing HEK cells, genistein stimulated TRPC5-mediated Ca2+ influx, concentration dependently (EC50= 93 µM). Genistein and lanthanum activated TRPC5 channels synergistically. Effects of genistein on TRPC5 channels were mimicked by daidzein (100 µM), a genistein analogue inactive as a tyrosine kinase inhibitor, but not by known tyrosine kinase inhibitors herbimycin (2 µM), PP2 (20 µM) and lavendustin A (10 µM). Action of genistein on TRPC5 channels was not affected by an oestrogen receptor inhibitor ICI-182780 (50 µM) or a phospholipase C inhibitor U73122 (10 µM), suggesting genistein did not act through oestrogen receptors or phospholipase C. In BAECs, genistein (100 µM) stimulated TRPC5-mediated Ca2+ influx. In patch clamp studies, both genistein (50 µM) and daidzein (50 µM) augmented TRPC5-mediated whole-cell cation current in TRPC5 over-expressing HEK cells. Genistein stimulated TRPC5 channel activity in excised inside-out membrane patch, suggesting that its action was relatively direct and did not require cytosolic factors. Conclusions and implications:, The present study is the first to demonstrate stimulation of a TRP channel by isoflavones. Genistein is a lipophilic compound able to stimulate TRPC5 activity in TRPC5-over-expressing HEK cells and in native vascular endothelial cells. [source] Conformational Stability of A, -(25,35) in the Presence of Thiazolidine DerivativesCHEMICAL BIOLOGY & DRUG DESIGN, Issue 2 2007Pietro Campiglia In the attempt to identify a new lead compound able to modify the conformational preferences of the , -amyloid peptides, a set of new compounds characterized by a thiazolidine ring linked to several different aryl moieties were synthesized. The ability of these compounds to prevent the , -amyloid aggregation was evaluated using circular dichroism and nuclear magnetic resonance techniques. Molecular docking procedure allowed an interpretation of spectroscopic in the key of molecular interaction. [source] Pulp and paper mill effluents induce distinct gene expression changes linked to androgenic and estrogenic responses in the fathead minnow (Pimephales promelas)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2010Julieta Werner Abstract Although effluent treatment systems within pulp and paper mills remove many toxicants and improve wastewater quality, there is a need to understand and quantify the effectiveness of the treatment process. At a combined news and kraft pulp and paper mill in northwestern Ontario, Canada, fathead minnow (FHM) reproduction and physiology were examined before, during, and after a short-term (6-d) exposure to 10% (v/v) untreated kraft mill effluent (UTK), 25% (v/v) secondary treated kraft mill effluent (TK), and 100% (v/v) combined mill outfall (CMO). Although UTK exposure significantly decreased egg production, neither TK nor CMO caused any reproductive changes. The expression of six genes responsive to endocrine-disrupting compounds, stress, or metals was then examined in livers of these fish using real-time polymerase chain reaction. In female FHMs, none of the three effluents induced significant expression changes in any genes investigated. By contrast, in males there were significant increases in the mRNA levels of androgen receptor, estrogen receptor (ER) ,, and cytochrome P4501A (CYP1A) upon UTK and TK exposure but no changes in ER, or vitellogenin (VTG) gene expression, whereas CMO exposure significantly increased the mRNA levels of ER,, VTG, and CYP1A. Together, these results suggest that kraft effluent before and after biological treatment contained compounds able to induce androgenic effects in FHMs, and that combination of kraft and newsmill effluents eliminated the androgenic compounds while inducing distinct and significant patterns of gene expression changes that were likely due to estrogenic compounds produced by the newsmill. Environ. Toxicol. Chem. 2010;29:430,439. © 2009 SETAC [source] Subcellular localization of proteins labeled with GFP in Xanthomonas citri ssp. citri: targeting the division septumFEMS MICROBIOLOGY LETTERS, Issue 1 2010Paula M.M. Martins Abstract Xanthomonas citri ssp. citri (Xac) is the causal agent of citrus canker, an economically important disease that affects citrus worldwide. To initiate the characterization of essential biological processes of Xac, we constructed integrative plasmids for the ectopic expression of green fluorescent protein (GFP)-labeled proteins within this bacterium. Here, we show that the disruption of the ,-amylase gene (amy), the site of plasmid integration into the bacterial chromosome, does not alter its pathogenesis while abolishing completely the ability of Xac to degrade starch. Furthermore, our GFP expression system was used to characterize ORF XAC3408, a hypothetical protein encoded by Xac that shares significant homology to the FtsZ-stabilizing factor ZapA from Bacillus subtilis (ZapABsu). GFP-XAC3408 expressed in Xac exhibited a septal localization pattern typical of GFP-ZapABsu, which indicates that XAC3408 is the Xac orthologue of the cell division protein ZapABsu. The results demonstrate the potential of GFP labeling for protein functional characterizations in Xac, and, in addition, the Xac mutant strain labeled at the septum constitutes a biological model for the exploration of antibacterial compounds able to inhibit cell division in this plant pathogen. [source] Cannabinoid CB2 receptor agonists protect the striatum against malonate toxicity: Relevance for Huntington's diseaseGLIA, Issue 11 2009Onintza Sagredo Abstract Cannabinoid agonists might serve as neuroprotective agents in neurodegenerative disorders. Here, we examined this hypothesis in a rat model of Huntington's disease (HD) generated by intrastriatal injection of the mitochondrial complex II inhibitor malonate. Our results showed that only compounds able to activate CB2 receptors were capable of protecting striatal projection neurons from malonate-induced death. That CB2 receptor agonists are neuroprotective was confirmed by using the selective CB2 receptor antagonist, SR144528, and by the observation that mice deficient in CB2 receptor were more sensitive to malonate than wild-type animals. CB2 receptors are scarce in the striatum in healthy conditions, but they are markedly upregulated after the lesion with malonate. Studies of double immunostaining revealed a significant presence of CB2 receptors in cells labeled with the marker of reactive microglia OX-42, and also in cells labeled with GFAP (a marker of astrocytes). We further showed that the activation of CB2 receptors significantly reduced the levels of tumor necrosis factor-, (TNF-,) that had been increased by the lesion with malonate. In summary, our results demonstrate that stimulation of CB2 receptors protect the striatum against malonate toxicity, likely through a mechanism involving glial cells, in particular reactive microglial cells in which CB2 receptors would be upregulated in response to the lesion. Activation of these receptors would reduce the generation of proinflammatory molecules like TNF-,. Altogether, our results support the hypothesis that CB2 receptors could constitute a therapeutic target to slowdown neurodegeneration in HD. © 2008 Wiley-Liss, Inc. [source] Selenium- and Tellurium-Containing Multifunctional Redox Agents as Biochemical Redox Modulators with Selective CytotoxicityCHEMISTRY - A EUROPEAN JOURNAL, Issue 36 2010Dr. Vincent Jamier Abstract Various human diseases, including different types of cancer, are associated with a disturbed intracellular redox balance and oxidative stress (OS). The past decade has witnessed the emergence of redox-modulating compounds able to utilize such pre-existing disturbances in the redox state of sick cells for therapeutic advantage. Selenium- and tellurium-based agents turn the oxidizing redox environment present in certain cancer cells into a lethal cocktail of reactive species that push these cells over a critical redox threshold and ultimately kill them through apoptosis. This kind of toxicity is highly selective: normal, healthy cells remain largely unaffected, since changes to their naturally low levels of oxidizing species produce little effect. To further improve selectivity, multifunctional sensor/effector agents are now required that recognize the biochemical signature of OS in target cells. The synthesis of such compounds provides interesting challenges for chemistry in the future. [source] | |||||||||||||