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High Inhibitory Activity (high + inhibitory_activity)
Selected AbstractsDevelopment of a New Pharmacophore Model That Discriminates Active Compstatin AnalogsCHEMICAL BIOLOGY & DRUG DESIGN, Issue 4 2008Ting-Lan Chiu Compstatin and its active peptide analogs can potentially be used for therapeutic purposes because their binding to the third component of complement prohibits its conversion into the proteolytically activated form of the third component of complement, thus inhibiting complement cascades in all three complement pathways. Mallik and Morikis built three quasi-dynamic pharmacophore models for compstatin peptide analogs before, but only nine compstatin peptide analogs were incorporated in their study and the most active compstatin analog had only medium inhibitory activity. Since then, many more compstatin analogs have been synthesized and their inhibitory activities tested. Furthermore, the X-ray structure of AcCompNH2-V4W-H9A bound to the third component of complement has become available (PDB ID: 2QKI). In this paper, we utilized all the new information and built a new pharmacophore model using a distinct approach. Our model demonstrated good performance in a separate test set of 82 compstatin analogs: it accurately identified 70% of the analogs of medium or high inhibitory activities and misclassified only 8.5% of the analogs of low or no inhibitory activities. The results proved our pharmacophore model to be a filter of great sensitivity and specificity. [source] A heat-stable trypsin inhibitor in adzuki bean (Vigna angularis): effect of extraction media, purification and biochemical characteristicsINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 1 2010Sappasith Klomklao Summary Trypsin inhibitor from adzuki bean (Vigna angularis) seed was isolated and characterised. Extraction of seed with NaCl at the concentration of 0.15 m showed a higher recovery of trypsin inhibitor than other solvents tested (P < 0.05). Optimal extraction time for the recovery trypsin inhibitor from adzuki bean seed was 30 min (P < 0.05). Purification of inhibitor was achieved by heat-treatment at 90 °C for 10 min, followed by ammonium sulphate precipitation with 30,65% saturation and size exclusion chromatography on Sephacryl S-200, presenting a yield and purification of 53.9% and 10.91-fold, respectively. The apparent molecular weight of trypsin inhibitor was estimated to be 14 kDa based on SDS-PAGE and inhibitor activity of zones separated by electrophoresis. The purified inhibitor was stable over a broad pH range and retained high inhibitory activity toward trypsin after incubation at 90 °C for 60 min. NaCl, at 0,3% concentration, did not affect the inhibitory activity of purified trypsin inhibitor, however, the activity was lost when sample was treated with ,-mercaptoethanol prior to electrophoresis. [source] A new method for the synthesis and herbicidal activity of 3-phenoxy-6-(1H- (substituted)pyrazol-1-yl) pyridazinesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 4 2009Fang-Zhong Hu A series of 3-substituted phenoxy-6-((substituted)1H -pyrazol-1-yl) pyridazines were synthesized from the condensation of various phenols and 3-chloro-6-(1H -pyrazol-1-yl) pyridazine 2 or 3-chloro-6-(5,-methyl-4-ethoxycarbonyl- 1H -pyrazol-1-yl) pyridazine 6 in N,N-dimethylformamide (DMF) at 120°C with K2CO3 as an acid receptor. The intermediates 2 or 6 were obtained from the cyclization of 3-chloro-6-hydrazinyl pyridazine 1 with 3-dimethylamino-acrylaldehyde or ethyl 2-((dimethylamino) methylene)-3-oxobutanoate in n -butanol under reflux, respectively, and side products 3 or 7 were also generated. All of the title compounds were confirmed by 1H NMR, infrared spectometry (IR) and elemental analyses. Preliminary bioassay indicated that some of the title compounds showed high inhibitory activity against Brassica campestris L. (B. campestris) and moderate inhibitory activity against Echinochloa crusgalli. For example, the inhibition percentages of compound 4b and 4c against B. campestris were both 94% at 10 ,g/mL. J. Heterocyclic Chem., (2009). [source] Biosynthesis of New Indigoid Inhibitors of Protein Kinases Using Recombinant Cytochrome P450 2A6CHEMISTRY & BIODIVERSITY, Issue 1 2005Zhongliu-Liu Wu Glycogen synthase kinase-3 (GSK-3) is a potential drug target for a number of human diseases. Some indigoids have been found to be potent inhibitors of GSK-3, and individual compounds with better activity, specificity, and solubility are desired. In this work, a new disubstituted indigoid generation system was developed with a tryptophanase-deficient Escherichia coli strain as a host to express the human cytochrome P450 2A6 mutant L240C/N297Q, which catalyzes the oxidation of indole to isatin and indoxyl, which in turn react to generate indigoids. Forty-five substituted 1H -indoles from commercial sources were used as substrates in the system, and indigoid mixtures were tested as potential inhibitors of GSK-3. After preliminary screening, cell extracts with high inhibitory activity towards GSK-3,/, were fractionated, and the IC50 values of twelve individual indigoids were measured for GSK-3,/, as well as the protein kinases CDK1/cyclinB and CDK5/p25. Several indigoids, including an indigo, showed stronger inhibition than found in previous work. The most potent towards GSK-3,/,, dimethyl indirubin 5,5,-dicarboxylate (IC50 of 51,nM), was modified by chemical reactions. One product, indirubin 5,5,-dicarboxylic acid 5-methyl ester, inhibited GSK-3,/, with an IC50 of 14,nM and selectivity nearly 40-fold over CDK1 and CDK5. Indirubin-5-5,-dicarbonitrile was also modified to the corresponding 3,-oxime, which had low specificity but showed very high inhibition of all three kinases with IC50 values of 5, 13, and 10,nM towards GSK-3,/,, CDK1, and CDK5, respectively. Thus, this system has the potential to generate new indigoids with therapeutic potential. [source] | ||||||||||