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961.
A group of N-acetyl-2-(or 3-)carboxymethylbenzenesulfonamides, possessing either a F or a substituted-phenyl ring substituent (4-F, 2,4-F2, 4-SO2Me, 4-OCHMe2) attached to its C-4 or C-6 position, was prepared using a palladium-catalyzed Suzuki cross-coupling reaction for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. Although N-acetyl-3-carboxymethyl-6-fluorobenzenesulfonamide [14, COX-1 IC50 = 2.26 microM; COX-2 IC50 = 0.012 microM; COX-2 selectivity index (SI) = 188] and N-acetyl-3-carboxymethyl-6-(4-isopropoxyphenyl)benzenesulfonamide (20c, COX-1 IC50 >100 microM; COX-2 IC50 = 0.15 microM; COX-2 SI >667) exhibited potent in vitro COX-2 inhibitory activity and high COX-2 selectivity, both compounds were inactive anti-inflammatory agents in a carrageenan-induced rat paw edema assay. In contrast, the less potent and less selective COX-2 inhibitors N-acetyl-2-carboxymethyl-4-fluorobenzenesulfonamide (12, COX-1 IC50 = 4.25 microM; COX-2 IC50 = 0.978 microM; COX-2 SI = 4.3), N-acetyl-2-carboxymethyl-4-(2,4-difluorophenyl)benzenesulfonamide (17c, COX-1 IC50 = 1.02 microM; COX-2 IC50 = 1.00 microM; COX-2 SI = 1.02), and N-acetyl-3-carboxymethyl-6-(4-methanesulfonylphenyl)benzenesulfonamide (20e, COX-1 IC50 = 0.109 microM; COX-2 IC50 = 1.14 microM; COX-2 SI = 0.095) exhibited moderate anti-inflammatory activity where a 75 mg/kg oral dose reduced inflammation 26%, 14%, and 20%, respectively, at 3 h postdrug administration relative to the reference drug aspirin where a 50 mg/kg oral dose reduced inflammation by 25% at 3 h postdrug administration. 相似文献
962.
A group of 3,4-diphenyl-1,2,5-oxadiazole-2-oxides (3,4-diphenylfuroxans) and the corresponding N-desoxy 3,4-diphenyl-1,2,5-oxadiazoles (3,4-diphenylfurazans) analogs, were synthesized for in vitro evaluation as hybrid cyclooxygenase (COX) inhibitor/nitric oxide donor agents. Reaction of 1-[4-(methylsulfonyl)phenyl]-2-phenylethene with an aqueous sodium nitrite solution in acetic acid afforded a mixture (3:1 ratio) of the inseparable 4-[4-(methylsulfonyl)phenyl]-3-phenyl-1,2,5-oxadiazole-2-oxide (13a) and 3-[4-(methylsulfonyl)phenyl]-4-phenyl-1,2,5-oxadiazole-2-oxide (13b) regioisomers. A group of related regioisomers possessing either a p-aminosulfonylphenyl (16) or a p-azidosulfonylphenyl (17), moiety were obtained by chlorosulfonation of the unsubstituted 3,4-diphenylfuroxan (10) and subsequent reaction with either ammonium hydroxide or sodium azide, respectively. The methanesulfonyl regioisomers 13a,b [COX-1 IC50=11.6 microM; COX-2 IC50=0.12 microM; COX-2 selectivity index (SI)=97] and aminosulfonyl regioisomers 16 (COX-1 IC50=9.8 microM; COX-2 IC50=0.78 microM; COX-2 SI=12), like the reference drug celecoxib (COX-1 IC50=33.1 microM; COX-2 IC50=0.07 microM; COX-2 SI=472), were potent in vitro COX-2 inhibitors with a good COX-2 selectivity index. Release of nitric oxide (NO) from the 3,4-diphenylfuroxan compounds (10, 13a,b, 16, 17) was thiol-dependent since the % NO released was higher upon incubation in the presence of l-cysteine (0.57-3.18%) compared to that in phosphate buffer solution at pH7.4 (0.06-0.15%). Molecular modeling (docking) studies show that the methanesulfonyl (MeSO2) COX-2 pharmacophore present in regioisomers 13a,b is positioned in the vicinity of the COX-2 secondary pocket. The in vitro NO release data, COX-1/COX-2 inhibition and COX-2 SI structure-activity relationships acquired, and molecular modeling docking studies suggest that the 1,2,5-oxadiazole-2-oxide (furoxan) ring possesses beneficial features that should be present in a suitable central ring template (bioisostere) pertinent to the design novel hybrid COX-2 inhibitor/nitric oxide donor agents with a low ulcerogenicity profile that may be free from adverse cardiovascular effects. 相似文献
963.
Murty US Kumar DV Rao MS Reuben R Tewari SC Hiriyan J Akiyama J Akavaram D 《Bioinformation》2005,1(2):40-41
Rapid identification of mosquito (vector) species is critical for vector control and disease management. Pictorial keys of mosquito species are currently used for the identification of new mosquito species. However, this approach is not very effective. Here, we describe the use of an ID3 algorithm (part of artificial intelligence) for the rapid identification of the South East Asian female Culex mosquito species.
Availability 相似文献
964.
Abhishek?A.?Chakraborty Ravindra?P.?PhadkeEmail author Fauzia?A.?Chaudhary Prakash?S.?Shete Bhalchandra?S.?Rao Kushan?D.?Jasani 《World journal of microbiology & biotechnology》2005,21(3):221-227
The ability of Saccharomyces cerevisiae to catalyse the reduction reaction of carboxylic acids into alcohols is described. Earlier reports have led to the characterization of the reduction of carbonyl groups into alcohols mediated by the enzyme alcohol dehydrogenase. We investigated the ability of this organism to catalyse the said conversion using the carboxylic acids, acetic acid and butyric acid. In the absence of any previous characterization, whole cell catalysis proved effective. The uptake of these acids from the medium was estimated using a plate assay method involving litmus-agar. The plate assay was found to be a convenient and extremely adaptable method for quantitation of acids in organic as well as aqueous medium. The comparison of existing paradigms in pure protein catalysis with whole cells catalysis proved anomalous. We report that it is solvent toxicity rather than hydrophobic index that correlates with the activity observed in non-aqueous conditions for whole cell biocatalysis. Reduction of acetic acid as well as butyric acid occurred, with efficiency of reaction with butyric acid being marginally higher. The reduction therefore occurs for both the short chain carboxylic acids used in this study. We therefore illustrate the reduction route of acids into alcohols and propose a model two-step pathway for the reaction. Process optimization may be further attempted to enhance the presently moderate reaction efficiencies. Steps made in the direction by studying the pH dependency and use of sacrificial substrate have yielded encouraging results. 相似文献
965.
Structural insights into SARS coronavirus proteins 总被引:11,自引:0,他引:11
966.
Culture development for human embryonic stem cell propagation: molecular aspects and challenges 总被引:4,自引:0,他引:4
Basic fibroblast growth factor and members of the transforming growth factor-beta superfamily are important regulators of human embryonic stem cell (hESC) self-renewal. Extensive cross-talk between the intracellular signaling pathways activated by these factors contributes to maintenance of the undifferentiated hESC state. Understanding the molecular regulation of hESC self-renewal will facilitate the design of improved systems for hESC propagation and provide a foundation for strategies to direct the differentiation of hESCs to clinically relevant cell types. 相似文献
967.
968.
Ravi?Shankar?PiskaEmail author A.?Madhusudhan?Rao 《Reviews in Fish Biology and Fisheries》2005,15(3):167-173
The present study deals with the impact of juvenile stocking sizes of the major carp on production in a minor reservoir, Bibinagar,
Nalgonda, India. Reservoir surface area equaled over 23.8 ha and water from the reservoir was used for irrigation and fisheries.
Four experiments were conducted for 4 years from 2000–2001 to 2003–2004. The experiments were planned in such a way that every
year juvenile stocking size was held constant and subsequent fish production analyzed. During the first year’s experiment
(2000–2001) a stocking size of 25–30 mm (fry) was maintained. Similarly 50–55 (advanced fry), 75–80 mm (fingerling) and 100–105 mm
(advanced fingerling) were stocked during 2001–2002, 2002–2003 and 2003–2004 respectively. Uniform yearly stocking densities
(2000/ha) were established in each experiment in the month of July and fish were harvested in June of the subsequent year.
Major carp production was enhanced with larger stocking size. Yearly productions equaled 144.00, 231.48, 632.91 and 1005.03 kg/ha/year
with the above stocking sizes. Variation in stocking sizes had significant (P<0.05) effects on fish production. The number of fish per kg production decreased gradually with increases in stocking size
with an average value of 3.97. Reservoir production of catla was the most abundant species, followed by rohu, common carp,
mrigal and grass carp. These results show that stocking size has a great impact on fish production and the stocking of advanced
fingerlings will provide maximum carp production in minor reservoirs in India. 相似文献
969.
Das B Rudra S Yadav A Ray A Rao AV Srinivas AS Soni A Saini S Shukla S Pandya M Bhateja P Malhotra S Mathur T Arora SK Rattan A Mehta A 《Bioorganic & medicinal chemistry letters》2005,15(19):4261-4267
Novel oxazolidinones were synthesized containing a number of substituted five-membered heterocycles attached to the 'piperazinyl-phenyl-oxazolidinone' core of eperezolid. Further, the piperazine ring of the core was replaced by other diamino-heterocycles. These modifications led to several compounds with potent activity against a spectrum of resistant and susceptible gram-positive organisms, along with the identification of ranbezolid (RBx 7644) as a clinical candidate. 相似文献
970.
The racemic trans- and cis-isomers of 1-amino-2-phosphonomethyl-cyclobutanecarboxylic acid (5 and 6) and 1-amino-2-phosphonomethyl-cyclopentanecarboxylic acid (7 and 8) were synthesized as extensions of the mGluR4 agonists trans- and cis-1-amino-2-phosphonomethyl-cyclopropanecarboxylic acid (3 and 4). Although the methylene bridge in 3 and 4 allows for retention of affinity toward the mGluR4 receptor, increasing the bridging unit to the ethylene group as in 5 and 6 or to the trimethylene group as in 7 and 8 introduces sufficient steric hindrance to eliminate affinity for the mGluR4 receptor. 相似文献