Synthesis, biological evaluation and docking analysis of 3-methyl-1-phenylchromeno[4,3-c]pyrazol-4(1H)-ones as potential cyclooxygenase-2 (COX-2) inhibitors

被引：22
作者：
Grover, Jagdeep [1 ]
Kumar, Vivek [2 ]
Sobhia, M. Elizabeth [2 ]
Jachak, Sanjay M. [1 ]
机构：
[1] Natl Inst Pharmaceut Educ & Res, Dept Nat Prod, Mohali 160062, Punjab, India
[2] Natl Inst Pharmaceut Educ & Res, Dept Pharmacoinformat, Mohali 160062, Punjab, India
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 19期
关键词：
3-Methyl-1-phenylchromeno[4,3-c]pyrazol-4(1H)-ones; Cyclooxygenase-2; Anti-inflammatory; Molecular docking; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COUMARIN DERIVATIVES; MOLECULAR DOCKING; CURCUMIN ANALOGS; ANALGESIC AGENTS; DESIGN; IDENTIFICATION; ANTIOXIDANT; CHEMISTRY; PYRAZOLE;
D O I：
10.1016/j.bmcl.2014.08.050
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
As a part of our continued efforts to discover new COX inhibitors, a series of 3-methyl-1-phenylchromeno[4,3-c]pyrazol-4(1H)-ones were synthesized and evaluated for in vitro COX inhibitory potential. Within this series, seven compounds (3a-d, 3h, 3k and 3q) were identified as potential and selective COX-2 inhibitors (COX-2 IC50's in 1.79-4.35 mu M range; COX-2 selectivity index (SI) = 6.8-16.7 range). Compound 3b emerged as most potent (COX-2 IC50 = 1.79 mu M; COX-1 IC50 > 30 mu M) and selective COX-2 inhibitor (SI > 16.7). Further, compound 3b displayed superior anti-inflammatory activity (59.86% inhibition of edema at 5 h) in comparison to celecoxib (51.44% inhibition of edema at 5 h) in carrageenan-induced rat paw edema assay. Structure-activity relationship studies suggested that N-phenyl ring substituted with p-CF3 substituent (3b, 3k and 3q) leads to more selective inhibition of COX-2. To corroborate obtained experimental biological data, molecular docking study was carried out which revealed that compound 3b showed stronger binding interaction with COX-2 as compared to COX-1. (C) 2014 Elsevier Ltd. All rights reserved.
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收藏
页码：4638 / 4642
页数：5
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