Design,Synthesis and Evaluation of Benzenesulfonamide-substituted 1,5-Diarylpyrazoles containing Phenylacetohydrazide Derivatives as COX-1/COX-2 Agents Against Solid Tumors
Novel benzenesulfonamide-substituted 1,5-diarylpyrazoles containing phenylacetohydrazide derivatives have been designed,synthesized and evaluated for their biological activities as selective COX-2 inhibitor with anticancer potential.In vitro the bioassay results revealed that some of them displayed potent inhibitory activity in the enzymatic and cellular assays.Among them,compound 48 showed most powerful and potent selective inhibitory activity(IC50 = 82.21 μM for COX-1 and IC50 = 0.37 μM for COX-2),comparable to the control positive compound Celecoxib(40.29 μM,0.15μM).Antiproliferative assay results indicated that compound 48 possess potent antiproliferative activity against A549 cells in vitro with IC50 value of 0.78 μM.We then performed PI staining assay and cell apoptosis analysis for compound 48 and found that it effectively causing A549 cell apoptosis.Docking simulation was further performed to position compound 48 into the COX-2 active site to determine the probable binding model.The 3D-QSAR models were built for reasonable design of selective COX-2 inhibitor in future.
Diarylpyrazoles Benzenesulfonamide Anticancer COX-1/COX-2 Docking
Xiao-Yuan Lu Zhong-Chang Wang Ting Wei Xiao-qiang Yan Peng-Fei Wang Hai-Liang Zhu
Stale Key Laboratory of Pharmaceutical Biotechnology.Nanjing University,Nanjing 210023,People”s Republic of China
国内会议
大连
英文
193-243
2016-09-24（万方平台首次上网日期，不代表论文的发表时间）