Chen Zhong, Wang Zhong-Chang, Yan Xiao-Qiang, Wang Peng-Fei, Lu Xiao-Yuan, Chen Long-Wang, Zhu Hai-Liang, Zhang Hong-Wei
Department of Plastic and Burn Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 21003, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Bioorg Med Chem Lett. 2015 May 1;25(9):1947-51. doi: 10.1016/j.bmcl.2015.03.022. Epub 2015 Mar 22.
Novel dihydropyrazole sulfonamide derivatives (30-56) were designed, synthesized, and evaluated for their biological activities as COX-1 and COX-2 inhibitors. In vitro biological evaluation against three human tumor cell lines revealed that most target compounds showed antiproliferative activities. Among the compounds, compound 48 exhibited the most potent and selective COX-2 inhibitor (COX-2 IC50=0.33 μM; COX-1 IC50=68.49 μM) relative to the reference drugs celecoxib (IC50=0.052 μM). Docking simulation was performed to position compound 48 into the COX-2 active site and the result showed that compound 48 could bind well at the COX-2 active site and it indicated that compound 48 could be a potent and selective COX-2 inhibitor.
设计、合成了新型二氢吡唑磺酰胺衍生物（30 - 56），并对其作为COX - 1和COX - 2抑制剂的生物活性进行了评估。针对三种人类肿瘤细胞系的体外生物学评估表明，大多数目标化合物具有抗增殖活性。在这些化合物中，相对于参考药物塞来昔布（IC50 = 0.052 μM），化合物48表现出最有效和选择性的COX - 2抑制剂（COX - 2 IC50 = 0.33 μM；COX - 1 IC50 = 68.49 μM）。进行了对接模拟，将化合物48定位到COX - 2活性位点，结果表明化合物48可以很好地结合在COX - 2活性位点，这表明化合物48可能是一种有效且选择性的COX - 2抑制剂。
