2. Academic Validation
  3. Design, synthesis, biological evaluation and molecular modeling of dihydropyrazole sulfonamide derivatives as potential COX-1/COX-2 inhibitors

Design, synthesis, biological evaluation and molecular modeling of dihydropyrazole sulfonamide derivatives as potential COX-1/COX-2 inhibitors

  • Bioorg Med Chem Lett. 2015 May 1;25(9):1947-51. doi: 10.1016/j.bmcl.2015.03.022.
Zhong Chen 1,  Zhong-Chang Wang 2,  Xiao-Qiang Yan 2,  Peng-Fei Wang 2,  Xiao-Yuan Lu 2,  Long-Wang Chen 2,  Hai-Liang Zhu 3,  Hong-Wei Zhang 4
Affiliations

Affiliations

  • 1 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.
  • 2 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
  • 3 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: zhuhl@nju.edu.cn.
  • 4 Department of Plastic and Burn Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 21003, People's Republic of China. Electronic address: zhanghw1966@aliyun.com.
PMID: 25866240 DOI: 10.1016/j.bmcl.2015.03.022
Abstract

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.

Keywords

Anticancer; COX-1/COX-2; Dihydropyrazole sulfonamide; Docking; MTT.

Figures