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Novel small-molecule CDK2-cyclinA2 inhibitors: design, synthesis, and biological evaluation

WEI Ying-qing1, ZHANG Lu2, HU Yu-tong1, ZHANG Jian1, SHEN Ying1   

  1. 1. Basic Medicine Faculty of Shanghai Jiao Tong University, Shanghai 200025, China; 2.College of Pharmacy, Dalian Medical University, Dalian 116044, China
  • Online:2017-03-28 Published:2017-03-30


Objective · To design and synthesize a series of benzenesulfonamide derivatives, test their inhibitory activity to CDK2-cyclinA2 kinase, and investigate the structure-activity relationship. Methods · Virtual screening was executed via computer-aided drug design according to the ATP binding site in CDK2-cyclinA2 protein crystal. A series of benzenesulfonamide derivatives were designed and synthesized on the basis of the interaction modes between the lead compound and the CDK2-cyclinA2. The biological evaluation of compounds was made through the CDK2-cyclinA2 in-vitro kinase activity detection system. Results · Twenty-nine new benzenesulfonamide compounds were prepared, and their inhibitory activity to CDK2-cyclinA2 was elicited. WZ-026 had the highest inhibitory parameter, which half maximal inhibitory concentration (IC50) was 3.81 μmol/L. Conclusion · By multipurpose utilization of virtual screening, chemical synthesis, and biological activity test, a benzenesulfonamide compound WZ-026 was found, which has great inhibitory activity towards CDK2-cyclinA2. Preliminary structure-activity relationship of compounds was obtained.

Key words: CDK2-cyclinA2, cell cycle, inhibitor, structure-activity relationship