Novel small-molecule CDK2-cyclinA2 inhibitors: design, synthesis, and biological evaluation
10.3969/j.issn.1674-8115.2017.03.010
- VernacularTitle:新型CDK2-cyclinA2小分子抑制剂的设计、合成及生物学活性研究
- Author:
Yingqing WEI
;
Lu ZHANG
;
Yutong HU
;
Jian ZHANG
;
Ying SHEN
- Keywords:
CDK2-cyclinA2;
cell cycle;
inhibitor;
structure-activity relationship
- From:
Journal of Shanghai Jiaotong University(Medical Science)
2017;37(3):330-336
- CountryChina
- Language:Chinese
-
Abstract:
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.
