Synthesis of 6-(het) ary Xylocydine analogues and evaluating their inhibitory activities of CDK1 and CDK2 in vitro
- Bioorg Med Chem. 2011 Dec 1;19(23):7100-10. doi: 10.1016/j.bmc.2011.10.003.
- 1. College of Chemistry, Jilin University, Changchun 130012, China.
A series of purine nucleoside analogues bearing an aryl and hetaryl group in position 6 were prepared and their biological activities were assessed by in vitro CDK1/Cyclin B1 and CDK2/Cyclin A2 kinase assay. From the synthesized chemicals, three Xylocydine derivatives 3h, 3i, and 3j exhibited specific inhibitory activities on CDK2/Cyclin A2 with IC(50) values of 4.6, 4.8, and 55 μM, respectively. Those three compounds all induced G1/S phase arrest in Human epithelial carcinoma cell line (HeLa), and the results suggested they may inhibit CDK2 activity in vitro. Furthermore, molecular modeling study, their docking into Cyclin Dependant Kinase 2 (CDK2) active site showed high docking scores. Taken together, these data suggest that, those three compounds are good inhibitors of CDK2 for studying this kinase signal transduction pathway in cell system.