Synthesis of 6-(het) ary Xylocydine analogues and evaluating their inhibitory activities of CDK1 and CDK2 in vitro.
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.
College of Chemistry, Jilin University, Changchun 130012, China.
Chuan
C
Xiao
Chao
C
Sun
Weiwei
W
Han
Feng
F
Pan
Zhu
Z
Dan
Yu
Y
Li
Zhi-Guang
ZG
Song
Ying-Hua
YH
Jin
D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011684:Purine Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
C547380:4-amino-6-bromo-7-(xylofuranosyl)pyrrolo(2,3-d)pyrimidine-5-carboxamide; D009705:Nucleosides; D011684:Purine Nucleosides; D016203:CDC2 Protein Kinase; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2