A convenient synthesis and molecular modeling study of novel purine and pyrimidine derivatives as CDK2/cyclin A3 inhibitors

A series of novel purine and pyrimidine derivatives were prepared and biologically evaluated for their in vitro anti-CDK2/cyclin A3 and antitumor activities in Ehrlich ascites carcinoma (EAC) cell based assay. The novel purine derivatives 13a,b demonstrated potent inhibitor activities with IC50 values of 14 ± 9 and 13 ± 9 μM, respectively. Additionally, compound 15a showed the highest potency (IC50 = 10 ± 6 μM) in EAC cell based assay. Molecular modeling study, including fitting to a 3D-pharmacophore model and their docking into cyclin dependant kinase2 (CDK2) active site showed high fit values and docking scores.

The manuscript describes the investigation of a series of novel purine and pyrimidine derivatives, which were prepared in good yield by using diaminomaleonitrile and tosylisocyanate in acetonitrile. Molecular modeling studies, including fitting to a 3D-pharmacophore model their docking into cycline-dependent kinase2 (CDK2) active site were performed to understand the structural features of CDK2 inhibitors. Biological evaluation for both in vitro CDK2/cyclinA3 inhibition activity and antitumor activity in Ehrlich ascites carcinoma (EAC) cell based assay were also carried out.Figure optionsDownload as PowerPoint slide