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

作者：Elgazwy Abdel Sattar S Hamad^*; Ismail Nasser S M; Elzahabi Heba S A

来源：Bioorganic & Medicinal Chemistry, 2010, 18(21): 7639-7650.

DOI：10.1016/j.bmc.2010.08.033

• Diaminomaleonitrile (DAMN)
• Purine
• Pyrimidine
• CDK2
• Molecular modeling
• Antitumor
• Docking
• Bioinformatics

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 IC(50) values of 14 +/- 9 and 13 +/- 9 mu M, respectively. Additionally, compound 15a showed the highest potency (IC(50) = 10 +/- 6 mu M) 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.

• 出版日期2010-11-1