Abstract

Background: CDK2 shows a fundamental role as a controller of cell growing, which makes it as one of the goals of anticancer inhibitors.

Methods: The current study participated in design (docking and binding energy), which used to select the promising proposed compounds, synthesis of novel diverse 14 pyrido[2,3-d]pyrimidine derivatives and biological studies of the prepared compounds as promising anticancer agents aiming CDK2. All the fresh generated compounds were scanned for their anticancer activity versus MCF-7 and CaCO2 and 14 compounds were found to be active. Compounds 6c and 8d displayed expressive activity with IC50 values 7.4 and 5.5 on MCF-7 respectively. The created compounds were submitted to enzyme inspection (CDK2) for assigning their inhibitory activity.

Results: The initial results showed that compound 8d, which demonstrates potent inhibitory activity towards tumor development and powerful inhibitions of CDK2 enzyme (89% inhibition) could be utilized as a lead candidate. The products were characterized by IR, 1H NMR, 13CNMR and MS.

Conclusion: Preliminary bioassays indicated that most of the compounds exhibited very good antitumor activity and powerful inhibitions of CDK2 enzyme.

Keywords: Pyrido[2, 3-d] pyrimidines, CDK2 inhibitors, docking study, binding energy, anti-proliferative activity, tumor.

Graphical Abstract