Development of pyrazolo[1,5-a]pyrimidine derivatives: Synthesis, anticancer activity and docking study

Abstract

It has been revealed that scaffolds made from pyrazolo [1,5-a]pyrimidines exhibit valuable biological activities, particularly anti-proliferative efficacy and blocking CDK activity. Therefore, new derivatives of pyrazolo[1,5-a]pyrimidines 5a-c were synthesized, and their chemical structures were validated using several spectral studies. These compounds were screened against MCF-7, HCT-116, and HepG2 malignant cell lines in comparison to doxorubicin to determine their anticancer activity. From the results, it is found that the order of activity of the examined compounds in general is 5b with a methoxy group, which is better in activity than 5a having phenyl group and 5c bearing methyl group. The anti-tumor potency against HCT-116 demonstrated that compound 5b was promising and close to the reference (IC50 = 8.64 µM). In addition, the synthesized compounds were submitted to molecular docking research against the CDK2 kinase enzyme in order to investigate the method of binding and understand the mechanism of the promising cytotoxic activity.