Synthesis, anticancer evaluation, CDK2 inhibition, and apoptotic activity assessment with molecular docking modeling of new class of pyrazolo[1,5-a]pyrimidines.

2-Cyanopyrazolo[1,5-a]pyrimidine derivative 3 reacted with some aromatic aldehydes, arenediazonium salts, hydrazine hydrate, and guanidine hydrochloride to create a series of novel pyrazolo[1,5-a]pyrimidine derivatives. Spectroscopic data confirmed the structure of the newly synthesized compounds. Some target compounds were tested in vitro for anticancer efficacy against three cancer cell lines: HepG-2, MCF-7, and Hela. On the most efficient anticancer compounds 6b,c, 6f, and 6h,i, the CDK-2 enzyme was evaluated. Using the HepG-2 cancer cell line, compounds 6b and 6i demonstrated the most effective inhibitory activity against CDK-2, with IC50 values of 0.199 ± 0.005 μg/ml and IC50 = 0.206 ± 0.007 μg/ml, respectively, compared to Dinaciclib and Roscovitine, which had IC50 values of 0.021 ± 0.002 and 0.230 ± 0.007 μg/ml, respectively. In cell cycle assay, compounds 6b, 6f and 6i arrest cell cycle at G2/M, G1/S and G2/M phases, respectively. Compound 6f has a stronger apoptosis induction effect (27.82%) than compounds 6b (7.92%) and 6i (19.21%). Also, silico studies (Molecular docking and Lipinski's rules) for compounds 6b, 6f and 6i were carried out. [ABSTRACT FROM AUTHOR]