Synthesis, Molecular Docking Studies and ADME Properties of Some New Pyrazolo[1,5-a]pyrimidines as Antimicrobial, and Anticancer Agents

Abstract

New antibacterial and anticancer drugs are needed to protect global health. Purine anti-cancer analogs are structurally similar but act differently. In this study, a series of new pyrazolo[1,5-a]pyrimidines 5a-g, 9a-c and pyrazolo[3,4-b]pyridines 15a, b were synthesized to evaluate their in vitro antibacterial efficacy against various microbial species. Pyrazolo[1,5-a]pyrimidine derivatives 5a and 5g showed moderate antibacterial efficacy against Staphylococcus aureus and Bacillus subtilis. In vitro antitumor activity of 5a-g, 9a-c and 15a, b against Lung carcinoma (A-549), promyelocytic Leukemia (HL-60) and breast cancer MCF-7 showed that 5d exhibited significant anticancer activity towards A-549 with IC50 value = 7.19±0.34 µM when compared to cisplatin (IC50=7.48±0.56 µM). The molecular docking study of 5d showed good binding scores in the active site of CK2 and CDK9. The molecule's physicochemical, pharmacokinetic, and drug-like properties were assessed for the synthesized compounds using the SwissADME database. The molecular properties data showed that all compounds obey Veber rule with zero violations, indicating drug-likeliness.