Purine analogs Synthesis, Molecular Docking Studies and ADME Properties of Some New Pyrazolo[1,5-a]pyrimidines and Evaluation of their Antimicrobial and Anticancer Activities as CDK inhibitors

Abstract Cancer and antibacterial resistance threaten global health. Purine anti-cancer analogues are Nucleoside triphosphates and antimetabolites compete for DNA/RNA synthesis. new Pyrazolo[1,5-a]pyrimidine (5a-b) compounds were synthesized to test their antibacterial efficacy in vitro against microbial species, but  give no activity Compared to 4 mg/mL Gentamycin (13mm and 11mm inhibition zones). In vitro antitumor activity of 5a-b against A-549 lung carcinoma and HL-60 promyelocytic Leukemia showed significant CDK2 and CDK9 inhibition (14.40±0.69  and 16.27   ± 0.71 µM, respectively). The SwissADME database assessed the molecule’s pharmacokinetic, drug-like, and physicochemical properties. Drug-likeness is confirmed by all compounds following Veber rule in molecular properties. All compounds had 0.55 bioavailability radar scores. Except for. 5b have one Pain and 3 Brenk alerts. Unlike the 5a, Ninec has no Pain and two Brenk alerts. Thus, CDK2 and CDK9 inhibitors may treat proliferative disorders. these compounds inhibit CDK ENZYME, indicating good digestion. Our study found a powerful novel molecule that could improve anti-tumor treatments.

Keywords Pyrazolo[1,5-a]pyrimidine; Antimicrobial activity; Anticancer activity; CDK2; CDK9; A-549 and HL-60 cell line.

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Updated: January 20, 2024 — 7:08 am