Antiproliferative Activity and Molecular Docking of Some Pyrazole‐Based Quinazolinone, Benzimidazole, and Tetrazinethione Derivatives

Researchers are actively looking for novel anticancer medications because cancer is one of the leading causes of mortality worldwide. A fascinating area of study in medicinal chemistry is the screening of antioxidants for novel anticancer medicines, as antioxidants have lately been used as therapeutic candidates to combat a variety of ailments in aerobic species. Additionally, pyrazole-based heterocycle synthesis is a productive approach to the drug development process. To ascertain the molecular geometry and frontier orbital analysis, a DFT simulation of the produced compounds was conducted. Compound 7 showed the lowest energy gap and hardness, while compound 7 had the maximum softness. Therefore, a few quinazoline, benzimidazole, and tetrazinethione derivatives based on pyrazoles that were synthesized in our earlier work and exhibited antioxidant qualities were tested for their in vitro antiproliferative activity against the MCF7 and HCT116 cancer cell lines. The two cancer cell lines were most effectively inhibited by derivatives of sulfonamide and tetrazinethione. The molecular docking simulation toward CDK2 protein specified the best docking score of tetrazinethione 7 followed by sulfonamide derivative 4, compared to doxorubicin and roscovitine (kinase inhibitor). Most of the amino acids interacting with these compounds were involved in that interaction with the co-crystallized ligand. Their favorable oral bioavailability and drug-likeness characteristics were demonstrated by a modeling pharmacokinetics investigation. This research could help create novel antiproliferative drugs that are both efficient and selective.