Design, Synthesis, Computational, and In Vitro Cytotoxic Potential of Novel 5,7,8,9-Tetrahydrotetrazolo[5,1-b]quinazolines Analogs

Objective: Quinazolines and condensed quinazolines got a significant role to be treated as the pharmacophore nucleus for various diseases by acting on selected targets, cancer therapeutics is one of such ailments. By considering the importance of this privileged scaffold, some novel tetrazolo [5,1-b]quinazolines (Va–Vh) and (VIa–VIh) were designed and screened computationally for drug likeness properties. Methods: The selected compounds were synthesized and later were evaluated for in vitro anticancer activity on the human cervical carcinoma cell lines by MTT assay. Later the compounds were subjected for the molecular docking analysis on the matrix metalloproteinase 9 (PDB ID: 1GKC) and dihydroorotase (PDB ID: 2EG7). Results and Discussion: The compounds were found to possess good anticancer properties with IC₅₀ value of 1.21 ± 0.10 to 6.32 ± 0.32 µM, some of the compounds were found to be more active than the standard drug, methotrexate. Conclusions: The same pattern has been observed in the docking study too, where the compounds were binding effectively to the two proteins studied.