Scandium triflate-catalyzed synthesis of novel azo-fused benzo[4,5]thiazolo[2,3-b]quinazolin-1-ones: bridging molecular docking, DFT insights, and anticancer applications

Abstract

A novel series of azo-fused benzo[4,5]thiazolo[2,3-b]quinazolin-1-one derivatives were synthesized through the reaction of aryl azo salicylaldehydes, dimedone, and 2-aminobenzothiazole, utilizing scandium triflate as a catalyst under reflux conditions in an environmentally friendly solvent, ethanol. The synthesized compounds were characterized successfully by spectroscopic techniques, such as FT-IR, NMR and ESI-MS. Molecular docking studies unveiled significant interactions with cancer-associated proteins, emphasizing their potential as therapeutic candidates. Computational investigations, employing DFT and TD-DFT methodologies with the B3LYP/6-31+G** basis set, provided insights into frontier molecular orbital energies, dipole moments, vibrational frequencies, and NMR parameters. Preliminary in vitro anticancer assays against a selected cancer cell line demonstrated promising cytotoxicity, reinforcing their potential as lead compounds for further optimization. This study synergizes experimental synthesis, computational analysis, and biological evaluation, offering a holistic perspective on these novel scaffolds for applications in medicinal chemistry.