Synthesis, Biological Evaluation and Molecular Modeling of Novel Ethyl 2′-Amino-5′-oxo-1′- (4-phenylthiazol-2-yl)-2-(phenylthio)-1′,4′,5′,6′,7′,8′-hexahydro-[3,4′-biquinoline]-3′- carboxylate Derivatives and their Computational Quantum Mechanical Modelling

Abstract

A new series of biquinoline-phenylthiazole hybrids were designed and synthesized by a base-catalyzed cyclocondensation through one-pot multicomponent reaction. All compounds were tested for in vitro antimicrobial and anticancer activities. Enzyme inhibitory activities of all compounds were carried out against FabH and EGFR. Majority of the synthesized compounds displayed promising antimicrobial as well as anticancer activity against used strains and cancer cell lines, respectively. All the compounds were tested for in vitro anticancer activities against two cancer cell lines A549 and Hep G2. Compound 9n (IC50 = 0.09 μM) against EGFR and (IC50 = 1.03 μM) against A549 kinase displayed the most potent inhibitory activity as compared to other member of the series. In the molecular modelling study, compound 9p was bound in to the active pocket of EGFR with two hydrogen bonds and one π-cation interactions having minimum binding energy ΔGb = -8.5626 kcal/mol. For FabH molecule 9u was found to be binding in the active pocket with minimum binding energy of -8.4033 kcal/mol.