“Triazole-oxadiazole-based schiff bases as potential kinase inhibitors: synthesis, DFT studies, molecular docking and anticancer evaluation”

Abstract

A series of novel (E)-5-methyl-N′-(4-((5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)methoxy)benzylidene)-1-phenyl-1H-1,2,3-triazole-4-carbohydrazide derivatives (11a-j) has been developed using a multi-step synthetic approach. The formation of the synthesized compounds was confirmed using various spectroscopic techniques, including NMR, FTIR, and mass spectrometry. Among the synthesized derivatives, compounds 11a, 11c, 11d, and 11j exhibited notable anticancer activity against the Human Lung Carcinoma (A549) cell line. Additionally, the physicochemical characteristics, including ADMET properties, drug-likeness, and bioactivity scores, were evaluated to assess their pharmacokinetic potential. To gain deeper insights into the electronic behavior of compound 11j, density functional theory (DFT) calculations were performed at the B3LYP/6-31G++(d,p) level to optimize its structure and geometry. The first-order hyperpolarizability was calculated to explore its nonlinear optical properties, while HOMO-LUMO analysis was conducted to elucidate the charge transfer interactions within the molecule. Furthermore, molecular docking studies have also been conducted for the synthesized derivatives against the target protein (PDB ID: 1M17) to assess their binding interactions and potential as kinase inhibitors.