Synthesis, characterization and molecular docking studies of highly selective new hydrazone derivatives of anthranilic acid and their ring closure analogue Quinazolin-4(3H)-ones against lung cancer cells A549

Abstract

In this study, new Schiff bases derived from anthranilic acid hydrazide (3a-j) and quinazolin-4(3H)-one (4a-j) were synthesized with high yields (99-90%) and characterized by FTIR, NMR (1H and 13C), and HRMS spectroscopic techniques. The effects of the synthesized compounds on the human lung adenocarcinoma cells (A549, CCL-185, ATCC) and the human bronchial epithelial cells (BEAS-2B, ECACC) were examined. IC50 values of the compounds were found in the range of 12.40 – 424.9 µM against A549 and 15.81 – 752.30 µM against BEAS-2B cell lines. Compounds 3i, 3j, 4b, and 4f are the most active compounds in the series, with low IC50 values against A549, high against BEAS-2B, and high selectivity. For the most active compounds in the series, molecular docking study was performed to understand ligand-protein interactions between the compounds and Epidermal Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor Receptor (VEGFR1). The docking scores were calculated in the range of -5.870 – -6.711 kcal/mol for EGFR and -4.142 – -8.501 kcal/mol for VEGFR1.