Investigation of Quinoline-based (4-oxo-1,4-dihydroquinolin-2-yl) methyl nitrate derivatives: Synthesis, Anti-cancer activity, Nitric oxide release and Molecular docking studies

This study synthesized and evaluated substituted (4-oxo-1,4-dihydroquinolin-2-yl) methyl nitrate derivatives to identify those with strong anticancer activity and nitric oxide (NO) release. This study aimed to synthesize and evaluate a series of substituted (4-oxo-1,4-dihydroquinolin-2-yl) methyl nitrate derivatives to determine their efficacy in nitric oxide release, binding affinity to EGFR tyrosine kinase, and anticancer activity against non-small cell lung cancer (A-549) and pancreatic cancer (PANC-1) cell lines. Substituted derivatives were synthesized through a multi-step chemical process involving reactions with boron trichloride, chloroacetyl chloride, and silver nitrate. The synthesized compounds were characterized using analytical methods. Molecular docking studies were performed to assess binding affinities to EGFR tyrosine kinase (PDB ID: 4HJO). Nitric oxide release was measured using the Griess method in adherent cells. Anticancer activity was evaluated through IC50 assays in A-549 and PANC-1 cell lines, and selectivity indices were calculated to determine the compounds’ preference for cancerous cells over normal cells. Molecular docking revealed compounds 6h (-4-OH), 6c (-4-Br), and 6e (-4-CH3) as having strong binding affinities to EGFR tyrosine kinase. In NO release assays, 6h showed the highest NO production (49.95 μmol/L). Anticancer evaluations identified 6e, 6h, and 6m (-3,4-CH3) as the most effective, with IC50 values of 21.46 ± 1.41 μM, 22.22 ± 1.10 μM, and 24.39 ± 2.39 μM, respectively, and high selectivity indices in both A-549 and PANC-1 cell lines. Compounds 6e, 6h, and 6m showed potent anticancer effects and strong binding to EGFR tyrosine kinase, indicating their potential as leads for further cancer therapy development.