Synthesis and biological studies of oxoquinolines: Experimental and theoretical investigations

Abstract

The incorporation of quinolines into drugs is critical for accomplishing important tasks and acting as an active ingredient in a variety of treatments. In the present investigation, N-aryl-7-hydroxy-4-methyl-2-oxoquinoline-1(2H)-carboxamides (5a–c) were prepared substituted coumarin (3) and substituted phenyl ureas (4a–c). The newly synthesized derivatives were characterized by infrared (IR), nuclear magnetic resonance (1H/13C NMR) and mass spectroscopic techniques. The geometric parameters of compounds 5a–c were computed by density functional theoryat the level of B3LYP/aug-cc-pVDZand energies of highest occupied/lowest unoccupied molecular orbitals (HOMO/LUMO) were analyzed. Anticancer activity was tested against 60 NCI cancer cell lines at 10 µM. N-(4-Fluorophenyl)-7-hydroxy-4-methyl-2-oxoquinoline-1(2H)-carboxamides (5a) showed the most promising anticancer activity against HOP-92, UO-31, CAKI 1, and PC-3 with percent growth inhibitions (%GIs) of 22.77, 21.30, 8.04, and 5.42, respectively. This compound also exhibited promising antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay with an IC50 value of 15.06 ± 1.01 µM. In order to rationalize the anticancer activity of the synthesized compounds, molecular docking study was performed with epidermal growth factor receptor (EGFR) using AutoDock Vina program. Docked ligands 5a–c efficiently bound to the active site of the EGFR. Key interacting residues affording polar interactions include Met793 and Asp855 whereas Leu718, Phe723, Val726 and Leu844 were involved in hydrophobic contacts with the receptor.