Design, synthesis of 4-[2-(substituted phenyl) hydrazono]-3-(1-hydroxyethyl)-1-phenyl/methyl-3,4-dihydroquinolin-2(1H)-one derivatives and evaluation of their in vitro tyrosine kinase inhibitor activity

Abstract

The present investigation deals with molecular docking, synthesis, characterization, and evaluation of in vitro tyrosine kinase inhibitor activity of a series of 4-[2-(substituted phenyl) hydrazono]-3-(1-hydroxyethyl)-1-phenyl/methyl-3,4-dihydroquinolin-2(1 H )-one derivatives {III-a(1-12)/III-b(1-12)}. Molecular docking studies of the title compounds were carried out using Molegro Virtual Docker (MVD-2013, 6.0) software. The MolDock scores of the derivatives ranged from ( − 66.508) to ( − 101.274); whereas the MolDock score of standard 4-anilinoquinazoline ligand was found to be ( − 105.219). Most of the synthesized qunolin-2-one derivatives showed better affinity towards EGFRK protein as compared to standard drug imatinib ( − 104.253). All the synthesized compounds were satisfactorily characterized by physical and spectral analysis (UV, IR, 1 H NMR and 13 C NMR and mass spectral data). Twelve derivatives were tested for their in vitro tyrosine kinase inhibitor activity using MDA-MB cell line. Compound 4-[2-(4-bromophenyl)hydrazono]-3-(1-hydroxyethyl)-1-methyl- 3,4-dihydroquinolin-2(1 H )-one (III-b4) was found to be the most cytotoxic compound as compared to other synthesized derivatives, with IC 50 value of 0.0515 μ M against MDA- MB cell line.