Synthesis, biological evaluation and molecular docking of pyrimidine and quinazoline derivatives of 1,5-benzodiazepine as potential anticancer agents

Abstract

A new series of Pyrimidine (A, D and F) and quinazoline (B, C and E) analogues of 1,5-benzodiazepines were prepared via its nitrile-derived amidoximes in and nitrilium ions, respectively using one pot Domino reaction with DMAD in presence of DABCO catalyst and benzanilide in presence of Tf2O and 2-chloropyridine. The prepared molecules were examined for their biological property namely apoptotic and antiproliferative effects through cell cycle arrest using breast cancer cell line of human (MCF-7). Receptor-ligand interactions were studied on human epidermal evolution factor receptor (HER-2) with the help of molecular docking using Autodock 4.2.6 molecular modeling software. All the compounds demonstrated inhibitory effects on cell proliferation in a concentration dependent fashion (20–100 μg/mL). Notably, compound C exhibited highest inhibitory activity and caused inhibition of S and G2 phase in cell cycle arrest via caspase dependent apoptotic pathway in MCF-7 cells lines.