Abstract
In the present work, new benzimidazole linked 1,2,3-triazole hybrids have been synthesized and screened for antiproliferative and EGFR kinase inhibitory activities. The structures of these hybrids were elucidated using IR, NMR, mass spectrometry and elemental analysis. Most of the tested compounds exerted significant cytotoxicity against MCF-7, HCT-116 and HepG2 cell lines. Among these, compound 2-(4-{[4-(1H-benzimidazol-2-yl)-2-methoxyphenoxy]methyl}-1H-1,2,3-triazol-1-yl)benzoic acid(5e) was the best candidate towards all the tested cell lines with IC50 in the range 1.49-2.35 mu M, comparable to doxorubicin (IC50 1.45-2.12 mu M) and inhibited EGFR with IC(50)0.52 mu M. The structural properties of the synthesized hybrids were performed using DFT methods at the B3LYP/6-311 ++ G (d,p) level of theory. The frontier molecular orbitals (FMO), chemical reactivity, molecular electrostatic potential (MEP) and docking studies were performed to investigate interaction behavior of our hybrids with the EGFR active site. The hybrids with highest biological activity displayed highest binding interactions into active site. (C) 2021 Elsevier B.V. All rights reserved.