Synthesis, Characterization, Molecular Docking and Biological Evaluation of 1,4-Bis(aryl-1H- 1,2,3-triazole-4yl)methoxy)benzaldehyde Derivatives as Potential Anticancer Agents

Abstract

A series of novel analogues of 1,4-bis((aryl-1H-1,2,3-triazole-4-yl)methoxy)benzaldehydes were synthesized efficiently by click reaction via conventional method using 2,4-dipropyloxy benzaldehyde and aryl azides characterized by spectroscopic methods including 1H NMR, 13C NMR, mass and IR spectrometry. Comparative molecular docking studies were carried out for all the synthesized compounds (4a-l) using cancer therapeutics levatinib and vandetanib targeting the VEGFR2 protein’s active region using the Glide tool in the Schrödinger suite. Among these, compounds 4b, 4f and 4h showed better drug likeness functions than current cancer inhibitors of VEGFR2 protein. Furthermore, to determine ADME and toxicity properties, the pkCSM server and the QikProp module were used. Glide scores and binding free energy analyses were used to determine the lead molecules. Compounds 4b, 4f and 4h revealed from docking exhibited potential in vitro cytotoxic activity against both MCF7 and HepG2 cell lines.