Design and Synthesis of Benzimidazole Core Moieties and Structure Activity Relationship Studies Based on In Vitro Evaluation as Anticancer Drugs

Abstract

We have combined the structural artifacts of benzimidazole with quinazoline and purine moieties to make a hybrid and substituted them with different secondary and primary amines in order to observe the effect of electron-donor and acceptor nitrogen groups within the moieties. Introduction of allyl and butyl groups at 1- or 3-position of benzimidazole were also increase lipid solubility of polar compounds, a character very much needed for the activity. Characterizations of these molecules were done with different spectroscopic techniques such as NMR, IR, mass spectrocopy and X-ray crystallography. These synthesized molecules were evaluated in vitro over 60 human cancer cell lines and Aurora A kinase inhibition. SAR and QSAR studies were used to identify the structural features required for the antitumor properties of these new hybrid series. In order to have an insight into the molecular interaction of compounds, their dockings were studies for determine the mode of interactions of compound with amino acids in the active site of the enzyme. We have also reported the first one pot palladium catalysed hydroxylation at C4 position and subsequent arylation at C2 position of 2,4-dichloroquinazoline with variety of boronic acids.