Palladium-Catalyzed Aryl C-H Activation and Tandem ortho-Hydroxylation/Alkoxylation of 2-Aryl Benzimidazoles: Cytotoxicity and DNA-Binding Studies

摘要

An efficient regio-selective aryl C—H activation and tandem o-hy-droxylation method for 2-arylbenzimi-dazoles has been developed by using a Pd(OAc)2/oxone/Cs2CO3 catalytic system. This reaction was successfully optimized by using various catalysts, oxidants, bases, and solvents to achieve the desired products in good yields. Further, preliminary mechanistic studies were conducted to examine the source of oxygen for this transfor-mation. Gratifyingly, this catalytic system is also suitable for the introduction of various alkoxy groups, and delivered the products in good yields. The synthesized compounds were evaluated for their cytotoxic activity in selected human cancer cell lines. Some of the representative compounds (1 f, 2 f, 3 f and 4 f) have significant IC_(50) values ranging from 1-10 um. Structure-activity relationship studies indicate that in these com-pounds the ethoxy substituent is probably responsible for the improved activity. In addition, the DNA-binding potential of these compounds was also investigated by UV/vis, fluorescence, and circular dichroism spectroscopy.