Design and Synthesis of 2-Arylbenzimidazole Analogues as Novel SIRT1 Activators for the Treatment of Type II Diabetes

Abstract

SIRT1, an NAD + -dependent sirtuin deacetylase, has emerged as potential therapeutic target for treatment of human illnesses such as type II diabetes, cancer, cardiovascular and neurodegenerative diseases. Resveratrol, a naturally occurring small molecule activator of SIRT1, has been demonstrated to improve metabolism and glucose tolerance. SRT1720, an imidazothiazole derivative, recently made as the most potent SIRT1 activator is structurally unrelated to resveratrol. In this work, we design and synthesize a series of compounds as novel potential SIRT1 activators through a two-step convenient synthetic procedure. Fourteen 2-Arylbenzimidazole analogues were characterized on the basis of 1 H NMR spectra. Tests for biological activity of these compounds are underway.