Studies on Developing a Preclinical Candidate to Fight Helicobacter Pylori Infection.

Abstract

Helicobacter pylori (H. pylori) infection, a precursor to gastritis and gastric cancer, is one of the many infectious diseases that pose a challenge to the progress of developing nations. The present study is the first report on the development of a set of benzopyridine-fused benzimidazoles, leading to the identification of a lead and its further optimization as a potential preclinical candidate for treating H. pylori infection. The designed synthetic method for these derivatives is devoid of toxic chemicals and sophisticated reaction setups, using economical and readily available chemicals to produce benzopyridine-fused (namely, quinoline/isoquinoline-fused) benzimidazole derivatives in moderate-to-good yields. These small molecules showed promising H. pylori growth inhibition, and a lead molecule was identified and evaluated for its antibacterial potential. Following the promising results of the growth inhibition displayed by this series of inhibitors, lead optimization studies were carried out on the best inhibitor of H. pylori growth, highlighting the possibility of developing this core molecule for preclinical trials.