A Review on Benzimidazole Scaffolds as Inhibitors of Mycobacterium tuberculosis Mycolyl-arabinogalactan-peptidoglycan Complex Biosynthesis

Abstract

Background: Tuberculosis is one of the oldest known infectious diseases to mankind, caused by Mycobacterium tuberculosis. Although current treatment using first-line anti-tubercular drugs is proven to be effective, an infection caused by resistant strains, as in multidrug-resistant and extensive drug- resistant tuberculosis is still an impending challenge to treat.

Objective: Our objective is to focus on reporting benzimidazole derivatives that are targeting mycobacterial membrane biosynthesis, particularly the mycobacterial mycolyl-arabinogalactanpeptidoglycan complexes. From the literature survey, it has been noted that targeting Mycobacterium tuberculosis cell membrane biosynthesis is an effective approach to fight against drug resistance in tuberculosis.

Methods: Articles on benzimidazole derivatives as inhibitors of proteins responsible for the biosynthesis of the mycobacterial mycolyl-arabinogalactan-peptidoglycan complex have been selected.

Results: By reviewing the anti-tubercular activity of the reported benzimidazole derivatives, we have concluded that a correlation between benzimidazole derivatives and their biological activity is found. It has been noted that benzimidazole derivatives with substitution at N1, C2, C5, and C6 positions have shown a greater affinity towards target proteins.

Conclusion: Even though scientific advancement toward the prevention of tuberculosis has been quite significant in the past few decades, infection caused by resistant strains is a major concern. We have collected data on benzimidazole derivatives that inhibit the biosynthesis of mycolic acid, arabinogalactan and, peptidoglycan. From our observations, we conclude that majority of the molecules have given anti-tubercular activity in nanomolar range. Still there are few mycobacterial membrane biosynthesis proteins where benzimidazole as an inhibitor has yet to be explored.

Keywords: Tuberculosis; anti-tubercular; arabinogalactan; benzimidazole; mAGP; mycolic acid; peptidoglycan.