Experimental and theoretical studies on antituberculosis activity of different benzimidazole derivatives

Tuberculosis (TB) continues to be one of the deadliest infectious diseases with a rapid increase in multidrug-resistant cases. The discovery of new agents against tuberculosis is urgently needed. Thus, the research article focuses on the antituberculosis activity of a series of benzimidazolium compounds. The antituberculosis activities of compounds including benzimidazole core (7a-h) against Mycobacterium tuberculosis H37Rv strain were tested in vitro using the BACTEC MGIT 960 system. The concentrations of benzimidazole compounds were adjusted to range from 0.25 to 4 μg/ml. The antituberculosis interactions of the compounds were investigated by molecular docking and molecular dynamics simulation. The results revealed that only benzimidazolium salt 7h showed antituberculosis activity at MIC value of 2 μg/ml although the other compounds showed no antituberculosis activity. The docking data revealed that 7h could bind to InhA thus indicating its inhibition potential on the enzyme. Molecular dynamics simulation exhibited that 7h formed a stable complex with the enzyme and was able to remain inside the binding region of the enzyme. Besides, the pharmacokinetic and drug-likeness properties of the compounds were assessed through computational approaches. The compounds exhibited drug-like properties. Consequently, 7h could be a good candidate for the development of new TB drugs.