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 (<b>7a-h</b>) against <i>Mycobacterium tuberculosis</i> H37Rv strain were tested <i>in vitro</i> 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 <b>7h</b> showed antituberculosis activity at MIC value of 2 μg/ml although the other compounds showed no antituberculosis activity. The docking data revealed that <b>7h</b> could bind to InhA thus indicating its inhibition potential on the enzyme. Molecular dynamics simulation exhibited that <b>7h</b> 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, <b>7h</b> could be a good candidate for the development of new TB drugs.