Inhibitors of type II NADH-dehydrogenase, cytochrome bd oxidase, and ATP synthase for anti-tubercular response

The identification of novel anti-tubercular agents capable of eliciting lethal responses against drug-resistant tuberculosis is critically needed to address the escalating mortality from tuberculosis. Mycobacterium tuberculosis, the etiological agent of this disease, employs a highly efficient energy-producing machinery, the oxidative phosphorylation pathway. Mycobacterium can withstand extreme environmental conditions due to the robust functionality of this multicomponent pathway, which satisfies its energy requirements, during both the persistent phase under stress and the active growth phase. Considering the significance of this biological pathway, in this review we described the dynamics of oxidative phosphorylation and the rationale for targeting its essential components. Furthermore, we provide a comprehensive overview of literature-reported inhibitors, targeting key elements of this pathway, namely, type II NADH dehydrogenase, cytochrome-bd oxidase, and ATP synthase.