A Review On Current Status Of ATP Synthase Inhibitors As Anti-Tuberculosis Agents

Abstract

Tuberculosis (TB) remains a global health crisis, aggravated by multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis. Traditional therapies are losing efficacy, highlighting the urgent need for novel drug targets. The mycobacterial ATP synthase, essential for energy metabolism in both replicating and dormant bacilli, has emerged as a promising target. Inhibitors such as diarylquinolines (e.g., bedaquiline), along with novel quinolines, squaramides, and imidazo[1,2-a]pyridine ethers, demonstrate potent activity and offer structural diversity for drug development. These advances underscore ATP synthase inhibition as a paradigm shift in TB chemotherapy, enabling more effective strategies against resistance.