Potential Inhibitors Targeting M.tb DNA Replication, Transcription, and Translation to Combat Drug Resistance

Introduction: Tuberculosis (TB), often called the “white death,” is a deadly dis-ease that primarily affects the lungs and is caused by the tubercle bacillus, known as Myco-bacterium tuberculosis (M.tb). Multi-drug-resistant tuberculosis is one of the major global health issues to be addressed for improving morbidity and mortality associ-ated with tuberculosis. This study explores key molecular targets in Mycobacterium for developing effective anti-TB drugs, focusing on inhibitors of DNA gyrase, RNA polymer-ase, and aminoacyl-tRNA synthetases, which are central to the M.tb. It highlights drug mech-anisms, resistance mutations, and novel compounds to combat multidrug-resistant tubercu-losis. Methods: The present review has been done using literature published in PubMed, Pub-Chem, and ResearchGate. ChemDraw Pro 8.0 has been used to draw the 2D structure of the chemical compounds. The manuscript has been presented in Microsoft Word and Power-Point. Results: Pharmacological agents targeting the fundamental processes of Mycobacterium tu-berculosis—namely, DNA replication, transcription, and translation—can effectively dis-rupt the bacterial central dogma. By inhibiting these essential protein targets, these com-pounds demonstrate significant potential for treating multidrug-resistant tuberculosis. Discussion: Treatment plan using inhibitors that bind distinct spatial regions of the same target or block alternate pathways can shorten TB treatment and prevent resistance. Conclusion: Emphasizing multitarget therapeutics can enable more effective and sustainable MDR-TB treatments, improving global health outcomes.