Tuberculosis (TB) remains one of the deadliest infectious diseases caused by Mycobacterium tuberculosis (M.tb). It is responsible for significant causes of mortality and morbidity worldwide. M.tb possesses robust defense mechanisms against most antibiotic drugs and host responses due to their complex cell membranes with unique lipid molecules. Thus, the efficacy of existing front-line drugs is diminishing, and new and recurring cases of TB arising from multidrug-resistant M.tb are increasing. TB begs the scientific community to explore novel therapeutic avenues. A precise knowledge of the compounds with their mode of action could aid in developing new anti-TB agents that can kill latent and actively multiplying M.tb. This can help in the shortening of the anti-TB regimen and can improve the outcome of treatment strategies. Natural products have contributed several antibiotics for TB treatment. The sources of anti-TB drugs/inhibitors discussed in this work are target-based identification/cell-based and phenotypic screening from natural products. Some of the recently identified natural products derived leads have reached clinical stages of TB drug development, which include rifapentine, CPZEN-45, spectinamide-1599 and 1810. We believe these anti-TB agents could emerge as superior therapeutic compounds to treat TB over known Food and Drug Administration drugs.
Keywords: TB drug discovery; efflux pumps; multidrug-resistance; natural products; secondary metabolites; tuberculosis.
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