Natural Products with Potent Antimycobacterial Activity (2000-2024): A Review

Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis, affects nearly one third of the world population. It is estimated that TB infects around ten million people worldwide with not less than two million fatalities annually. It is one of the treatable diseases thanks to the development of diagnostic tools and therapeutic agents. However, the disease remains a threat to humankind due to the emergence of multi-and-extensive drug resistance M. tuberculosis. This has driven many researchers to look for new antitubercular medications with better efficacy, safety and affordability. As has always been the case, natural products have provided huge potential as a source of remedies for various infectious and non-infectious diseases. The aim of this review is to report new discoveries and updates pertaining to antitubercular natural products with minimum inhibitory concentration (MIC) values of less than or 10µg/mL or 50 µM and selectivity indices of greater than 10. This review discusses 49 naturally occurring compounds from various classes, isolated from both terrestrial and aquatic organisms, including higher plants and microorganisms. Perusal of the literature reveals that most of these promising compounds are alkaloids, terpenoids, steroids and peptides. The most effective compound against the M. tuberculosis H37Rv sensitive strain was found to be rufomycin I (MIC= 0.02 µM), which outperformed isoniazid (MIC=0.23 µM). It was proposed that this cyclic peptide interferes with protein hemostasis through the transcription of ClpC1, a protein that is crucial to M. tuberculosis hemostasis. Current TB drugs have paradoxically turned out to become less effective; so due to its potent activity, selectivity, and novelty, different natures of products, including hapalindole A and rufomycin I, are now centered as the best leads against TB.