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

Tuberculosis (TB), an infection caused by Mycobacterium tuberculosis, affects nearly one-third of the world’s population. It is estimated that TB infects around ten million people worldwide, with no less than two million fatalities annually. It is one of the treatable infections due to improved diagnostic tools and therapeutic agents. However, the disease remains a threat to humankind due to the emergence of multidrug- and extensively drug-resistant strains of 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. This review aims to report discoveries and updates of antitubercular natural products with minimum inhibitory concentration (MIC) values of less than or 10 µg/mL or 50 µM and selectivity indices of greater than 10. The review discusses 36 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. Rufomycin I, a cyclic heptapeptide from Streptomyces sp., showed potent activity against drug-sensitive and isoniazid-resistant M. tuberculosis H37Rv (MIC < 0.004 µM), surpassing isoniazid (MIC = 0.23 µM), likely by inhibiting ClpC1 transcription. Hapalindole A also displayed strong activity (MIC < 0.6 µM). Current TB drugs have become less effective; therefore, natural products such as hapalindole A and rufomycin I, owing to their potent activity, selectivity, and novelty, are increasingly recognized as potential lead compounds against TB.