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Life sciences · Journal article
Arabian Journal of Chemistry · September 26, 2026
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Tuberculosis (TB) is a severe airborne infectious disease caused by Mycobacterium tuberculosis ( M. tb ), primarily impacting the lungs and other organs. Antimicrobial resistance in TB is an emerging problem that requires immediate treatment and management. It is difficult to cure tuberculosis as there are increasing cases of multidrug resistant and extensively drug resistant tuberculosis. It is essential to develop a new generation of anti-tubercular medications to address the growing challenge of drug resistant tuberculosis and minimize resistance. The survival and pathogenicity of Mycobacterium species, including Mycobacterium tuberculosis, depend heavily on mycolic acids, which are vital parts of the mycobacterial cell wall. Targeting the biosynthesis of mycolic acid has proven to be a promising approach for developing anti-tubercular agents. Among various scaffolds, indole-based small molecules have garnered significant attention due to their structural versatility, drug-likeness, and potential to disrupt key enzymatic pathways involved in mycolic acid synthesis. This review provides a comprehensive analysis of recent progress in the design, synthesis, and biological evaluation of indole derivatives as inhibitors of mycolic acid biosynthetic enzymes, focusing on key targets such as β-ketoacyl-ACP synthase (KasA/B) and the fatty acid synthase (FAS-I and FAS-II) systems. Furthermore, the potential of indole-based scaffolds to overcome existing drug resistance mechanisms is discussed, providing a promising avenue for the creation of novel therapeutics against tuberculosis. This review underscores the importance of indole chemistry in mycobacterial research and aims to inspire future work in this critical domain.