Review maps indole derivatives targeting mycolic acid enzymes (MmpL3, InhA, KasA/B), their SAR and synthetic routes, and notes most series still lack enzymatic and genetic target validation
This review systematically compiles progress in the design, synthesis, and biological evaluation of indole-based small molecules as antitubercular candidates targeting the mycolic acid biosynthesis pathway (MmpL3, InhA, KasA/KasB), listing per-series optimized-compound MIC values (e.g., compounds 20-22 at 0.0195 µg/mL, compound 36a at 0.024 µM, and compound 82 with MIC50 0.015 µM in the MmpL3 direction; compounds 122a at 0.39 µM and 143f at 3.99 µM in the InhA direction) alongside molecular docking results, and noting that many indole series still lack direct biochemical inhibition data such as purified-enzyme IC50/Ki and genetic validation including resistance mutations or target overexpression.