Anti-tubercular activity and molecular docking studies of indolizine derivatives targeting mycobacterial InhA enzyme

A series of 1,2,3-trisubstituted indolizines (2a–2f, 3a–3d, and 4a–4c) were screened for in vitro whole-cell anti-tubercular activity against the susceptible H37Rv multidrug-resistant (MDR) Mycobacterium tuberculosis (MTB) strains. Compounds 2b–2d, 4a–4c active H37Rv-MTB strain with minimum inhibitory concentration (MIC) ranging from 4 to 32 µg/mL, whereas 4a–4c, ethyl ester group at 4-position benzoyl ring also exhibited anti-MDR-MTB (MIC = 16–64 µg/mL). In silico docking study revealed enoyl-acyl carrier protein reductase (InhA) anthranilate phosphoribosyltransferase as potential molecular targets indolizines. The X-ray diffraction analysis compound 4b was carried out. Further, a safety (in vitro) demonstrated no toxicity these compounds. Thus, warrant further development may represent novel promising class InhA inhibitors multi-targeting agents combat drug-sensitive drug-resistant MTB