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

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