Pyrrole-Thiazolidin-4-one Analogues Exhibit Promising Anti-Tuberculosis Activity

A series of pyrrole-thiazolidin-4-one conjugates were synthesized and evaluated for their anti-mycobacterial and anti-bacterial activities. Two compounds, 10 a and 10 k, were the most effective conjugates and produced identical MICs (0.5 mu g/mL) against M. tuberculosis H37Rv with a high selectivity index. Upon evaluation against the ESKAP bacteria panel, compound 10 g emerged most effective against S. aureus (MIC=8.0 mu g/mL) while compound 10 o produced activity against A. baumannii (MIC=4.0 mu g/mL). A molecular docking study revealed that the most active compound 10 a has similar binding interactions as those of BM212 and rimonabant, with a comparable docking score against M. tuberculosis mycolic acid transporter MmpL3. This work describes the synthesis, anti-tuberculosis, and antibacterial activities of pyrrole-thiazolidin-4-one conjugates. The best analogue exhibits an MIC of 0.5 mu g/mL against the M. tuberculosis H37Rv strain and also shows promising antibacterial activities. The docking study indicates that the M. tuberculosis mycolic acid transporter MmpL3 is a possible molecular target. image