Benzylsulfanyl benzo-heterocycle amides and hydrazones as new agents against drug-susceptible and resistant <i>Mycobacterium tuberculosis</i>.
Lu X, Hu X, Liu Z, Zhang T, Wang R, Wan B, Franzblau SG, You Q.
A series of benzylsulfanyl benzo-heterocycle amides and hydrazones were synthesized and evaluated for anti-tubercular activities. The isonicotinyl hydrazone derivatives <b>12d</b>, <b>12e</b> and <b>12f</b> exhibited good anti-tubercular activity against <i>Mycobacterium tuberculosis</i> H<sub>37</sub>Rv (ATCC #27294) with MIC values of 0.23, 0.24 and 0.24 μM, respectively, and were also active against SDR-TB, MDR-TB and XDR-TB. More importantly, compound <b>12e</b> also showed low cytotoxicity and good metabolic stability, and could significantly reduce the mycobacterial burden in a mouse model infected with autoluminescent H37Ra strain, which may serve as a lead compound for further development.