Design, synthesis and in vitro anti-mycobacterial evaluation of gatifloxacin-1H-1,2,3-triazole-isatin hybrids

A set of novel gatifloxacin-1H-1,2,3-triazole-isatin hybrids 6a-1 was designed, synthesized and evaluated for their in vitro anti-mycobacterial activities against M. tuberculosis (MTB) H(37)Rv and MDR-TB as well as cytotoxicity. The results showed that all the targets (MIC: 0.025-3.12 mu g/mL) exhibited excellent inhibitory activity against MTB H37Rv and MDR-TB, but were much more toxic (CC50: 7.8-62.5 mu g/mL) than the parent gatifloxacin (GTFX) (CC50: 125 mu g/mL). Among them, 61 (MIC: 0.025 mu g/mL) was 2-32 times more potent in vitro than the references INH (MIC: 0.05 mu g/mL), GTFX (MIC: 0.78 mu g/mL) and RIF (MIC: 0.39 mu g/mL) against MTB H(37)Rv. The most active conjugate 6 k (MIC: 0.06 mu g/mL) was 16 -> 2048 times more potent than the three references (MIC: 1.0 -> 128 mu/mL) against MDR-TB. Both of the two hybrids warrant further investigations. (C) 2017 Elsevier Ltd. All rights reserved.