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Design, synthesis and in vitro anti-mycobacterial evaluation of gatifloxacin-1H-1,2,3-triazole-isatin hybrids.
Bioorganic & Medicinal Chemistry Letters 2017 August 16
A set of novel gatifloxacin-1H-1,2,3-triazole-isatin hybrids 6a-l was designed, synthesized and evaluated for their in vitro anti-mycobacterial activities against M. tuberculosis (MTB) H37 Rv and MDR-TB as well as cytotoxicity. The results showed that all the targets (MIC: 0.025-3.12μg/mL) exhibited excellent inhibitory activity against MTB H37 Rv and MDR-TB, but were much more toxic (CC50 : 7.8-62.5μg/mL) than the parent gatifloxacin (GTFX) (CC50 : 125μg/mL). Among them, 61 (MIC: 0.025μg/mL) was 2-32 times more potent in vitro than the references INH (MIC: 0.05μg/mL), GTFX (MIC: 0.78μg/mL) and RIF (MIC: 0.39μg/mL) against MTB H37 Rv. The most active conjugate 6k (MIC: 0.06μg/mL) was 16->2048 times more potent than the three references (MIC: 1.0->128μg/mL) against MDR-TB. Both of the two hybrids warrant further investigations.
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