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

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

  • Bioorg Med Chem Lett. 2017 Aug 15;27(16):3643-3646. doi: 10.1016/j.bmcl.2017.07.023.
Zhi Xu 1,  Shu Zhang 2,  Xufeng Song 3,  Min Qiang 1,  Zaosheng Lv 4
Affiliations

Affiliations

  • 1 Key Laboratory of Hubei Province for Coal Conversion and New Carbon Materials, Wuhan University of Science and Technology, Hubei, PR China.
  • 2 Pony Testing International Group (Wuhan), Hubei, PR China.
  • 3 Beijing University of Technology, Beijing, PR China.
  • 4 Key Laboratory of Hubei Province for Coal Conversion and New Carbon Materials, Wuhan University of Science and Technology, Hubei, PR China. Electronic address: chemorgchem@126.com.
PMID: 28720502 DOI: 10.1016/j.bmcl.2017.07.023
Abstract

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) H37Rv 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 H37Rv 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 H37Rv. 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.

Keywords

1,2,3-Triazole; Anti-mycobacterial activity; Anti-tubercular activity; Gatifloxacin; Hybrids; Isatin; Structure-activity relationship.

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