2. Academic Validation
  3. Synthesis and biological evaluation of moxifloxacin-acetyl-1,2,3-1H-triazole-methylene-isatin hybrids as potential anti-tubercular agents against both drug-susceptible and drug-resistant Mycobacterium tuberculosis strains

Synthesis and biological evaluation of moxifloxacin-acetyl-1,2,3-1H-triazole-methylene-isatin hybrids as potential anti-tubercular agents against both drug-susceptible and drug-resistant Mycobacterium tuberculosis strains

  • Eur J Med Chem. 2019 Oct 15:180:648-655. doi: 10.1016/j.ejmech.2019.07.057.
Feng Gao 1,  Zijian Chen 1,  Long Ma 1,  Yilei Fan 2,  Linjun Chen 3,  Guangming Lu 4
Affiliations

Affiliations

  • 1 Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China.
  • 2 SUMHS-SHUANG JIA Institute of Emergency Medical Rescue Technology, Shanghai University of Medicine and Health Sciences, Shanghai, PR China.
  • 3 SUMHS-SHUANG JIA Institute of Emergency Medical Rescue Technology, Shanghai University of Medicine and Health Sciences, Shanghai, PR China. Electronic address: chenlj@sumhs.edu.cn.
  • 4 Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. Electronic address: cjr.luguangming@vip.163.com.
PMID: 31352245 DOI: 10.1016/j.ejmech.2019.07.057
Abstract

Herein, synthesis and biological evaluation of fourteen moxifloxacin-acetyl-1,2,3-1H-triazole-methylene-isatin hybrids as potential anti-tubercular agents against both drug-susceptible (MTB H37Rv), rifampicin-resistant and multidrug-resistant Mycobacterium tuberculosis strains were reported, and cytotoxicity towards VERO cells as well as inhibitory activity against MTB DNA gyrase were also discussed in this paper. The structure-activity relationship and structure-cytotoxicity relationship demonstrated that substituents on the C-3 and C-5/C-7 positions of isatin framework were closely related with the anti-mycobacterial activity and cytotoxicity. The most active hybrids 8h and 8l (MIC: 0.12-0.5 μg/mL) showed excellent activity which was no inferior to the parent moxifloxacin against the tested drug-susceptible, rifampicin-resistant and multidrug-resistant Mycobacterium tuberculosis strains, demonstrating their potential application as novel anti-tubercular candidates.

Keywords

1,2,3-Triazole; Anti-tubercular; Drug-resistant Mycobacterium tuberculosis; Isatin; Moxifloxacin; Structure-activity relationship; Structure-cytotoxicity relationship.

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