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
  • 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: [email protected].
  • 4. Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China. Electronic address: [email protected].
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.