1H-1,2,3-Triazole tethered isatin-moxifloxacin: Design, synthesis and in vitro anti-mycobacterial evaluation.

Abstract

A series of novel 1H-1,2,3-triazole tethered isatin-moxifloxacin (MXF) hybrids 5a-l with greater lipophilicity compared with the parent MXF were designed, synthesized and screened for their in vitro antimycobacterial activities against Mycobacterium tuberculosis (MTB) H37 Rv and multidrug-resistant MTB (MDR-MTB) as well as their cytotoxicity on the VERO cell line. All the synthesized hybrids (MIC: 0.025-0.78 μg/ml) showed considerable activities against MTB H37 Rv and MDR-MTB, and the most active conjugate 5c (MIC: 0.025 and 0.06 μg/ml) was 2 to >2048 times more potent in vitro than the three references MXF (MIC: 0.10 and 0.12 μg/ml), rifampicin (MIC: 0.39 and 32 μg/ml) and isoniazid (MIC: 0.05 and >128 μg/ml) against the two tested strains. All hybrids (CC50 : 4-64 μg/ml) were much more cytotoxic than the parent MXF (CC50: 128 μg/ml), but the most active hybrid 5c (CC50 : 32 μg/ml) also displayed acceptable cytotoxicity, warranting further investigation.