Ciprofloxacin-1,2,3-triazole-isatin hybrids tethered via amide: Design, synthesis, and in vitro anti-mycobacterial activity evaluation

The purpose of this study was to prepare various novel amide tethered ciprofloxacin-1,2,3-triazole-isatin hybrids 7a-l, and evaluate their in vitro anti-mycobacterial activity as well as cytotoxicity in VERO cells. The synthesized hybrids showed considerable in vitro activity against both MTB H₃₇Rv and MDR-MTB with MIC of 0.12 to 32 μg/mL, and acceptable cytotoxicity in VERO cells (CC₅₀: 8.0->128.0 μg/mL). In particular, the most active hybrid 7a (MIC_{MTB H37Rv}: 0.5 μg/mL and MIC_MDR-MTB: 0.12 μg/mL) had the activity in the same level with the first-line anti-tubercular agents isoniazid (MIC: 0.12 μg/mL) and rifampicin (MIC: 0.25 μg/mL), and it was 2-fold more active than the parent ciprofloxacin (MIC: 1.0 μg/mL) against MTB H₃₇Rv, and ≥16 folds more potent than ciprofloxacin (MIC: 2.0 μg/mL), isoniazid (MIC: >64 μg/mL) and rifampicin (MIC: >64 μg/mL) against MDR-MTB. Moreover, hybrid 7a (CC₅₀: 16.0 μg/mL) also displayed considerable cytotoxicity towards VERO cells. Thus, hybrid 7a could act as a platform for further investigations.

1,2,3-triazole; Anti-mycobacterial; Anti-tubercular; Ciprofloxacin; Drug-resistant; Isatin.