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 H(37)Rv and MDR-MTB with MIC of 0.12 to 32 mu g/ mL, and acceptable cytotoxicity in VERO cells (CC50: 8.0- > 128.0 mu g/mL). In particular, the most active hybrid 7a (MICMTB (H37Rv): 0.5 mu g/mL and MICMDR-MTB: 0.12 mu g/mL) had the activity in the same level with the first-line anti-tubercular agents isoniazid (MIC: 0.12 mu g/mL) and rifampicin (MIC: 0.25 mu g/mL), and it was 2-fold more active than the parent ciprofloxacin (MIC: 1.0 mu g/mL) against MTB H(37)Rv, and > 16 folds more potent than ciprofloxacin (MIC: 2.0 mu g/mL), isoniazid (MIC: > 64 mu g/mL) and rifampicin (MIC: > 64 mu g/mL) against MDR-MTB. Moreover, hybrid 7a (CC50: 16.0 mu g/mL) also displayed considerable cytotoxicity towards VERO cells. Thus, hybrid 7a could act as a platform for further investigations.