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

• Published in: Bioorganic & medicinal chemistry letters 2019-09, Vol.29 (18), p.2635-2637
• Main Authors: Chen, Rongxing, Zhang, Hao, Ma, Tianwei, Xue, Huarui, Miao, Zhong, Chen, Liyan, Shi, Xiangkui
• Format: Article
• Language: English
• Subjects: 1,2,3-triazole; Anti-mycobacterial; Anti-tubercular; Ciprofloxacin; Drug-resistant; Isatin
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2019.07.041

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 and in vivo anti-mycobacterial activity as well as cytotoxicity in VERO cells. Among them, the most active hybrid 7a was no inferior to the first-line anti-TB agents isoniazid, rifampicin, and the parent ciprofloxacin against the tested strains in vitro. The enriched structure-activity relationship may help global efforts for identification of new chemical entities as potent anti-TB agents. [Display omitted] •The novel hybrids 7a-l showed considerable antimycobacterial activity.•Hybrid 7a was no inferior to the first-line anti-TB.•The SAR and structure-cytotoxicity relationship were discussed. 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 (MICMTB H37Rv: 0.5 μg/mL and MICMDR-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.