Azide-alkyne cycloaddition towards 1H-1,2,3-triazole-tethered gatifloxacin and isatin conjugates: Design, synthesis and in vitro anti-mycobacterial evaluation

作者：Xu, Zhi; Song, Xu-Feng; Hu, Yuan-Qiang; Qiang, Min; Lv, Zao-Sheng^*

来源：European Journal of Medicinal Chemistry, 2017, 138: 66-71.

DOI：10.1016/j.ejmech.2017.05.057

• Gatifloxacin
• Isatin
• Triazole
• Conjugates
• Anti-tuberculosis activity
• Anti-mycobacterial activity
• Structure-activity relationship

Twelve novel 1H-1,2,3-triazole-tethered gatifloxacin (GTFX) isatin conjugates 5a-I with greater lipophilicity compared with GTFX were designed, synthesized and evaluated for their in vitro antimycobacterial activities against M. tuberculosis (MTB) H(37)Rv and MDR-TB as well as cytotoxicity. The preliminary results showed that all the targets (MIC: 0.10-8 mu g/mL) exhibited excellent inhibitory activity against MTB H37Rv and MDR-TB, but eight of them (CC50: 7.8-62.5 gimp were much more toxic than the parent GTFX (CC50: 125,agimL). Among them, 5g (MIC: 0.10 mu g/mL) was 4-8 times more potent in vitro than the references GTFX (MIC: 0.78 mu g/mL) and RIF (MIC: 0.39 mu g/mL) against MTB H37Rv, but less active than INH (MIC: 0.05, mu g/mL). The most potent 5g and 5h (MIC: 0.25 mu g/mL) were 4->512 times more active than the three references (MIC: 1.0->128 mu g/mL) against MDR-TB. Unfortunately, both of the two hybrids (CC50: 7.8 mu g/mL) were much more cytotoxic than the other derivatives, need to be further optimized.

• 出版日期2017-9-29
• 单位湖北工程学院; 北京工业大学; 武汉科技大学