Xu Zhi, Zhang Shu, Song Xufeng, Qiang Min, Lv Zaosheng
Key Laboratory of Hubei Province for Coal Conversion and New Carbon Materials, Wuhan University of Science and Technology, Hubei, PR China.
Pony Testing International Group (Wuhan), Hubei, PR China.
Bioorg Med Chem Lett. 2017 Aug 15;27(16):3643-3646. doi: 10.1016/j.bmcl.2017.07.023. Epub 2017 Jul 8.
A set of novel gatifloxacin-1H-1,2,3-triazole-isatin hybrids 6a-l was designed, synthesized and evaluated for their in vitro anti-mycobacterial activities against M. tuberculosis (MTB) HRv and MDR-TB as well as cytotoxicity. The results showed that all the targets (MIC: 0.025-3.12μg/mL) exhibited excellent inhibitory activity against MTB HRv and MDR-TB, but were much more toxic (CC: 7.8-62.5μg/mL) than the parent gatifloxacin (GTFX) (CC: 125μg/mL). Among them, 61 (MIC: 0.025μg/mL) was 2-32 times more potent in vitro than the references INH (MIC: 0.05μg/mL), GTFX (MIC: 0.78μg/mL) and RIF (MIC: 0.39μg/mL) against MTB HRv. The most active conjugate 6k (MIC: 0.06μg/mL) was 16->2048 times more potent than the three references (MIC: 1.0->128μg/mL) against MDR-TB. Both of the two hybrids warrant further investigations.
设计、合成了一组新型加替沙星-1H-1,2,3-三唑-异吲哚酮杂合物6a-l，并对其针对结核分枝杆菌（MTB）H37Rv和耐多药结核分枝杆菌的体外抗分枝杆菌活性以及细胞毒性进行了评估。结果表明，所有目标化合物（MIC：0.025 - 3.12μg/mL）对MTB H37Rv和耐多药结核分枝杆菌均表现出优异的抑制活性，但比母体加替沙星（GTFX）（CC：125μg/mL）毒性大得多（CC：7.8 - 62.5μg/mL）。其中，61（MIC：0.025μg/mL）在体外针对MTB H37Rv的活性比参考药物异烟肼（INH，MIC：0.05μg/mL）、加替沙星（GTFX，MIC：0.78μg/mL）和利福平（RIF，MIC：0.39μg/mL）高2 - 32倍。活性最高的共轭物6k（MIC：0.06μg/mL）针对耐多药结核分枝杆菌的活性比三种参考药物（MIC：1.0 - 128μg/mL）高16 -> 2048倍。这两种杂合物都值得进一步研究。
