Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China.
SUMHS-SHUANG JIA Institute of Emergency Medical Rescue Technology, Shanghai University of Medicine and Health Sciences, Shanghai, PR China.
Eur J Med Chem. 2019 Oct 15;180:648-655. doi: 10.1016/j.ejmech.2019.07.057. Epub 2019 Jul 22.
Herein, synthesis and biological evaluation of fourteen moxifloxacin-acetyl-1,2,3-1H-triazole-methylene-isatin hybrids as potential anti-tubercular agents against both drug-susceptible (MTB HRv), rifampicin-resistant and multidrug-resistant Mycobacterium tuberculosis strains were reported, and cytotoxicity towards VERO cells as well as inhibitory activity against MTB DNA gyrase were also discussed in this paper. The structure-activity relationship and structure-cytotoxicity relationship demonstrated that substituents on the C-3 and C-5/C-7 positions of isatin framework were closely related with the anti-mycobacterial activity and cytotoxicity. The most active hybrids 8h and 8l (MIC: 0.12-0.5 μg/mL) showed excellent activity which was no inferior to the parent moxifloxacin against the tested drug-susceptible, rifampicin-resistant and multidrug-resistant Mycobacterium tuberculosis strains, demonstrating their potential application as novel anti-tubercular candidates.
本文报道了合成和生物评价十四种莫西沙星-乙酰基-1,2,3-1H-三唑-亚甲酰基靛红杂合体作为潜在的抗结核药物，针对耐药（MTB HRv）、利福平耐药和多药耐药结核分枝杆菌菌株，并讨论了对 VERO 细胞的细胞毒性以及对 MTB DNA 回旋酶的抑制活性。结构-活性关系和结构-细胞毒性关系表明，靛红骨架的 C-3 和 C-5/C-7 位取代基与抗分枝杆菌活性和细胞毒性密切相关。最活跃的杂合体 8h 和 8l（MIC：0.12-0.5μg/mL）表现出优异的活性，与测试的药敏、利福平耐药和多药耐药结核分枝杆菌菌株的母体莫西沙星相当，表明它们有作为新型抗结核候选药物的潜力。
