抗结核辅助疗法：针对结核分枝杆菌能量代谢的 2-氨基噻唑的发现。
Adjuvant therapies against tuberculosis: discovery of a 2-aminothiazole targeting Mycobacterium tuberculosis energetics.
机构信息
Global Health & Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Lisboa, Portugal.
P4T group, Department of Food & Drug, University of Parma, Parco Area delle Scienze 27/A, Parma, Italy.
出版信息
Future Microbiol. 2018 Sep;13:1383-1402. doi: 10.2217/fmb-2018-0110. Epub 2018 Sep 27.
AIM
To evaluate the activity of the 2-aminothiazole UPAR-174 following an unexplored approach: targeting Mycobacterium tuberculosis with lipophilic compounds that present antituberculosis and efflux inhibitory activity.
METHODS
Antituberculosis activity was assessed against replicating, nonreplicating and intracellular bacilli. Its capacity to inhibit active efflux was determined. ATP quantification and membrane potential analysis were performed. Intracellular activity was studied on human-monocyte-derived macrophages.
RESULTS
UPAR-174 is an efflux inhibitor active against replicating, nonreplicating and intracellular M. tuberculosis. It dissipates the membrane potential and causes ATP depletion.
CONCLUSION
Targeting M. tuberculosis with lipophilic efflux inhibitors, exploring their dual activity - dissipation of the proton motive force and efflux inhibition - represents an attractive strategy to fight against drug-resistant tuberculosis.
目的
采用一种尚未探索的方法评估 2-氨基噻唑 UPAR-174 的活性：用具有抗结核和外排抑制活性的亲脂性化合物靶向结核分枝杆菌。
方法
评估了复制、非复制和细胞内分枝杆菌对抗结核活性。测定其抑制主动外排的能力。进行了 ATP 定量和膜电位分析。在人单核细胞衍生的巨噬细胞中研究了细胞内活性。
结果
UPAR-174 是一种针对复制、非复制和细胞内结核分枝杆菌的外排抑制剂。它会使膜电位去极化并导致 ATP 耗竭。
结论
用亲脂性外排抑制剂靶向结核分枝杆菌，探索其双重活性——质子动力势耗散和外排抑制——代表了一种有吸引力的策略，可以对抗耐药性结核病。
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