与铁载体结构相似的小分子作为抗结核分枝杆菌和鼠疫耶尔森菌的新型抗菌剂。
Small molecules with structural similarities to siderophores as novel antimicrobials against Mycobacterium tuberculosis and Yersinia pestis.
作者信息
Stirrett Karen L, Ferreras Julian A, Jayaprakash Venkatesan, Sinha Barij N, Ren Tao, Quadri Luis E N
机构信息
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
出版信息
Bioorg Med Chem Lett. 2008 Apr 15;18(8):2662-8. doi: 10.1016/j.bmcl.2008.03.025. Epub 2008 Mar 18.
Abstract
Drugs inhibiting the iron scarcity-induced, siderophore-mediated iron-scavenging systems of Mycobacterium tuberculosis (Mtb) and Yersinia pestis (Yp) may provide new therapeutic lines of defense. Compounds with structural similarities to siderophores were synthesized and evaluated as antimicrobials against Mtb and Yp under iron-limiting conditions, which mimic the iron scarcity these pathogens encounter and must adapt to in the host, and under standard iron-rich conditions for comparison. New antimicrobials were identified, some of which warrant exploration as initial leads against potentially novel targets and small-molecule tools to assist in the elucidation of targets specific to iron-scarcity adapted Mtb and Yp.
摘要
抑制结核分枝杆菌（Mtb）和鼠疫耶尔森菌（Yp）铁缺乏诱导的、铁载体介导的铁清除系统的药物可能提供新的治疗防线。合成了与铁载体结构相似的化合物，并在铁限制条件下评估其对Mtb和Yp的抗菌活性，铁限制条件模拟了这些病原体在宿主体内遇到并必须适应的铁缺乏情况，同时在标准富铁条件下进行比较以作对照。鉴定出了新的抗菌剂，其中一些值得作为针对潜在新靶点的初始先导物以及用于协助阐明适应铁缺乏的Mtb和Yp特异性靶点的小分子工具进行探索。
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