Quinones as antimycobacterial agents.
Quinones as antimycobacterial agents.
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醌类作为抗分枝杆菌剂。
DOI：
10.1016/j.bmc.2004.07.015
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Primm,ToddP
中科院分区：
文献类型：
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作者：
Tran,Thuyanh;Saheba,Ekta;Arcerio,ArianaV;Chavez,Violeta;Li,Qing-Yi;Martinez,LuisE;Primm,ToddP
结核分枝杆菌是一种严重的全球性健康威胁，每年造成近300万人死亡。其他分枝杆菌物种，特别是鸟分枝杆菌，是免疫功能低下人群中的新兴病原体，最明显的是艾滋病患者。这些非结核分枝杆菌（NTM）在环境中普遍存在，并且对许多消毒程序具有天然抗性。治疗选择有限，自20世纪70年代以来，没有开发出针对分枝杆菌的新抗生素。迫切需要新的杀生物剂和抗生素来预防和治疗分枝杆菌感染。已经筛选了一个小的芳香族化合物文库，用于生长抑制或杀死分枝杆菌的有效性。4个种，代表M.使用结核复合体、缓慢生长的NTM和快速生长的NTM。活性化合物具有低至12.5μg/mL的最小抑制浓度，其中活性组分为醌。观察到的主要杀菌活性代表了独特的作用机制。用荧光法测定M.作为预测抑制活性的快速测定法，分析表达GFP的smeglycoprotein，但不能很好地预测活性。我们的化合物可能具有重要的效用，作为可溶性杀生物剂对分枝杆菌和其他哈代医院病原体。
Mycobacterium tuberculosis is a serious worldwide health threat, killing almost 3 million people per year. Other mycobacterial species, especially Mycobacterium avium, are emerging pathogens in the immunocompromised population, most notably AIDS patients. These nontuberculous mycobacteria (NTM) are ubiquitous in the environment, and naturally resistant to many disinfection procedures. Treatment options are limited, and no new antibiotics have been developed against mycobacteria since the 1970s. There is a desperate need for new biocides and antibiotics to prevent and treat mycobacterial infections. A small aromatic compound library has been screened for effectiveness in growth inhibition or killing of mycobacteria. Four species, representing the M. tuberculosis complex, the slow-growing NTM, and the rapid-growing NTM were used. Active compounds had minimal inhibitory concentrations as low as 12.5μg/mL, with the active component being a quinone. The primarily bactericidal activity observed represents a unique mechanism of action. A fluorescent assay involving M. smegmatis expressing gfp was analyzed as a rapid assay for predicting inhibitory activity, but failed to predict activity well. Our compounds may have significant utility as soluble biocides against mycobacteria and other hardy nosocomial pathogens.