Bioautography with TLC-MS/NMR for Rapid Discovery of Anti-tuberculosis Lead Compounds from Natural Sources.
Bioautography with TLC-MS/NMR for Rapid Discovery of Anti-tuberculosis Lead Compounds from Natural Sources.
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DOI：
10.1021/acsinfecdis.5b00150
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发表时间：
2016-04-08
影响因子：
5.3
通讯作者：
Jaki BU
中科院分区：
文献类型：
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作者：
Grzelak EM;Hwang C;Cai G;Nam JW;Choules MP;Gao W;Lankin DC;McAlpine JB;Mulugeta SG;Napolitano JG;Suh JW;Yang SH;Cheng J;Lee H;Kim JY;Cho SH;Pauli GF;Franzblau SG;Jaki BU
虽然天然产品构成了一个既定的来源的铅化合物，经典的迭代生物测定引导的分离过程是时间和劳动密集型的，并倾向于无法识别活性次要成分。（HP）TLC-生物自显影-MS/NMR结合了尖端的微生物、色谱和光谱技术，旨在通过在分离过程的早期阶段获取结构信息，加速从天然来源发现抗结核（TB）药物。使用无毒的，生物发光的结核分枝杆菌菌株mc 27000 luxABCDE，生物自显影的三种变化进行了评估和优化的灵敏度检测抗结核药物，包括建立临床代理和新的铅与新的作用机制。该方法在微生物提取物中的几个示例性应用证明了其作为从天然来源发现抗TB药物的常规方法的潜力。
While natural products constitute an established source of lead compounds, the classical iterative bioassay-guided isolation process is both time- and labor-intensive and prone to failing to identify active minor constituents. (HP)TLC-bioautography-MS/NMR, which combines cutting-edge microbiological, chromatographic, and spectrometric technologies, was developed to accelerate anti-tuberculosis (TB) drug discovery from natural sources by acquiring structural information at a very early stage of the isolation process. Using the avirulent, bioluminescent Mtb strain mc27000 luxABCDE, three variations of bioautography were evaluated and optimized for sensitivity in detecting anti-TB agents, including established clinical agents and new leads with novel mechanisms of action. Several exemplary applications of this approach to microbial extracts demonstrate its potential as a routine method in anti-TB drug discovery from natural sources.