Bioautography with TLC-MS/NMR for Rapid Discovery of Anti-tuberculosis Lead Compounds from Natural Sources

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• 作者：Edyta M. Grzelak ; Changhwa Hwang ; Geping Cai ; Joo-Won Nam ; Mary P. Choules ; Wei Gao ; David C. Lankin ; James B. McAlpine ; Surafel G. Mulugeta ; José G. Napolitano ; Joo-Won Suh ; Seung Hwan Yang ; Jinhua Cheng ; Hanki Lee ; Jin-Yong Kim ; Sang-Hyun Cho ; Guido F. Pauli ; Scott G. Franzblau ; Birgit U. Jaki
• 刊名：ACS Infectious Diseases
• 出版年：2016
• 出版时间：April 8, 2016
• 年：2016
• 卷：2
• 期：4
• 页码：294-301
• 全文大小：444K
• ISSN：2373-8227

文摘

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.