| Literature DB >> 27478868 |
Edyta M Grzelak1, Changhwa Hwang2, Geping Cai1, Joo-Won Nam2, Mary P Choules2, Wei Gao1, David C Lankin2, James B McAlpine2, Surafel G Mulugeta1, José G Napolitano3, Joo-Won Suh4, Seung Hwan Yang4, Jinhua Cheng4, Hanki Lee4, Jin-Yong Kim4, Sang-Hyun Cho1, Guido F Pauli2, Scott G Franzblau1, Birgit U Jaki2.
Abstract
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.Entities:
Keywords: Mycobacterium tuberculosis; TLC-MS/NMR; bioautography; drug discovery; natural products
Year: 2016 PMID： 27478868 PMCID： PMC4963014 DOI： 10.1021/acsinfecdis.5b00150
Source DB: PubMed Journal: ACS Infect Dis ISSN： 2373-8227 Impact factor: 5.084