title: Bioautography with TLC-MS/NMR for Rapid Discovery of Anti-tuberculosis Lead Compounds from Natural Sources.
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, bioluminescentMtbstrain 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.
authors.affiliation: Institute for Tuberculosis Research, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
authors.forename: Edyta M
authors.initials: EM
authors.lastname: Grzelak
authors.affiliation: Institute for Tuberculosis Research, University of Illinois at Chicago, Chicago, Illinois 60612, United States; Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
authors.forename: Changhwa
authors.initials: C
authors.lastname: Hwang
authors.affiliation: Institute for Tuberculosis Research, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
authors.forename: Geping
authors.initials: G
authors.lastname: Cai
authors.affiliation: Institute for Tuberculosis Research, University of Illinois at Chicago, Chicago, Illinois 60612, United States; Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Nam
authors.affiliation: Institute for Tuberculosis Research, University of Illinois at Chicago, Chicago, Illinois 60612, United States; Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
authors.forename: Mary P
authors.initials: MP
authors.lastname: Choules
authors.affiliation: Institute for Tuberculosis Research, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Institute for Tuberculosis Research, University of Illinois at Chicago, Chicago, Illinois 60612, United States; Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
authors.forename: David C
authors.initials: DC
authors.lastname: Lankin
authors.affiliation: Institute for Tuberculosis Research, University of Illinois at Chicago, Chicago, Illinois 60612, United States; Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
authors.forename: James B
authors.initials: JB
authors.lastname: McAlpine
authors.affiliation: Institute for Tuberculosis Research, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
authors.forename: Surafel G
authors.initials: SG
authors.lastname: Mulugeta
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
authors.forename: José G
authors.initials: JG
authors.lastname: Napolitano
authors.affiliation: Center for Nutraceutical and Pharmaceutical Materials and Division of Bioscience and Bioinformatics, College of Natural Science, Myongji University, Cheoin-gu, Gyeonggi-Do 449-728, Republic of Korea.
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Suh
authors.affiliation: Center for Nutraceutical and Pharmaceutical Materials and Division of Bioscience and Bioinformatics, College of Natural Science, Myongji University, Cheoin-gu, Gyeonggi-Do 449-728, Republic of Korea.
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Center for Nutraceutical and Pharmaceutical Materials and Division of Bioscience and Bioinformatics, College of Natural Science, Myongji University, Cheoin-gu, Gyeonggi-Do 449-728, Republic of Korea.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Center for Nutraceutical and Pharmaceutical Materials and Division of Bioscience and Bioinformatics, College of Natural Science, Myongji University, Cheoin-gu, Gyeonggi-Do 449-728, Republic of Korea.
authors.forename: Hanki
authors.initials: H
authors.lastname: Lee
authors.affiliation: Center for Nutraceutical and Pharmaceutical Materials and Division of Bioscience and Bioinformatics, College of Natural Science, Myongji University, Cheoin-gu, Gyeonggi-Do 449-728, Republic of Korea.
authors.forename: Jin-Yong
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Institute for Tuberculosis Research, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Cho
authors.affiliation: Institute for Tuberculosis Research, University of Illinois at Chicago, Chicago, Illinois 60612, United States; Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
authors.forename: Guido F
authors.initials: GF
authors.lastname: Pauli
authors.affiliation: Institute for Tuberculosis Research, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Franzblau
authors.affiliation: Institute for Tuberculosis Research, University of Illinois at Chicago, Chicago, Illinois 60612, United States; Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
authors.forename: Birgit U
authors.initials: BU
authors.lastname: Jaki
keywords: Mycobacterium tuberculosis; TLC-MS/NMR; bioautography; drug discovery; natural products