Abstract
Precursor-directed biosynthesis was used to generate a series of fluorinated verticillins. The biosynthesis of these epipolythiodioxopiperazine alkaloids was monitored in situ via the droplet liquid microjunction surface sampling probe (droplet probe), and a suite of NMR and mass spectrometry data were used for their characterization. All analogues demonstrated nanomolar IC50 values vs a panel of cancer cell lines. This approach yielded new compounds that would be difficult to generate via synthesis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Antibiotics, Antineoplastic / biosynthesis*
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Antibiotics, Antineoplastic / chemistry
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Ascomycota / genetics
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Ascomycota / metabolism
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Cell Line, Tumor
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Drug Screening Assays, Antitumor
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Fermentation
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Fluorine / metabolism*
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Genetic Engineering
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Halogenation
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Humans
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Indoles / chemistry
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Indoles / metabolism
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Magnetic Resonance Spectroscopy
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Molecular Structure
Substances
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Antibiotics, Antineoplastic
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Indoles
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verticillins
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Fluorine