Nucleophilic Addition of Thiols to Deoxynivalenol

Conjugation of deoxynivalenol (DON) with sulfur compounds is recognized as a significant reaction pathway, and putative DON–glutathione (DON–GSH) conjugates have been reported in planta. To understand and control the reaction of trichothecenes with biologically important thiols, we studied the react...

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Bibliographic Details
Published in:Journal of agricultural and food chemistry 2015-09, Vol.63 (34), p.7556-7566
Main Authors: Stanic, Ana, Uhlig, Silvio, Solhaug, Anita, Rise, Frode, Wilkins, Alistair L., Miles, Christopher O.
Format: Article
Language:English
Subjects:
beta-mercaptoethanol
Cell Line
cysteine
cytokines
Cytokines - immunology
deoxynivalenol
glutathione
Humans
isomers
macrophages
Macrophages - drug effects
Macrophages - immunology
Magnetic Resonance Spectroscopy
Molecular Structure
monocytes
Monocytes - drug effects
Monocytes - immunology
Mycotoxins - chemical synthesis
Mycotoxins - chemistry
Mycotoxins - pharmacology
nuclear magnetic resonance spectroscopy
Sulfhydryl Compounds - chemistry
sulfur
thiols
toxicity
Trichothecenes - chemical synthesis
Trichothecenes - chemistry
Trichothecenes - pharmacology
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Summary:Conjugation of deoxynivalenol (DON) with sulfur compounds is recognized as a significant reaction pathway, and putative DON–glutathione (DON–GSH) conjugates have been reported in planta. To understand and control the reaction of trichothecenes with biologically important thiols, we studied the reaction of DON, T-2 tetraol, and de-epoxy-DON with a range of model thiols. Reaction conditions were optimized for DON with 2-mercaptoethanol. Major reaction products were identified using HRMS and NMR spectroscopy. The results indicate that thiols react reversibly with the double bond (Michael addition) and irreversibly with the epoxide group in trichothecenes. These reactions occurred at different rates, and multiple isomers were produced including diconjugated forms. LC-MS analyses indicated that glutathione and cysteine reacted with DON in a similar manner to the model thiols. In contrast to DON, none of the tested mercaptoethanol adducts displayed toxicity in human monocytes or induced pro-inflammatory cytokines in human macrophages.
ISSN:0021-8561
1520-5118
DOI:10.1021/acs.jafc.5b02864