title: Nucleophilic Addition of Thiols to Deoxynivalenol.
abstract: 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.
authors.affiliation: Norwegian Veterinary Institute , P.O. Box 750 Sentrum, NO-0106 Oslo, Norway.|Department of Chemistry, University of Oslo , P.O. Box 1033 Blindern, NO-0315 Oslo, Norway.
authors.forename: Ana
authors.initials: A
authors.lastname: Stanic
authors.affiliation: Norwegian Veterinary Institute , P.O. Box 750 Sentrum, NO-0106 Oslo, Norway.|Department of the Chemical and Biological Work Environment, National Institute of Occupational Health , P.O. Box 8149 Dep, NO-0033 Oslo, Norway.
authors.forename: Silvio
authors.initials: S
authors.lastname: Uhlig
authors.affiliation: Norwegian Veterinary Institute , P.O. Box 750 Sentrum, NO-0106 Oslo, Norway.
authors.forename: Anita
authors.initials: A
authors.lastname: Solhaug
authors.affiliation: Department of Chemistry, University of Oslo , P.O. Box 1033 Blindern, NO-0315 Oslo, Norway.
authors.forename: Frode
authors.initials: F
authors.lastname: Rise
authors.affiliation: Norwegian Veterinary Institute , P.O. Box 750 Sentrum, NO-0106 Oslo, Norway.|Chemistry Department, University of Waikato , Private Bag 3105, 3240 Hamilton, New Zealand.
authors.forename: Alistair L
authors.initials: AL
authors.lastname: Wilkins
authors.affiliation: Norwegian Veterinary Institute , P.O. Box 750 Sentrum, NO-0106 Oslo, Norway.|Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo , P.O. Box 1068 Blindern, NO-0316 Oslo, Norway.
authors.forename: Christopher O
authors.initials: CO
authors.lastname: Miles
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009183:Mycotoxins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D014255:Trichothecenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D016207:Cytokines; D009183:Mycotoxins; D013438:Sulfhydryl Compounds; D014255:Trichothecenes; C007262:deoxynivalenol
keywords: DON; HRMS; MS/MS; Michael reaction; NMR; T-2 tetraol; cysteine; de-epoxy-DON; deoxynivalenol; glutathione; mercaptoethanol; thiol; trichothecene