title: Methylthiodeoxynivalenol (MTD): insight into the chemistry, structure and toxicity of thia-Michael adducts of trichothecenes.
abstract: Methylthiodeoxynivalenol (MTD), a novel derivative of the trichothecene mycotoxin deoxynivalenol (DON), was prepared by applying a reliable procedure for the formal Michael addition of methanethiol to the conjugated double bond of DON. Structure elucidation revealed the preferred formation of the hemiketal form of MTD by intramolecular cyclisation between C8 and C15. Computational investigations showed a negative total reaction energy for the hemiketalisation step and its decrease in comparison with theoretical model compounds. Therefore, this structural behaviour seems to be a general characteristic of thia-Michael adducts of type B trichothecenes. MTD was shown to be less inhibitory for a reticulocyte lysate based in vitro translation system than the parent compound DON, which supports the hypothesis that trichothecenes are detoxified through thia-adduct formation during xenobiotic metabolism.
authors.affiliation: Institute of Applied Synthetic Chemistry, Vienna University of Technology (VUT), Getreidemarkt 9/163, 1060 Vienna, Austria. hannes.mikula@tuwien.ac.at.
authors.forename: Philipp
authors.initials: P
authors.lastname: Fruhmann
authors.forename: Theresa
authors.initials: T
authors.lastname: Weigl-Pollack
authors.forename: Hannes
authors.initials: H
authors.lastname: Mikula
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Wiesenberger
authors.forename: Gerhard
authors.initials: G
authors.lastname: Adam
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Varga
authors.forename: Franz
authors.initials: F
authors.lastname: Berthiller
authors.forename: Rudolf
authors.initials: R
authors.lastname: Krska
authors.forename: Christian
authors.initials: C
authors.lastname: Hametner
authors.forename: Johannes
authors.initials: J
authors.lastname: Fröhlich
mesh_terms: D000818:Animals; D001711:Biotransformation; D002474:Cell-Free System; D003500:Cyclization; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009183:Mycotoxins / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity*; D014176:Protein Biosynthesis / Q000187:drug effects; D011817:Rabbits; D012156:Reticulocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013816:Thermodynamics; D014255:Trichothecenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*
chemical_list: D009183:Mycotoxins; D013438:Sulfhydryl Compounds; D014255:Trichothecenes; C005231:methylmercaptan; D008156:Luciferases; C007262:deoxynivalenol