title: Evidence for thiophene-S-oxide as a primary reactive metabolite of thiophene in vivo: formation of a dihydrothiophene sulfoxide mercapturic acid.
abstract: Urine of rats treated with thiophene contains a very major metabolite which represents about 30% of the administered dose. A detailed analysis of its 1H and 13C NMR spectra and a study of its IR and mass spectra clearly showed that it was a 2,5-dihydrothiophene sulfoxide bearing a N-acetyl-cysteinyl group on position 2. Upon heating, it lost water with formation of N-acetyl-S-(2-thienyl)-L-cysteine. A likely mechanism for the formation of this metabolite should involve the S-oxidation of thiophene as a primary step and the addition of glutathione to the very reactive thiophene-S-oxide. These data provide a first evidence for the intermediate formation in vivo of thiophene-S-oxides as reactive metabolites.
authors.affiliation: Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, URA 400 CNRS, Université René Descartes, Paris, France.
authors.forename: P M
authors.initials: PM
authors.lastname: Dansette
authors.forename: D C
authors.initials: DC
authors.lastname: Thang
authors.forename: H
authors.initials: H
authors.lastname: el Amri
authors.forename: D
authors.initials: D
authors.lastname: Mansuy
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000652:urine; D000818:Animals; D001711:Biotransformation; D002247:Carbon Isotopes; D006859:Hydrogen; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013876:Thiophenes / Q000737:chemistry / Q000378:metabolism* / Q000652:urine*; D014316:Tritium
chemical_list: D002247:Carbon Isotopes; D013876:Thiophenes; D014316:Tritium; C076148:2,5-dihydrothiophene sulfoxide-2-mercapturic acid; D006859:Hydrogen; D000111:Acetylcysteine