Evidence for thiophene-S-oxide as a primary reactive metabolite of thiophene in vivo: formation of a dihydrothiophene sulfoxide mercapturic acid.
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.
Dansette
P M
PM
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, URA 400 CNRS, Université René Descartes, Paris, France.
Thang
D C
DC
el Amri
H
H
Mansuy
D
D
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
D002247:Carbon Isotopes; D013876:Thiophenes; D014316:Tritium; C076148:2,5-dihydrothiophene sulfoxide-2-mercapturic acid; D006859:Hydrogen; D000111:Acetylcysteine