Identification of a dithiol intermediate metabolite of malotilate in rats

Xenobiotica. 1990 Jan;20(1):91-8. doi: 10.3109/00498259009046815.

Abstract

1. A chemically unstable dithiol intermediate metabolite of malotilate was identified by g.l.c.-mass spectrometry after conversion of the dithiol to a stable derivative by a cyclization reaction with 1,3-dichloroacetone. The dithiol, namely, 2,2-di(isopropoxycarbonyl)ethylene-1,1-dithiol, was present in rat liver at low concentrations. 2. A study of glucuronidation in vitro indicated that the dithiol was converted to the corresponding thio-glucuronide by rat hepatic microsomal enzymes. 3. It was thus confirmed that metabolism of malotilate proceeds via the dithiol intermediate to form the thio-glucuronide, which is a major metabolic pathway.

MeSH terms

  • Animals
  • Chemical Phenomena
  • Chemistry
  • Dose-Response Relationship, Drug
  • Gas Chromatography-Mass Spectrometry
  • Glucuronates / metabolism
  • Injections, Intravenous
  • Male
  • Malonates / metabolism*
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Toluene / administration & dosage
  • Toluene / analogs & derivatives*
  • Toluene / metabolism
  • Xenobiotics

Substances

  • Glucuronates
  • Malonates
  • Xenobiotics
  • Toluene
  • diisopropyl 1,3-dithiol-2-ylidenemalonate
  • dithiol