IDENTIFICATION OF 2 NEW TYPES OF S-LINKED CONJUGATES OF ETOC IN RAT

Citation
Y. Tomigahara et al., IDENTIFICATION OF 2 NEW TYPES OF S-LINKED CONJUGATES OF ETOC IN RAT, Xenobiotica, 24(9), 1994, pp. 839-852
Citations number
30
Categorie Soggetti
Pharmacology & Pharmacy
Journal title
ISSN journal
00498254
Volume
24
Issue
9
Year of publication
1994
Pages
839 - 852
Database
ISI
SICI code
0049-8254(1994)24:9<839:IO2NTO>2.0.ZU;2-3
Abstract
1. Two major metabolites of C-14-labelled (4S, c[(S)-2-methyl-4-oxo-3( 2-propynyl)cyclopent-2-enyl (1R)-trans-chrysanthemate] were purified u sing a combination of chromatographic techniques and identified by spe ctroanalysis (nmr(HMBC) and FAB-, TSP-MS). These were established as n ew types of S-linked conjugates (sulphonic acid and mercapturic acid t ypes). 2. To examine the mechanism of formation of the sulphonic acid and mercapturic acid conjugates, sodium sulphate or glutathione labell ed with S-35 were administered to rat along with unlabelled trans-Etoc . Both sulphonic acid and mercapturic acid conjugates were found in th e excreta, more of the former being yielded with S-35-sodium sulphate than with S-35-glutathione, implying that a sulphonic acid was incorpo rated into the double bond of a possible intermediate after reduction of sulphate to sulphite. The mercapturic acid conjugate was produced o nly with S-35-glutathione, implying incorporation of glutathione into the triple bond before subsequent generation of mercapturic acid from the glutathione conjugate. 3. Additional investigation of whether or n ot the mercapturic acid conjugate was produced by mixing the alcohol m oiety of Etoc(R) PGL ydroxy-3-methyl-2(2-propynyl)cyclopent-2-en-1-one ) and N-acetyl-L-cysteine under alkaline conditions. However, spectral data for the synthesized compound were not the same as those of the m etabolite generated in vivo. That is, the addition reaction appeared t o proceed by anti-Markownikov's rule, whereas the in vivo metabolite w as apparently formed according to Markownikov's rule. Addition of glut athione at a triple bond has not been reported to our knowledge for an y other foreign compounds in mammalian species.