Title
Integration of metabolomics and in vitro metabolism assays for investigating the stereoselective transformation of triadimefon in rainbow trout
Document Type
Article
Publication Date
2-1-2010
Publication Title
Chirality
Volume
22
Issue
2
First Page
183
Keywords
Conazoles, Diastereomers, Enantiomers, Exposure, Metabolism, Metabolomics, Rainbow trout, Stereoisomers, Stereoselectivity, Triadimefon, Triadimenol, Triazoles
Last Page
192
Abstract
Triadimefon is a systemic agricultural fungicide of the triazole class whose major metabolite, triadimenol, also a commercial fungicide, provides the majority of the actual fungicidal activity, i.e., inhibition of steroid demethylation. Both chemicals are chiral: triadimefon has one chiral center with two enantiomers while its enzymatic reduction to triadimenol produces a second chiral center and two diastereomers with two enantiomers each. All six stereoisomers of the two fungicides were separated from each other using a chiral BGB-172 column on a GC-MS system so as to follow stereospecificity in metabolism by rainbow trout hepatic microsomes. In these microsomes the S-(+) enantiomer of triadimefon was transformed to triadimenol 27% faster than the R-(-) enantiomer, forming the four triadimenol stereoisomers at rates different from each other. The most fungi-toxic stereoisomer (1S,2R) was produced at the slowest rate; it was detectable after 8 h, but below the level of method quantitation. The triadimenol stereoisomer ratio pattern produced by the trout microsomes was very different from that of the commercial triadimenol standard, in which the most rat-toxic pair of enantiomers (known as "Diastereomer A") is about 85% of the total stereoisomer composition. The trout microsomes produced only about 4% of "Diastereomer A". Complementary metabolomic studies with NMR showed that exposure of the separate triadimefon enantiomers and the racemate to rainbow trout for 48 h resulted in different metabolic profiles in the trout liver extracts, i.e., different endogenous metabolite patterns that indicated differences in effects of the two enantiomers. © 2009 Wiley-Liss, Inc.
DOI
10.1002/chir.20725
ISSN
08990042
E-ISSN
1520636X
Recommended Citation
Kenneke, John F.; Ekman, Drew R.; Mazur, Chris S.; Konwick, Brad J.; Fisk, Aaron T.; Avants, Jimmy K.; and Garrison, A. Wayne. (2010). Integration of metabolomics and in vitro metabolism assays for investigating the stereoselective transformation of triadimefon in rainbow trout. Chirality, 22 (2), 183-192.
https://scholar.uwindsor.ca/glierpub/402
PubMed ID
19418553