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Integration of Metabolomics and In vitro Metabolism Assays for Investigating the Stereoselective Transformation of Triadimefon in Rainbow Trout
Citation:
KENNEKE, J. F., D. R. EKMAN, C. S. MAZUR, B. J. Konwick, A. T. Fisk, J. K. AVANTS, AND A. W. GARRISON. Integration of Metabolomics and In vitro Metabolism Assays for Investigating the Stereoselective Transformation of Triadimefon in Rainbow Trout. Chirality. Wiley InterScience, Silver Spring, MD, 22(2):183-192, (2010).
Impact/Purpose:
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Description:
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 2 diastereomers with 2 enantiomers each. All six stereoisomers of the 2 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 microsomes. The S-(+) enantiomer of triadimefon was transformed to triadimenol faster than the R-(-) enantiomer; forming the four tiradimenol stereoisomers at different rates. Complementary metabolomic studies with NMR showed that exposure of the separate triadimefon enantiomers and the racemate to rainbow trout 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.
