Triticonazole enantiomers induced enantioselective metabolic phenotypes in Fusarium graminearum and HepG2 cells.

The management of Fusarium head blight relies heavily on triazole fungicides. Most of triazole fungicides are chiral, and their enantioselective effects on metabolic phenotypes are poorly understood. Herein, we analyzed the bioactivity of triticonazole against Fusarium graminearum, and 1 H-nuclear magnetic resonance-based metabolomics was used to assess the metabolic disturbances of triticonazole enantiomers in Fusarium graminearum and human hepatocarcinoma cells. Results indicated that the bioactivity of R-triticonazole was 4.28-fold higher than its antipode since it bound stronger with fungal CYP51B and induced more abnormal metabolic processes of Fusarium graminearum, including lipid metabolism, glycolysis, and amino acid metabolism. In human hepatocarcinoma cells, pathways of "alanine, aspartic acid and glutamate metabolism" and "pyruvate metabolism" were disturbed significantly by R-triticonazole; "phenylalanine metabolism" and "taurine-hypotaurine metabolism" were abnormal in the exposure of S-triticonazole. These results suggested that R- and S-triticonazole could affect different metabolic pathways of human hepatocarcinoma cells, and the massively use of inefficient S-triticonazole should be avoided. Our data will help to better understand the enantioselectivity of chiral pesticides and provide a reference for the development of green pesticides.