Multiomics Sequencing and AlphaFold2 Analysis of the Stereoselective Behavior of Mefentrifluconazole for Bioactivity Improvement and Risk Reduction

Novel Insights into Stereoselective Reproductive Toxicity Induced by Mefentrifluconazole in Earthworms (Eisenia fetida): First Report of Estrogenic Effects

“…This provides further evidence that MFZ induces enantioselective reproductive abnormalities in earthworms. Several studies have shown that R-(−)-MFZ demonstrates higher bioactivity against targets compared to S-(+)-MFZ. ,, Although our study tentatively suggests that R-(−)-MFZ may be less toxic to earthworms, further advice on the utilization of R-(−)-MFZ ought to be grounded in a comprehensive risk assessment of a broader spectrum of species.…”

“…The machine learning technique AlphaFold2 has shown near experimental accuracy in predicting the 3D structure of monomeric proteins, , and in combination with molecular docking techniques, the mode of action of MFZ enantiomers with E. fetida ER can be further explored at the molecular structure level.…”

“…Several studies have suggested that differences in the binding ability and mode of action of the enantiomers to key target proteins may be the main reason for the differences in their biotoxicity. ,, Thus, the different binding energies and modes of binding between R-(−)-MFZ and S-(+)-MFZ with ER may be the causative factor for enantioselective reproduction toxicity. Interestingly, upregulation of ER genes did not exhibit stereoselectivity between enantiomers (Figure A).…”

“…In this study, we focused on a novel triazole fungicide, mefentrifluconazole (MFZ) {(2 R,S)–2-[4-(4-chlorophenoxy)-α,α,α-trifluoro-o-tolyl]–1-(1 H-1,2,4-triazol-1-yl)propan-2-ol}. In recent years, MFZ has been widely used worldwide due to its excellent biological activity against a wide range of pathogenic fungi. , Its widespread use inevitably enters environmental media, and soil is the main sink for MFZ due to its low water solubility and long soil half-life. , In addition, MFZ is a chiral pesticide consisting of a pair of enantiomers, which adds to the complexity of its environmental behavior and toxic effects. , It was reported that the degradation of MFZ in soil and bioaccumulation of E. fetida were nonenantioselective; however, its toxicity to E.…”

Insights into the Enantiomeric Uptake, Translocation, and Distribution of Triazole Chiral Pesticide Mefentrifluconazole in Wheat (Triticum aestivum L.)

“…Triazole pesticides are widely used in agriculture practices due to their outstanding bactericidal effects. − Functionally, they served as sterol demethylation inhibitor (DMI) fungicides, obstructing the biosynthesis of ergosterol, destroying the cell membrane of pathogenic fungi, and ultimately leading to fungal death and protecting plants from fungal diseases. , Since the prothioconazole came out in 2008, there have been no updates on triazole pesticides for over a decade, which enhanced the resistance of pathogenic fungi and decreased pesticide efficacy . For example, the field efficiency of epoxiconazole, propionazole, and difenoconazole declined from 91, 83, and 81 to 36, 47, and 56%, respectively, from 2011 to 2019 in Denmark .…”