Key Laboratory of Tobacco Pest Monitoring & Integrated Management, Tobacco Research Institute of Chinese Academy of Agricultural Sciences, Qingdao 266101, China.
College of Plant Science, Jilin University, Changchun 130062, P.R. China.
Environ Sci Technol. 2023 Dec 19;57(50):21348-21357. doi: 10.1021/acs.est.3c05327. Epub 2023 Dec 5.
As the first isopropanol chiral triazole fungicide, mefentrifluconazole has broad prospects for application. In this study, the stereoselective stability, bioactivity, fate, and biotoxicity were systematically investigated. Our results indicated that the stability of mefentrifluconazole enantiomers differed between environmental media, and they were stable in water and sediment in the dark. The bactericidal activity of -mefentrifluconazole against the four target pathogens was 4.6-43 times higher than that of -mefentrifluconazole. In the water-sediment system, -mefentrifluconazole dissipated faster than -mefentrifluconazole in water; however, its accumulation capacity was higher than that of -mefentrifluconazole in sediment and zebrafish. -Mefentrifluconazole induced more differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) in zebrafish than did -mefentrifluconazole. Multiomics sequencing results showed that -mefentrifluconazole enhanced the antioxidant, detoxification, immune, and metabolic functions of zebrafish by interacting with related proteins. Based on AlphaFold2 modeling and molecular docking, mefentrifluconazole enantiomers had different binding modes with key target proteins in pathogens and zebrafish, which may be the main reason for the stereoselective differences in bioactivity and biotoxicity. Based on its excellent bioactivity and low biotoxicity, the -enantiomer can be developed to improve the bioactivity and reduce the risk of mefentrifluconazole.
作为首个异丙醇手性三唑类杀菌剂，丙硫菌唑具有广阔的应用前景。本研究系统地研究了其对映体的立体选择性稳定性、生物活性、归趋和生物毒性。结果表明，丙硫菌唑对映体在环境介质中的稳定性不同，在黑暗条件下，它们在水和沉积物中稳定。-丙硫菌唑对 4 种靶标病原菌的杀菌活性比-mefentrifluconazole 高 4.6-43 倍。在水-沉积物体系中，-mefentrifluconazole 在水中的消解速度快于-mefentrifluconazole，但在沉积物和斑马鱼中的积累能力高于-mefentrifluconazole。-mefentrifluconazole 在斑马鱼中诱导的差异表达基因（DEGs）和差异表达蛋白（DEPs）多于-mefentrifluconazole。多组学测序结果表明，-mefentrifluconazole 通过与相关蛋白相互作用，增强了斑马鱼的抗氧化、解毒、免疫和代谢功能。基于 AlphaFold2 建模和分子对接，丙硫菌唑对映体与病原菌和斑马鱼中的关键靶标蛋白具有不同的结合模式，这可能是生物活性和生物毒性立体选择性差异的主要原因。基于其优异的生物活性和低生物毒性，-对映体可被开发用于提高生物活性并降低丙硫菌唑的风险。
