Department of Pesticide Science, College of Plant Protection, State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, Nanjing Agricultural University, Nanjing 210095, China.
Institute of Plant Protection and Agro-Product Safety, Anhui Academy of Agricultural Sciences, Hefei 230031, China.
J Agric Food Chem. 2022 Mar 2;70(8):2520-2528. doi: 10.1021/acs.jafc.1c06928. Epub 2022 Feb 21.
Pydiflumetofen (PYD) has been used worldwide. However, the enantioselective fate of PYD within mammals is not clear. Thus, the enantioselective metabolism and its potential mechanisms of PYD were explored via and . Consistent results were observed between metabolism and enzyme kinetics experiments, with -PYD metabolizing faster than -PYD in rat liver microsomes. Moreover, CYP3A1 and carboxylesterase 1 were found to be major enzymes participating in the metabolism of PYD. Based on the computational results, -PYD bound with CYP3A1 and carboxylesterase 1 more tightly with lower binding free energy than -PYD, explaining the mechanism of enantioselective metabolism. Nine phase I metabolites of PYD were identified, and metabolic pathways of PYD were speculated. This study is the first to clarify the metabolism of PYD in mammals, and further research to evaluate the toxicological implications of these metabolites will help in assessing the risk of PYD.
吡氟草胺（PYD）已在全球范围内使用。然而，哺乳动物体内 PYD 的对映选择性命运尚不清楚。因此，通过 和 研究了 PYD 的对映选择性代谢及其潜在机制。代谢和酶动力学实验观察到一致的结果，即 -PYD 在大鼠肝微粒体中的代谢速度快于 -PYD。此外，CYP3A1 和羧酸酯酶 1 被发现是参与 PYD 代谢的主要酶。基于计算结果，-PYD 与 CYP3A1 和羧酸酯酶 1 的结合更紧密，结合自由能更低，这解释了对映选择性代谢的机制。鉴定了 PYD 的 9 种 I 相代谢物，并推测了 PYD 的代谢途径。本研究首次阐明了哺乳动物中 PYD 的代谢情况，进一步研究评估这些代谢物的毒理学意义将有助于评估 PYD 的风险。
