Enantioselective Metabolic Mechanism and Metabolism Pathway of Pydiflumetofen in Rat Liver Microsomes: In Vitro and In Silico Study

文献类型： 外文期刊

第一作者： Wang, Zhen

作者： Wang, Zhen;Li, Rui;Wu, Qiqi;Tan, Yuting;Sun, Xiaofang;Chen, Rou;Shi, Haiyan;Wang, Minghua;Duan, Jinsheng

作者机构：

关键词： pydiflumetofen; rat liver microsomes; enantioselective metabolism; molecular dynamics; metabolism pathway

期刊名称：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY （ 影响因子：5.895； 五年影响因子：6.048 ）

ISSN： 0021-8561

年卷期： 2022 年 70 卷 8 期

页码：

收录情况： SCI

摘要： 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 in vitro and in silico. Consistent results were observed between metabolism and enzyme kinetics experiments, with S-PYD metabolizing faster than R-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, S-PYD bound with CYP3A1 and carboxylesterase 1 more tightly with lower binding free energy than R-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.

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