1. Academic Validation
  2. Enantioselective Metabolic Mechanism and Metabolism Pathway of Pydiflumetofen in Rat Liver Microsomes: In Vitro and In Silico Study

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

  • J Agric Food Chem. 2022 Mar 2;70(8):2520-2528. doi: 10.1021/acs.jafc.1c06928.
Zhen Wang 1 Rui Li 1 Qiqi Wu 1 Jinsheng Duan 2 Yuting Tan 1 Xiaofang Sun 1 Rou Chen 1 Haiyan Shi 1 Minghua Wang 1
Affiliations

Affiliations

  • 1 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.
  • 2 Institute of Plant Protection and Agro-Product Safety, Anhui Academy of Agricultural Sciences, Hefei 230031, China.
Abstract

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.

Keywords

enantioselective metabolism; metabolism pathway; molecular dynamics; pydiflumetofen; rat liver microsomes.

Figures
Products