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  2. A potential biomarker of isofenphos-methyl in humans: A chiral view

A potential biomarker of isofenphos-methyl in humans: A chiral view

  • Environ Int. 2019 Jun;127:694-703. doi: 10.1016/j.envint.2019.04.018.
Beibei Gao 1 Shuangshuang Zhao 1 Zhaoxian Zhang 1 Lianshan Li 1 Kunming Hu 1 Amir E Kaziem 2 Zongzhe He 1 Xiude Hua 1 Haiyan Shi 1 Minghua Wang 3
Affiliations

Affiliations

  • 1 Department of Pesticide Science, College of Plant Protection, Nanjing Agricultural University, State and Local Joint Engineering Research Center of Green Pesticide Invention and Application, Nanjing, Jiangsu 210095, China.
  • 2 Department of Pesticide Science, College of Plant Protection, Nanjing Agricultural University, State and Local Joint Engineering Research Center of Green Pesticide Invention and Application, Nanjing, Jiangsu 210095, China; Department of Environmental Agricultural Science, Institute of Environmental Studies and Research, Ain Shams University. Cairo11566, Egypt.
  • 3 Department of Pesticide Science, College of Plant Protection, Nanjing Agricultural University, State and Local Joint Engineering Research Center of Green Pesticide Invention and Application, Nanjing, Jiangsu 210095, China. Electronic address: wangmha@njau.edu.cn.
Abstract

Isofenphos-methyl (IFP) is a very active and persistent chiral insecticide. However, IFP has lower activity against acetylcholinesterases (AChEs). Previously, it was confirmed that phosphorothioate organophosphorus pesticides with N-alkyl (POPN) require activation by oxidative desulfuration and N-dealkylation. In this work, we demonstrated that IFP could be metabolized in human liver microsomes to isofenphos-methyl oxon (IFPO, 52.7%), isocarbophos (ICP, 14.2%) and isocarbophos oxon (ICPO, 11.2%). It was found that (R)-IFP was preferentially degraded compared to the (S)-enantiomer, and the enantiomeric fraction (EF) value reached 0.61 at 60 min. However, (S)-enantiomers of the three metabolites, were degraded preferentially, and the EF values ranged from 0.34 to 0.45. Cytochrome P450 (CYP) isoforms CYP3A4, CYP2E1, and CYP1A2 and Carboxylesterase enzyme have an essential role in the enantioselective metabolism of IFP; but, the Enzymes that participate in the degradation of IFP metabolites are different. The AChE inhibition bioassay indicated that ICPO is the only effective inhibitor of AChE. The covalent molecular docking has proposed that the metabolites of IFP and its analogs after N-dealkylation and oxidative desulfuration will possess the highest inhibitory activity against AChE. This study is the first to demonstrate that ICPO can be regarded as a potential biomarker for the biomonitoring of IFP and ICP exposure in humans.

Keywords

Biomarker; Chiral; Isofenphos-methyl; Metabolites; Molecular docking.

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