title: Stereoselective Degradation of alpha-Cypermethrin and Its Enantiomers in Rat Liver Microsomes.
abstract: Alpha-cypermethrin (α-CP), [(RS)-a-cyano-3-phenoxy benzyl (1RS)-cis-3-(2, 2-dichlorovinyl)-2, 2-dimethylcyclopropanecarboxylate], comprises a diastereoisomer pair of cypermethrin, which are (+)-(1R-cis-αS)-CP (insecticidal) and (-)-(1S-cis-αR)-CP (inactive). In this experiment, the stereoselective degradation of α-CP was investigated in rat liver microsomes by high-performance liquid chromatography (HPLC) with a cellulose-tris- (3, 5-dimethylphenylcarbamate)-based chiral stationary phase. The results revealed that the degradation of (-)-(1S-cis-αR)-CP was much faster than (+)-(1R-cis-αS)-CP both in enantiomer monomers and rac-α-CP. As for the enzyme kinetic parameters, there were some variances between rac-α-CP and the enantiomer monomers. In rac-α-CP, the Vmax and CLint of (+)-(1R-cis-αS)-CP (5105.22 ± 326.26 nM/min/mg protein and 189.64 mL/min/mg protein) were about one-half of those of (-)-(1S-cis-αR)-CP (9308.57 ± 772.24 nM/min/mg protein and 352.19 mL/min/mg protein), while the Km of the two α-CP enantiomers were similar. However, in the enantiomer monomers of α-CP, the Vmax and Km of (+)-(1R-cis-αS) -CP were 2-fold and 5-fold of (-)-(1S-cis-αR)-CP, respectively, which showed a significant difference with rac-α-CP. The CLint of (+)-(1R-cis-αS)-CP (140.97 mL/min/mg protein) was still about one-half of (-)-(1S-cis-αR)-CP (325.72 mL/min/mg protein) in enantiomer monomers. The interaction of enantiomers of α-CP in rat liver microsomes was researched and the results showed that there were different interactions between the IC50 of (-)- to (+)-(1R-cis-αS)-CP and (+)- to (-)-(1S-cis-αR)-CP(IC50(-)/(+) / IC50(+)/(-)  = 0.61).
authors.affiliation: Department of Applied Chemistry, China Agricultural University, Beijing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Applied Chemistry, China Agricultural University, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Applied Chemistry, China Agricultural University, Beijing, China.
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Applied Chemistry, China Agricultural University, Beijing, China.
authors.forename: Meiqi
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Applied Chemistry, China Agricultural University, Beijing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Applied Chemistry, China Agricultural University, Beijing, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Applied Chemistry, China Agricultural University, Beijing, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Zhu
mesh_terms: D000818:Animals; D007306:Insecticides / Q000737:chemistry* / Q000378:metabolism; D008862:Microsomes, Liver / Q000737:chemistry* / Q000378:metabolism; D011722:Pyrethrins / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D013237:Stereoisomerism
chemical_list: D007306:Insecticides; D011722:Pyrethrins; C017160:cypermethrin
keywords: alpha-cypermethrin; liver microsomes; rat; stereoselectivity