Stereoselective Degradation of alpha‐Cypermethrin and Its Enantiomers in Rat Liver Microsomes. Issue 1 (8th October 2015)

• Record Type: Journal Article
• Authors: Yan, Jin; Zhang, Ping; Wang, Xinru; Xu, Meiqi; Wang, Yao; Zhou, Zhiqiang; Zhu, Wentao
• Is Part Of: Chirality. Volume 28:Issue 1(2016)
• Page Start: 58
• Page End: 64
• Publication Date: 2015-10-08
• Subjects: alpha‐cypermethrin -- stereoselectivity -- liver microsomes -- rat; Chirality -- Periodicals; Pharmaceutical chemistry -- Periodicals; 541.22
• DOI: 10.1002/chir.22538
• Languages: English
• ISSNs: 0899-0042

Abstract

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, thestereoselective degradation of α‐CP was investigated in rat liver microsomes by high‐performanceliquid 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). Chirality 28:58–64, 2016 . © 2015 Wiley Periodicals, Inc. Abstract :