2. Academic Validation
  3. The prenylated phenolic natural product isoglycycoumarin is a highly selective probe for human cytochrome P450 2A6

The prenylated phenolic natural product isoglycycoumarin is a highly selective probe for human cytochrome P450 2A6

  • Eur J Pharm Sci. 2017 Nov 15;109:472-479. doi: 10.1016/j.ejps.2017.08.035.
Qi Wang 1,  Yi Kuang 2,  Junbin He 2,  Kai Li 2,  Wei Song 2,  Hongwei Jin 2,  Xue Qiao 3,  Min Ye 4
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Baojian Road 157, Nangang District, Harbin 150081, China; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
  • 2 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
  • 3 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China. Electronic address: qiaoxue@bjmu.edu.cn.
  • 4 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China. Electronic address: yemin@bjmu.edu.cn.
PMID: 28867491 DOI: 10.1016/j.ejps.2017.08.035
Abstract

Prenylated phenolic compounds are an important class of bioactive Natural Products. One major in vivo metabolic pathway of these compounds is hydroxylation at terminal methyl of the isoprenyl group. This study aims to identify the P450 isozyme catalyzing this metabolic reaction. In human liver microsomes, 16 out of 24 screened compounds could be metabolized into their hydroxylated derivatives. Chemical inhibition assays using 11 isozyme specific inhibitors indicated the hydroxylation reactions of 12 compounds were primarily catalyzed by Cytochrome P450 2A6 (CYP2A6). In particular, CYP2A6 was the major Enzyme participating in the metabolism of isoglycycoumarin (IGCM). The product of IGCM was obtained and identified as licopyranocoumarin (4″-hydroxyl isoglycycoumarin) using NMR spectroscopic analysis. The Km values for human liver microsomes and recombinant human CYP2A6 were 7.98 and 10.14μM, respectively. According to molecular docking analysis, the catalytic mechanism may involve cyclized isoprenyl group of IGCM entering the active cavity of CYP2A6. These results demonstrate that IGCM could serve as an ideal isozyme selective probe to evaluate CYP2A6 activities.

Keywords

Bioactive natural products; Cytochrome P450 2A6; Hydroxylation metabolism; Isoglycycoumarin; Isozyme selective probe; Prenylated phenolic compounds.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z