Cycloartane-type triterpenes from Euphorbia fischeriana stimulate human CYP3A4 promoter activity

被引：13

作者：

Kuang, Xingzhu ^{[1
]}

Li, Wei ^{[1
]}

Kanno, Yuichiro ^{[1
]}

Mochizuki, Michiru ^{[1
]}

Inouye, Yoshio ^{[1
]}

Koike, Kazuo ^{[1
]}

机构：

[1] Toho Univ, Fac Pharmaceut Sci, Funabashi, Chiba 2478510, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 23期

关键词：

Euphorbia fischeriana; Cycloartane; CYP3A4; Promoter; Pregnane X receptor; PREGNANE-X-RECEPTOR; CONSTITUENTS; ACTIVATION; INHIBITORS; APOPTOSIS;

D O I：

10.1016/j.bmcl.2014.10.032

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A chemical study of the roots of Euphorbia fischeriana resulted in the isolation of seven triterpenes (1-7), including two new compounds: (24R, S)-3 beta-24,31-epoxy-24-methylcycloartane (1) and (24R, S)-3 beta, 31-dihydroxy-24-methoxy-24-methylcycloartane (2). Their structures were elucidated through extensive spectroscopic analyses. Cycloartanes 1-4 showed significant human CYP3A4 promoter activity through a series of luciferase reporter assays. Of these compounds, 3 and 4 activated the pregnane X receptor (PXR) and induced CYP3A4 mRNA expression in human primary hepatocytes. However, despite showing the most potent human CYP3A4 promoter activity via a PXR-independent pathway, 2 did not affect CYP3A4 mRNA expression in human primary hepatocytes. This difference is correlated to substitutions in C-24 and C-25 of the cycloartane structure. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：5423 / 5427

页数：5

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