Human ACAT inhibitory effects of shikonin derivatives from Lithospermum erythrorhizon

被引：44

作者：

An, Sojin

Park, Yong-Dae

Paik, Young-Ki

Jeong, Tae-Sook ^{[1
]}

Lee, Woo Song

机构：

[1] KRIBB, Natl Res Lab Lipid Metab & Atherosclerosis, Taejon 305806, South Korea

[2] Univ Sci & Technol, Taejon 305806, South Korea

[3] Yonsei Univ, Dept Biochem, Seoul 131749, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 04期

关键词：

ACAT inhibitor; shikonin derivatives;

D O I：

10.1016/j.bmcl.2006.11.024

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

Three naphthoquinones were isolated by bioassay-guided fractionation from the CHCl3 extracts of roots of Lithospermum erythrorhizon. They were identified as acetylshikonin (1), isobutyrylshikonin (2), and (3-hydroxyisovalerylshikonin (3) on the basis of their spectroscopic analyses. The compounds 1-3 were tested for their inhibitory activities against human ACAT-1 (hACAT-1) or human ACAT-2 (hACAT-2). Compound 2 preferentially inhibited hACAT-2 (IC50 = 57.5 wM) than hACAT-1 (32% at 120 mu M), whereas compounds 1 and 3 showed weak inhibitory activities in both hACAT-1 and -2. To develop more potent hACAT inhibitor, shikonin derivatives (5-11) were synthesized by semi-synthesis of shikonin (4), which was prepared by hydrolysis of 1-3. Among them, compounds 5 and 7 exhibited the strong inhibitory activities against hACAT-1 and -2. Furthermore, we demonstrated that compound 7 behaved as a potent ACAT inhibitor in not only in vitro assay system but also cell-based assay system. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：1112 / 1116

页数：5

共 20 条

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A critical role for the histidine residues in the catalytic function of acyl-CoA:cholesterol acyltransferase catalysis:: Evidence for catalytic difference between ACAT1 and ACAT2 [J].