Human ACAT inhibitory effects of shikonin derivatives from Lithospermum erythrorhizon

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• 作者：Sojin An ; Yong-Dae Park ; Young-Ki Paik ; Tae-Sook Jeong ; Woo Song Lee
• 关键词：ACAT inhibitor ; Shikonin derivatives
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2007
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：15 February 2007
• 卷：17
• 期：4
• 页码：1112-1116
• 文件大小：351 K

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 β-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 μM) than hACAT-1 (32%at 120 μM), 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.