Human ACAT inhibitory effects of shikonin derivatives from Lithospermum erythrorhizon

Sojin An, Yong Dae Park, Young-Ki Paik, Tae Sook Jeong, Woo Song Lee

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1112-1116
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume17
Issue number4
DOIs
Publication statusPublished - 2007 Feb 15

Fingerprint

Lithospermum
Assays
Derivatives
Naphthoquinones
Bioassay
Fractionation
Human Activities
Hydrolysis
Biological Assay
Inhibitory Concentration 50
shikonin

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

An, Sojin ; Park, Yong Dae ; Paik, Young-Ki ; Jeong, Tae Sook ; Lee, Woo Song. / Human ACAT inhibitory effects of shikonin derivatives from Lithospermum erythrorhizon. In: Bioorganic and Medicinal Chemistry Letters. 2007 ; Vol. 17, No. 4. pp. 1112-1116.
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Human ACAT inhibitory effects of shikonin derivatives from Lithospermum erythrorhizon. / An, Sojin; Park, Yong Dae; Paik, Young-Ki; Jeong, Tae Sook; Lee, Woo Song.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 17, No. 4, 15.02.2007, p. 1112-1116.

Research output: Contribution to journalArticle

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