Synthesis of a novel series of 2-alkylthio substituted naphthoquinones as potent acyl-CoA: Cholesterol acyltransferase (ACAT) inhibitors

Kyeong Lee, Soo Hyun Cho, Jee Hyun Lee, Jail Goo, Sung Yoon Lee, Shanthaveerappa K. Boovanahalli, Siok Koon Yeo, Sung-Joon Lee, Young Kook Kim, Dong Hee Kim, Yongseok Choi, Gyu Yong Song

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

We report a new series of naphthoquinone derivatives as potent ACAT inhibitors, which were obtained through structural variations of previously disclosed lead 1. Several analogs represented by 3i-l, 4k-m, 6a-n, 7a, and 7i demonstrated potent human macrophage ACAT inhibitory activity by a cell-based reporter assay with human HepG2 cell lines. In particular, compounds 4l and 6j emerged as highly potent inhibitors, exhibiting significantly high inhibitory potencies with IC50 values of 0.44 μM and 0.6 μM, respectively. Moreover, compound 4l significantly reduced the accumulation of cellular cholesterol in HepG2 cell lines.

Original languageEnglish
Pages (from-to)515-525
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Volume62
DOIs
Publication statusPublished - 2013 Apr 1

Fingerprint

Anticholesteremic Agents
Sterol O-Acyltransferase
Naphthoquinones
Hep G2 Cells
Cells
Cell Line
Macrophages
Inhibitory Concentration 50
Assays
Cholesterol
Derivatives
Lead

Keywords

  • ACAT inhibitors
  • Cellular cholesterol
  • LDL
  • Naphthoquinones
  • Triglycerides
  • VLDL

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Synthesis of a novel series of 2-alkylthio substituted naphthoquinones as potent acyl-CoA : Cholesterol acyltransferase (ACAT) inhibitors. / Lee, Kyeong; Cho, Soo Hyun; Lee, Jee Hyun; Goo, Jail; Lee, Sung Yoon; Boovanahalli, Shanthaveerappa K.; Yeo, Siok Koon; Lee, Sung-Joon; Kim, Young Kook; Kim, Dong Hee; Choi, Yongseok; Song, Gyu Yong.

In: European Journal of Medicinal Chemistry, Vol. 62, 01.04.2013, p. 515-525.

Research output: Contribution to journalArticle

Lee, Kyeong ; Cho, Soo Hyun ; Lee, Jee Hyun ; Goo, Jail ; Lee, Sung Yoon ; Boovanahalli, Shanthaveerappa K. ; Yeo, Siok Koon ; Lee, Sung-Joon ; Kim, Young Kook ; Kim, Dong Hee ; Choi, Yongseok ; Song, Gyu Yong. / Synthesis of a novel series of 2-alkylthio substituted naphthoquinones as potent acyl-CoA : Cholesterol acyltransferase (ACAT) inhibitors. In: European Journal of Medicinal Chemistry. 2013 ; Vol. 62. pp. 515-525.
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