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

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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

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Keywords

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

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

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