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 journalArticlepeer-review

    11 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

    Bibliographical note

    Funding Information:
    This work was supported by Priority Research Centers Program (G. Y. Song) and Basic Science Research Program (#2011-0026325 to Y. C) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2009-000093815 ), and the RIC program of MKE (Ministry of Knowledge Economy) in Daejeon University.

    Keywords

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

    ASJC Scopus subject areas

    • Pharmacology
    • Drug Discovery
    • Organic Chemistry

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