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

doi:10.1016/j.ejmech.2013.01.020

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 journal › Article › peer-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 language	English
Pages (from-to)	515-525
Number of pages	11
Journal	European Journal of Medicinal Chemistry
Volume	62
DOIs	https://doi.org/10.1016/j.ejmech.2013.01.020
Publication status	Published - 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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10.1016/j.ejmech.2013.01.020

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Lee, K., Cho, S. H., Lee, J. H., Goo, J., Lee, S. Y., Boovanahalli, S. K., Yeo, S. K., Lee, S. J., Kim, Y. K., Kim, D. H., Choi, Y., & Song, G. Y. (2013). Synthesis of a novel series of 2-alkylthio substituted naphthoquinones as potent acyl-CoA: Cholesterol acyltransferase (ACAT) inhibitors. European Journal of Medicinal Chemistry, 62, 515-525. https://doi.org/10.1016/j.ejmech.2013.01.020

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

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.",

keywords = "ACAT inhibitors, Cellular cholesterol, LDL, Naphthoquinones, Triglycerides, VLDL",

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

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. ",

year = "2013",

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doi = "10.1016/j.ejmech.2013.01.020",

language = "English",

volume = "62",

pages = "515--525",

journal = "European Journal of Medicinal Chemistry",

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T1 - Synthesis of a novel series of 2-alkylthio substituted naphthoquinones as potent acyl-CoA

T2 - Cholesterol acyltransferase (ACAT) inhibitors

AU - Lee, Kyeong

AU - Cho, Soo Hyun

AU - Lee, Jee Hyun

AU - Goo, Jail

AU - Lee, Sung Yoon

AU - Boovanahalli, Shanthaveerappa K.

AU - Yeo, Siok Koon

AU - Lee, Sung Joon

AU - Kim, Young Kook

AU - Kim, Dong Hee

AU - Choi, Yongseok

AU - Song, Gyu Yong

N1 - 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.

PY - 2013/4

Y1 - 2013/4

N2 - 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.

AB - 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.

KW - ACAT inhibitors

KW - Cellular cholesterol

KW - LDL

KW - Naphthoquinones

KW - Triglycerides

KW - VLDL

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AN - SCOPUS:84873723661

SN - 0223-5234

VL - 62

SP - 515

EP - 525

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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