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.
authors: College of Pharmacy, Dongguk University-Seoul, Seoul 100-715, Republic of Korea.
authors: Kyeong
authors: K
authors: Lee
authors: Soo Hyun
authors: SH
authors: Cho
authors: Jee Hyun
authors: JH
authors: Lee
authors: Jail
authors: J
authors: Goo
authors: Sung Yoon
authors: SY
authors: Lee
authors: Shanthaveerappa K
authors: SK
authors: Boovanahalli
authors: Siok Koon
authors: SK
authors: Yeo
authors: Sung-Joon
authors: SJ
authors: Lee
authors: Young Kook
authors: YK
authors: Kim
authors: Dong Hee
authors: DH
authors: Kim
authors: Yongseok
authors: Y
authors: Choi
authors: Gyu-Yong
authors: GY
authors: Song
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D009285:Naphthoquinones; D013438:Sulfhydryl Compounds; D000101:Acetyl-CoA C-Acetyltransferase