title: First identification of xanthone sulfonamides as potent acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors.
abstract: Inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT) would be useful anti-atherogenic agents, since an absence of ACAT affects the absorption and transformation of cholesterol, indirectly resulting in the reduction of cholesteryl ester accumulation in blood vessels. This report discloses xanthone sulfonamides as novel class small molecule inhibitors of ACAT. A series of xanthone sulfonamides were synthesized and evaluated to result in the identification of several potent ACAT inhibitors, among which 2n proved to be more potent than the positive control Sandoz58-35. Moreover, a molecular model for the binding between 2n and the active site of ACAT-2 was provided based computational docking results.
authors.affiliation: Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Hu
authors.forename: Hongli
authors.initials: H
authors.lastname: Liao
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Weifeng
authors.initials: W
authors.lastname: Wu
authors.forename: Jufang
authors.initials: J
authors.lastname: Yan
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Yan
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zou
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Chai
authors.forename: Shichong
authors.initials: S
authors.lastname: Yu
authors.forename: Qiuye
authors.initials: Q
authors.lastname: Wu
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020134:Catalytic Domain; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D057166:High-Throughput Screening Assays; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D044004:Xanthones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D013449:Sulfonamides; D044004:Xanthones; D000101:Acetyl-CoA C-Acetyltransferase