title: Design, synthesis and biological evaluation of hydroxamic acid derivatives as potential high density lipoprotein (HDL) receptor CLA-1 up-regulating agents.
abstract: Trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) were reported in our recent publication as novel human high density lipoprotein (HDL) receptor CD36 and Lysosomal integral membrane protein-II Analogous-1 (CLA-1) up-regulators. As part of a broader effort to more fully explore the structure-activity relationships (SAR) of CLA-1 up-regulators, we synthesized a series of hydroxamic acid derivatives and evaluated their CLA-1 up-regulating activities in HepG2 cells. Some compounds exhibited over 10-fold up-regulation of CLA-1 expression in HepG2 cells at 10 μg/mL concentration. The compound 1g showed the best potency, with a lower EC(50) than TSA (EC(50) = 0.32 μM versus 1.2 μM). These compounds provide early new CLA-1 up-regulators with potential for treating atherosclerosis.
authors: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. chenchemistry@hotmail.com
authors: Xiaofang
authors: X
authors: Chen
authors: Li
authors: L
authors: Wang
authors: Yu
authors: Y
authors: Du
authors: Yanbin
authors: Y
authors: Wu
authors: Xiaojian
authors: X
authors: Jia
authors: Yuan
authors: Y
authors: Yang
authors: Bin
authors: B
authors: Hong
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D008075:Lipoproteins, HDL / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D051122:Scavenger Receptors, Class B / Q000378:metabolism*; D013329:Structure-Activity Relationship; D015854:Up-Regulation; D000077337:Vorinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D008075:Lipoproteins, HDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; C012589:trichostatin A; D000077337:Vorinostat