Design, synthesis and biological evaluation of hydroxamic acid derivatives as potential high density lipoprotein (HDL) receptor CLA-1 up-regulating agents

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 stru...

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Veröffentlicht in:	Molecules (Basel, Switzerland) Switzerland), 2011-11, Vol.16 (11), p.9178-9193
Hauptverfasser:	Chen, Xiaofang, Wang, Li, Du, Yu, Wu, Yanbin, Jia, Xiaojian, Yang, Yuan, Hong, Bin
Format:	Artikel
Sprache:	eng
Schlagworte:	Acids Animals Atherosclerosis Atherosclerosis - drug therapy Cardiovascular disease Cholesterol CLA-1 Dose-Response Relationship, Drug Hep G2 Cells High density lipoprotein high density lipoprotein receptor Histone Deacetylase Inhibitors - chemical synthesis Histone Deacetylase Inhibitors - chemistry Histone Deacetylase Inhibitors - metabolism Histone Deacetylase Inhibitors - therapeutic use Humans hydroxamic acid Hydroxamic Acids - chemical synthesis Hydroxamic Acids - chemistry Hydroxamic Acids - metabolism Hydroxamic Acids - therapeutic use Lipoproteins Lipoproteins, HDL - metabolism Mice Molecular Structure Scavenger Receptors, Class B - metabolism Structure-Activity Relationship suberoylanilide hydroxamic acid (SAHA) trichostatin A (TSA) Up-Regulation up-regulator Vorinostat
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Beschreibung
Zusammenfassung:	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.
ISSN:	1420-3049 1420-3049
DOI:	10.3390/molecules16119178