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设计、合成及生物评价作为潜在的高密度脂蛋白（HDL）受体 CLA-1 上调剂的羟肟酸衍生物。

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

机构信息

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

出版信息

Molecules. 2011 Nov 2;16(11):9178-93. doi: 10.3390/molecules16119178.

DOI:10.3390/molecules16119178
PMID:22048700
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6264451/
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.

摘要

我们在最近的出版物中报道，三氮唑酮 A（TSA）和琥珀酰亚胺基羟肟酸（SAHA）是新型的人高密度脂蛋白（HDL）受体 CD36 和溶酶体整合膜蛋白-II 类似物-1（CLA-1）上调剂。作为更全面探索 CLA-1 上调剂结构-活性关系（SAR）的一部分，我们合成了一系列羟肟酸衍生物，并在 HepG2 细胞中评估了它们对 CLA-1 的上调活性。一些化合物在 10μg/mL 浓度下使 HepG2 细胞中 CLA-1 的表达上调了 10 多倍。化合物 1g 表现出最好的活性，其 EC50低于 TSA（EC50=0.32μM 对 1.2μM）。这些化合物提供了具有治疗动脉粥样硬化潜力的新型 CLA-1 上调剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86e8/6264451/8325209ef308/molecules-16-09178-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86e8/6264451/28deadc2df48/molecules-16-09178-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86e8/6264451/0874826f4ceb/molecules-16-09178-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86e8/6264451/495510cd5a62/molecules-16-09178-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86e8/6264451/45af3a61c86c/molecules-16-09178-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86e8/6264451/8325209ef308/molecules-16-09178-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86e8/6264451/28deadc2df48/molecules-16-09178-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86e8/6264451/0874826f4ceb/molecules-16-09178-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86e8/6264451/495510cd5a62/molecules-16-09178-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86e8/6264451/45af3a61c86c/molecules-16-09178-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86e8/6264451/8325209ef308/molecules-16-09178-g004.jpg

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本文引用的文献

1
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2
N-Hydroxy-(4-oxime)-cinnamide: a versatile scaffold for the synthesis of novel histone deacetylase [correction of deacetilase] (HDAC) inhibitors.N-羟基-（4-肟基）肉桂酰胺：一种用于合成新型组蛋白脱乙酰酶（HDAC）抑制剂的通用骨架。 （注：原文中“deacetilase”有误，正确的是“deacetylase”，翻译时已修正）
Bioorg Med Chem Lett. 2009 Apr 15;19(8):2346-9. doi: 10.1016/j.bmcl.2009.02.029. Epub 2009 Feb 12.
3
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J Nat Prod. 2013 Nov 22;76(11):2026-33. doi: 10.1021/np400198r. Epub 2013 Oct 28.
在HepG2和RAW 264.7细胞中鉴定曲古抑菌素A作为清道夫受体BI的新型转录上调因子。
Atherosclerosis. 2009 May;204(1):127-35. doi: 10.1016/j.atherosclerosis.2008.08.041. Epub 2008 Sep 11.
4
Benzo[b]thiophene-based histone deacetylase inhibitors.基于苯并[b]噻吩的组蛋白脱乙酰酶抑制剂。
Bioorg Med Chem Lett. 2007 Aug 15;17(16):4562-7. doi: 10.1016/j.bmcl.2007.05.091. Epub 2007 Jun 6.
5
Design of novel histone deacetylase inhibitors.新型组蛋白去乙酰化酶抑制剂的设计
Bioorg Med Chem Lett. 2007 Aug 15;17(16):4619-24. doi: 10.1016/j.bmcl.2007.05.080. Epub 2007 May 27.
6
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J Med Chem. 2005 Jul 28;48(15):5047-51. doi: 10.1021/jm058214k.
9
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10
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Biochem J. 2003 Mar 15;370(Pt 3):737-49. doi: 10.1042/BJ20021321.