Synthesis and biological characterisation of sirtuin inhibitors based on the tenovins

被引：46

作者：

McCarthy, Anna R. ^{[1
,3
]}

Pirrie, Lisa ^{[1
]}

Hollick, Jonathan J. ^{[1
]}

Ronseaux, Sebastien ^{[2
]}

Campbell, Johanna ^{[2
]}

Higgins, Maureen ^{[2
]}

Staples, Oliver D. ^{[2
]}

Fanny Tran ^{[1
]}

Slawin, Alexandra M. Z. ^{[1
]}

Lain, Sonia ^{[2
,3
]}

Westwood, Nicholas J. ^{[1
]}

机构：

[1] Univ St Andrews, Sch Chem & Biomed Sci Res Complex, St Andrews KY16 9ST, Fife, Scotland

[2] Univ Dundee, Ninewells Hosp & Med Sch, Dept Surg & Mol Oncol, Dundee DD1 9SY, Scotland

[3] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, SE-17177 Stockholm, Sweden

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 05期

关键词：

Sirtuin; Parallel synthesis; Chemical tool; Metabolism; Neurodegenerative diseases; CAMBINOL ANALOGS; P53; TOXICITY;

D O I：

10.1016/j.bmc.2012.01.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The tenovins are small molecule inhibitors of the NAD(+)-dependent family of protein deacetylases known as the sirtuins. There remains considerable interest in inhibitors of this enzyme family due to possible applications in both cancer and neurodegenerative disease therapy. Through the synthesis of novel tenovin analogues, further insights into the structural requirements for activity against the sirtuins in vitro are provided. In addition, the activity of one of the analogues in cells led to an improved understanding of the function of SirT1 in cells. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：1779 / 1793

页数：15

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