Design, synthesis and structure-activity relationship studies of novel sirtuin 2 (SIRT2) inhibitors with a benzamide skeleton

被引：17

作者：

Sakai, Taki ^{[1
]}

Matsumoto, Yotaro ^{[1
]}

Ishikawa, Minoru ^{[1
]}

Sugita, Kazuyuki ^{[1
]}

Hashimoto, Yuichi ^{[1
]}

Wakai, Nobuhiko ^{[2
]}

Kitao, Akio ^{[2
]}

Morishita, Era ^{[3
]}

Toyoshima, Chikashi ^{[3
]}

Hayashi, Tomoatsu ^{[4
]}

Akiyama, Tetsu ^{[4
]}

机构：

[1] Univ Tokyo, Inst Mol & Cellular Biosci, Bioorgan Chem Lab, Bunkyo Ku, Tokyo 1130032, Japan

[2] Univ Tokyo, Inst Mol & Cellular Biosci, Lab Computat Prot Sci, Bunkyo Ku, Tokyo 1130032, Japan

[3] Univ Tokyo, Inst Mol & Cellular Biosci, Lab Membrane Prot, Bunkyo Ku, Tokyo 1130032, Japan

[4] Univ Tokyo, Inst Mol & Cellular Biosci, Lab Mol & Genet Informat, Bunkyo Ku, Tokyo 1130032, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2015年 / 23卷 / 02期

关键词：

Sirtuin; SIRT2; HISTONE DEACETYLASE; PROTEIN; DEHYDROGENASE; REGULATOR; LONGEVITY; INTERACTS; HOMOLOG;

D O I：

10.1016/j.bmc.2014.11.027

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：

Human sirtuin 2 (SIRT2) is an attractive target molecule for development of drugs to treat neurodegenerative diseases and cancer, because SIRT2 inhibitors have a protective effect against neurodegeneration and an anti-proliferative effect on cancer stem cells. We designed and synthesized a series of benzamide derivatives as SIRT2 inhibitor candidates. Among them, compound 17k showed the most potent SIRT2-inhibitory activity (IC50 = 0.60 mu M), with more than 150-fold selectivity over SIRT1 and SIRT3 isoforms (IC50 > 100 mu M). (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：328 / 339

页数：12

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