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
收藏
页码：328 / 339
页数：12
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