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

[Display omitted] 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 synth...

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Veröffentlicht in:Bioorganic & medicinal chemistry 2015-01, Vol.23 (2), p.328-339
Hauptverfasser: Sakai, Taki, Matsumoto, Yotaro, Ishikawa, Minoru, Sugita, Kazuyuki, Hashimoto, Yuichi, Wakai, Nobuhiko, Kitao, Akio, Morishita, Era, Toyoshima, Chikashi, Hayashi, Tomoatsu, Akiyama, Tetsu
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Sprache:eng
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Zusammenfassung:[Display omitted] 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=0.60μM), with more than 150-fold selectivity over SIRT1 and SIRT3 isoforms (IC50 >100μM).
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2014.11.027