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

Taki Sakai, Yotaro Matsumoto, Minoru Ishikawa, Kazuyuki Sugita, Yuichi Hashimoto, Nobuhiko Wakai, Akio Kitao, Era Morishita, Chikashi Toyoshima, Tomoatsu Hayashi, Tetsu Akiyama

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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 μM), with more than 150-fold selectivity over SIRT1 and SIRT3 isoforms (IC50 >100 μM).

Original languageEnglish
Pages (from-to)328-339
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume23
Issue number2
DOIs
Publication statusPublished - 2015 Jan 15
Externally publishedYes

Keywords

  • SIRT2
  • Sirtuin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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