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

Add time:07/13/2019    Source:sciencedirect.com

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).

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