含N-硫代乙酰赖氨酸的细胞活性非肽类沉默调节蛋白抑制剂的鉴定
Identification of a cell-active non-peptide sirtuin inhibitor containing N-thioacetyl lysine.
作者信息
Suzuki Takayoshi, Asaba Tomomi, Imai Erika, Tsumoto Hiroki, Nakagawa Hidehiko, Miyata Naoki
机构信息
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
出版信息
Bioorg Med Chem Lett. 2009 Oct 1;19(19):5670-2. doi: 10.1016/j.bmcl.2009.08.028. Epub 2009 Aug 12.
To identify cell-active sirtuin inhibitors containing N-thioacetyl lysine, we synthesized compound 1, which was designed based on the structure of the reported N-ethoxycarbonylacetyl lysine-based sirtuin inhibitor NCS-12k. Compound 1 selectively inhibited SIRT1 in enzyme assays. Compound 1 also caused a dose-dependent increase in p53 acetylation in human colon cancer HCT116 cells, indicating the inhibition of SIRT1 in these cells.
为了鉴定含N-硫代乙酰赖氨酸的细胞活性沉默调节蛋白抑制剂，我们合成了化合物1，它是基于已报道的基于N-乙氧羰基乙酰赖氨酸的沉默调节蛋白抑制剂NCS-12k的结构设计的。在酶分析中，化合物1选择性地抑制SIRT1。化合物1还导致人结肠癌HCT116细胞中p53乙酰化呈剂量依赖性增加，表明在这些细胞中SIRT1受到抑制。
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