Identification of a cell-active non-peptide sirtuin inhibitor containing N-thioacetyl lysine

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 caus...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2009-10, Vol.19 (19), p.5670-5672
Hauptverfasser:	Suzuki, Takayoshi, Asaba, Tomomi, Imai, Erika, Tsumoto, Hiroki, Nakagawa, Hidehiko, Miyata, Naoki
Format:	Artikel
Sprache:	eng
Schlagworte:	Acetylation Antineoplastic agents Biological and medical sciences General aspects HCT116 Cells Humans Lysine - analogs & derivatives Lysine - chemical synthesis Lysine - chemistry Lysine - pharmacology Medical sciences Niacinamide - pharmacology Non-peptide Pharmacology. Drug treatments Recombinant Proteins - antagonists & inhibitors Recombinant Proteins - metabolism Sirtuin inhibitor Sirtuins - antagonists & inhibitors Sirtuins - metabolism Thioacetyl lysine Thioamides - chemical synthesis Thioamides - chemistry Thioamides - pharmacology Tumor Suppressor Protein p53 - metabolism
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Zusammenfassung:	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. 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.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2009.08.028