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 caused a dose-dependent increase in p53 acetylation in human colon cancer HCT116 cells, indicating the inhibition of SIRT1 in these cells.
Suzuki
Takayoshi
T
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. suzuki@phar.nagoya-cu.ac.jp
Asaba
Tomomi
T
Imai
Erika
E
Tsumoto
Hiroki
H
Nakagawa
Hidehiko
H
Miyata
Naoki
N
D000107:Acetylation; D045325:HCT116 Cells; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009536:Niacinamide / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013854:Thioamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D011994:Recombinant Proteins; D013854:Thioamides; D016159:Tumor Suppressor Protein p53; D009536:Niacinamide; D037761:Sirtuins; D008239:Lysine