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

Takayoshi Suzuki; Tomomi Asaba; Erika Imai; Hiroki Tsumoto; Hidehiko Nakagawa; Naoki Miyata

doi:10.1016/j.bmcl.2009.08.028

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

Bioorg Med Chem Lett. 2009 Oct 1;19(19):5670-2. doi: 10.1016/j.bmcl.2009.08.028. Epub 2009 Aug 12.

Authors

Takayoshi Suzuki¹, Tomomi Asaba, Erika Imai, Hiroki Tsumoto, Hidehiko Nakagawa, Naoki Miyata

Affiliation

¹ 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

PMID: 19700324
DOI: 10.1016/j.bmcl.2009.08.028

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylation
HCT116 Cells
Humans
Lysine / analogs & derivatives*
Lysine / chemical synthesis
Lysine / chemistry*
Lysine / pharmacology
Niacinamide / pharmacology
Recombinant Proteins / antagonists & inhibitors
Recombinant Proteins / metabolism
Sirtuins / antagonists & inhibitors*
Sirtuins / metabolism
Thioamides / chemical synthesis
Thioamides / chemistry*
Thioamides / pharmacology
Tumor Suppressor Protein p53 / metabolism

Substances

Recombinant Proteins
Thioamides
Tumor Suppressor Protein p53
Niacinamide
Sirtuins
Lysine