Synthesis and biological characterisation of sirtuin inhibitors based on the tenovins

Bioorg Med Chem. 2012 Mar 1;20(5):1779-93. doi: 10.1016/j.bmc.2012.01.001. Epub 2012 Jan 12.

Abstract

The tenovins are small molecule inhibitors of the NAD(+)-dependent family of protein deacetylases known as the sirtuins. There remains considerable interest in inhibitors of this enzyme family due to possible applications in both cancer and neurodegenerative disease therapy. Through the synthesis of novel tenovin analogues, further insights into the structural requirements for activity against the sirtuins in vitro are provided. In addition, the activity of one of the analogues in cells led to an improved understanding of the function of SirT1 in cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Benzamides / chemical synthesis
  • Benzamides / chemistry
  • Benzamides / pharmacology
  • Histone Deacetylase Inhibitors / chemical synthesis
  • Histone Deacetylase Inhibitors / chemistry*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Hydrogen Bonding
  • MCF-7 Cells
  • Molecular Conformation
  • Sirtuins / antagonists & inhibitors*
  • Sirtuins / chemistry
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Benzamides
  • Histone Deacetylase Inhibitors
  • tenovin-6
  • Sirtuins