Carprofen analogues as sirtuin inhibitors: enzyme and cellular studies

ChemMedChem. 2012 Nov;7(11):1905-8. doi: 10.1002/cmdc.201200318.

Abstract

The best of both: SIRT1/2 inhibitors were developed by combining chemical features of selisistat (SIRT1-selective inhibitor; blue) and carprofen (anti-inflammatory drug; red). The most potent compound (shown) increased acetyl-p53 and acetyl-α-tubulin levels, and induced slight apoptosis at 50 μM in U937 cells, differently from selisistat and carprofen.

Keywords: SIRT1/2; apoptosis; histone deacetylases; inhibitors; sirtuins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Carbazoles / chemistry*
  • Carbazoles / pharmacology*
  • Cell Line, Tumor
  • Histone Deacetylase Inhibitors / chemistry*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / enzymology*
  • Sirtuin 1 / antagonists & inhibitors*
  • Sirtuin 1 / metabolism
  • Sirtuin 2 / antagonists & inhibitors*
  • Sirtuin 2 / metabolism
  • Tubulin / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Carbazoles
  • Histone Deacetylase Inhibitors
  • Tubulin
  • Tumor Suppressor Protein p53
  • Sirtuin 1
  • Sirtuin 2
  • carprofen