N-Hydroxy-(4-oxime)-cinnamide: a versatile scaffold for the synthesis of novel histone deacetylase [correction of deacetilase] (HDAC) inhibitors

Bioorg Med Chem Lett. 2009 Apr 15;19(8):2346-9. doi: 10.1016/j.bmcl.2009.02.029. Epub 2009 Feb 12.

Abstract

With the aim to discover novel HDAC inhibitors with high potency and good safety profiles, we have designed a small library based on a N-hydroxy-(4-oxime)-cinnamide scaffold. We describe the synthesis of these novel compounds and some preliminary in vitro cytotoxic activity on three tumor cell lines, NB4, H460 and HCT116, as well as their inhibitory activity against class I, II and IV HDAC. Several 4-oxime derivatives demonstrated a promising inhibitory activity on HDAC6 and HDAC8 coupled to a good selectivity profile.

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cinnamates / chemical synthesis*
  • Cinnamates / metabolism
  • Cinnamates / pharmacology
  • Histone Deacetylase Inhibitors*
  • Histone Deacetylases / classification
  • Histone Deacetylases / metabolism
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / classification
  • Isoenzymes / metabolism
  • Protein Binding / physiology

Substances

  • Antineoplastic Agents
  • Cinnamates
  • Histone Deacetylase Inhibitors
  • Isoenzymes
  • Histone Deacetylases