Design, synthesis, and biological activity of hydroxamic tertiary amines as histone deacetylase inhibitors

ChemMedChem. 2012 Apr;7(4):694-702. doi: 10.1002/cmdc.201100531. Epub 2012 Jan 25.

Abstract

Herein we describe the design, synthesis, and biological evaluation of new hydroxamic tertiary amines as histone deacetylase (HDAC) inhibitors. These compounds have allowed us to clarify the influence of cap group dimension and hydrophobicity on HDAC inhibitory activity. This report also reveals the recognition pattern between the linear compounds and the histone deacetylase-like protein (HDLP) model receptor, and discusses the synthesis and in vitro evaluation of HDAC inhibitory activity in HeLa cell nuclear extracts. We obtained good qualitative agreement between experimental results and theoretical predictions, confirming that appropriately substituted hydroxamic tertiary amines are potential active HDAC inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Drug Design
  • Drug Evaluation, Preclinical / methods
  • HeLa Cells
  • Histone Deacetylase Inhibitors / chemical synthesis
  • Histone Deacetylase Inhibitors / chemistry*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / metabolism
  • Humans
  • Hydroxamic Acids / chemistry
  • Inhibitory Concentration 50
  • Models, Molecular
  • Molecular Structure

Substances

  • Amines
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Histone Deacetylases