Investigation on the ZBG-functionality of phenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase inhibitors

Bioorg Med Chem Lett. 2015 Oct 15;25(20):4457-60. doi: 10.1016/j.bmcl.2015.09.006. Epub 2015 Sep 5.

Abstract

A series of alternative Zn-binding groups were explored in the design of phenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors. Most of the synthesized compounds were less effective than the parent hydroxamic acid. However, the profile of activity shown by the analog bearing a hydroxyurea head group, makes this derivative promising for further investigation.

Keywords: Antiproliferative activity; Histone deacetylase (HDAC) inhibitors; Synthesis; Zn-binding group.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Histone Deacetylase 2 / antagonists & inhibitors*
  • Histone Deacetylase 2 / metabolism
  • Histone Deacetylase Inhibitors / chemical synthesis
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Hydroxamic Acids / chemistry
  • Hydroxamic Acids / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Structure-Activity Relationship
  • Zinc / chemistry
  • Zinc / pharmacology*

Substances

  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Organometallic Compounds
  • HDAC2 protein, human
  • Histone Deacetylase 2
  • Zinc