Design, synthesis and biological evaluation of di-substituted cinnamic hydroxamic acids bearing urea/thiourea unit as potent histone deacetylase inhibitors

Bioorg Med Chem Lett. 2013 Dec 1;23(23):6432-5. doi: 10.1016/j.bmcl.2013.09.051. Epub 2013 Sep 25.

Abstract

A novel class of di-substituted cinnamic hydroxamic acid derivatives containing urea or thiourea unit was designed, synthesized and evaluated as HDAC inhibitors. All tested compounds demonstrated significant HDAC inhibitory activities and anti-proliferative effects against diverse human tumor cell lines. Among them, 7l exhibited most potent pan-HDAC inhibitory activity, with an IC50 value of 130 nM. It also showed strong cellular inhibition against diverse cell lines including HCT-116, MCF-7, MDB-MB-435 and NCI-460, with GI50 values of 0.35, 0.22, 0.51 and 0.48 μM, respectively.

Keywords: Cinnamic hydroxamaic acid; HDAC; Histone deacetylase; Thiourea; Urea.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cinnamates / chemical synthesis
  • Cinnamates / chemistry*
  • Cinnamates / pharmacology*
  • Drug Design
  • Drug Screening Assays, Antitumor
  • HCT116 Cells
  • Histone Deacetylase Inhibitors / chemical synthesis
  • Histone Deacetylase Inhibitors / chemistry*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Hydroxamic Acids / chemical synthesis
  • Hydroxamic Acids / chemistry*
  • Hydroxamic Acids / pharmacology*
  • MCF-7 Cells
  • Models, Molecular
  • Structure-Activity Relationship
  • Thiourea / analogs & derivatives
  • Thiourea / chemistry
  • Thiourea / pharmacology
  • Urea / analogs & derivatives
  • Urea / chemistry
  • Urea / pharmacology

Substances

  • Cinnamates
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • cinnamic acid
  • Urea
  • Thiourea