Novel inhibitors of human histone deacetylases: design, synthesis and bioactivity of 3-alkenoylcoumarines

Bioorg Med Chem Lett. 2014 Aug 15;24(16):3797-801. doi: 10.1016/j.bmcl.2014.06.067. Epub 2014 Jun 28.

Abstract

Histone deacetylases (HDACs) are well-established, promising targets for anticancer therapy due to their critical role in cancer development. Accordingly, an increasing number of HDAC inhibitors displaying cytotoxic effects against cancer cells have been reported. Among them, a large panel of chemical structures was described including coumarin-containing molecules. In this study, we described synthesis and biological activity of new coumarin-based derivatives as HDAC inhibitors. Among eight derivatives, three compounds showed HDAC inhibitory activities and antitumor activities against leukemia cell lines without affecting the viability of peripheral blood mononuclear cells from healthy donors.

Keywords: Anti-proliferative activity; Cancer; Chalcone; Coumarin; Histone deacetylase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coumarins / chemical synthesis
  • Coumarins / chemistry
  • Coumarins / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Histone Deacetylase Inhibitors / chemical synthesis
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / metabolism*
  • Humans
  • K562 Cells
  • Molecular Structure
  • Structure-Activity Relationship
  • U937 Cells

Substances

  • Antineoplastic Agents
  • Coumarins
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases