Design, synthesis, and biological evaluation of novel histone deacetylase 1 inhibitors through click chemistry

Bioorg Med Chem Lett. 2013 Jun 1;23(11):3295-9. doi: 10.1016/j.bmcl.2013.03.102. Epub 2013 Apr 4.

Abstract

We report the design, synthesis, and biological evaluation of a new series of HDAC1 inhibitors using click chemistry. Compound 17 bearing a phenyl ring at meta-position was identified to show much better selectivity for HDAC1 over HDAC7 than SAHA. The compond 17 also showed better in vitro anticancer activities against several cancer cell lines than that of SAHA. This work could serve as a foundation for further exploration of selective HDAC inhibitors using the compound 17 molecular scaffold.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Binding Sites
  • Catalytic Domain
  • Cell Line
  • Cell Proliferation / drug effects
  • Click Chemistry
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Drug Screening Assays, Antitumor
  • Histone Deacetylase 1 / antagonists & inhibitors*
  • Histone Deacetylase 1 / metabolism
  • Histone Deacetylase Inhibitors / chemical synthesis*
  • Histone Deacetylase Inhibitors / metabolism
  • Histone Deacetylase Inhibitors / toxicity
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / metabolism
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydroxamic Acids / chemistry
  • Hydroxamic Acids / metabolism
  • Hydroxamic Acids / toxicity
  • Molecular Docking Simulation
  • Protein Binding
  • Structure-Activity Relationship
  • Vorinostat

Substances

  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Vorinostat
  • HDAC7 protein, human
  • Histone Deacetylase 1
  • Histone Deacetylases