Synthesis, biological characterization and molecular modeling insights of spirochromanes as potent HDAC inhibitors

Eur J Med Chem. 2016 Jan 27:108:53-67. doi: 10.1016/j.ejmech.2015.11.010. Epub 2015 Nov 11.


In the last decades, inhibitors of histone deacetylases (HDAC) have become an important class of anti-cancer agents. In a previous study we described the synthesis of spiro[chromane-2,4'-piperidine]hydroxamic acid derivatives able to inhibit histone deacetylase enzymes. Herein, we present our exploration for new derivatives by replacing the piperidine moiety with various cycloamines. The goal was to obtain highly potent compounds with a good in vitro ADME profile. In addition, molecular modeling studies unravelled the binding mode of these inhibitors.

Keywords: Antiproliferation; Epigenetics; Histone deacetylases; Molecular modeling; Privileged structures.

MeSH terms

  • Chromones / chemical synthesis
  • Chromones / chemistry
  • Chromones / pharmacology*
  • Dose-Response Relationship, Drug
  • Histone Deacetylase Inhibitors / chemical synthesis*
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / metabolism*
  • Humans
  • Models, Molecular*
  • Molecular Structure
  • Spiro Compounds / chemical synthesis
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology*
  • Structure-Activity Relationship


  • Chromones
  • Histone Deacetylase Inhibitors
  • Spiro Compounds
  • Histone Deacetylases