(E)-3-Heteroarylidenechroman-4-ones as Potent and Selective Monoamine oxidase-B Inhibitors

Eur J Med Chem. 2016 Jul 19;117:292-300. doi: 10.1016/j.ejmech.2016.03.081. Epub 2016 Mar 29.


A series of (E)-3-heteroarylidenechroman-4-ones (1a-r) was designed, synthesized and investigated in vitro for their ability to inhibit the enzymatic activity of both human monoamine oxidase (hMAO) isoforms, hMAO-A and hMAO-B. All the compounds were found to be selective hMAO-B inhibitors showing IC50 values in the nanomolar or micromolar range. (E)-5,7-Dichloro-3-{[(2-(dimethylamino)pyrimidin-5-yl]methylene}chroman-4-one (1c) was the most interesting compound identified in this study, endowed with higher hMAO-B potency (IC50 = 10.58 nM) and selectivity (SI > 9452) with respect to the reference selective inhibitor selegiline (IC50 = 19.60 nM, IC50 > 3431). Molecular modelling studies were performed for rationalizing at molecular level the target selective inhibition of our compounds, revealing a remarkable contribution of hydrogen bond network and water solvent.

Keywords: Chroman-4-ones; Docking studies; Homoisoflavonoids; Monoamine oxidases; Selective hMAO-B inhibitors.

MeSH terms

  • Chromans / chemistry*
  • Chromans / pharmacology
  • Humans
  • Hydrogen Bonding
  • Inhibitory Concentration 50
  • Models, Molecular
  • Monoamine Oxidase / drug effects
  • Monoamine Oxidase Inhibitors / chemistry*
  • Monoamine Oxidase Inhibitors / pharmacology
  • Sensitivity and Specificity
  • Solvents / pharmacology
  • Structure-Activity Relationship


  • Chromans
  • Monoamine Oxidase Inhibitors
  • Solvents
  • Monoamine Oxidase