New 2H-chromene-3-carboxamide derivatives: design, synthesis and use as inhibitors of hMAO

Eur J Med Chem. 2014 Jun 10:80:278-84. doi: 10.1016/j.ejmech.2014.04.060. Epub 2014 Apr 23.

Abstract

A series new 2H-chromene-3-carboxamide derivatives 4a-4t were synthesized and evaluated as monoamine oxidase A and B (MAO-A and MAO-B) inhibitors. Among them, compound 4d (IC50 = 0.93 μM, IC(50 iproniazid) = 7.80 μM) showed the most activity and higher MAO-B selectivity (64.5-fold vs. 1-fold) with respect to the MAO-A isoform. The active compound 4d was also docked into the hMAO-B complex structure active site to determine the probable binding model. The results indicated that conserved residue CYSA 172 was important for ligand binding via hydrogen bond interaction, Pi-Pi interaction was found between the benzene-ring of compound 4d and residue ILEA 199.

Keywords: Coumarin; Design; Inhibitors; Synthesis; hMAO-B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzopyrans / chemical synthesis*
  • Benzopyrans / chemistry
  • Benzopyrans / metabolism
  • Benzopyrans / pharmacology*
  • Chemistry Techniques, Synthetic
  • Drug Design*
  • Humans
  • Inhibitory Concentration 50
  • Molecular Docking Simulation
  • Monoamine Oxidase / chemistry
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / chemical synthesis*
  • Monoamine Oxidase Inhibitors / chemistry
  • Monoamine Oxidase Inhibitors / metabolism
  • Monoamine Oxidase Inhibitors / pharmacology*

Substances

  • Benzopyrans
  • Monoamine Oxidase Inhibitors
  • Monoamine Oxidase