A new series of 3-phenylcoumarins as potent and selective MAO-B inhibitors

Bioorg Med Chem Lett. 2009 Jun 15;19(12):3268-70. doi: 10.1016/j.bmcl.2009.04.085. Epub 2009 Apr 24.

Abstract

6-Methyl-3-phenylcoumarins 3-6 were designed, synthesized and evaluated as monoamine oxidase A and B (MAO-A and MAO-B) inhibitors. The synthesis of these new compounds (resveratrol-coumarin hybrids) was carried out with good yield by a Perkin reaction, from the 5-methylsalicylaldehyde and the corresponding phenylacetic acid. They show high selectivity to the MAO-B isoenzyme, with IC(50) values in the nanomolar range. Compound 5 is the most active compound and is several times more potent and selective than the reference compound, R-(-)-deprenyl.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants
  • Coumarins / chemical synthesis
  • Coumarins / chemistry*
  • Coumarins / pharmacology*
  • Drug Design
  • Humans
  • Inhibitory Concentration 50
  • Monoamine Oxidase / drug effects
  • Monoamine Oxidase Inhibitors / chemical synthesis
  • Monoamine Oxidase Inhibitors / chemistry*
  • Resveratrol
  • Selegiline / pharmacology
  • Stilbenes / chemistry*
  • Structure-Activity Relationship

Substances

  • Antioxidants
  • Coumarins
  • Monoamine Oxidase Inhibitors
  • Stilbenes
  • Selegiline
  • Monoamine Oxidase
  • Resveratrol