Novel (coumarin-3-yl)carbamates as selective MAO-B inhibitors: synthesis, in vitro and in vivo assays, theoretical evaluation of ADME properties and docking study

Eur J Med Chem. 2013 May:63:151-61. doi: 10.1016/j.ejmech.2013.02.009. Epub 2013 Feb 16.

Abstract

A series of (coumarin-3-yl)carbamates was synthesized and evaluated in vitro as monoamine oxidase (MAO-A and MAO-B) inhibitors. Most of the new compounds selectively inhibited MAO-B isoenzyme with IC50 values in the micro or nanoMolar ranges. Since these compounds must achieve the brain cells, theoretical evaluation of ADME properties were also carried out. Compound 8 (benzyl(coumarin-3-yl)carbamate), which presented the most interesting in vitro MAO-B inhibitory profile (IC50 against MAO-B = 45 nM), was subjected to further studies. This in vitro MAO-B inhibitory activity is comparable with that of the selegiline, the reference compound (IC50 against MAO-B = 20 nM). Taking into account the in vitro results of compound 8, in vivo assays and docking calculations were also carried out for this derivative.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocatalysis / drug effects
  • Carbamates / chemical synthesis
  • Carbamates / chemistry*
  • Coumarins / chemistry*
  • Dose-Response Relationship, Drug
  • Humans
  • Hydrogen Peroxide / metabolism
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Monoamine Oxidase / chemistry*
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors / chemical synthesis
  • Monoamine Oxidase Inhibitors / chemistry*
  • Monoamine Oxidase Inhibitors / pharmacology
  • Motor Activity / drug effects
  • Protein Binding
  • Protein Structure, Tertiary
  • Selegiline / pharmacology
  • Substrate Specificity
  • Tyramine / metabolism

Substances

  • Carbamates
  • Coumarins
  • Monoamine Oxidase Inhibitors
  • Selegiline
  • coumarin
  • Hydrogen Peroxide
  • Monoamine Oxidase
  • Tyramine