Synthesis and Selective Human Monoamine Oxidase Inhibition of 3-carbonyl, 3-acyl, and 3-carboxyhydrazido Coumarin Derivatives

Eur J Med Chem. 2011 Oct;46(10):4846-52. doi: 10.1016/j.ejmech.2011.07.017. Epub 2011 Jul 19.

Abstract

Several 3-carbonyl (1-26), 3-acyl (27-52), and 3-carboxyhydrazido (53-58) coumarins have been synthesized in high yields (72-99%) and tested in vitro for their human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitory activity. Different substituents on the coumarin nucleus were evaluated for their effect on biological activity and isoform selectivity. Substitution at position C7 of the 3-ethyl ester coumarin ring, or the introduction of a hydrazido substituent at C3, were important to obtain highly potent and selective hMAO-B inhibitors with IC(50) values in the nanomolar range. Some derivatives were also submitted to a stability test and showed no chemical cleavage in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coumarins / chemical synthesis
  • Coumarins / chemistry*
  • Coumarins / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular
  • Monoamine Oxidase / chemistry
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / chemical synthesis
  • Monoamine Oxidase Inhibitors / chemistry*
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Coumarins
  • Monoamine Oxidase Inhibitors
  • Monoamine Oxidase