Investigation of the antioxidant properties of some new 4-hydroxycoumarin derivatives

Eur J Med Chem. 2009 Jul;44(7):3077-82. doi: 10.1016/j.ejmech.2008.07.007. Epub 2008 Jul 16.

Abstract

The aim of this investigation was to measure the activity of four 4-hydroxycoumarin derivatives - three of them were described before and one was newly synthesized. The substances were ethyl 2-[(4-hydroxy-2-oxo-2H-chromen-3-yl)(4-hydroxyphenyl)methyl]-3-oxobutanoate (SS-14), 4-[1-(4-hydroxy-2-oxo-2H-chromen-3-yl)-2-(ethoxycarbonyl)-3-oxobutyl]benzoic acid (SS-17), ethyl 2-[(4-hydroxy-2-oxo-2H-chromen-3-yl)(3-nitrophenyl)methyl]-3-oxobutanoate (SS-21) and ethyl 2-[(3,4,5-trimethoxyphenyl)(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]-3-oxobutanoate (T-2). The synthesis of T-2 consists of two steps. First step was Knoevenagel reaction between 3,4,5-trimethoxybenzaldehyde and ethylacetoacetate. Ethyl 2-(3,4,5-trimethoxy)-phenylmethyleneacetoacetate was the product. Second step was Michael addition reaction between the latter product and 4-hydroxycoumarin. All the compounds were tested in vitro for antioxidant activity in hypochlorous system. The assay was based on the luminol-dependent chemiluminescence of free radicals, which decreased in the presence of 4-hydroxycoumarin derivative. Compound SS-14 (ethyl 2-[(4-hydroxy-2-oxo-2H-chromen-3-yl)(4-hydroxyphenyl)methyl]-3-oxobutanoate) expresses the best scavenger activity at the highest concentration (10(-4)mol/L).

MeSH terms

  • 4-Hydroxycoumarins / chemical synthesis
  • 4-Hydroxycoumarins / chemistry*
  • 4-Hydroxycoumarins / pharmacology*
  • Drug Design*
  • Free Radical Scavengers / chemical synthesis
  • Free Radical Scavengers / chemistry*
  • Free Radical Scavengers / pharmacology*
  • Humans
  • Luminescence
  • Structure-Activity Relationship

Substances

  • 4-Hydroxycoumarins
  • Free Radical Scavengers
  • 4-hydroxycoumarin