Selective inhibition of platelet lipoxygenase by esculetin

Biochim Biophys Acta. 1982 Oct 14;713(1):68-72.

Abstract

The effects of coumarin and its derivatives on rat platelet lipoxygenase and cyclooxygenase activities were studied. Esculetin (6,7-dihydroxycoumarin) was found to inhibit the lipoxygenase more strongly than the cyclooxygenase; its concentration for 50% inhibition (IC50) was 0.65 microM for platelet lipoxygenase and 0.45 mM for platelet cyclooxygenase. Esculin (the 6-glucoside of esculetin) and umbelliferone (7-hydroxy-coumarin) also selectively inhibited the lipoxygenase, though less strongly (IC50 = 290 and 500 microM, respectively). 4-Hydroxycoumarin and coumarin had no inhibitory effect on either enzyme at concentrations up to 1 mM. The mechanism of the lipoxygenase inhibition by esculetin was non-competitive. Other antioxidants (hydroquinone, gallic acid and ascorbic acid) were less inhibitory to both enzymes and showed little selectivity.

MeSH terms

  • 4-Hydroxycoumarins / pharmacology
  • Animals
  • Antioxidants / pharmacology
  • Blood Platelets / enzymology*
  • Coumarins / pharmacology
  • Cyclooxygenase Inhibitors
  • Esculin / pharmacology
  • Lipoxygenase / blood*
  • Lipoxygenase Inhibitors
  • Prostaglandin-Endoperoxide Synthases / blood*
  • Rats
  • Rats, Inbred Strains
  • Umbelliferones / pharmacology*

Substances

  • 4-Hydroxycoumarins
  • Antioxidants
  • Coumarins
  • Cyclooxygenase Inhibitors
  • Lipoxygenase Inhibitors
  • Umbelliferones
  • Esculin
  • Lipoxygenase
  • Prostaglandin-Endoperoxide Synthases
  • esculetin