Selective inhibition of platelet lipoxygenase by esculetin.
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.
D015110:4-Hydroxycoumarins / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology*; D003374:Coumarins / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D004929:Esculin / Q000494:pharmacology; D008084:Lipoxygenase / Q000097:blood*; D016859:Lipoxygenase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains; D014468:Umbelliferones / Q000494:pharmacology*
D015110:4-Hydroxycoumarins; D000975:Antioxidants; D003374:Coumarins; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D014468:Umbelliferones; D004929:Esculin; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; C007628:esculetin