Inhibition of prostaglandin biosynthesis by coumarin, 4-hydroxycoumarin, and 7-hydroxycoumarin

Coumarin, 4-hydroxycoumarin and 7-hydroxycoumarin were found to inhibit the biosynthetic conversion of arachidonic acid to prostaglandin products by a synthetase complex from guinea pig lung. It was shown that there was only limited biotransformation of the parent coumarin molecule to hydroxylated metabolites in the test system and the inhibition of prostaglandin biosynthesis by coumarin was therefore a result of the intact molecule. The extent of inhibition produced by coumarin was equipotent to that of 4-hydroxycoumarin, 7-hydroxycoumarin, and acetylsalicylic acid in a particulate enzyme preparation. Interruption of the synthesis occurred during the initial cyclooxygenation reaction.