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Nine acetylenic acids were evaluated to determine what structural features are required for selective inhibition of platelet lipoxygenase. Both 4,7,10,13-icosatetraynoic acid and 5,8,11,14-henicosatetraynoic acid inhibited the synthesis of 12-L-hydroxy-5,8,10,14-icosatetraenoic acid (HETE) more than 95 percent without significantly altering the production of either thromboxane B2 or 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT). The ID50 concentrations (microM) for inhibiting the synthesis of thromboxane B2 and HETE were respectively 51 and 0.46 with 4,7,10,13-icosatetraynoic acid while similar concentrations of 64 and 0.31 were found for 5,8,11,14-henicosatetraynoic acid.
T E Wilhelm, and
S K Sankarappa, and
M VanRollins, and
H Sprecher
August 1983,
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