Lipoxygenase inhibitory activity of anacardic acids

6[8'(Z)-Pentadecenyl]salicylic acid, otherwise known as anacardic acid (C-15:1), inhibited the linoleic acid peroxidation catalyzed by soybean lipoxygenase-1 (EC 1.13.11.12, type 1) with an IC50 of 6.8 mu M. The inhibition of the enzyme by anacardic acid (C-15:1) is a slow and reversible reaction without residual activity. The inhibition kinetics analyzed by Dixon plots indicates that anacardic acid (C-15:1) is a competitive inhibitor and the inhibition constant, K-I, was obtained as 2.8 mu M. Although anacardic acid (C-15:1) inhibited the linoleic acid peroxidation without being oxidized, 6[8'(Z),11'(Z)-pentadecadienyl]salicylic acid, otherwise known as anacardic acid (C-15:2), was dioxygenated at low concentrations as a substrate. In addition, anacardic acid (C-15:2) was also found to exhibit time-dependent inhibition of lipoxygenase-1. The alk(en)yl side chain of anacardic acids is essential to elicit the inhibitory activity. However, the hydrophobic interaction alone is not enough because cardanol (C-15:1), which possesses the same side chain as anacardic acid (C-15:1), acted neither as a substrate nor as an inhibitor.