Inhibition of Polymorphonuclear Leukocyte 5-Lipoxygenase and Platelet Cyclooxygenase by α-(3, 5-Di-Tert-Butyl-4-Hydroxybenzylidene)-γ-Butyrolactone (KME-4), a New Anti-Inflammatory Drug

Abstract

The effect of α-(3, 5-di-tert-butyl-4-hydroxybenzylidene)-γ-butyrolactone (KME-4), a new anti-inflammatory compound, on arachidonate lipoxygenase and cyclooxygenase was investigated. KME-4 showed a dose-dependent inhibition of 5-lipoxygenase activity in both the cytosol (IC50: 0.85 μM) and ionophore A23187-stimulated cells (IC50: 11.5 μM) of guinea pig peritoneal polymorphonuclear leukocytes. KME-4 was also found to inhibit rabbit platelet cyclooxygenase (IC50: 0.44 μM), but had no inhibitory effect on platelet 12-lipoxygenase at concentrations up to 100 μM, whereas BW755C inhibited both enzymes in the same range of concentrations. The results indicate that KME-4 is a dual 5-lipoxygenase and cyclooxygenase inhibitor which is different from BW755C in affecting 1 2-lipoxygenase. These effects may provide information for understanding the pharmacological activity of KME-4.