Inhibition of polymorphonuclear leukocyte 5-lipoxygenase and platelet cyclooxygenase by alpha-(3,5-di-tert-butyl-4-hydroxybenzylidene)-gamma-butyrolacto ne (KME-4), a new anti-inflammatory drug.
The effect of alpha-(3,5-di-tert-butyl-4-hydroxybenzylidene)-gamma-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 microM) and ionophore A23187-stimulated cells (IC50: 11.5 microM) of guinea pig peritoneal polymorphonuclear leukocytes. KME-4 was also found to inhibit rabbit platelet cyclooxygenase (IC50: 0.44 microM), but had no inhibitory effect on platelet 12-lipoxygenase at concentrations up to 100 microM, 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 12-lipoxygenase. These effects may provide information for understanding the pharmacological activity of KME-4.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001091:Arachidonate Lipoxygenases; D001792:Blood Platelets / Q000201:enzymology*; D000001:Calcimycin / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D016861:Cyclooxygenase Inhibitors; D005663:Furans / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D008297:Male; D009504:Neutrophils / Q000201:enzymology*; D011720:Pyrazoles / Q000494:pharmacology; D011817:Rabbits
D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D005663:Furans; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D000001:Calcimycin; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; C043236:KME 4; D001091:Arachidonate Lipoxygenases; D015107:4-Butyrolactone; D007213:Indomethacin