Pharmacological Properties of a New Anti-Inflammatory Compound, α-(3,5-Di-Tert-Butyl-4-Hydroxybenzylidene)-γ-Butyrolactone (KME-4), and Its Inhibitory Effects on Prostaglandin Synthetase and 5-Lipoxygenase

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Abstract
The pharmacological effects of a new antiinflammatory compound, .alpha.-(3,5-di-tert-butyl-4-hydroxybenzylidene)-.gamma.-butyrolactone (KME-4) and its inhibitory effects on arachidonate prostaglandin synthetase and 5-lipoxygenase activities were examined. KME-4 showed antiinflammatory activity. It was less active than indomethacin, but more active than naproxen and ibuprofen in carrageenin-induced paw edema in rats; and less active than indomethacin, equipotent as naproxen, but more active than ibuprofen in granuloma formation in rats. The ulcerogenic activity of KME-4 was weaker than indomethacin and naproxen, but stronger than ibuprofen in starved rats. The ratio of UD50 stomach to ED30 carrageenin edema or to ED25 granuloma for KME-4 showed higher values than those of the reference drugs. KME-4 showed antipyretic activity in yeast-induced fever in rats. It also inhibited platelet aggregation induced by arachidonic acid and protected rabbits from arachidonic acid-induced death. KME-4 was equipotent in inhibiting both prostaglandin synthetase and 5-lipoxygenase activities of rat basophilic leukemia cells, unlike indomethacin, naproxen and ibuprofen. It also inhibited the prostaglandin synthetase activity of bovine seminal vesicle. KME-4 may be a new type of antiinflammatory drug with dual prostaglandin synthetase and 5-lipoxygenase inhibition.