Inhibitory effect of esculetin on 5-lipoxygenase and leukotriene biosynthesis

Esculetin (6,7-dihydroxycoumarin) showed inhibitory effects on 5- and 12-lipoxygenases of cloned mastocytoma cells. The half-inhibition dose (ID50) for each enzyme was 4 X 10(-6) and 2.5 X 10(-6) M, respectively. No inhibition at all, but rather a stimulating effect on prostaglandin synthesis, was observed, especially at higher doses of esculetin. Leukotriene synthesis by mouse mast tumour cells was also reduced in the presence of esculetin in parallel with 5-lipoxygenase inhibition. From these results, esculetin may be useful as a tool for research on regulatory mechanisms or physiological functions of leukotrienes.