Daphnetin (DP)

Daphnin is a plant toxin.[1] It can be produced from dihydroxycoumarin by O-dihydroxycoumarin 7-O-glucosyltransferase. Protein kinases play key roles in the control of cell proliferation, differentiation and metabolism. It was found that, in these compounds, only daphnetin was a protein kinase inhibitor. This compound inhibited tyrosine-specific protein kinase, The inhibition of EGF receptor tyrosine kinase by daphnetin was competitive to ATP and non-competitive to the peptide substrate. The inhibition of EGF-induced tyrosine phosphorylation of EGF receptor by daphnetin was not observed in human hepatocellular carcinoma HepG2 cells. The structural comparison of daphnetin with coumarin and other coumarin derivatives suggests that the hydroxylation at C8 may be required for daphnetin acting as a protein kinase inhibitor.