Antiangiogenic metabolites from a marine-derived fungus, Hypocrea vinosa.

The aims of this study were to investigate the role of tyrosine kinase in intracellular signaling and to search for lead compounds with tyrosine kinase inhibitory activity from metabolites of marine-derived fungi. We initially prepared 400 extracts from 200 species of marine fungi and then subjected them to a tyrosine kinase screening assay using human umbilical vein endothelial cell lysate. Tyrosine kinase inhibitory activity was observed among certain metabolites of Hypocrea vinosa. We isolated one known compound, SC2051 (1), as well as two new compounds, hypochromins A (2) and B (3), which have a bis(naphtho-gamma-pyrone) skeleton. Compounds 1-3 showed tyrosine kinase inhibitory activity, with IC(50) values of 42.1, 58.7, and 18.0 microMu, respectively. Furthermore, compounds 1-3 exhibited inhibitory effects on proliferation, migration, and tubule formation.