title: Antiangiogenic metabolites from a marine-derived fungus, Hypocrea vinosa.
abstract: 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.
authors.affiliation: Department of Pharmacy, Japanese Foundation for Cancer Research, Cancer Institute Hospital, Ariake 3-10-6, Koto-ku, Tokyo 135-8550, Japan.
authors.forename: Yuu
authors.initials: Y
authors.lastname: Ohkawa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Miki
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugita
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kinoshita
authors.forename: Kunio
authors.initials: K
authors.lastname: Takahashi
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Koyama
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D035901:Hypocrea / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D007564:Japan; D008386:Marine Biology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D011753:Pyrones; C549654:SC2051; C549656:hypochromin A; C549655:hypochromin B; D011505:Protein-Tyrosine Kinases