Antiangiogenic Metabolites from a Marine-Derived Fungus, Hypocrea vinosa
Antiangiogenic Metabolites from a Marine-Derived Fungus, Hypocrea vinosa
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DOI：
10.1021/np900698p
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发表时间：
2010-04-01
影响因子：
5.1
通讯作者：
Koyama, Kiyotaka
中科院分区：
文献类型：
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作者：
Ohkawa, Yuu;Miki, Kazuhiko;Koyama, Kiyotaka
本研究的目的是研究酪氨酸激酶在细胞内信号传导中的作用，并从海洋源性真菌的代谢物中寻找具有酪氨酸激酶抑制活性的先导化合物。我们最初从 200 种海洋真菌中制备了 400 种提取物，然后使用人脐静脉内皮细胞裂解物对它们进行酪氨酸激酶筛选测定。在 Hypocrea vinosa 的某些代谢物中观察到酪氨酸激酶抑制活性。我们分离出一种已知化合物 SC2051 (1)，以及两种新化合物次色素 A (2) 和 B (3)，它们具有双（萘并-γ-吡喃酮）骨架。化合物1-3显示出酪氨酸激酶抑制活性，IC(50)值分别为42.1、58.7和18.0μM。此外，化合物1-3对增殖、迁移和肾小管形成具有抑制作用。
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 mu M, respectively. Furthermore, compounds 1-3 exhibited inhibitory effects on proliferation, migration, and tubule formation.