Department of Pharmacy, Japanese Foundation for Cancer Research, Cancer Institute Hospital, Ariake 3-10-6, Koto-ku, Tokyo 135-8550, Japan.
J Nat Prod. 2010 Apr 23;73(4):579-82. doi: 10.1021/np900698p.
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.
本研究旨在探讨酪氨酸激酶在细胞内信号转导中的作用，并从海洋来源真菌的代谢产物中寻找具有酪氨酸激酶抑制活性的先导化合物。我们首先从 200 种海洋真菌中制备了 400 种提取物，然后用人脐静脉内皮细胞裂解物进行酪氨酸激酶筛选试验。在 Hypocrea vinosa 的某些代谢产物中观察到酪氨酸激酶抑制活性。我们分离到一个已知化合物 SC2051（1）以及两个新化合物，hypochromins A（2）和 B（3），它们具有双（萘并-γ-吡喃酮）骨架。化合物 1-3 表现出酪氨酸激酶抑制活性，IC50 值分别为 42.1、58.7 和 18.0 μM。此外，化合物 1-3 对增殖、迁移和管腔形成具有抑制作用。
