Phenolic compounds as antiangiogenic CMG2 inhibitors from costa rican endophytic fungi

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:22

Article

Cao, Shugeng¹  Cryan, Lorna²  Habeshian, Kaiane A.²  Murillo, Catalina³  Tamayo-Castillo, Giselle^3,4  Rogers, Michael S.²  Clardy, Jon¹ 

[1] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Childrens Hosp Boston, Vasc Biol Program, Boston, MA 02115 USA

[3] Inst Nacl Biodiversidad INBio, Unidad Estrateg Bioprospecc, Santo Domingo De Heredia, Costa Rica

[4] Univ Costa Rica, Escuela Quim, San Jose, Costa Rica

关键词: Fungus;    Coccomyces proteae;    Aurapex penicillata;    CMG2;    Phenolic;   

DOI  :  10.1016/j.bmcl.2012.07.075

来源: Elsevier

【 摘 要 】

Targeting and inhibiting CMG2 (Capillary Morphogenesis Gene protein 2) represents a new strategy for therapeutic agents for cancer and retinal diseases due to CMG2's role in blood vessel growth (angiogenesis). A high throughput FRET (Forster Resonance Energy Transfer) assay was developed for the identification of CMG2 inhibitors as anti-angiogenetic agents. Bioassay-guided separation led to the isolation and identification of two new compounds (1 and 2) from CR252M, an endophytic fungus Coccomyces proteae collected from a Costa Rican rainforest, and one known compound (3) from CR1207B (Aurapex penicillata). Secondary in vitro assays indicated anti-angiogenic activity. Compound 3 inhibited the endothelial cell migration at 52 mu M, but did not show any endothelial cell antiproliferative effect at 156 mu M. The structure of the two new compounds, A (1) and B (2), were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR experiments. (C) 2012 Elsevier Ltd. All rights reserved.

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