Phenolic compounds as antiangiogenic CMG2 inhibitors from costa rican endophytic fungi

作者：Cao Shugeng; Cryan Lorna; Habeshian Kaiane A; Murillo Catalina; Tamayo Castillo Giselle; Rogers Michael S; Clardy Jon^*

来源：Bioorganic & Medicinal Chemistry Letters, 2012, 22(18): 5885-5888.

DOI：10.1016/j.bmcl.2012.07.075

• Fungus
• Coccomyces proteae
• Aurapex penicillata
• CMG2
• Phenolic

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.

• 出版日期2012-9-15