1. Phenolic compounds as antiangiogenic CMG2 inhibitors from Costa Rican endophytic fungi.
- Author
-
Cao S, Cryan L, Habeshian KA, Murillo C, Tamayo-Castillo G, Rogers MS, and Clardy J
- Subjects
- Cell Movement drug effects, Cell Proliferation drug effects, Costa Rica, Dose-Response Relationship, Drug, Endothelial Cells drug effects, Humans, Molecular Structure, Phenols chemistry, Phenols isolation & purification, Receptors, Peptide, Stereoisomerism, Structure-Activity Relationship, Ascomycota chemistry, Membrane Proteins antagonists & inhibitors, Phenols pharmacology
- Abstract
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 (Förster 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 μM, but did not show any endothelial cell antiproliferative effect at 156 μM. 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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF