Phenolic compounds as antiangiogenic CMG2 inhibitors from Costa Rican endophytic fungi.
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.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Shugeng
S
Cao
Lorna
L
Cryan
Kaiane A
KA
Habeshian
Catalina
C
Murillo
Giselle
G
Tamayo-Castillo
Michael S
MS
Rogers
Jon
J
Clardy
D001203:Ascomycota / Q000737:chemistry*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003364:Costa Rica; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018000:Receptors, Peptide; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C447150:ANTXR2 protein, human; D008565:Membrane Proteins; D010636:Phenols; D018000:Receptors, Peptide