Bioassay-Guided Isolation of Proanthocyanidins with Antiangiogenic Activities

The proangiogenic members of the vascular endothelial growth factor (VEGF) family and related receptors play a central role in the modulation of pathological angiogenesis. In order to identify plant compounds able to interfere in the VEGFs/VEGFR-1 (Flt-1) recognition by VEGF family members, the extracts of the aerial parts of <i>Campsiandra guayanensis</i> and <i>Feretia apodanthera</i> were screened by a competitive ELISA-based assay. By using this bioassay-oriented approach five proanthocyanindins, including the new natural compounds (2<i>S</i>)-4′,5,7-trihydroxyflavan-(4β→8)-afzelechin (<b>1</b>) and (2<i>S</i>)-4′,5,7-trihydroxyflavan-(4β→8)-epiafzelechin (<b>2</b>) and the known geranin B (<b>3</b>), proanthocyanidin A2 (<b>4</b>), and proanthocyanidin A1 (<b>5</b>), were isolated. The study of the antiangiogenic activities of compounds <b>1</b>–<b>5</b> using ELISA and SPR assays showed compound <b>1</b> as being the most active. The antiangiogenic activity of <b>1</b> was also confirmed in vivo by the chicken chorioallantoic membrane assay. Our results indicated <b>1</b> as a new antiangiogenic compound inhibiting the interaction between VEGF-A or PlGF and their receptor VEGRF-1