title: Bioassay-guided isolation of proanthocyanidins with antiangiogenic activities.
abstract: 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 Campsiandra guayanensis and Feretia apodanthera were screened by a competitive ELISA-based assay. By using this bioassay-oriented approach five proanthocyanindins, including the new natural compounds (2S)-4',5,7-trihydroxyflavan-(4β→8)-afzelechin (1) and (2S)-4',5,7-trihydroxyflavan-(4β→8)-epiafzelechin (2) and the known geranin B (3), proanthocyanidin A2 (4), and proanthocyanidin A1 (5), were isolated. The study of the antiangiogenic activities of compounds 1-5 using ELISA and SPR assays showed compound 1 as being the most active. The antiangiogenic activity of 1 was also confirmed in vivo by the chicken chorioallantoic membrane assay. Our results indicated 1 as a new antiangiogenic compound inhibiting the interaction between VEGF-A or PlGF and their receptor VEGRF-1.
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Salerno, via Ponte Don Melillo, 84084 Fisciano (SA), Italy.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Pesca
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Dal Piaz
authors.forename: Rokia
authors.initials: R
authors.lastname: Sanogo
authors.forename: Antonio
authors.initials: A
authors.lastname: Vassallo
authors.forename: Maryan
authors.initials: M
authors.lastname: Bruzual de Abreu
authors.forename: Antonio
authors.initials: A
authors.lastname: Rapisarda
authors.forename: Maria P
authors.initials: MP
authors.lastname: Germanò
authors.forename: Giovanna
authors.initials: G
authors.lastname: Certo
authors.forename: Sandro
authors.initials: S
authors.lastname: De Falco
authors.forename: Nunziatina
authors.initials: N
authors.lastname: De Tommasi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Braca
mesh_terms: D000465:Algorithms; D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D029911:Caesalpinia / Q000737:chemistry; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D009389:Neovascularization, Pathologic / Q000378:metabolism; D044945:Proanthocyanidins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019666:Rubiaceae / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014687:Venezuela
chemical_list: D020533:Angiogenesis Inhibitors; D044945:Proanthocyanidins; D042461:Vascular Endothelial Growth Factor A; C120206:geranin B; C473739:proanthocyanidin A1; C473740:proanthocyanidin A2