A comparative study of the antiangiogenic activity of hydroxytyrosyl alkyl ethers

• Published in: Food chemistry 2020-12, Vol.333, p.127476-127476, Article 127476
• Main Authors: Marrero, Ana Dácil, Castilla, Laura, Espartero, José L., Madrona, Andrés, R. Quesada, Ana, Medina, Miguel Ángel, Martínez-Poveda, Beatriz
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenesis Inhibitors - pharmacology; Animals; Aorta; Apoptosis; Bovine aorta endothelial cells (BAEC); Chorioallantoic membrane (CAM) assay; Endothelial Cells - drug effects; Endothelial Cells - physiology; Ethers - chemistry; Ethers - pharmacology; Hydroxytyrosyl alkyl ethers; Olive Oil - chemistry; Phenols - chemistry; Phenols - pharmacology; Phenylethyl Alcohol - analogs & derivatives; Phenylethyl Alcohol - chemistry; Phenylethyl Alcohol - pharmacology
• ISSN: 0308-8146; 1873-7072
• DOI: 10.1016/j.foodchem.2020.127476

•A series of hydroxytyrosyl alkyl ethers show antiangiogenic potential in vitro.•Studied compounds inhibit endothelial cell growth, migration and tube formation.•Hydroxytyrosyl hexyl ether is a potent antiangiogenic compound in vitro and in vivo.•Hydroxytyrosyl hexyl ether induces apoptosis in endothelial cells. The phenolic compound hydroxytyrosol and its derivatives are responsible for some of the health benefits of the intake of virgin olive oil, having shown antiangiogenic properties. In this study, we explored the antiangiogenic potential of six synthetic hydroxytyrosyl alkyl ethers (HT C1, C2, C4, C6, C8 and C12). Our results showed that all compounds affected endothelial cell viability in vitro at low micromolar doses. In addition, compounds HT C1, C2, C4 and C6 inhibited endothelial cell migration and formation of tubular-like structures. In these assays, hydroxytyrosyl hexyl ether (HT C6) exhibited the most potent inhibitory activity in vitro, activating as well apoptosis in endothelial cells. Furthermore, the antiangiogenic activity of HT C6 was confirmed in vivo in the chick chorioallantoic membrane assay. Hence, we present hydroxytyrosol synthetic derivative HT C6 as a new antiangiogenic compound and as a good candidate for an antiangiogenic drug in the treatment of angiogenesis-dependent diseases.