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 angiogenesisdependent
diseases.
