4-Anilinoquinazolines endowed with antiangiogenic activity

Starting from Vandetanib strucyure, we synthesized several 4-anilinoquinazoline derivatives employing our recently reported synthetic strategy. Synthesized compounds were eveluated for their inhibitory effects on cell proliferation and the active compounds were submitted to several other preliminary biological assays in order to investigate the mechanism of action. The antiproliferative effects of Vandetanib and quinazoline derivatives were related to a pro-apoptotic activity and showed a reversible growth activity. All compounds, as for the reference one, induced significant decreases in cell migration compared to that determined in control cultures. Almost all the compounds showed very interesting anti-angiogenic activity and the ability to counteract the pro-angiogenic effects both in vitro and in vivo of cytokines (FGF-2 and VEGF). The effect on cell growth and migration induced was also evaluated in Human Umbilical Vein Endothelial Cells (HUVEC).