Synthesis and antiangiogenic activity study of new hop chalcone Xanthohumol analogues

摘要

Abstract Angiogenesis induction is a hallmark of cancer. Antiangiogenic properties of Xanthohumol (XN), a naturally occurring prenylated chalcone from hops, have been widely reported. Here we describe the synthesis and study the antiangiogenic activity in?vitro of a series of XN derivatives, where different substituents on the B-ring of the chalcone scaffold were inserted. The new XN derivatives inhibited human umbilical-vein endothelial cell (HUVEC) proliferation, adhesion, migration, invasion and their ability to form capillary-like structures in?vitro at 10?μM concentration. The preliminary results indicate that the phenolic OH group in R, present in natural XN, is not necessary for having antiangiogenic activity. In fact, the most effective compound from this series, 13 , was characterized by a para-methoxy group in R and a fluorine atom in R 2 on B-ring. This study paves the way for future development of synthetic analogues of XN to be used as cancer angiopreventive and chemopreventive agents. Graphical abstract Display Omitted Highlights ? The prenylated chalcone Xanthohumol (XN) has emerged as a cancer chemopreventive agent. ? New Xanthohumol analogues were designed and synthesized. ? Synthesized compounds were tested for their antiangiogenic activity on HUVE cells. ? 13 was a stronger inhibitor of cell adhesion, migration and morphogenesis than XN.