Synthesis and antiangiogenic activity study of new hop chalcone Xanthohumol analogues

• DOI: 10.1016/j.ejmech.2017.07.024
• Publication Date: 2017-07-17T02:16:53Z
• Authors: Elisa Nuti; Barbara Bassani; Caterina Camodeca; Lea Rosalia; AnnaRita Cantelmo; Cristina Gallo; Denisa Baci; Antonino Bruno; Elisabetta Orlandini; Susanna Nencetti; Douglas M. Noonan; Adriana Albini; Armando Rossello
• Keywords: Flavonoids; 0301 basic medicine; Propiophenones; Dose-Response Relationship, Drug; Molecular Structure; Xanthohumol analogues, Prenylated chalcones, Antiangiogenic activity, Chemopreventive agents; Neovascularization, Physiologic; Angiogenesis Inhibitors; Apoptosis; Antiangiogenic activity; Chemopreventive agents; Prenylated chalcones; Xanthohumol analogues; Pharmacology; Drug Discovery3003 Pharmaceutical Science; Organic Chemistry; 3. Good health; Structure-Activity Relationship; 03 medical and health sciences; Chalcone; Cell Movement; Cell Adhesion; Human Umbilical Vein Endothelial Cells; Humans; Cells, Cultured; Cell Proliferation

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 R2 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.