Nitric Oxide-Donating Derivatives of Chrysin Stimulate Angiogenesis and Upregulating VEGF Production

Angiogenesis, the development of new capillaries from pre-existing vessels, requires the coordinate activation of endothelial cells, which migrate and proliferate to form functional vessels. Endothelial dysfunction and decreased nitric oxide bioavailability may underscore the impairment of angiogenesis. As such, the delivery of exogenous NO is an attractive therapeutic option that has been used to therapeutic angiogenesis. In this paper, a novel group of hybrid nitric oxide-releasing chrysin derivatives was synthesized. The results indicated that all these chrysin derivatives exhibited promotion of endothelial migration and tubulogenesis in vitro as well as stimulation angiogenesis in vivo.Furthermore, all compounds released NO upon incubation with phosphate buffer at pH 7.4 and enhanced VEGF secretion and VEGF mRNA expression of endothelial cells. These hybrid ester NO donor prodrugs offer a potential drug design concept for the development of therapeutic or preventive agents for angiogenesis deficiency due to ischemic diseases.