Synthesis, characterization and vasculoprotective effects of nitric oxide-donating derivatives of chrysin.
Vascular complications are major causes of disability and death in patients with diabetes mellitus. It is often characterized by endothelial dysfunction. Studies have shown that either the loss of nitric oxide bioactivity or the decreased biosynthesis of NO is a central mechanism in endothelial dysfunction. As such, the delivery of exogenous NO is an attractive therapeutic option that has been used to slow the progress of diabetic vascular complications. In this paper, a novel group of hybrid nitric oxide-releasing chrysin derivatives was synthesized. The results indicated that all these chrysin derivatives exhibited in vitro inhibitory activities against aldose reductase and advanced glycation end-products formation. And some of them were even found to increase the glucose consumption of HepG2 cells. Furthermore, all compounds released NO upon incubation with phosphate buffer at pH 7.4. These hybrid ester NO donor prodrugs offer a potential drug design concept for the development of therapeutic or preventive agents for vascular complications due to diabetes.
Zou
Xiao-Qing
XQ
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Peng
Sheng-Ming
SM
Hu
Chang-Ping
CP
Tan
Li-Feng
LF
Yuan
Qiong
Q
Deng
Han-Wu
HW
Li
Yuan-Jian
YJ
D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000517:prevention & control; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D015394:Molecular Structure; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism; D020011:Protective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D005419:Flavonoids; D020011:Protective Agents; D009569:Nitric Oxide; C043561:chrysin