Synthesis, characterization and vasculoprotective effects of nitric oxide-donating derivatives of chrysin

• Published in: Bioorganic & medicinal chemistry 2010-05, Vol.18 (9), p.3020-3025
• Main Authors: Zou, Xiao-Qing, Peng, Sheng-Ming, Hu, Chang-Ping, Tan, Li-Feng, Yuan, Qiong, Deng, Han-Wu, Li, Yuan-Jian
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chrysin derivatives; Diabetic Angiopathies - drug therapy; Diabetic Angiopathies - prevention & control; Flavonoids - chemical synthesis; Flavonoids - chemistry; Flavonoids - pharmacology; General and cellular metabolism. Vitamins; Hep G2 Cells; Humans; Hybrid; Medical sciences; Molecular Structure; Nitric Oxide - chemistry; Nitric Oxide - metabolism; NO donor; Pharmacology. Drug treatments; Protective Agents - chemical synthesis; Protective Agents - chemistry; Protective Agents - pharmacology; Vasculoprotection
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2010.03.056

A novel group of hybrid nitric oxide-releasing chrysin derivatives was synthesized. All these chrysin derivatives released NO upon incubation with PBS at pH 7.4, exhibited inhibitory activities against aldose reductase and advanced glycation end-products formation in vitro. And some of them were even found to increase the glucose consumption of HepG2 cells. 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.