title: Synthesis, nitric oxide release, and α-glucosidase inhibition of nitric oxide donating apigenin and chrysin derivatives.
abstract: α-Glucosidase (AG) play crucial roles in the digestion of carbohydrates. Inhibitors of α-glucosidase (AGIs) are promising candidates for the development of anti-diabetic drugs. Here, five series of apigenin and chrysin nitric oxide (NO)-donating derivatives were synthesised and evaluated for their AG inhibitory activity and NO releasing capacity in vitro. Except for 9a-c, twelve compounds showed remarkable inhibitory activity against α-glucosidase, with potency being better than that of acarbose and 1-deoxynojirimycin. All organic nitrate derivatives released low concentrations of NO in the presence of l-cysteine. Structure activity relationship studies indicated that 5-OH, hydrophobic coupling chain, and carbonyl groups of the coupling chain could enhance the inhibitory activity. Apigenin and chrysin derivatives therefore represents a new class of promising compounds that can inhibit α-glucosidase activity and supply moderate NO for preventing the development of diabetic complications.
authors: Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, China; Department of Pharmacy and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine & New Drug Research, Jinan University, Guangzhou 510632, China.
authors: Qi-Qin
authors: QQ
authors: Wang
authors: Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, China.
authors: Ning
authors: N
authors: Cheng
authors: Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, China.
authors: Wen-Bing
authors: WB
authors: Yi
authors: Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, China; Postdoctoral Programme of Chemical Engineering & Technology, Xiangtan University, Xiangtan 411105, China. Electronic address: pengshengming@21cn.com.
authors: Sheng-Ming
authors: SM
authors: Peng
authors: Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, China.
authors: Xiao-Qing
authors: XQ
authors: Zou
mesh_terms: D047310:Apigenin / Q000138:chemical synthesis* / Q000737:chemistry; D048909:Diabetes Complications / Q000517:prevention & control*; D003920:Diabetes Mellitus / Q000188:drug therapy*; D005419:Flavonoids / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015394:Molecular Structure; D009569:Nitric Oxide / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D005419:Flavonoids; D007004:Hypoglycemic Agents; D009569:Nitric Oxide; C043561:chrysin; D047310:Apigenin; D000520:alpha-Glucosidases
keywords: Apigenin derivatives; Chrysin derivatives; NO donor; NO-releasing; α-Glucosidase inhibitor