title: Discovery of xanthine oxidase inhibitors and/or α-glucosidase inhibitors by carboxyalkyl derivatization based on the flavonoid of apigenin.
abstract: Three series of apigenin derivatives have been prepared by coupling the carboxyl alkyl group to 4'-, 5- or 7-hydroxyl groups of apigenin respectively. Preliminary biological evaluation in vitro revealed that xanthine oxidase inhibitory activity was improved by modifications at 4'-position and decreased by similar modifications at 5-, 7-positions while α-glucosidase inhibitory activity was maintained by modifications at 5-, 7-positions but lost by modifications at 4'-position. Administration (ip) of 7e markedly lowered serum uric acid levels in potassium oxonate induced hyperuricemic mouse model and administration (p.o.) of 11d or 11e effectively suppressed the elevation of serum glucose in the oral sucrose tolerance test in mice, while apigenin were not significantly effective in both tests.
authors.affiliation: Beijing Institute of Pharmacology & Toxicology, 27th Taiping Road, Beijing 100850, China.
authors.forename: Zhuo-Ran
authors.initials: ZR
authors.lastname: Su
authors.affiliation: Beijing Institute of Pharmacology & Toxicology, 27th Taiping Road, Beijing 100850, China.
authors.forename: Shi-Yong
authors.initials: SY
authors.lastname: Fan
authors.affiliation: Beijing Institute of Pharmacology & Toxicology, 27th Taiping Road, Beijing 100850, China.
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Shi
authors.affiliation: Beijing Institute of Pharmacology & Toxicology, 27th Taiping Road, Beijing 100850, China. Electronic address: bohuazhong@yahoo.com.
authors.forename: Bo-Hua
authors.initials: BH
authors.lastname: Zhong
mesh_terms: D000818:Animals; D047310:Apigenin / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005419:Flavonoids / Q000737:chemistry; D005951:Glucose Tolerance Test; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D033461:Hyperuricemia / Q000139:chemically induced / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D007263:Infusions, Parenteral; D051379:Mice; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014527:Uric Acid / Q000097:blood; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000520:alpha-Glucosidases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D005419:Flavonoids; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D014527:Uric Acid; D047310:Apigenin; D014969:Xanthine Oxidase; D000520:alpha-Glucosidases
keywords: Apigenin; Diabetes; Gout; Xanthine oxidase; α-Glucosidase