Carboxylated aurone derivatives as potent inhibitors of xanthine oxidase

• Published in: Bioorganic & medicinal chemistry Vol. 25; no. 14; pp. 3606 - 3613
• Main Authors: Muzychka, Oksana V., Kobzar, Oleksandr L., Popova, Antonina V., Frasinyuk, Mykhaylo S., Vovk, Andriy I.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.07.2017; Elsevier
• Subjects: Aurone derivatives; Benzofurans - chemical synthesis; Benzofurans - chemistry; Benzofurans - metabolism; Binding Sites; Biochemistry & Molecular Biology; Carboxylic Acids - chemistry; Catalytic Domain; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Enzyme inhibition; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - metabolism; Inhibitory Concentration 50; Kinetics; Life Sciences & Biomedicine; Molecular docking; Molecular Docking Simulation; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Structure-Activity Relationship; Xanthine oxidase; Xanthine Oxidase - antagonists & inhibitors; Xanthine Oxidase - metabolism; Enzyme inhibition; Aurone derivatives; Xanthine oxidase; Structure-activity relationship; Molecular docking; DESIGN; MECHANISM; MOLYBDENUM; OXIDOREDUCTASE; FLAVONOIDS; SCAVENGERS; DISCOVERY; ENZYMES; AGENTS; SCAFFOLD
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2017.04.048

[Display omitted] •Carboxylated aurone derivatives are able to inhibit xanthine oxidase in vitro.•The inhibition efficiency of the aurone derivatives is higher than that of sulfuretin.•Modes of inhibitor binding to the enzyme active site are proposed. Xanthine oxidase is a potential target for treatment of hyperuricemia and gout. In this study, a number of A- and B-ring carboxylated aurone derivatives were synthesized and evaluated for their ability to inhibit xanthine oxidase in vitro. According to the results obtained, two different ranges of inhibitory activity were observed. The aurones with carboxylic acid group at the 4′-position of B-ring were found to be potent inhibitors of the enzyme with IC50 values in the low micromolar range. The effects of these compounds were about 50 fold higher than of A-ring modified aurones with carboxymethoxy group at the 6-position. The binding modes of the carboxylated aurones in the active site of xanthine oxidase were explained using molecular docking calculations.