Carboxylated aurone derivatives as potent inhibitors of xanthine oxidase

Bioorg Med Chem. 2017 Jul 15;25(14):3606-3613. doi: 10.1016/j.bmc.2017.04.048. Epub 2017 May 6.

Abstract

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.

Keywords: Aurone derivatives; Enzyme inhibition; Molecular docking; Structure-activity relationship; Xanthine oxidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzofurans / chemical synthesis
  • Benzofurans / chemistry*
  • Benzofurans / metabolism
  • Binding Sites
  • Carboxylic Acids / chemistry
  • Catalytic Domain
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • Inhibitory Concentration 50
  • Kinetics
  • Molecular Docking Simulation
  • Structure-Activity Relationship
  • Xanthine Oxidase / antagonists & inhibitors*
  • Xanthine Oxidase / metabolism

Substances

  • Benzofurans
  • Carboxylic Acids
  • Enzyme Inhibitors
  • aurone
  • Xanthine Oxidase