Design, synthesis and molecular modeling of aloe-emodin derivatives as potent xanthine oxidase inhibitors

Eur J Med Chem. 2014 Mar 21:75:289-96. doi: 10.1016/j.ejmech.2014.01.058. Epub 2014 Jan 31.

Abstract

A series of aloe-emodin derivatives were synthesized and evaluated as xanthine oxidase inhibitors. Among them, four aloe-emodin derivatives showed significant inhibitory activities against xanthine oxidase. The compound 4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2-carbaldehyde (A1) possessed the best xanthine oxidase inhibitory activity with IC50 of 2.79 μM. Lineweaver-Burk plot analysis revealed that A1 acted as a mixed-type inhibitor for xanthine oxidase. The docking study revealed that the molecule A1 had strong interactions with the active site of xanthine oxidase and this result was in agreement with kinetic study. Consequently, compound A1 is a new-type candidate for further development for the treatment of gout.

Keywords: Aloe-emodin; Gout; Inhibitor; Xanthine oxidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aloe / chemistry*
  • Animals
  • Anthraquinones / chemical synthesis
  • Anthraquinones / chemistry*
  • Anthraquinones / pharmacology*
  • Catalytic Domain / drug effects
  • Cattle
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Kinetics
  • Molecular Docking Simulation
  • Structure-Activity Relationship
  • Xanthine Oxidase / antagonists & inhibitors*
  • Xanthine Oxidase / chemistry
  • Xanthine Oxidase / metabolism

Substances

  • Anthraquinones
  • Enzyme Inhibitors
  • aloe emodin
  • Xanthine Oxidase