Schiff base transition metal complexes as novel inhibitors of xanthine oxidase

Eur J Med Chem. 2008 Apr;43(4):862-71. doi: 10.1016/j.ejmech.2007.06.015. Epub 2007 Jul 10.

Abstract

Twenty transition metal complexes with Schiff bases were evaluated for their inhibitory activities on xanthine oxidase (XO), of which 11 were newly synthesized and characterized by X-ray single crystal diffraction. It was found that 9 of the 20 complexes showed potent inhibitory activities against XO near to the standard inhibitor allopurinol. The cadmium(II) complex (8) had the most potent inhibitory activity with the IC(50) value of 2.16 microM. Relationships between the structures and the activities showed that the ligands and the metal ions influenced the inhibitory activities. The XO inhibition of the Schiff base metal complexes most probably resulted from their direct interactions with the enzymes "in the whole complex form". These results demonstrated that the Schiff base transition metal complexes could be potential selective XO inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allopurinol / pharmacology
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Hydrogen Bonding
  • Models, Molecular
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / pharmacology*
  • Schiff Bases / chemistry*
  • Transition Elements / chemistry*
  • Uric Acid / metabolism
  • Xanthine Oxidase / antagonists & inhibitors*

Substances

  • Enzyme Inhibitors
  • Organometallic Compounds
  • Schiff Bases
  • Transition Elements
  • Uric Acid
  • Allopurinol
  • Xanthine Oxidase