Binding of 2-hydroxypyridine-N-oxide on dicopper(II) centers: insights into tyrosinase inhibition mechanism by transition-state analogs

Inorg Chem. 2009 Dec 7;48(23):10874-6. doi: 10.1021/ic901593x.

Abstract

2-Hydroxypyridine-N-oxide (HOPNO) is described as a new and efficient transition-state analog (TS-analog) inhibitor for the mushroom tyrosinase with an IC(50) = 1.16 microM and a K(I) = 1.8 microM. Using the binuclear copper(II) complex [Cu(2)(BPMP)(mu-OH)](ClO(4))(2) (2) known as a functional model for the tyrosinase catecholase activity, we isolated and fully characterized a 1:1 (2)/OPNO adduct in which the HOPNO is deprotonated and chelates only one Cu-atom of the binuclear site in a bidentate mode. On the basis of these results, a structural model for the tyrosinase inhibition by HOPNO is proposed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Copper / chemistry*
  • Crystallography, X-Ray
  • Cyclic N-Oxides / chemistry*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Models, Molecular
  • Molecular Conformation
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Pyridines / chemistry*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 2-hydroxypyridine-N-oxide
  • Cyclic N-Oxides
  • Enzyme Inhibitors
  • Organometallic Compounds
  • Pyridines
  • Copper
  • Monophenol Monooxygenase