Catechol-based matrix metalloproteinase inhibitors with additional antioxidative activity

J Enzyme Inhib Med Chem. 2016;31(sup4):25-37. doi: 10.1080/14756366.2016.1217853. Epub 2016 Aug 24.

Abstract

New catechol-containing chemical entities have been investigated as matrix metalloproteinase inhibitors as well as antioxidant molecules. The combination of the two properties could represent a useful feature due to the potential application in all the pathological processes characterized by increased proteolytic activity and radical oxygen species (ROS) production, such as inflammation and photoaging. A series of catechol-based molecules were synthesized and tested for both proteolytic and oxidative inhibitory activity, and the detailed binding mode was assessed by crystal structure determination of the complex between a catechol derivative and the matrix metalloproteinase-8. Surprisingly, X-ray structure reveals that the catechol oxygens do not coordinates the zinc atom.

Keywords: Antioxidants; X-ray crystallography; inhibitors; metalloenzymes; structure–activity relationships.

MeSH terms

  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Catechols / chemical synthesis
  • Catechols / chemistry
  • Catechols / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Matrix Metalloproteinase 8 / isolation & purification
  • Matrix Metalloproteinase 8 / metabolism*
  • Matrix Metalloproteinase Inhibitors / chemical synthesis
  • Matrix Metalloproteinase Inhibitors / chemistry
  • Matrix Metalloproteinase Inhibitors / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Quantitative Structure-Activity Relationship
  • Reactive Oxygen Species / metabolism

Substances

  • Antioxidants
  • Catechols
  • Matrix Metalloproteinase Inhibitors
  • Reactive Oxygen Species
  • MMP8 protein, human
  • Matrix Metalloproteinase 8
  • catechol