Heparin-polynitroxides: synthesis and preliminary evaluation as cardiovascular EPR/MR imaging probes and extracellular space-targeted antioxidants

Eur J Med Chem. 2012 Dec:58:265-71. doi: 10.1016/j.ejmech.2012.09.028. Epub 2012 Oct 5.

Abstract

We report here the synthesis of heparin-polynitroxide derivatives (HPNs) in which nitroxide moieties are linked either to uronic acid or glycosamine residues of the heparin macromolecule. HPNs have low anticoagulant activity, possess superoxide scavenging properties, bind to the vascular endothelium/extra-cellular matrix and can be detected by EPR and MRI techniques. As the vascular wall-targeted redox-active paramagnetic compounds, HPNs may have both diagnostic (molecular MRI) and therapeutic (ecSOD mimics) applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / blood
  • Anticoagulants / chemistry
  • Anticoagulants / metabolism
  • Anticoagulants / pharmacology
  • Antioxidants / chemistry
  • Antioxidants / metabolism*
  • Electron Spin Resonance Spectroscopy
  • Endothelium, Vascular / chemistry
  • Endothelium, Vascular / metabolism
  • Extracellular Matrix / chemistry
  • Extracellular Matrix / metabolism
  • Factor Xa / metabolism
  • Factor Xa Inhibitors
  • Heparin / chemistry
  • Heparin / metabolism
  • Hexosamines / chemistry
  • Humans
  • Magnetic Resonance Imaging*
  • Molecular Probes / chemistry
  • Molecular Probes / metabolism*
  • Nitrogen Oxides / chemistry
  • Nitrogen Oxides / metabolism
  • Partial Thromboplastin Time
  • Superoxides / chemistry
  • Superoxides / metabolism
  • Uronic Acids / chemistry

Substances

  • Anticoagulants
  • Antioxidants
  • Factor Xa Inhibitors
  • Hexosamines
  • Molecular Probes
  • Nitrogen Oxides
  • Uronic Acids
  • Superoxides
  • Heparin
  • Factor Xa