Iron binding dendrimers: a novel approach for the treatment of haemochromatosis

J Med Chem. 2006 Jul 13;49(14):4171-82. doi: 10.1021/jm0600949.

Abstract

A range of iron binding dendrimers terminated with hexadentate ligands formed from hydroxypyridinone, hydroxypyranone, and catechol moieties have been synthesized in order to investigate their potential as clinically useful iron(III)-selective chelators capable of removing dietary iron from the gastrointestinal tract and preventing the development of iron overload typical of haemochromatosis and thalassaemia intermedia. The iron chelating abilities of these molecules have been characterized by MALDI-TOF mass spectrometry and UV spectrometry. Hydroxypyridinone-terminated dendrimers were found to possess a high affinity and selectivity for iron(III). A hydroxypyridinone-based dendrimer was demonstrated to be highly efficient at reducing the absorption of iron(III) in rat intestine. This family of dendrimers may find an application in the treatment of iron overload.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendrimers / chemical synthesis*
  • Dendrimers / chemistry
  • Dendrimers / pharmacology
  • Hemochromatosis / drug therapy*
  • In Vitro Techniques
  • Intestinal Absorption / drug effects
  • Iron / metabolism
  • Iron Chelating Agents / chemical synthesis*
  • Iron Chelating Agents / chemistry
  • Iron Chelating Agents / pharmacology
  • Male
  • Pyridones / chemical synthesis
  • Pyridones / chemistry
  • Pyridones / pharmacology
  • Rats
  • Rats, Wistar
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Spectrophotometry, Ultraviolet
  • Structure-Activity Relationship

Substances

  • Dendrimers
  • Iron Chelating Agents
  • Pyridones
  • Iron