New Hybrid Structure for Multitarget Therapies

  • ChemPubSoc Europe Logo
  • Author: ChemMedChem
  • Published Date: 09 August 2019
  • Source / Publisher: ChemMedChem/Wiley-VCH
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA
thumbnail image: New Hybrid Structure for Multitarget Therapies

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High concentrations of metal ions can lead to oxidative stress or lipid imbalances, among other problems. Chelating agents bind metal ions in complexes and accelerate their excretion, which makes them suitable for the treatment of such disorders.


John Spencer, University of Sussex, Brighton, UK, Graziella Vecchio, University of Catania, Italy, Valentina Oliveri, University of Sussex and University of Catania, and colleagues have developed hybrid structures of cyclodextrins and the iron chelator deferasirox, a drug for the treatment of hemosiderosis (iron overload). Cyclodextrins are made of cyclic glucose units and were chosen because of their encapsulating properties. They show potential for the treatment of neurodegenerative diseases, which makes the hybrids interesting for multitarget therapies.

Deferasirox was conjugated with two different β-cyclodextrin derivatives in an amide coupling reaction. Both conjugates formed stable complexes with metal ions, showed good antioxidant activities, and were less toxic than deferasirox alone. According to the team, these structures are among the first nontoxic hybrids of cyclodextrins and a drug which is in clinical use. Deferasirox is already in clinical use marketed as Janedu, Exjade, Desifer, Desirox, Defrijet, Rasiroxpine.


 

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