Synthesis and evaluation of the permeability transition inhibitory characteristics of paramagnetic and diamagnetic amiodarone derivatives

Tamás Kálai, Gábor Várbiró, Zita Bognár, Anita Pálfi, Katalin Hantó, Balázs Bognár, Erzsébet Osz, Balázs Sümegi, Kálmán Hideg

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Several amiodarone analogues were synthesized varying the 2-substituent on the benzofuran ring and diethylaminoethyl side chain of phenolether by introducing 2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrole and 1,2,5,6- tetrahydropyridine nitroxides or their amino or hydroxylamino precursors. The new compounds were screened on isolated mitochondria and perfused heart and their toxicity was evaluated on WRL-68 liver cells and H9C2 cardiomyocytes. Most of the newly synthesized derivatives exerted uncoupling effect on the mitochondrial oxidative phosphorilation at higher concentrations, compared to amiodarone and one of the modified amiodarone analogues showed an effect similar to that of amiodarone on the mitochondrial permeability transition and on restoring of mitochondrial high-energy phosphate metabolites in perfused hearts. This amiodarone analogue can be new leading compound among the experimental amiodarone analogues with the same or enhanced efficiency of amiodarone, but with less side effects.

Original languageEnglish
Pages (from-to)2629-2636
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume13
Issue number7
DOIs
Publication statusPublished - Apr 1 2005

Keywords

  • Amiodarone
  • Langendorff-perfused heart
  • Mitochondria
  • Nitroxides
  • Permeability transition

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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