title: Synthesis and evaluation of the permeability transition inhibitory characteristics of paramagnetic and diamagnetic amiodarone derivatives.
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.
authors.affiliation: Department of Organic and Medicinal Chemistry, University of Pécs, 12 Szigeti street, H-7624 Pécs, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Kálai
authors.forename: Gábor
authors.initials: G
authors.lastname: Várbiró
authors.forename: Zita
authors.initials: Z
authors.lastname: Bognár
authors.forename: Anita
authors.initials: A
authors.lastname: Pálfi
authors.forename: Katalin
authors.initials: K
authors.lastname: Hantó
authors.forename: Balázs
authors.initials: B
authors.lastname: Bognár
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Osz
authors.forename: Balázs
authors.initials: B
authors.lastname: Sümegi
authors.forename: Kálmán
authors.initials: K
authors.lastname: Hideg
mesh_terms: D000638:Amiodarone / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects*; D008280:Magnetics; D051379:Mice; D008928:Mitochondria / Q000187:drug effects*; D015394:Molecular Structure; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000638:Amiodarone