Document Report Card

ID: ALA1128484

Journal: J Med Chem

Title: Cardioselective ammonium, phosphonium, and sulfonium analogues of alpha-tocopherol and ascorbic acid that inhibit in vitro and ex vivo lipid peroxidation and scavenge superoxide radicals.

Authors: Grisar JM, Marciniak G, Bolkenius FN, Verne-Mismer J, Wagner ER.

Abstract: Analogues of alpha-tocopherol and ascorbic acid with permanently cationic substituents, i.e., phosphonium (8, 9), sulfonium (11), acylhydrazinium (13, 14), and ammonium (1, 16, 21), were synthesized, and the 2R and 2S enantiomers of the alpha-tocopherol analogues 1, 8, 11, and 13 were separated. The compounds were found to scavenge lipoperoxyl and superoxide radicals in vitro and accumulate in heart tissue (cardioselectivity) as demonstrated by measurement of ex vivo inhibition of lipid peroxidation in mouse heart homogenates and confirmed by HPLC determination of drug concentrations for 1 and 11. The 2R and 2S enantiomers of 1 inhibited ex vivo lipid peroxidation to an equal extent. Thus the in vivo uptake into myocytes (cardioselectivity) is independent of the geometry at the chiral center and common to permanently cationic compounds.

CiteXplore: 7636848

DOI: 10.1021/jm00015a010