CARDIOSELECTIVE AMMONIUM, PHOSPHONIUM, AND SULFONIUM ANALOGS OF ALPHA-TOCOPHEROL AND ASCORBIC-ACID THAT INHIBIT IN-VITRO AND EX-VIVO LIPID-PEROXIDATION AND SCAVENGE SUPEROXIDE RADICALS

被引：28

作者：

GRISAR, JM ^{[1
]}

MARCINIAK, G ^{[1
]}

BOLKENIUS, FN ^{[1
]}

VERNEMISMER, J ^{[1
]}

WAGNER, ER ^{[1
]}

机构：

[1] MARION MERRELL DOW RES INST,F-67080 STRASBOURG,FRANCE

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1995年 / 38卷 / 15期

关键词：

D O I：

10.1021/jm00015a010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

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页码：2880 / 2886

页数：7

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