A Water-Soluble Quaternary Ammonium Analog of α-Tocopherol, that Scavenges Lipoperoxyl, Superoxyl and Hydroxyl Radicals

Abstract

The new water-soluble ammonium-analog of α-tocopherol (vitamin E) (compound1: 3, 4-dihydro-6-hydroxy-N, N, N-2, 5, 7, 8-heptamethyl-2H-1-benzopyran-2-ethanaminium 4-methylbenzenesulfonate) and its tertiary amine derivative (compound2: 3, 4-dihydro-2-(2-dimethylaminoethyl)-2, 5, 7, 8-tetramethyl-2H-1-benzopyran-6-ol hydrochloride) were investigated as scavengers of oxygen-derived free radicals. Compounds 1 and 2 were at least 40 times more potent inhibitors of Fe-driven heart microsomal lipid peroxidation than Trolox. While the α-tocopherol analogs had the same potency as scavengers of xanthine/xanthine oxidase-generated superoxyl radicals, the thiol compounds D, L-penicillamine and N-2-mercaptopropionyl glycine reacted at a much slower rate. The O-acetyl derivatives of compounds 1 and 2 were not scavengers of superoxyl radicals. Considerable differences between the α-tocopherol analogs were observed in their competition with 2-deoxyribose for hydroxyl radicals (OH.). Compound 2 was equipotent with Trolox and thiourea, whereas the reactivity of these substances was diminished by more than 30% as compared to compound 1 Although showing lower reactivity, the O-acetyl derivatives of compounds 1 and 2 were active nevertheless as OH-scavengers.

The previously reported high potency of compound 1 in reducing infarct size during myocardial ischemia/reperfusion appears to be due to its radical-scavenging properties, likely to be enhanced by its previously described cardioselectivity.

Key Words:

• α-tocopherol analog
• lipid peroxidation
• hydroxyl radical
• superoxyl radical