Antioxidant Properties of 2,3-Dimethoxy-5-methyl- 6-(10-hydroxydecyl)-1,4-benzoquinone (Idebenone)

• Published in: Chemical research in toxicology Vol. 11; no. 1; pp. 54 - 63
• Main Authors: Mordente, Alvaro, Martorana, Giuseppe E, Minotti, Giorgio, Giardina, Bruno
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.01.1998
• Subjects: Antioxidants - chemistry; Arachidonic Acid - chemistry; Benzoquinones - chemistry; Free Radicals - chemistry; Lipid Peroxidation; Peroxides - chemistry; Ubiquinone - analogs & derivatives
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/tx970136j

Idebenone [2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone] is a synthetic analogue of coenzyme Q that is currently employed in the treatment of vascular and degenerative diseases of the central nervous system. There is some evidence to suggest that idebenone might function as an antioxidant; however, it has not been demonstrated whether this function pertains to the quinone or hydroquinone form of idebenone. Here we demonstrate that idebenone can scavenge a variety of free radical species, including organic radicals such as 2,2‘-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and diphenylpicrylhydrazyl, peroxyl and tyrosyl radicals, and peroxynitrite. Idebenone can also redox couple with hypervalent species of Mb or Hb, thus preventing lipid peroxidation promoted by these species. Likewise, idebenone inhibits microsomal lipid peroxidation induced by ADP−iron complexes or organic hydroperoxides. In so doing, idebenone prevents the destruction of cytochrome P450, which otherwise would accompany lipid peroxidation. Irrespective of the experimental system under investigation, idebenone functions by virtue of the electron-donating properties of the hydroquinone form. Redox coupling of this hydroquinone with free radicals generates the quinone compound, which per se lacks antioxidant activity. In many experiments, the antioxidant effects of idebenone become appreciable at ∼2 μM, which is well in the range of plasma levels attainable in patients given oral doses of this drug. Moreover, comparative experiments have shown that the antioxidant efficiency of idebenone varies from no less than 50% to slightly more than 100% of that of vitamin E or Trolox. We would therefore propose that the neuroprotective effects of idebenone can be attributed, at least in part, to its ability to function as an antioxidant, involving redox cycling between hydroquinone and quinone.