Antioxidant Properties, Autooxidation, and Mutagenic Activity of Echinochrome A Compared with Its Etherified Derivative

A. V. Lebedev^*, E. L. Levitskaya, E. V. Tikhonova, and M. V. Ivanova

Institute of Experimental Cardiology, Cardiology Research Center, Russian Ministry of Health, 3-ya Cherepkovskaya ul.15a, Moscow, 121552 Russia; fax: (095) 414-6699; E-mail: avleb@mail.ru

^* To whom correspondence should be addressed.

Received December 15, 2000; Revision received January 29, 2001

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Antioxidant properties of 2,3,5,7,8-pentahydroxy-6-ethyl-1,4-naphthoquinone (echinochrome A) were linked with the scavenging of peroxy radicals in liposomes, trapping of superoxide anion radicals, and binding of ferrous ions to inactive complexes in the aqueous phase. The antioxidant property of 6-ethyl-2,3,7-trimethoxy-5,8-dihydroxy-1,4-naphthoquinone (trimethoxyechinochrome A) was negligible. Autooxidation of echinochrome A was increased in basic media according to the degree of its dissociation. Autooxidation of polyvalent anions in basic media was accompanied by generation of naphthosemiquinone and superoxide anion radicals as free radical intermediates. An increased rate of echinochrome A autooxidation was noted in the presence of calcium ions. This was explained by a shift of pK of Ca²⁺-echinochrome A complexes toward acidic pH comparably with echinochrome A. Echinochrome A possessed pronounced mutagenic activity, while trimethoxyechinochrome A was inactive in the Salmonella/mammalian microsome reverse mutation assay (Ames test) for all examined cells (TA98, TA100, TA1537). Comparison of the chemical and biological activity of echinochrome A and trimethoxyechinochrome A demonstrated the key role of the beta-hydroxyl groups in the 2nd, 3rd, and 7th naphthol cycle positions. The O₂^-· and naphthosemiquinone radicals generated in the redox transition of 2,3-oxygroups may be the reason for the strongly pronounced mutagenicity of echinochrome A.

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KEY WORDS: polyhydoxy-1,4-naphthoquinones, hydroxynaphthazarins, echinochrome A, autooxidation, antioxidants, redox properties, mutagenicity, calcium

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