Novel "scavestrogens" and their radical scavenging effects, iron-chelating, and total antioxidative activities: delta 8,9-dehydro derivatives of 17 alpha-estradiol and 17 beta-estradiol.
Antioxidant effects of delta 8,9-dehydro derivatives of 17 alpha-estradiol and 17 beta-estradiol were investigated using four different in vitro models: rat synaptosomal lipid peroxidation induced by Fenton's reagent, Fe(II)-chelating activities, the formation of superoxide anion radicals, and total antioxidative activities. The parent molecules, 17 alpha-estradiol and 17 beta-estradiol as well as estrone and estriol inhibit iron-dependent lipid peroxidation and stimulate total antioxidant activity. In contrast, delta 8,9-dehydro estrogens such as J811, J861, J835, or J851 not only exhibit the antioxidative activities as the parent molecules do but also directly alter the iron redox chemistry and drastically inhibit the formation of superoxide anion radicals generated by a xanthine/xanthine oxidase-dependent luminescence reactions. These in vitro findings indicate that 17 alpha-estradiol as well as 17 beta-estradiol, modified with an additional double bond in the basic structure, trigger more potent antioxidant properties. These results suggest that relatively minor modifications in the chemical structure of estrogenic compounds can enhance antioxidative actions.
Römer
W
W
Department of Research and Development, Jenapharm GmbH, Jena, Germany.
Oettel
M
M
Droescher
P
P
Schwarz
S
S
D000166:Acridines / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004967:Estrogens / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008163:Luminescent Measurements; D008165:Luminol / Q000737:chemistry / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism
D000166:Acridines; D000975:Antioxidants; D004967:Estrogens; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D014970:Xanthines; D013481:Superoxides; D019820:Xanthine; C033472:10,10'-dimethyl-9,9'-biacridinium; D004958:Estradiol; D008165:Luminol; D007501:Iron; D014969:Xanthine Oxidase