Novel estrogens and their radical scavenging effects, iron-chelating, and total antioxidative activities: 17 alpha-substituted analogs of delta 9(11)-dehydro-17 beta-estradiol.
Antioxidant effects of N,N-dimethyl-p-toluidine, p-cresol, and p-(hydroxy)thioanisol 17 alpha-substituted analogs of 17 beta-estradiol and their delta 9(11)-dehydro homologs 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 activity. Whereas the classical estrogen 17 beta-estradiol as well as selected phenolic compounds was only moderately inhibiting iron-dependent lipid peroxidation and stimulating total antioxidative activity, besides delta 9(11)-dehydro-17 beta-estradiol (J 1213), novel estrogens such as C-17-oriented side chain analogs of 17 beta-estradiol (J 843, J 872, and J 897) and delta 9(11)-dehydro homologs (J 844, J 864, and J 898) directly altered the iron redox chemistry and diminished the formation of superoxide anion radicals generated by a xanthine/xanthine oxidase-dependent luminescence reaction to a great extent. These results suggest that definite modifications in the chemical structure of 17 beta-estradiol, e.g., the introduction of a delta 9(11)-double bond and/or p-cresol as well as p-(hydroxy)thioanisol C-17 substitution, may result in substantial changes in their antioxidant behavior. These compounds may be drug candidates for treating pathologies related to free radical formation.
Römer
W
W
Department of Research and Development, Jenapharm GmbH & Co. KG, Jena, Germany.
Oettel
M
M
Menzenbach
B
B
Droescher
P
P
Schwarz
S
S
D000818:Animals; D000840:Anisoles / Q000737:chemistry; D000975:Antioxidants / Q000494:pharmacology*; D003408:Cresols / Q000737:chemistry; D004958:Estradiol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D005290:Ferric Compounds / Q000737:chemistry; D005296:Ferrous Compounds / Q000737:chemistry; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008163:Luminescent Measurements; D008297:Male; D051381:Rats; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000737:chemistry; D013481:Superoxides / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D014052:Toluidines / Q000737:chemistry; D019820:Xanthine / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D000840:Anisoles; D000975:Antioxidants; D003408:Cresols; D005290:Ferric Compounds; D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D013440:Sulfides; D014052:Toluidines; C110022:delta(9(11))-dehydro-17beta-estradiol; D013481:Superoxides; D019820:Xanthine; C032538:4-cresol; D004958:Estradiol; C009760:mequinol; C093850:methylphenylsulfide; D014969:Xanthine Oxidase; C015835:dimethyl-4-toluidine