Novel estrogens and their radical scavenging effects, iron-chelating, and total antioxidative activities: 17α-substituted analogs of Δ9(11)-dehydro-17 β-estradiol

Abstract

Antioxidant effects of N,N-dimethyl-p-toluidine, p-cresol, and p-(hydroxy)thioanisol 17α-substituted analogs of 17β-estradiol and their Δ 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 17β-estradiol as well as selected phenolic compounds was only moderately inhibiting iron-dependent lipid peroxidation and stimulating total antioxidative activity, besides Δ 9(11)-dehydro-17 β-estradiol (J 1213), novel estrogens such as C-17-oriented side chain analogs of 17β-estradiol (J 843, J 872, and J 897) and Δ 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 17β-estradiol, e.g., the introduction of a Δ 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.