In vitro antioxidant effects of estrogens with a hindered 3-OH function on the copper-induced oxidation of low density lipoprotein

• Published in: Steroids 1996-05, Vol.61 (5), p.305-308
• Main Authors: Miller, Chris P., Jirkovsky, Ivo, Hayhurst, Daniel A., Adelman, Steven J.
• Format: Article
• Language: English
• Subjects: Alkylation; antioxidant; Antioxidants - chemical synthesis; Antioxidants - pharmacology; Biological and medical sciences; cardioprotection; Copper - chemistry; estradiol; estrogen; Estrogens - chemical synthesis; Estrogens - metabolism; Estrogens - pharmacology; Hormones. Endocrine system; Lipoproteins, LDL - metabolism; Medical sciences; Molecular Conformation; Molecular Structure; Oxidation-Reduction; Pharmacology. Drug treatments; probucol; Receptors, Estrogen - metabolism; Thiobarbituric Acid Reactive Substances - analysis
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/0039-128X(95)00234-H

Estrogens with some bulky alkyl substituents in both the 2- and 4-positions have been synthesized and evaluated for the ability to inhibit the in vitro oxidation of low density lipoprotein as determined by the thiobarbituric reactive substances method. The present compounds with bulky groups in either the 2- or the 4-position (but not both the 2- and 4-) were especially effective as antioxidants, having IC 50 values lower than either estradiol or probucol; however, they do not bind to the estrogen receptor with any great affinities (RBA < 0.1 versus estradiol). This separation of antioxidant efficacy from estrogenicity may allow these compounds to serve as useful probes for ascertaining the relative importance of these effects in the cardioprotective role played by estrogens.