IN-VITRO ANTIOXIDANT EFFECTS OF ESTROGENS WITH A HINDERED 3-OH FUNCTION ON THE COPPER-INDUCED OXIDATION OF LOW-DENSITY-LIPOPROTEIN

Estrogens with some bulky alkyl substituents in both the 2- and 4-posi tions have been synthesized and evaluated for the ability to inhibit t he 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- a nd 4-) were especially effective as antioxidants, having IC50 values l ower than either estradiol or probucol; however, they do not bind to t he estrogen receptor with any great affinities (RBA < 0.1 versus estra diol). This separation of antioxidant efficacy from estrogenicity may allow these compounds to serve as useful probes for ascertaining the r elative importance of these effects in the cardioprotective role playe d by estrogens.