Coumestrol, Plant Phenolics, and Synthetic Estrogens: a Correlation of Structure and Activity

Abstract

A correlation of structure with estrogenic activity of plant phenolics (including coumestrol, isoflavones and desoxybenzoins) and certain synthetic estrogens has been made. Pertinent compounds were re-evaluated under standardized conditions. The most active of the compounds synthesized for this study was 7,4'diacetoxy-2-methyl-4-ethyl-A3-isoflaven.Current interest in this laboratory regarding the biological activity of coumestrol and other plant estrogens as compared to the growthpromoting effect of diethylstilbestrol has led to a continued2 investigation of the structure-activity relationship of certain coumarins, isoflavones, desoxybenzoins and related compounds. In addition, the estrogenic activity of representative samples from these different classes of compounds has been re-evaluated and these activities correlated under identical bioassay conditions.The activity of the compounds was evaluated by linearly plotting the mean mouse uterine weight for a series of doses. The dose level recorded in the Tables represents the quantity of material fed to produce a 25-mg. uterine response as compare to a uterine weight of 10 mg. for untreated animals.3a,bCertain derivatives of diethylstilbestrol and coumestrol have been bioassayed for comparison purposes and the values included in Tables I and II. Some isoflavens (Table III) are extremely potent estrogens4

Steroid and Phyto-Oestrogen Binding to Sheep Uterine Receptors in Vitro

“…However, most of the com¬ pounds in these two groups appear much more active in vitro than might be expected from the biological results in vivo of Micheli, Booth, Livingston & Bickoff (1962) and Emmens et al (1962) respectively. In such comparisons it may be relevant that some weak oestrogens have shallow dose-response curves in bioassays (Folman & Pope, 1966).…”

“…In such comparisons it may be relevant that some weak oestrogens have shallow dose-response curves in bioassays (Folman & Pope, 1966). Compounds with shallow response curves could give a relatively low estimate of biological activity in the method of Micheli et al (1962) who express uterotrophic potency as that amount of oestrogen required to produce a defined increase in uterine weight. However, the differences probably indicate variations in absorption, metabolism, conjugation, and uptake at the target tissue all of which may influence oestrogenic potency in vivo.…”

Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer

“…Flavan-3-ols Epigallocatechin 3-gallate (ECGC) J, P de Pascual-Teresa et al Micheli et al (1962) Phenyl aliphatic glycosides octadecatrienoic fatty acids, with a high content of cis 9, trans 11, cis 13 acid (i.e. punicic acid), synthesized in situ from nonconjugated octadecadienoic fatty acid, linoleic acid (Hopkins and Chisholm, 1968;Hornung et al, 2002), itself about 7% of PSO.…”

Structure-Activity Relationships of Estrogens

“…There are no published reports of the structure-activity relationships of this cis cyclopropyl derivative, but it is possible that potency, and possibly effectiveness as an antiestrogen, could be improved by para substitutions with hydroxyl and an alkylaminoethoxyside chain [this is a recurrent feature of nonsteroidal antiestrogens (91)]. The structure-activity relationship of the plant phenolics has been compared with synthetic estrogens (92). In Figure 14 the potency of various compounds was determined as the minimum oral dose level required to produce an immature mouse uterine weight of 20 mg (control = 10 mg).…”