Stilbene, estrogenic activity

Many stilbenelike thiophene compounds have been prepared for a study of estrogenic activity, especially by Buu-Hoi et al. Thiophene derivatives of nonhydroxylated stilbene types showed no significant activitywhereas weak estrogenic activity was found in 5-acetyl-, 5-propionyl-, and 5-benzoyl-2-(-stilbenyl)thiophene. 1-Bromo-l,2-diphenyl-2-(5-bromo-2-thienyl)ethylene (258) was found to inhibit body growth and to produce extensive testicular atropy in male rats. A thiophene analog of estrogenic isoflavones (259)... 

Diethylstilbestrol is a derivative of stilbene, and it differs from sin-estrol by the presence of a double bond with trans-configuration of the two phenyl groups. In terms of estrogenic activity, this drug surpasses both estrone and hexestrol. Synonyms of this drug are distil-ben, menopax, stilphostrol, tilosteron, antigestil, and many others. 

Of these various nonsteroidal compounds, the first were fran.y-diethylstilbestrol (DES) (5.31) and its reduced derivative hexestrol (5.33). The way in which these nonsteroidal stilbene (diphenylethylene) derivatives are usually drawn suggests a resemblance to the steroid skeleton. However, this resemblance is purely incidental, since the two ethyl groups are not indispensable for estrogenic activity. For example, four methyl groups will give comparable pharmacological activity. It seems, however, that the... 

Diethylstilbestrol and hexestrol have been legally permitted for use as anabolics for quite some time in many countries, while the use of dienestrol, which is a metabolite of diethylstilbestrol, was restricted to illegal practice. Since all stilbene estrogens have high oral activity, both oral and parenteral formulations have been in use in catde and, to a lesser extent, in sheep and swine. 

In cattle feces, 64% of the total residues was identified as diethylstilbestrol, 23% as 3-(p-hydroxyphenyl)-2-hexene-4-one, and less than 1% as 4 -hydroxypro-piophenone (43). The identification of 4 -hydroxypropiophenone as a metabolite of diethylstilbestrol implies that dienestrol is formed through an epoxide-diol pathway and that these metabolites show electrophilic reactivity (45). These observations have to be seen in connection with the mutagenic and carcinogenic activity of diethylstilbestrol and possibly also the other stilbene estrogens. 

One concern raised about isoflavones, coumestanes, and stilbenes is that they have estrogenic activities. Indeed, some of the health benefit claims for these compounds... 

Chemical/Pharmaceutical/Other Class A nonsteroidal, synthetic stilbene derivative with estrogenic activity. It is an odorless, white crystalline powder, with a molecular weight of 268.36. Its ds-isomer tends to revert to the trans-ioim Chemical Formula C18H20O2 Chemical Structure ... 

The steroid nucleus is not required for estrogenic action. Several derivatives of stilbene (diphenylethylene) that were used therapeutically demonstrate potent estrogenic activity. Diethylstilbestrol (DES), prepared in 1939, was one of these stilbenes (Fig. 46.8). A trans stilbene, DES has 10-fold the estrogenic potency of its cis isomer, largely because the trans isomer more closely resembles estradiol (20). Unfortunately, when DES was administered to relieve pregnancy-related symptoms, it was correlated with abnormal growth in the offspring. 

CAS 56-53-1. A nonsteroid, synthetic estrogen, always in the trans form. It is the most active of the commonly used stilbene compounds. 

The active stilbene agents, reported in this chapter, derived from either marine or terrestrial sources tested in clinics have a unique chemistry that offers valuable information for their use as compounds for further chemical synthesis of more potent chemotherapeutic drugs against a variety of cancers. The stilbenes also possess the antioxidative, anti-inflammatory, and estrogenic effects and chemo-preventive activities. A challenging goal is the search for more active natural products as therapeutic agents in cancer and other diseases. This search should be continued until a novel and very effective compound is found. 

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