Diethylstilbestrol structure

The E-isomer of the diethylstilbestrol structure (104) has 10 times the estrogenic potency of the Z-isomer this effect has been rationalized from the conclusion that the E-... 

Figure 10.3-25. a) Structure of diethylstilbestrol (DES) b) 3 D pharmacophore query of DES two hits were found c) estrone and d) estradiol. 

Diethylstilbestrol (DES) has estrogenic activity even though it is structurally unrelated to steroids. Once used as an additive in animal feed, DES has been implicated as a causative agent in several types of cancer. Show how DES can be drawn so that it is sterically similar to estradiol. 

Exposure to the fetus in the first 2 weeks after conception may have an all or nothing effect (i.e., could destroy the embryo or have no ill effect). Exposure during the period of organogenesis (18 to 60 days postconception) may result in structural anomalies (e.g., methotrexate, cyclophosphamide, diethylstilbestrol, lithium, retinoids, thalidomide, certain antiepileptic drugs, and coumarin derivative). 

Induction of morphological transformation of SHE cells can occur in the absence of detectable induction of gene mutations measured concomitantly in the same cells (Barrett et al, 1983). Diethylstilbestrol and asbestos are two examples of chemicals that incluce cell transformation but not gene mutations (Barrett et al, 1981, 1983). However, a gcxxl correlation is observed between induction of chromosomal mutations (numerical and structural changes) and induction of cell transformation (Barrett etol, 1983 Oshimiueerol, 1984). 

Fig. 14). The DNA-immobilized columns effectively accumulated more DNA-intercalating materials than the planar DNA films. The DNA-immobilized columns bound endocrine disruptors with a planar structure, such as dioxins, and benzo[a]pyrene. Bisphenol A and diethylstilbestrol, which lack a planar structure, did not bind to the DNA-coated columns. Table 1 shows the selective adsorptions of the insoluble DNA-based materials. 

Tamoxifen [ta MOX i fen] is an estrogen antagonist, structurally related to the synthetic estrogen, diethylstilbestrol, and is active in the treatment of estrogen receptor-positive breast cancer. Tamoxifen has weak estrogenic activity. 

The three-dimensional structure of the ER was resolved by Brzozowski et al. [61]. Four additional X-ray structures of the receptor liganded with different molecules - estradiol, diethylstilbestrol, a nonsteroidal stilben derivative, and two antagonists raloxifen and 4-hydroxytamoxifen - were also solved [61, 62]. The availability of several structurally diverse structures bound to the active site of the receptor provided important experimental information detailing the molecular alignment of the studied molecules. 

Figure 7.1. Comparison oftheX-ray structures ofthe estrogen receptor bound to estradiol (dark-gray) and diethylstilbestrol (gray). The two crystal structures were overlaid using the backbone atoms. Only the amino acid residues in proximity to the binding pocket are shown for clarity.

Approximately equimolar mixtures of trideuterated diethylstilbestrol and unlabeled diethylstilbestrol also have been used to study the metabolic activation of diethylstilbestrol to potentially toxic metabolites by rat liver homogenates. 0 Reactive polar metabolites were converted to non-polar metabolites by enzymatic methylation. The ion-doublets arising in the mass spectra of these derivatives guaranteed that these compounds were metabolites of the substrate and also helped to establish their structures. 

Crystal structures of steroid receptors in complex with synthetic ligands have revealed alternative binding modes as compared to the natural steroid hormone. To date, ERa and ERyS subtypes [32] have provided the most variety of crystal structures with bound synthetic ligands [33], There are currently several examples of ER in complex with synthetic ligands diethylstilbestrol (DES), 4-hydroxytamoxifen (OHT) [34], genestein [35], raloxifene [36],... 

Our structure-activity studies revealed that aromatization of the A-ring with a free hydroxy group at C-3 position of a steroidal structure is necessary for higher repellent activity [123]. Surprisingly, methylation of diethylstilbestrol (DES) yielded completely different activity i.e. both mono- and di-O-methyl ethers of DES (compounds 53 and 54) showed attractant activity. Moreover, the attracted zoospores were found to be... 

Diethylstilbestrol (DES) was given to pregnant women to prevent miscarriage, until it was found that the drug caused cancer in both the mothers and their female children. DES has estradiol activity even though it is not a steroid. Draw DES in a way that shows that it is structurally similar to estradiol. 

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