Antiestrogenic compounds

I 10. The answer is a. (Hardman, p 1302J Cyclophosphamide is classified as a poly functional alkylating drug that transfers its alkyl groups to cellular components. The cytotoxic effect of this agent is directly associated with the alkylation of components of DNA. Methotrexate and 5-FU are classified as anti metabolites that block intermediary metabolism to inhibit cell proliferation. Tamoxifen is an antiestrogen compound. Doxorubicin is classified as an antibiotic chemotherapeutic agent. 

Heikkinen, M., Rissanen, P., Blanco, G., Tholix, E., Nordman, E., Taskinen, P., Holsti, L. and Hajba, A. (1988) Toremifene, a new antiestrogenic compound, for treatment of advanced breast cancer. Phase II study. European Journal of Cancer and Clinical Oncology, 24, 785-790. 

In a hormone-responsive endometrial cell line (ECC-1), a methanolic extract of heal all exhibited antiestrogenic activity. Specifically, a reduction in alkaline phosphatase activity and cell proliferation in response to estrogen in a dose-dependent manner was observed. The expression of an estrogen-induced protein was blocked in the cell line both by a standard antiestrogen compound and by the heal all extract (Collins et al. 2009). 

In vivo experiments have been performed with toremifene citrate, a non-steroidal antiestrogenic compound that exhibits antitumor activity in breast and endometrial cancer. Toremifene containing xerogels were sub-cutaneously implanted in mice. The drug was labeled with tritium in order to follow the amount of toremifene remaining in the silica implant (Kortesuo, 2000). About 16% of the drug was still trapped in silica implants after 6 weeks. Moreover, silica xerogels do not lead to any tissue irritation and a fibrotic capsule forms around the implant. 

For the purposes of this article, antiestrogens are compounds that counteract the biological activity of estrogens at the receptor level. In the late 1970s, there were no steroidal antiestrogens in widespread clinical use. Clomiphene [911 -45-5]( ) and tamoxifen/7(954(9-25 -/7(9) were nonsteroidal antiestrogens that had been employed for the treatment of female infertility and breast cancer, respectively. 

A stmcturally related series of phenyfiiydrazones resulted ia the selection of compound A-007 [2675-35-6] (DEKK-TEC)(37) for the treatment of hormone-dependent tumors. A-007 is an antiestrogen that, ia contrast to tamoxifen, demonstrated inhibitory activity both ia the presence and absence of estradiol ia ZR-75-1 estrogen-dependent human breast cancer cells, and afforded more protection than tamoxifen ia the 7,12-dimethylbenz[i7]anthracene... 

Other compounds of this general class which have been found to have antiestrogenic properties include the cytochrome P-450 inhibitor, SKF 525A P02-33-0](Sl) (24) JV, JV-diethyl-2-[(4-phenylmethyl)phenoxy]ethanamine [98774-23-3] (DPPE)(58) (42) /-Butylphenoxyethyl diethylamine [57586-10-4] (BPEA)(59) (43) and cyclofenil [110042-18-7] (60, R = C H ) (24) analogues. 

The area of nonsteroidal antiestrogens along with other classes of nonsteroidal antagonists of sex-steroid hormone action has been reviewed to 1986, and these compounds have been grouped by chemical stmcture as a basis of classification rather than any biochemical or biological test system utilized to assess antagonist activity (46). 

The concept that different ligands play an active role in ER function is apparent at the biochemical level. In addition to competitive inhibition of estrogen binding, antiestrogens induce unique conformations/stiuctures of both ERa and ER 3. This provides a structural basis for the unique biological activities displayed by the different compounds [1]. 

Interestingly, the antagonist activity of ICI and other antiestrogens has also been recently attributed to the ability of these compounds to induce degradation of the ER protein in estrogen target tissues. It is thought that... 

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