Synthesis of Triphenylethylene Bisphenols as Aromatase Inhibitors That Also Modulate Estrogen Receptors.
J Med Chem
; 59(1): 157-70, 2016 Jan 14.
Article
em En
| MEDLINE
| ID: mdl-26704594
ABSTRACT
A series of triphenylethylene bisphenol analogues of the selective estrogen receptor modulator (SERM) tamoxifen were synthesized and evaluated for their abilities to inhibit aromatase, bind to estrogen receptor α (ER-α) and estrogen receptor ß (ER-ß), and antagonize the activity of ß-estradiol in MCF-7 human breast cancer cells. The long-range goal has been to create dual aromatase inhibitor (AI)/selective estrogen receptor modulators (SERMs). The hypothesis is that in normal tissue the estrogenic SERM activity of a dual AI/SERM could attenuate the undesired effects stemming from global estrogen depletion caused by the AI activity of a dual AI/SERM, while in breast cancer tissue the antiestrogenic SERM activity of a dual AI/SERM could act synergistically with AI activity to enhance the antiproliferative effect. The potent aromatase inhibitory activities and high ER-α and ER-ß binding affinities of several of the resulting analogues, together with the facts that they antagonize ß-estradiol in a functional assay in MCF-7 human breast cancer cells and they have no E/Z isomers, support their further development in order to obtain dual AI/SERM agents for breast cancer treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenóis
/
Estilbenos
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Moduladores Seletivos de Receptor Estrogênico
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Inibidores da Aromatase
Limite:
Female
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Humans
Idioma:
En
Revista:
J Med Chem
Ano de publicação:
2016
Tipo de documento:
Article