Synthesis and biological evaluation of stilbene-based pure estrogen antagonists.
Replacement of one of the ethyl substituents in diethylstilbestrol by side chains with functional groups converted this potent estrogen into pure antiestrogens with the potential for the treatment of breast cancer. These agents completely suppressed estrogen receptor-mediated gene activation and inhibited the growth of estrogen-sensitive MCF-7 breast cancer cells in submicromolar concentrations. The most potent derivative displayed similar activity as fulvestrant (ICI 182,780) in vitro and in the mouse uterine weight test. Obviously, the stilbene structure can act as a substitute for estradiol in the development of pure estrogen antagonists.
Walter
Georg
G
Institut für Pharmazie, Universität Regensburg, D-93040 Regensburg, Germany.
Liebl
Renate
R
von Angerer
Erwin
E
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014599:Uterus / Q000187:drug effects
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D013267:Stilbenes; D000077267:Fulvestrant; D004958:Estradiol