Effect of fluorination on the pharmacological profile of 11beta isomers of fulvestrant in breast carcinoma cells.
We describe the synthesis of an 11beta isomer 3 of the steroidal antiestrogen fulvestrant 2. Partial fluorination of the 11beta side chain in 3 leads to 4, which still shows strong antiproliferative activity on MCF-7 cells. However, unlike 2 and 3, compound 4 fails to down-regulate estrogen receptor alpha (ERalpha). This result suggests that ERalpha down-regulation is not a sine qua non condition for the antitumor activity of steroidal antiestrogens.
Agouridas
Vangelis
V
Institut Lavoisier de Versailles, UMR CNRS 8180, Université de Versailles St. Quentin en Yvelines, 78035 Versailles Cedex, France.
Magnier
Emmanuel
E
Blazejewski
Jean-Claude
JC
Laïos
Ioanna
I
Cleeren
Anny
A
Nonclercq
Denis
D
Laurent
Guy
G
Leclercq
Guy
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000138:chemical synthesis / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000187:drug effects; D000077267:Fulvestrant; D006801:Humans
D000970:Antineoplastic Agents; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D000077267:Fulvestrant; D004958:Estradiol