Synthesis of 17beta-estradiol-linked platinum(II) complexes and their cytocidal activity on estrogen-dependent and -independent breast tumor cells.
The synthesis of two new highly potent 17beta-estradiol-linked platinum(II) complexes is described. The new molecules are linked at position 16 of the steroid nucleus with an alkyl chain. They are made from estrone in nine chemical steps with an overall yield exceeding 10%. The biological activity of these compounds was evaluated in vitro on estrogen dependent and independent (ER(+) and ER(-)) human breast tumor cell lines: MCF-7 and MDA-MB-231. The novel compounds prove to be highly cytotoxic against breast cancer cell lines. The most cytotoxic derivative shows high affinity for the estrogen receptor alpha.
Perron
Valérie
V
Département de Chimie-Biologie, Université du Québec à Trois-Rivières, C.P. 500, Trois-Rivières, Québec, Canada, G9A 5H7.
Rabouin
Daniel
D
Asselin
Eric
E
Parent
Sophie
S
C-Gaudreault
René
R
Bérubé
Gervais
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
C487473:17beta-estradiol platinum(II); D000970:Antineoplastic Agents; D047628:Estrogen Receptor alpha; D009944:Organoplatinum Compounds; D004958:Estradiol