title: Synthesis of unique 17beta-estradiol homo-dimers, estrogen receptors binding affinity evaluation and cytocidal activity on breast, intestinal and skin cancer cell lines.
abstract: A rapid and efficient synthesis of a series of C2-symmetric 17beta-estradiol homo-dimers is described. The new molecules are linked at position 17alpha of the steroid nucleus with either an alkyl chain or a polyethylene glycol chain. They are made from estrone in only five chemical steps with an overall yield exceeding 30%. 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. Some of the dimers present selective cytotoxic activity against the ER+ cell line. However, they are not very cytotoxic when compared to the antiestrogen tamoxifen. Unfortunately, they show only weak affinity for the estrogen receptor alpha (ERalpha) and no affinity for the estrogen receptor beta (ERbeta). The new compounds were also tested on human intestinal (HT-29) cancer and on murine skin cancer (B16-F10) cell lines for further biological assessment. Interestingly, the dimers were found to be cytotoxic to the murine skin cancer cell line but were inactive towards the intestinal cancer cell line.
authors.affiliation: Groupe de Recherche en Biopathologies Cellulaires et Moléculaires, Département de Chimie-Biologie, Université du Québec à Trois-Rivières, C.P. 500, Trois-Rivières, Québec, Canada G9A 5H7. Gervais.Berube@uqtr.ca
authors.forename: Gervais
authors.initials: G
authors.lastname: Bérubé
authors.forename: Daniel
authors.initials: D
authors.lastname: Rabouin
authors.forename: Valérie
authors.initials: V
authors.lastname: Perron
authors.forename: Blaise
authors.initials: B
authors.lastname: N'Zemba
authors.forename: René-C
authors.initials: RC
authors.lastname: Gaudreault
authors.forename: Sophie
authors.initials: S
authors.lastname: Parent
authors.forename: Eric
authors.initials: E
authors.lastname: Asselin
mesh_terms: D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D019281:Dimerization; D004958:Estradiol / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D006801:Humans; D007414:Intestinal Neoplasms; D009682:Magnetic Resonance Spectroscopy; D011485:Protein Binding; D012878:Skin Neoplasms; D013055:Spectrophotometry, Infrared
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004958:Estradiol