title: Synthesis of novel C2-symmetric testosterone dimers and evaluation of antiproliferative activity on androgen-dependent and -independent prostate cancer cell lines.
abstract: A series of 7α-linked testosterone dimers were made and tested for biological activity on both androgen-dependent (LNCaP) and androgen-independent (DU-145 and PC3) prostate cancer cell lines. The synthesis proceeds through the formation of a trans-4-(17β-acetoxy-4-androsten-3-one-7α-yl)-but-2-enoic acid 4-hydroxy-alkyl ester intermediate of various length (7a-d) followed by the final dimerization step. The dimers showed interesting biological activity in comparison to the ω-hydroxyalkyl ester intermediates 7a-d. The most active dimer 8a (n=1) showed IC50of 3.8, 1.4 and 1.8μM, respectively on LNCaP, DU-145 and PC3 cancer cell lines. On these cell lines, this dimer is about 12, 70 and 47 times more powerful than cyproterone acetate (CPA) the reference antiandrogen. Furthermore, dimers 8b-d (n=2, 3, 4) were less active than 8a but showed selective activity on androgen-dependent LNCaP prostate cancer cells. This indicates possible application for the treatment of androgen-dependent prostate cancer.
authors.affiliation: Département de Chimie, Biochimie et Physique, Université du Québec à Trois-Rivières, C.P. 500, Trois-Rivières, Québec G9A 5H7, Canada. Electronic address: Anne.Vesper@live.ca.
authors.forename: Anne-Rose
authors.initials: AR
authors.lastname: Vesper
authors.affiliation: Axe oncologie, Centre de recherche du CHU de Québec-Université Laval, Hôpital Saint-François d'Assise, 10, rue de l'Espinay, Québec G1L 3L5, Canada. Electronic address: Jacques.Lacroix@crchudequebec.ulaval.ca.
authors.forename: Jacques
authors.initials: J
authors.lastname: Lacroix
authors.affiliation: Axe oncologie, Centre de recherche du CHU de Québec-Université Laval, Hôpital Saint-François d'Assise, 10, rue de l'Espinay, Québec G1L 3L5, Canada. Electronic address: Rene.C-Gaudreault@crchudequebec.ulaval.ca.
authors.forename: René
authors.initials: R
authors.lastname: C-Gaudreault
authors.affiliation: Département de Chimie, Biochimie et Physique, Université du Québec à Trois-Rivières, C.P. 500, Trois-Rivières, Québec G9A 5H7, Canada. Electronic address: Heidar-Ali.Tajmir-Riahi@uqtr.ca.
authors.forename: Heidar-Ali
authors.initials: HA
authors.lastname: Tajmir-Rihai
authors.affiliation: Département de Chimie, Biochimie et Physique, Université du Québec à Trois-Rivières, C.P. 500, Trois-Rivières, Québec G9A 5H7, Canada. Electronic address: Gervais.Berube@uqtr.ca.
authors.forename: Gervais
authors.initials: G
authors.lastname: Bérubé
mesh_terms: D000728:Androgens / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000378:metabolism*; D013739:Testosterone / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000728:Androgens; D013739:Testosterone
keywords: Antiproliferative activity; Prostate cancer; Testosterone; Testosterone dimers