title: New progesterone derivatives as inhibitors of 5alpha-reductase enzyme and prostate cancer cell growth.
abstract: In this study we report the synthesis and pharmacological evaluation, in vivo as well as in vitro, of four new progesterone derivatives 4-7. The evaluation in vivo was carried out on gonadectomized male hamsters that were injected subcutaneously daily with 1 mg/Kg of testosterone (T) and/or 1 mg/Kg of finasteride, or with 2 mg/Kg of the novel compounds. It was observed that when testosterone (T) and finasteride or compound 4 were injected together, the weight of the prostate decreased significantly as compared to that oftestosterone-treated animals. Compounds 5-7 did not show any in vivo activity. The 5alpha-reductase inhibitory activity of the novel compounds was determined in vitro using human prostate homogenates; the steroids 4-7 inhibited the 5alpha-reductase activity with IC50 values lower than that for the reference compound finasteride. 3. The effect of compounds 4-7 on the growth of lymphocytes and prostate cancer culture cells line was that steroid 4 inhibited the growth of both cells lines at a concentration of 50 microM and showed a cytotoxic effect whereas compounds 5-7 showed a much lower inhibition. Nevertheless steroids 4-7 didn't exhibit any toxic effects in vivo since the animals remained alive during the six days of treatment.
authors.affiliation: Department of Biological Systems and Animal Production, Metropolitan University-Xochimilco, Mexico, DF Mexico. marisa@correo.xoc.uam.mx
authors.forename: Marisa
authors.initials: M
authors.lastname: Cabeza
authors.forename: Eugene
authors.initials: E
authors.lastname: Bratoeff
authors.forename: Ivonne
authors.initials: I
authors.lastname: Heuze
authors.forename: Arely
authors.initials: A
authors.lastname: Rojas
authors.forename: Nayely
authors.initials: N
authors.lastname: Terán
authors.forename: Martha'
authors.initials: M
authors.lastname: Ochoa
authors.forename: Teresa
authors.initials: T
authors.lastname: Ramírez-Apan
authors.forename: Elena
authors.initials: E
authors.lastname: Ramírez
authors.forename: Victor
authors.initials: V
authors.lastname: Pérez
authors.forename: Isabel
authors.initials: I
authors.lastname: Gracia
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D042944:Cholestenone 5 alpha-Reductase / Q000737:chemistry*; D006224:Cricetinae; D018120:Finasteride / Q000494:pharmacology; D006801:Humans; D008297:Male; D008647:Mesocricetus; D008956:Models, Chemical; D011374:Progesterone / Q000031:analogs & derivatives* / Q000737:chemistry*; D011467:Prostate / Q000187:drug effects / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D013256:Steroids / Q000737:chemistry; D013739:Testosterone / Q000494:pharmacology
chemical_list: D013256:Steroids; D013739:Testosterone; D011374:Progesterone; D018120:Finasteride; D042944:Cholestenone 5 alpha-Reductase