New progesterone derivatives as inhibitors of 5a-reductase enzyme and prostate cancer cell growth
Por:
Cabeza M., Bratoeff E., Heuze I., Rojas A., Terán N., Ochoa M., Ramírez-Apan M.T., Ramírez E., Pérez V., Gracia I.
Publicada:
1 ene 2006
Resumen:
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 of testosterone-treated animals. Compounds 5-7 did not show any in vivo activity. The 5?-reductase inhibitory activity of the novel compounds was determined in vitro using human prostate homogenates; the steroids 4-7 inhibited the 5?-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 ?M 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.
Filiaciones:
Cabeza M.:
Department of Biological Systems and Animal Production, Metropolitan University-Xochimilco, Mexico, D. F., Mexico
Bratoeff E.:
Department of Pharmacy, Faculty of Chemistry, National University of Mexico City, Mexico, D. F., Mexico
Heuze I.:
Department of Biological Systems and Animal Production, Metropolitan University-Xochimilco, Mexico, D. F., Mexico
Rojas A.:
Department of Pharmacy, Faculty of Chemistry, National University of Mexico City, Mexico, D. F., Mexico
Terán N.:
Department of Pharmacy, Faculty of Chemistry, National University of Mexico City, Mexico, D. F., Mexico
Ochoa M.:
Department of Pharmacy, Faculty of Chemistry, National University of Mexico City, Mexico, D. F., Mexico
Ramírez-Apan M.T.:
Institute of Chemistry, National University of Mexico City, Mexico, D. F., Mexico
Ramírez E.:
Department of Pharmacy, Faculty of Chemistry, National University of Mexico City, Mexico, D. F., Mexico
Pérez V.:
Department of Pharmacy, Faculty of Chemistry, National University of Mexico City, Mexico, D. F., Mexico
Gracia I.:
Department of Pharmacy, Faculty of Chemistry, National University of Mexico City, Mexico, D. F., Mexico
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