Relative binding affinity of novel steroids to androgen receptors in hamster prostate
Por:
Cabeza M., Heuze I., Sánchez M., Bratoeff E., Ramírez E., Rojas A., Orozco A., Mungía A., Agustín G., Cuatepotzo L., Gonzalez C., Palma S., Padilla D., Perez V., Jimenez G.
Publicada:
1 ene 2005
Resumen:
The in vivo and in vitro antiandrogenic activity of four aromatic esters 10a-10d, one aliphatic ester 10e based on the pregna-4,16-diene-6, 20-dione structure and two aromatic 17c, 17d and two aliphatic valeroyloxy esters 17a, 17b based on the more saturated 4-pregnene-6,20-dione skeleton was examined. The biological activity of steroids 9, 10a-10e and 17a-17d, was determined using prostate glands from gonadectomized adult male golden hamsters. In the in vitro studies, the relative binding affinity of these steroids to cytoplasmic androgen receptor (AR) of hamster prostate was determined from, the corresponding IC50 values obtained from the competitive binding plots. The standards dihydrotestosterone (DHT) and cyproterone (CA) acetate used have displaced [3H]DHT from the AR with an IC50 value of 3.2 and 4.4 nM respectively. All steroidal compounds synthesized in this study showed a binding affinity for the androgen receptor, present in the cytosol from prostate hamster; compounds 10a-10c showed the highest affinities for this receptor. The in vivo experiments showed that all steroidal derivatives were subcutaneously active, since they decreased the weight of the prostate gland in gonadectomized hamsters treated with DHT, and are antagonists for the androgen receptor since they block the DHT-induced prostate weight gain. The derivatives having the more conjugated 4,16-pregnadiene-6, 20-dione system (10a-10c) exhibited a higher antiandrogenic activity than the corresponding steroids (17a-17d) based on the more saturated 4-pregnene-6,20-dione system. © 2005 Taylor & Francis.
Filiaciones:
Cabeza M.:
Department of Biological Systems and Animal Production, Metropolitan University-Xochimilco, Calzada del Hueso no. 1100, México, D.F. 04960, Mexico
Heuze I.:
Department of Biological Systems and Animal Production, Metropolitan University-Xochimilco, Calzada del Hueso no. 1100, México, D.F. 04960, Mexico
Sánchez M.:
Department of Biological Systems and Animal Production, Metropolitan University-Xochimilco, Calzada del Hueso no. 1100, México, D.F. 04960, Mexico
Bratoeff E.:
Faculty of Chemistry, Department of Pharmacy, National University of Mexico City, Mexico, D.F., Mexico
Ramírez E.:
Faculty of Chemistry, Department of Pharmacy, National University of Mexico City, Mexico, D.F., Mexico
Rojas A.:
Faculty of Chemistry, Department of Pharmacy, National University of Mexico City, Mexico, D.F., Mexico
Orozco A.:
Faculty of Chemistry, Department of Pharmacy, National University of Mexico City, Mexico, D.F., Mexico
Mungía A.:
Faculty of Chemistry, Department of Pharmacy, National University of Mexico City, Mexico, D.F., Mexico
Agustín G.:
Faculty of Chemistry, Department of Pharmacy, National University of Mexico City, Mexico, D.F., Mexico
Cuatepotzo L.:
Faculty of Chemistry, Department of Pharmacy, National University of Mexico City, Mexico, D.F., Mexico
Gonzalez C.:
Faculty of Chemistry, Department of Pharmacy, National University of Mexico City, Mexico, D.F., Mexico
Palma S.:
Faculty of Chemistry, Department of Pharmacy, National University of Mexico City, Mexico, D.F., Mexico
Padilla D.:
Faculty of Chemistry, Department of Pharmacy, National University of Mexico City, Mexico, D.F., Mexico
Perez V.:
Faculty of Chemistry, Department of Pharmacy, National University of Mexico City, Mexico, D.F., Mexico
Jimenez G.:
Faculty of Chemistry, Department of Pharmacy, National University of Mexico City, Mexico, D.F., Mexico
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