New dehydroepiandrosterone-triazole derivatives identified as inhibitors of 17ß-hydroxysteroid dehydrogenase enzyme in the prostate
Por:
Sánchez-Márquez A., Silva-Ortíz A., Bratoeff E., Heuze Y., Soriano J., Medina Y., Cabeza M.
Publicada:
1 ene 2016
Resumen:
Introduction: Synthesis and biological activity of three different dehydroepiandrosteronederivatives which possess a triazole group at C-17 and various substituents at C-3 of the steroidal skeleton are presented. These compounds were designed to inhibit the activity of type 5 17ß-hydroxysteroid dehydrogenase (17ß-HSD 5) which is present in human prostate. These steroids have been proposed as an alternative for treatment of prostate cancer patients showing resistance to anti-androgen therapy. Materials and Methods: The role of these derivatives as inhibitors of 17ß-HSD activity was determined both in in vivo and in vitro conditions. In in vitro studies both human and hamster prostate were used as the source of this enzyme membrane fraction. The pharmacological effect on the weight of the prostate and seminal vesicles of castrated hamsters treated with androstenedione (4-dione) was determined for each of the derivatives tested. Results: The results showed that 17ß-HSD 5 activity is present in the prostate membrane of both species. However, it could be inhibited by the three derivatives studied. Pharmacological studies have demonstrated that these three compounds were able to decrease prostate weight. Conclusion: In conclusion, these dehydroepiandrosterone-triazole derivatives inhibited the activity of 17ß-HSD 5 and also displayed pharmacological activity, so they could have therapeutic potential for cancer patients who do not respond to treatment with anti-androgens. © 2016 Bentham Science Publishers.
Filiaciones:
Sánchez-Márquez A.:
Departamento de Sistemas Biológicos y de Producción Agrícola y Animal, Universidad, Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, Col. Villa Quietud, México, Mexico
Silva-Ortíz A.:
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Av. Universidad 3000, Copilco Universidad, Coyoacán, México, Mexico
Bratoeff E.:
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Av. Universidad 3000, Copilco Universidad, Coyoacán, México, Mexico
Heuze Y.:
Departamento de Sistemas Biológicos y de Producción Agrícola y Animal, Universidad, Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, Col. Villa Quietud, México, Mexico
Soriano J.:
Departamento de Patología, Hospital General de México, Dr. Balmis 148, México, Mexico
Medina Y.:
Departamento de Sistemas Biológicos y de Producción Agrícola y Animal, Universidad, Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, Col. Villa Quietud, México, Mexico
Cabeza M.:
Departamento de Sistemas Biológicos y de Producción Agrícola y Animal, Universidad, Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, Col. Villa Quietud, México, Mexico
|