Testosterone (T) plays a crucial role in prostate growth. In androgen-dependent tissues T is reduced to dihydrotestosterone (DHT) because of the presence of the 5α-reductase enzyme. This androgen is more active than T, since it has a higher affinity for the androgen receptor (AR).
When this mechanism is altered, androgen-dependent diseases, including prostate cancer, could result. The aim of this study was to synthesize several 16-dehydropregnenolone acetate derivatives containing a triazole ring at C-21 and a linear or alicyclic ester moiety at C-3 of the steroidal skeleton. These steroids were designed as potential inhibitors of the activity of both types (1 and 2) of 5α-reductase. The cytotoxic activity of these compounds was also evaluated on a panel of PC-3, MCF7, and SK-LU-1 human cancer cell lines. The results from this study showed that with the exception of steroids 20-oxo-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-3β-yl-propionate and 20-oxo-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-3β-yl-pentanoate, the compounds exhibit a lower inhibitory activity for both isoenzymes of 5α-reductase than finasteride. Furthermore the 3β-hydroxy-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-20-one and 20-oxo-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-3β-yl-acetate derivatives display 80% cytotoxic activity on the SK-LU-1 cell line. These results also indicated that the triazole derivatives, which have a hydroxyl or acetoxy group at C-3, could have an anticancer effect, whereas the derivatives with a alicyclic ester group at C-3 do not show biological activity.
Bioorganic & medicinal chemistry. 2015 Nov 04 [Epub ahead of print]
Aylin Viviana Silva-Ortiz, Eugene Bratoeff, Teresa Ramírez-Apan, Yvonne Heuze, Araceli Sánchez, Juan Soriano, Marisa Cabeza
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Av. Universidad 3000, Copilco Universidad, Coyoacán, 04510 Ciudad de México, Distrito Federal, México D. F. , Mexico. Faculty of Chemistry, Department of Pharmacy (Departamento de Farmacia), National Autonomous University of Mexico in Mexico City (Universidad Nacional Autónoma de México), Mexico. Intituto de Quimica, Universidad Nacional Autónoma de México, Av. Universidad 3000, Copilco Universidad, Coyoacán, 04510 Ciudad de México, Distrito Federal, México D. F. , Mexico. Departamento de Sistemas Biológicos y de Producción Agrícola y Animal, Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, Col. Villa Quietud, 04960 Ciudad de México, México D. F. C. P. 04960, Mexico. Departamento de Sistemas Biológicos y de Producción Agrícola y Animal, Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, Col. Villa Quietud, 04960 Ciudad de México, México D. F. C. P. 04960, Mexico. Departamento de Patología, Hospital General de México, Dr. Balmis 148, México D. F. , Mexico. Departamento de Sistemas Biológicos y de Producción Agrícola y Animal, Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso 1100, Col. Villa Quietud, 04960 Ciudad de México, México D. F. C. P. 04960, Mexico.