title: New ester derivatives of dehydroepiandrosterone as 5α-reductase inhibitors.
abstract: The aim of this study was to synthesize different ester derivatives of dehydroepiandrosterone with therapeutic potential as antiandrogens. The biological effect of these steroids was demonstrated in in vivo as well as in vitro experiments. In the in vivo experiments, we measured the activity of seven steroids on the weight of the prostate and seminal vesicles of gonadectomized hamsters treated with testosterone. For the in vitro studies, we determined the IC(50) values by measuring the concentration of the steroidal derivatives that inhibits 50% of the activity of 5α-reductase present in human prostate and also its binding capacity to the androgen receptors (AR) obtained from rat's prostate cytosol. The results from these experiments indicated that compounds 7 5α,6β-dibromo-3β-propanoyloxyandrostan-17-one, 8 5α,6β-dibromo-3β-butanoyloxyandrostan-17-one and 9 5α,6β-dibromo-3β-(3'-oxapentanoyloxy)-androstan-17-one, significantly decreased the weight of the prostate and seminal vesicles as compared to testosterone treated animals; this reduction of the weight of these glands was comparable to that produced by Finasteride 11. On the other hand, compounds 4 3β-acetoxyandrost-5-en-17-one, 5 3β-hexanoyloxyandrost-5-en-17-one 6 3β-(3'-oxapentanoyloxy)-androst-5-en-17-one, 7 and 12 dehydroepiandrosterone, (commercially available) inhibited the enzyme 5α-reductase. Compounds 4, 5, 6, 8 and 9 (IC(50) values of 5.2±1.2, 0.049±0.002, 6.4±1.1, 0.10±0.045, and 6.8±0.9 nM, respectively) exhibited the highest inhibitory activity. However, none of these compounds binds to the AR.
authors: Department of Pharmacy, Faculty of Chemistry, National University of Mexico, Mexico, D.F., Mexico.
authors: Yazmín
authors: Y
authors: Arellano
authors: Eugene
authors: E
authors: Bratoeff
authors: Mariana
authors: M
authors: Garrido
authors: Juan
authors: J
authors: Soriano
authors: Yvonne
authors: Y
authors: Heuze
authors: Marisa
authors: M
authors: Cabeza
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000138:chemical synthesis*; D000726:Androgen Antagonists / Q000138:chemical synthesis*; D000818:Animals; D042944:Cholestenone 5 alpha-Reductase / Q000378:metabolism*; D006224:Cricetinae; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008647:Mesocricetus; D051381:Rats
chemical_list: D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D003687:Dehydroepiandrosterone; D042944:Cholestenone 5 alpha-Reductase