10.6084/m9.figshare.1568397.v1
Isabel Moreno
Isabel
Moreno
Marisa Cabeza
Marisa
Cabeza
Alejandro Posada
Alejandro
Posada
Araceli Sánchez-Márquez
Araceli
Sánchez-Márquez
Yvonne Heuze
Yvonne
Heuze
Juan Soriano
Juan
Soriano
Mariana Garrido
Mariana
Garrido
Francisco Cortés
Francisco
Cortés
Eugene Bratoeff
Eugene
Bratoeff
Biological activity of pyrazole and imidazole-dehydroepiandrosterone derivatives on the activity of 17<b>β</b>-hydroxysteroid dehydrogenase 5
Taylor & Francis Group
2015
prostate weight
hsd
enzyme
androgen deprivation therapy
hydroxysteroid
Biological Activity
novel compounds
testosterone
inhibition assays
dehydrogenase
androstenedione
prostatic hyperplasia
cancer patients
Prostate cancer
pyrazole
castrated hamsters
flank organ diameter
dione
gonadectomized hamsters
ester moiety
dehydroepiandrosterone derivatives
imidazole function
2015-02-18 00:00:00
Journal contribution
https://tandf.figshare.com/articles/journal_contribution/Biological_activity_of_pyrazole_and_imidazole_dehydroepiandrosterone_derivatives_on_the_activity_of_17_b_946_b_hydroxysteroid_dehydrogenase_5/1568397
<div><p></p><p>The enzyme type 5 17β-hydroxysteroid dehydrogenase 5 (17β-HSD5) catalyzes the transformation of androstenedione (4-dione) to testosterone (T) in the prostate. This metabolic pathway remains active in cancer patients receiving androgen deprivation therapy. Since physicians seek to develop advantageous and better new treatments to increase the average survival of these patients, we synthesized several different dehydroepiandrosterone derivatives. These compounds have a pyrazole or imidazole function at C-17 and an ester moiety at C-3 and were studied as inhibitors of 17β-HSD5. The kinetic parameters of this enzyme were determined for use in inhibition assays. Their pharmacological effect was also determined on gonadectomized hamsters treated with Δ<sup>4</sup>-androstenedione (4-dione) or testosterone (T) and/or the novel compounds. The results indicated that the incorporation of a heterocycle at C-17 induced strong 17β-HSD5 inhibition. These derivatives decreased flank organ diameter and prostate weight in castrated hamsters treated with T or 4-dione. Inhibition of 17β-HSD5 by these compounds could have therapeutic potential for the treatment of prostate cancer and benign prostatic hyperplasia.</p></div>