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>