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 17-β
hydroxysteroid dehydrogenase (17β-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 17β-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 17β-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 17β-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.