Abstract
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.
Keywords: Androgen receptor, dehydroepiandrosterone-triazole derivatives, hamster prostate gland, human 17β-HSD 5, hamster 17β-HSD activity, prostatic cancer.
Graphical Abstract
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