New progesterone derivatives as inhibitors of 5α-reductase enzyme and prostate cancer cell growth

In this study we report the synthesis and pharmacological evaluation, in vivo as well as in vitro, of four new progesterone derivatives 4–7. The evaluation in vivo was carried out on gonadectomized male hamsters that were injected subcutaneously daily with 1 mg/Kg of testosterone (T) and/or 1 mg/Kg of finasteride, or with 2 mg/Kg of the novel compounds. It was observed that when testosterone (T) and finasteride or compound 4 were injected together, the weight of the prostate decreased significantly as compared to that of testosterone-treated animals. Compounds 5–7 did not show any in vivo activity.The 5α-reductase inhibitory activity of the novel compounds was determined in vitro using human prostate homogenates; the steroids 4–7 inhibited the 5α-reductase activity with IC50 values lower than that for the reference compound finasteride. 3.The effect of compounds 4–7 on the growth of lymphocytes and prostate cancer culture cells line was that steroid 4 inhibited the growth of both cells lines at a concentr...