Introduction: 5α-reductase inhibitors have been proven useful for the treatment of prostate
diseases, which can be due to the unregulated activity of 5α-reductase enzyme. This study was focused
on determining the activity of four different derivatives of 17β-phenyl carbamoyl-androst-4-en-3-one
1–4 as inhibitors of 5α-reductase (5RD5A), to improve the effects of current drugs.
Methods: In vitro effect of compounds 1-4 on the activity of the human prostate enzyme, 5α-reductase,
was determined by measuring IC50 values, the concentration of a compound that inhibits the activity of
5RD5A2 by 50%. In vivo, the pharmacological effects of compounds 1-4 were identified in a hamster
model of prostate hypertrophy.
Results: The steroidal 17β-carboxamides 1, 3, and 4 (IC50 = 5±0.5, 0.112±0.045, 0.167±0.056 nM) significantly
inhibited the in vitro activity of the 5RD5A2 enzyme with higher potency than finasteride,
which is a drug known as a specific 5RD5A2 inhibitor (IC50 = 8.5±0.3 nM). Compounds 1, 3, and 4
were more potent than finasteride to decrease the size of hamster flank organs in castrated animals
treated with testosterone. Also, compounds 1–4 were more effective than finasteride itself to reduce the
weight of the prostate in the hamster model, without producing toxicological effects during the six days
Conclusion: In conclusion, the steroidal 17β-carboxamides 1–4 were suitable inhibitors of human
5RD5A2 activity, in addition to being able to reduce prostate weight without causing toxicity. These
steroids could, therefore, have promising therapeutic potential for the treatment of benign prostatic hyperplasia.