Background: 5α-Reductase inhibitors have proven useful for the treatment of prostate diseases, which can result
from the unregulated activity of the 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 on the
effect of current drugs.
Methods: In vitro effect of compounds 1-4 on the activity of the human prostate enzyme, 5α-reductase, was determined
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 of treatment.
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.