Benign prostatic hyperplasia is non-malignant enlargement of prostate gland which results
in severe lower urinary tract symptoms and affects the quality of life of patients. 5-Reductase inhibitors
play a crucial role in the management of benign prostatic diseases with low toxicity and have
been a major thrust area for its application in prostate cancers with limited success. In continuation
of our program to develop novel 5-reductase inhibitors, we report herein the synthesis and biological
evaluation of 5a-oxo-5-aza-B-homo-3,5-seco-4-nor-cholestan-3-oic acid and 25(R)-5a-oxo-5-aza-
B-homo-3,5-seco-4-nor-spirostan-3-oic acid derivatives. In vitro evaluation using human embryonic
kidney cell line (HEK) based assay revealed compound MK-234 as most potent inhibitor with an
IC50 value of 0.474 ±0.041 M followed by MK-233 with an IC50 value 4.84 ± 0.088 µM as compared
to clinically used drug finasteride (IC50 = 30.3 nM). Compound MK-235 and MK-236 also exhibited
moderate inhibition with an IC50 value of 9.24 ± 0.796 and 13.148 ± 0.379 µM, respectively.
Additionally, in silico ADME predictive studies were also carried out to assess the ‘druggability
properties’ of the synthesised compounds.
Keywords: Benign prostatic hyperplasia, 5α-reductase inhibitors, 3, 5-seco steroids, in silico predictive ADME studies.
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