Background and Objective: Tremendous advances have been made in the development
of new pharmacotherapuetic agents and less invasive techniques to help men with lower urinary
tract symptoms. The use of 5α-reductase inhibitor (5-ARI) is restricted to the patients with large
prostate volumes, whose symptoms are refractory to antiandrogens or α–adrenergic blockers. Out
of the various synthesized 5-reductase inhibitors with different substituents on the steroidal nucleus,
esters have been found to exhibit high anti-androgenic activity.
Methods: In our attempt to find new, safer and potent 5-ARI and our continued interest in azasteorids,
esters of 17a-Aza-D-homo-5-androsten-3β-ol with synergistic effect were synthesized and
characterized using different analytical techniques. The compounds were evaluated for their 5α-reductase
inhibitory activity in-vivo by their effect on serum androgen level by ELISA assay procedure.
The interaction with receptors was studied using an advanced docking programme to predict
the correlation of the synthesized compounds with actual biological activity.
Results: The target compounds (6-12) showed increased anti-androgenic activity as compared to finasteride
and control, which imply that the target compounds are effective in inhibiting 5α-reductase.
Particularly, compound 6 showed the highest inhibitory activity and greater affinity for the 5-
AR receptor with the highest dock score. The results of these studies when compared with Finasteride
showed increased solubility and dissolution of target compound 6.
Conclusion: Compound 6 showed immense potential with improved efficacy and better bioavailability,
thus makes it a suitable candidate for further studies and optimal formulation.