Synthesis and Study of Some 17a-aza-D-homo Steroids as 5α-Reductase Inhibitors

Title:Synthesis and Study of Some 17a-aza-D-homo Steroids as 5α-Reductase Inhibitors

Volume: 18 Issue: 5

Author(s): Priyanka Rana, Neelima Dhingra*, Poonam Arora, Richa Dhingra, Chauhan Monika and Ankit Gupta

Affiliation:

• Department of Pharmaceutical Chemistry, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014,India

Keywords: 5α-Reductase, 5α-reductase inhibitors, benign prostatic hyperplasia, dihydrotestosterone, finasteride, testosterone, docking, lower urinary tract symptoms.

Abstract: 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.

Cite this article as:

Rana Priyanka , Dhingra Neelima *, Arora Poonam , Dhingra Richa , Monika Chauhan and Gupta Ankit , Synthesis and Study of Some 17a-aza-D-homo Steroids as 5α-Reductase Inhibitors, Current Drug Discovery Technologies 2021; 18 (5) : e22092020186180 . https://dx.doi.org/10.2174/1570163817666200922120406

DOI https://dx.doi.org/10.2174/1570163817666200922120406	Print ISSN 1570-1638
Publisher Name Bentham Science Publisher	Online ISSN 1875-6220