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Current Enzyme Inhibition

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ISSN (Print): 1573-4080
ISSN (Online): 1875-6662

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Research Article

Synthesis, Characterization and Evaluation of 5α, 6β-Dihalo Androsterone Derivatives as 5α-Reductase Inhibitors

Author(s): Akansha Sharma, Priyanka Rana, Poonam Arora, Tanzeer Kaur and Neelima Dhingra*

Volume 18, Issue 3, 2022

Published on: 30 September, 2022

Page: [180 - 193] Pages: 14

DOI: 10.2174/1573408018666220525123827

Price: $65

Abstract

Background and Objective: Testosterone under the influence of 5α-reductase enzyme gets converted to dihydrotestosterone and high levels are found to be causative for androgen dependent diseases like benign prostatic hyperplasia. Thus, 5α-reductase has been recognised as an important target for discovering new drugs against Benign Prostatic Hyperplasia and Prostate Cancer.

Methods: In the present study, a series of 5α, 6β-Dichloro-17-Oxoandrostan-3β-yl esters (7a-7f) were synthesized and characterized by analytical and spectroscopic methods. The compounds were evaluated for their 5α-reductase inhibitory activity in-vivo by their effect on serum androgen levels.

Results: The target compounds (7a-7f) showed increased anti-androgenic activity as compared to finasteride and control, which implies that the target compounds are effective in inhibiting 5α-reductase. Particularly, compound 7b showing highest inhibitory activity and noteworthy D-Score was further sorted by performing solubility and dissolution studies. Results of these studies, when compared with finasteride, showed increased solubility and dissolution of target compound 7b.

Conclusion: These results demonstrated that enhancement of activity by the presence of electronegative group at position 3 of the steroidal nucleus makes 7b a lead compound for further exploration and optimal formulation.

Keywords: 5α-Reductase. Testosterone, Benign Prostatic Hyperplasia, Finasteride, Docking, Solubility and Intrinsic dissolution.

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