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

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 disease 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 level. 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.