Synthesis and Antiproliferative Activity of 3-aza Steroids as 5α-reductase Inhibitors

Background: Dihyrdotestosterone (DHT), the most potent circulating androgen hormone, is produced by stereoselective reduction of testosterone (T) under catalysis of NADPH dependent enzyme steroid 5α-reductase (5AR). The DHT production is related to many pathological conditions and endocrine diseases such as Benign Prostatic Hyperplasia (BPH). Many years ago, the use of 5AR inhibitors for the possible control or suppression of DHT formation has become years ago a therapeutic target for the treatment of BPH. During last two decades, several non steroidal and steroidal compounds have been synthesized as reversible and irreversible 5AR inhibitors. Methods: Present study describes the synthesis of 17β-substituted amides of 3-aza-A-homo-4aandrosten- 4-one starting from 16-Dehydropregnelone acetate (16-DPA). The structure of newly synthesized compounds was established on the basis of TLC and various spectroscopic studies and compounds were subjected for their in vitro cytotoxicity studies using prostate cancer cell lines PC-3. Results and Conclusion: Synthesized compounds (13a to 13h) showed better cytotoxicity as compared to reference drug and 3-Aza-A-homo-17β-(4-nitrobenzamido)-4a-androsten-4-one (13b) showed an excellent antiproliferative activity as compared to Dutasteride.