The 17-oximino-5-androsten-3b-yl esters (10a– 10j) were synthesized from commercially available (25R)- 5-Spirosten-3b-ol (Diosgenin) (4) as starting material. The synthesized compounds were evaluated for their antiproliferative activity against prostate specific cancer cell line DU-145, acute toxicity, and effect on serum androgen level and were compared with Finasteride used as positive control. Some of the compounds exhibited better cytotoxicity and antiandrogenic activity than the reference control. The detailed synthesis, spectroscopic data, and biological evaluation for the synthesized compounds are reported.