title: Synthesis, antiproliferative activity, acute toxicity and assessment of the antiandrogenic activities of new androstane derivatives.
abstract: A number of 17-oxo-5-androsten-3β-yl esters (9a-9f) and 3β-alkoxy-5-androsten-17-ones (11a-11e) were synthesized from commercially available (25R)-5-spirosten-3β-ol (Diosgenin) (4) as starting material. The synthesized compounds were evaluated for their antiproliferative activity against the prostate-specific cancer cell line DU-145, acute toxicity and effect on serum androgen levels, and compared with finasteride as positive control. Some of the compounds exhibited better cytotoxicity and antiandrogenic activity than the reference control. The detailed synthesis, spectroscopic data and biological activity of the synthesized compounds are reported.
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014, India.
authors.forename: Neelima
authors.initials: N
authors.lastname: Dhingra
authors.forename: T R
authors.initials: TR
authors.lastname: Bhardwaj
authors.forename: Neeraj
authors.initials: N
authors.lastname: Mehta
authors.forename: Tapas
authors.initials: T
authors.lastname: Mukhopadhyay
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
mesh_terms: D000726:Androgen Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000728:Androgens / Q000096:biosynthesis / Q000097:blood; D000731:Androstanes / Q000378:metabolism; D000736:Androstenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000737:Androstenols / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D018120:Finasteride / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D020128:Inhibitory Concentration 50; D007928:Lethal Dose 50; D008264:Macrophages; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: C569591:17-oxo-5-androsten-3beta-yl 4-chlorobenzoate; D000726:Androgen Antagonists; D000728:Androgens; D000731:Androstanes; D000736:Androstenes; D000737:Androstenols; D000970:Antineoplastic Agents; D018120:Finasteride; D004144:Diosgenin; C033936:androstane