Discovery of 2-arylthiazolidine-4-carboxylic acid amides as a new class of cytotoxic agents for prostate cancer.
ABSTRACT To improve the selectivity and antiproliferative activity of previously reported serine amide phosphates (SAPs), we designed a new series of 4-thiazolidinone amides, in which the 4-thiazolidinone moiety was introduced as a phosphate mimic. However, these 4-thiazolidinone derivatives demonstrated less cytotoxicity in prostate cancer cells despite improved selectivity over RH7777 cells. To further optimize the thiazolidinone analogues in terms of cytotoxicity and selectivity, we made closely related structural modifications, which led us to the discovery of a new class of 2-arylthiazolidine-4-carboxylic acid amides. These compounds were potent cytotoxic agents with IC(50) values in the low micromolar concentration range and demonstrated enhanced selectivity in receptor-negative cells compared to SAPs and 4-thiazolidinone amides.
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ABSTRACT: AbstractThe 17-oximino-5-androsten-3β-yl esters (10a–10j) 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 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. Graphical abstract KeywordsDihydrotestosterone–5-Alpha reductase enzyme–Benign prostatic hyperplasia–Steroids–AndrogenMedicinal Chemistry Research 04/2012; 20(7):817-825. · 1.61 Impact Factor