Discovery of 2-arylthiazolidine-4-carboxylic acid amides as a new class of cytotoxic agents for prostate cancer.
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.
Gududuru
Veeresa
V
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Hurh
Eunju
E
Dalton
James T
JT
Miller
Duane D
DD
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy; D012333:RNA, Messenger / Q000096:biosynthesis; D049368:Receptors, Lysophosphatidic Acid / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000577:Amides; D000970:Antineoplastic Agents; D012333:RNA, Messenger; D049368:Receptors, Lysophosphatidic Acid; D013844:Thiazoles