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.

Selective Synthesis of Ortho-substituted 3-Cyclohexyl-2-phenyl-1,3-thiazolidin-4-one Sulfoxides and Sulfones by S-Oxidation with Oxone

“…The S-oxides may show enhanced activity; for example, Miller and coworkers converted one 4-thiazolidinone to its sulfoxide and sulfone and reported that the oxides showed greater activity against some cancer cell lines than the sulfide (Gududuru, Hurh, Dalton & Miller, 2004). Thiazolidin-4-ones have been oxidized to sulfoxides with peracetic acid (Surrey, 1967), Na 5 IO 6 (Smith, Lee & Cragoe, 1977), chloramine T (Omar, El-Kharmy & Sharif, 1981), NaIO 4 (Lee, Yergatian, Crowther & Downie, 1990), Oxone ® (one example, Rozwadowska, Sulima & Gzella, 2002), and m-CPBA (Rozwadowska & Sulima, 2003).…”

Synthesis and Antimicrobial Activities of Some Novel 2,3-Substituted-1,3-Thiazolidin-4-ones Derived from 2-Amino-1,3-thiazole

“…It needs to be accounted to show different physiological activities. They found uses as antitubercular [3], antimicrobial [4][5][6][7][8], antiinflammatory [9], anticancer [10], antihistamines [11], anticonvulsant [12] and as antiviral agents especially as anti-HIV agents [11,13,14]. It has been extensively reported that the antibacterial activity strongly depended on the nature of substituents at C2 and N3 of thiazolidinone ring.…”

Synthesis of some novel 2,5-disubstituted thiazolidinones from a long chain fatty acid as possible anti-inflammatory, analgesic and hydrogen peroxide scavenging agents

“…The broad and potent activity profile of thiazolidinones has established them as one of the biologically most active scaffolds. A myriad spectrum of biological activities such as antimicrobial [3,4], anticonvulsant [5,6], antitubercular [7,8], anticancer [9,10], anti-inflammatory and analgesics [11,12], antipsychotic [13], anti-HIV [14,15], antidiarrheal [16], CNS and CVS [17], antioxidant [18,19], diuretic [20] and hypnotic [21] activities have been reported to be associated with thiazolidinone. Moreover, some derivatives of thiazolidin-4-ones have been used for the treatment of cardiac disease.…”