Aldol derivatives of Thioxoimidazolidinones as potential anti-prostate cancer agents

The paper discusses the synthesis and stereochemical aspects of the anti aldol products, 3-(substituted phenyl)-5-[(substituted phenyl) hydroxy methyl]-5-methyl-4-oxo-2-thioxoimidazolidines. The stereochemistry observed in the aldol reactions with benzaldehydes was explained by transition state model of the endocyclic (E)-enolate formed from the rigid 4-oxo-2-thioxoimidazolidine skeleton. Proton NMR and ROESY spectral analyses were carried out to identify the syn and anti conformations of the aldol diastereomers. Configurations of the enantiomers of the representative anti aldol product 3-(4-chlorophenyl)-5-[(4-chlorophenyl) hydroxy methyl]-5-methyl-4-oxo-2-thioxoimidazolidine was determined by single crystal XRD studies. The compounds were screened in vitro against prostate cancer cell lines, PC-3 and LNCaP and the most potent derivatives were identified.

The anti aldol products, 3-(substituted phenyl)-5-[(substituted phenyl) hydroxy methyl]-5-methyl-4-oxo-2-thioxoimidazolidines were synthesized and screened for anti-prostate cancer activities on PC-3 and LNCaP cell lines.Figure optionsDownload as PowerPoint slideHighlights
► Anti aldol derivatives of 4-oxo-2-thioxoimidazolidines were synthesized.
► In vitro studies were done on PC-3 and LNCaP prostate cancer cell lines.
► Compound 7(c)(iii) demonstrated cytotoxicity better than flutamide on LNCaP cells.
► The compound was non-toxic at 1.0 μM concentration on non-cancerous cells MCF-10A.
► The compound exhibited selectivity towards prostate cancer cells.