Convenient synthesis of 1,3-disubstituted-2-thioxo-imidazolidin-4-ones as potential anti-tumor agents

Abstract

1-(Arylidene)amino-2-thioxo-imidazolidine-4-ones ( 3 a,b) have been synthesized via cyclization of 1-(arylidene)amino-3-(chloroacetyl)thiourease ( 2 a,b) in ethanol in presence of fused sodium acetate under heating. Acetylation of compounds ( 3 a,b) with acetic anhydride yielded the corresponding 1-(arylidene)amino-2-thioxo-3-acetylimidazolidin-4-ones ( 4 a, b). Condensation of compounds ( 3 a,b) with aromatic aldehydes in presence of piperidine yielded the corresponding aryl-[1-(arylidine)amino-2-thioxo-4-oxo-imidazolidin-3-yl)carbanols ( 6 a-d). Halogenation of 1-(phenylethylidene)amino-2-thioxoimidazolidin-4-one ( 3 b) with one mole of bromine produced N-bromo- 2- thioxoimidazolidin-4-one ( 9 ), while brominating 1-(benzylidene)amino-2-thioxoimidazolidin-4-one ( 3 a) with two mole of bromine gave the corresponding 3,5-dibromo-2-thioxoimidazolidin-4-one derivative ( 10 ). The characterization of all synthesized compounds were done by elemental analysis and spectral studies. Moreover, the cytotoxic activities of the synthesized compounds were evaluated against human hepatocellular carcinoma cell line (HePG2) using MTT viability test. The results showed that the investigated compounds have a significantly cytotoxic effect.