Synthesis and anticancer activity of 2-cyano-2-(4-oxo-3-phenylthiazolidin-2-ylidene)-N-arylacetamides

Abstract

Search for new biologically active compounds includes the directed design of molecules based on the so-called structural blocks – usually the privileged (structures, to which the 4-thiazolidinone cycle belongs. Therefore the development of methods for the synthesis of small "drug-like" molecules from 2-cyanomethylidene-4-thiazolidinone group as well as the study of their biological profile is an urgent task for modern medicinal chemistry. Aim. To design and to the synthesis of novel 5-ylidene derivatives of 2-cyano-2-(4-oxo-3-phenylthiazolidin-2-ylidene)-N-arylacetamides. Study of the antitumor activity of synthesized compounds. Materials and methods. Organic synthesis, study of the spectral characteristics of obtained 4-thiazolidinones (1H and 13C NMR spectroscopy, LC- MS spectrometry). In vitro antitumor activity study according to the DTP Program of the National Cancer Institute (USA). Results. A number of 5-substituted 2-cyano-2-(4-oxo-3-phenylthiazolidin-2-ylidene)-N-arylacetamide derivatives had been synthesized. The structure and purity of the synthesized compounds were confirmed by the methods of elemental analysis, 1H, 13C NMR spectroscopy and LC-MS. The antitumor activity of some of the synthesized compounds was investigated on a panel of 59 human tumor cell lines representing nine neoplastic diseases. Conclusions. Based on the C5 modification of the methylene group of the 4-thiazolidinone cycle, the target 5-ylidene and 5-aminomethylene-2-cyano-2-(4-oxo-3-phenylthiazolidin-2-ylidene)-N-arylacetamides had been synthesized. A hit-compound 2-cyano-2-[5-[(4-methoxyphenyl)methylene]-4-oxo-3-phenylthiazolidin-2-ylidene]-N-arylacetamide was identified that selectively inhibited the growth of some cell lines of CNS, kidney and breast cancers.

Keywords

• 4-thiazolidinones
• knoevenagel condensation
• enamines
• antitumor activity