Synthesis, molecular self-assembly and anti-carcinogenic study of 2-pyridone molecules

Abstract

4H-pyrans obtained from the multicomponent reactions of aromatic aldehyde, malononitrile, and ethyl acetoacetate were used as a starting scaffold for synthesizing 2-pyridone derivatives (1–3). Two catalytic methods were reported for the conversion of 4H-pyrans to 3,4-dihydropyridones. The non-aromatic 3,4-dihydropyridones obtained were then oxidized to give the final desired 2-pyridone derivatives (1–3). Crystals of the synthesized compounds were prepared and subjected to single-crystal X-ray crystallography (SCXRD) to acquire their structural parameters. Non-covalent interactions in the supramolecular systems 1–3 were studied, and it found that NH∙∙∙O interactions between the lactam groups are the most dominant hydrogen bonds. It is also observed that the aromatic rings are involved in lone pair∙∙∙π, CH∙∙∙π, and weak π∙∙∙π interactions in assisting the supramolecular framework. Hirshfeld surface studies are also performed to validate the interactions within the supramolecular crystals. The 2-pyridone derivatives (1–3) were also analyzed by in vitro techniques to evaluate their cytotoxic activities using human lung adenocarcinoma (A549). It is also found that ethyl 5-cyano-2-methyl-4-(3-nitrophenyl)-6-oxo-1,6-dihydropyridine-3-carboxylate (1) has shown the highest cytotoxic potency amongst the synthesized compound.