Supramolecular architectures in dihydropyridones: Synthesis, crystal structure, Hirshfeld analysis, cytotoxicity and in silico studies

Abstract

In this study, a series of five non-aromatic dihydropyridones were synthesized, crystallized, and single-crystal X-ray diffraction was used to obtain their molecular geometries. The supramolecular assembly of the molecules through non-covalent interactions was then studied and demonstrated. The weak intermolecular interactions in the molecular packing of compounds were further validated through Hirshfeld surface analysis. The synthesized compounds were screened in vitro using lung adenocarcinoma (A549) cells to assess their cytotoxic effects. A molecular docking study has also been employed to gain insight into the binding mode of the synthesized compounds in the allosteric binding pocket of the Eg5 motor domain and survivin protein. The results showed that the title compounds have mild to moderate cytotoxic effects in these cells. Ethyl-5-cyano-4-(2,5-dimethoxyphenyl)-2-methyl-6-oxo-1,4,5,6-tetrahydropyridine-3-carb-oxylate has shown more significant cytotoxicity among all the synthesized compounds. This study has further demonstrated the importance of non-covalent intermolecular interactions of dihydropyridones for exhibiting diverse supramolecular architectures as well as for having a significant binding affinity towards the receptor.