Design, synthesis, structural investigation and binding study of 2-pyridone-based pharmaceutical precursor with DNA

Abstract

Natural pyridones/pyridines and synthetic derivatives have shown different bio-activities and binding affinities with different receptors. Herein, we present the synthesis of four pyridone-based fleximers and characterization using SCXRD, 1HNMR, 13CNMR, and IR spectroscopy. Phthalimide is linked to different pyridines through a methylene bridge. Supramolecular self-assembly was studied with SCXRD and Hirshfeld analysis. Weak interactions were also analysed with IR study in solid and solution phases. More importantly, phthalimide and pyridine of all fleximers can bind with different receptors and are accessed with DNA binding interactions using ct-DNA. Compounds 1–4 exhibited interesting absorption shifts in the titration study with ct-DNA. In silico molecular docking of compounds, 1–4 was evaluated with B-DNA dodecamer (PDB ID: 1BNA). A docking score of -7.7 kcal/mol to -8.9 kcal/mol was observed from the docking results. Both results are promising for all compounds to go for in vivo/vitro study to develop a new drug.