Synthesis, Spectroscopic Characterization, and Computational Study of New (Z)-2-Cyano-3-(Arylfuran) Acrylamide Derivatives as Promising DNA-Targeting Anticancer Agents

Abstract

A new group of (Z)-2-cyano-3-aryl furan) acrylamide analogs were developed, synthesized and tested as anticancer agents. The synthesis of the compounds was performed by using a convenient two-step protocol using readily available anilines as starting material via aryl furfural intermediates, then condensed with cyan acetamide. The FT-IR and NMR spectroscopy were used to elucidate the structure. Molecular docking was performed against B-DNA (PDB ID: 1BNA) and the compounds SK-5, SK-2 and SK-1 showed docking scores of -9.1, -8.7 and -8.5 kcal/mol respectively. The hydrogen bonding and π-π stacking within the DNA helix were the main forces that stabilized the binding interactions. Pharmacokinetic and electronic properties were assessed with comprehensive in silico studies, such as the ADMET prediction, density functional theory (DFT) calculations, and frontier molecular orbital (FMO) analysis. Compound SK-7 was most favorable regarding its drug-like profile as it had the best solubility, stability in metabolism and electronic properties. These results demonstrate the promise of (Z)-2-cyano-3- (aryl furan) acryl amide derivatives as promising scaffolds to further develop DNA-targeting anticancer agents.