A Comprehensive In Vitro and In Silico Study of Acteoside: Cytotoxicity, Molecular Interactions, and DFT Reactivity Profiles

Abstract In this study, the cytotoxic effects of acteoside were comparatively evaluated in four cancer cell lines (MiaPaCa-2, HL-60, A549, and MDA-MB-231). Based on the greater sensitivity observed in MiaPaCa-2 cells, molecular docking against the EGFR/HER2 tyrosine kinase domain was subsequently performed to investigate a potential molecular interaction relevant to the observed cytotoxic response in all four cell lines, acteoside reduced cell viability in a dose-dependent manner, with the lowest IC50 observed in MiaPaCa-2 cells (IC50 = 166.9 μM). Molecular docking analysis revealed a favorable binding affinity of acteoside toward the EGFR/HER2 tyrosine kinase domain, with a predicted binding energy of −8.9 kcal/mol. DFT calculations revealed solvent-dependent electronic properties, while frontier molecular orbital, molecular electrostatic potential (MEP), noncovalent interaction, and electron localization analyses identified electron-rich reactive regions and potential interaction sites within the acteoside molecule. Overall, acteoside exhibits varying levels of cytotoxic activity across the tested cell lines, and further studies are required to elucidate its mechanism of action.