In this study, two new phosphoramides containing imidazolidine; diphenyl (2-imidazolidinone-1-yl)phosphonate (DIOP) and diphenyl (2-Imidazolidinethione −1-yl)phosphonate (DITP) as cytotoxic agents, were synthesized and characterized by using IR, 1H NMR, 13C NMR, 31P NMR, Mass spectroscopy and elemental analysis. The target products were obtained in moderate to good yields (69–86%) by using the time (3 h) and solvent (MeCN). The crystal structure of DIOP was investigated using X-ray crystallography. The main non-covalent intermolecular interactions were also studied by Hirshfeld surface analysis and fingerprint plots. The anticancer and growth inhibitory activities of the synthesized compounds were investigated against human breast cancer cell line MDA-MB-231 using MTT assay; DITP was found to be a better cytotoxic agent than DIOP. The cytotoxicity results were supported by a molecular docking study and in order to know the structure-activity relationship (SAR) of synthesized compounds, the values of HOMO and LUMO energies, dipole moments, hardness, softness, and electrophilicity index were investigated computationally by DFT method. These results were in good accordance with those of in vitro investigation and molecular docking study.
