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Graphene oxide (GO) nanocomposites have attracted much attention in biomedical and catalytic fields due to their outstanding water dispersibility, cell permeability, high mobility of charge carriers, etc. This article reports the successful synthesis of GO–Co3O4 and phytic acid (PA)-modified GO–Co3O4 (GO–Co3O4–PA) nanocomposites by a facile hydrothermal method and studies of their antiproliferative properties. Various analyses were performed to characterize the synthesized nanocomposites. XRD revealed the characteristic crystallinity of GO–Co3O4 and GO–Co3O4–PA. FT-IR spectroscopy identified the different functional groups of nanocomposites. FE-SEM, AFM, EDX, and DLS analyses of GO–Co3O4–PA demonstrated multigonal particles with an average size of 837 nm on the basal planes of GO with signatures of Co and P. The zeta potential was −49.9 mV for GO–Co3O4–PA, which showed the moderate stability of nanocomposites. The Raman spectra of GO–Co3O4 and GO–Co3O4–PA nanocomposites indicated an increase in the surface defect density of GO due to the adsorption of Co3O4 and PA on the surface of GO. The use of nanocomposites for targeted breast cancer therapy was evaluated via an MTT assay. GO–Co3O4–PA showed considerable cytotoxicity with an IC50 value of 12.94 μg mL−1 towards the breast cancer cell line (MCF-7), which was five times lower than that of GO–Co3O4 (64.36 μg mL−1). As an anticancer agent, PA enhances the interaction of MCF-7 cell lines with nanocomposites and leads to higher cytotoxicity. MTT cytotoxicity, Annexin V/PI double staining, and intracellular reactive oxygen species (ROS) assays were performed. The GO–Co3O4–PA nanocomposite is a promising candidate for breast cancer therapy. Quantum mechanical calculations based on the DFT-D correction and PA adsorption on GO and GO–Co3O4 (1 0 0) in the presence of water were done in the adsorption locator module. Free energy calculations showed that adsorption is a spontaneous and more favorable process. Molecular docking studies were conducted to investigate the interaction of compounds on human topoisomerase IIα bound to DNA (4fm9) and Bcl-2 protein. The results indicated that GO–Co3O4–PA could properly dock into more amino acids with high negative energy scores and confirmed the MTT data. Moreover, GO–Co3O4–PA nanocomposites exhibited excellent catalytic ability towards the Biginelli reaction and showed significant advantages including excellent yields, mild reaction conditions, and short reaction times. [ABSTRACT FROM AUTHOR]

[Display omitted] • Four new phosphoramide ligands and GO-phosphoramide compounds were prepared. • The characterization results of FT-IR, 31PNMR, 1HNMR, and MASS proved ligands. • XRD, FT-IR, FESEM, and EDX analysis confirmed GO-phosphoramide sample. • All compounds were used for MTT assay using MCF-7 cancerous cell lines. • The molecular dynamic and molecular docking simulations were performed. • Monte Carlo adsorption locator simulations and pharmacophore of compounds were used. In this study, four novel phosphoramide ligands (L1–L4) are synthesized and characterized by 31PNMR, 1HNMR, MASS, and FT-IR spectroscopies. In vitro cell growth inhibition is studied by the MTT assay to evaluate the cytotoxicity of ligands against MCF-7 cell line; the result of the assay demonstrates that all ligands significantly suppress the proliferation of breast cancer cells in a concentration-dependent manner. The calculated IC 50 values are in the range of 3.6–10.77 µg ml−1, of which the lowest value is attributed to L1. Then a facile approach was developed to functionalize graphene oxide (GO) surface by L1. The data which are obtained by XRD, FT-IR, and EDX analysis confirmed the deposition of phosphoramide on the surface of GO. The cell viability of GO-L1 compound at different concentrations is investigated in 24 h experiment. Excellent synergistic antitumor effects of GO and L1 lead to a decrease in IC 50 value up to 2.13 μg ml−1. The Quantum calculations of compounds are used to study energies and HOMO and LUMO values, dipole moments (µ), global hardness (η), global softness (σ), and electrophilicity index (ω) using DMol3 module in Material studio2017. The docking calculations are performed to describe the mode of the binding to DNA and DNA polymerase IIα. Adsorption calculations of ligands (L1-L4) on GO sheet in the presence of water showed that L1 and L2 were located on GO via π electrons of anisole ring. While, L3 and L4 were located on GO by π - π interactions of aniline ring. [ABSTRACT FROM AUTHOR]