Anti-cancer Activity of New Phosphoramide-functionalized Graphene Oxides: An Experimental and Theoretical Evaluation.

BACKGROUND: Graphene oxide (GO)-based systems are among the drug delivery systems and have drawn a lot of interest in the field of medicine. METHODS: In this work, two novel phosphoramides with the formulas of (NHCHCH2C(CH3)2NHC(CH3)2CH2P(S)(OEt)2 (L1) and (NHCHCH2C(CH3)2 NHC (CH3)2CH2P (O) (NHC6H5) (OC5H6) (L2) were synthesized and characterized by spectroscopic methods. Then, graphene oxide (GO) was functionalized by L1 and L2. FT-IR, XRD, FE- SEM/ MAP, and Zeta potential analyses were applied to confirm the synthesis of phosphoramide-functionalized graphene oxides (GO-L1 and GO-L2). Cytotoxicity of synthesized compounds was evaluated against breast cancer cell line (SK-BR-3) using MTT assay. Moreover, the flow cytometry assay was performed to evaluate the cell death mechanisms. RESULTS: The results showed that GO-L1 and GO-L2 had a more inhibitory effect against cancer cells than that of L1 and L2, and GO-L2 showed the highest cytotoxicity with an IC50 value of 38.13 µg/ml. Quantum calculations were employed to optimize structures. HOMO and LUMO energy values and physical adsorption of synthesized compounds were obtained by the DMol3 module in the Material Studio 2017. The docking studies were used to investigate the binding of L1, L2, GO-L1, and GO-L2 to DNA polymerase IIα. CONCLUSION: Anticancer activity of phosphoramide compounds was increased after attachment on the GO surface, and the docking studies' results were in good accordance with the experimental cytotoxicity results.

Therapeutic potential of phospho-thiadiazole derivatives as anti-glioblastoma agents: synthesis, biological assessment and computational study.

In this study, three new phospho thiadiazole compounds (A, F and W) were investigated as possible cytotoxic agents. The compounds were synthesised and characterised by using spectroscopy methods. The crystal structure of compound A was investigated using X-ray crystallography, since the title compounds can exist as different tautomeric forms, their conformational and geometrical aspects were investigated computationally by the DFT method. NBO analysis suggested that these compounds can function as appropriate ligands for the reaction with the nitrogen bases of DNA. All the synthesised compounds were evaluated in vitro for their cytotoxic activities against cancer in the human glioblastoma cell lines (U-251) using the MTT assay. According to the annexin V-FITC/PI results, a combination of synthesised compounds with ReoT3D showed a synergistic effect to increase the percentage of apoptotic cells. Molecular docking study for A (the most toxic compound) showed how it interacts with DNA. Both in vitro and in silico results showed that A has promising inhibitory potential (IC50: 48.1 ± 0.3 µM) and binding energy (-6.67 kcal/mol).