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

Abstract

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).