Novel Experimental Therapeutic Approaches in Glioma—New Hydrazide–Hydrazones as Chemical Agents Sensitizing Glioblastoma Cell Line to Radiotherapy

Gliomas are highly aggressive tumors of the nervous system and remain difficult to treat with currently available therapeutic approaches. Due to their poor prognosis and resistance to standard treatments, there is a growing need for novel strategies, including therapies based on the combined use of radiotherapy and chemotherapy. The aim of this study was to evaluate the potential of newly synthesized hydrazide–hydrazones to sensitize glioblastoma tumor cells to X-ray irradiation. Two novel hydrazide–hydrazones of 5-bromo-2-iodobenzoic acid (3 and 4) were synthesized on the basis of condensation reaction. The chemical structure of obtained compounds was established with the use of IR, 1H NMR and 13C NMR spectroscopy. In vitro biological studies demonstrated that the radiosensitizing effect of the tested hydrazide–hydrazones was strongly dependent on both compound concentration and glioblastoma cell line. In LN-229 cells, compound 3 at 164 μM combined with 2 Gy irradiation reduced cell viability by 65% and increased the subG1 population, indicating enhanced cytotoxicity and induction of cell death. Similarly, compound 4 at 242 μM combined with 2–5 Gy irradiation decreased LN-229 cell viability by more than 50% and promoted cell cycle arrest and apoptosis, whereas both compounds showed limited or even proliferative effects in U-87MG cells, highlighting the importance of tumor-specific biological characteristics in determining treatment response.