Gallium(III) complexes of 2-pyridineformamide thiosemicarbazones: Cytotoxic activity against malignant glioblastoma

The gallium(III) complexes [Ga(2Am4DH)2]NO3 (1), [Ga(2Am4Me)2]NO3 (2) and [Ga(2Am4Et)2]NO3 (3) were prepared with 2-pyridineformamide thiosemicarbazone (H2Am4DH) and its N(4)-methyl (H2Am4Me) and N(4)-ethyl (H2Am4Et) derivatives. The thiosemicarbazones were cytotoxic against malignant RT2 glioblastoma cells (expressing p53 protein) with IC50 values in the 7.3–360 μM range, and against malignant T98 glioblastoma cells (expressing mutant p53 protein) with IC50 values in the 3.6–143 μM range. Coordination to gallium strongly increased the cytotoxic potential in complexes 2 and 3, which showed IC50 values in the 0.81–9.57 μM range against RT2 cells and in the 3.6–11.30 μM range against T98 cells, and were 20-fold more potent than cisplatin. All thiosemicarbazones and gallium complexes were able to induce cell death by apoptosis.

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