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 mu M range, and against malignant T98 glioblastoma cells (expressing mutant p53 protein) with IC50 values in the 3.6-143 mu M range. Coordination to gallium strongly increased the cytotoxic potential in complexes 2 and 3, which showed IC50 values in the 0.81-9.57 mu M range against RT2 cells and in the 3.6-11.30 mu M 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. (C) 2008 Elsevier Masson SAS. All rights reserved.