Gallium(III) complexes of 2-pyridineformamide thiosemicarbazones: cytotoxic activity against malignant glioblastoma.
The gallium(III) complexes [Ga(2Am4DH)(2)]NO(3) (1), [Ga(2Am4Me)(2)]NO(3) (2) and [Ga(2Am4Et)(2)]NO(3) (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 IC(50) values in the 7.3-360 microM range, and against malignant T98 glioblastoma cells (expressing mutant p53 protein) with IC(50) values in the 3.6-143 microM range. Coordination to gallium strongly increased the cytotoxic potential in complexes 2 and 3, which showed IC(50) values in the 0.81-9.57 microM range against RT2 cells and in the 3.6-11.30 microM 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.
Mendes
Isolda C
IC
Departamento de Química, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
Soares
Marcela A
MA
Dos Santos
Raquel G
RG
Pinheiro
Carlos
C
Beraldo
Heloisa
H
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005708:Gallium; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D013882:Thiosemicarbazones; D005708:Gallium