Gold(I) complexes with thiosemicarbazones: cytotoxicity against human tumor cell lines and inhibition of thioredoxin reductase activity |
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Authors: | Lessa Josane A Guerra Juliana C de Miranda Luana F Romeiro Carla F D Da Silva Jeferson G Mendes Isolda C Speziali Nivaldo L Souza-Fagundes Elaine M Beraldo Heloisa |
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Institution: | a Departamento de Química, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazilb Departamento de Fisiologia, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazilc Escola de Belas Artes, Departamento de Artes Plásticas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazild Departamento de Física, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil |
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Abstract: | Complexes Au(H2Ac4DH)Cl]?MeOH (1) Au(H22Ac4Me)Cl]Cl (2) Au(H22Ac4Ph)Cl]Cl?2H2O (3) and Au(H22Bz4Ph)Cl]Cl (4) were obtained with 2-acetylpyridine thiosemicarbazone (H2Ac4DH), its N(4)-methyl (H2Ac4Me) and N(4)-phenyl (H2Ac4Ph) derivatives, as well as with N(4)-phenyl 2-benzoylpyridine thiosemicarbazone (H2Bz4Ph). The compounds were cytotoxic to Jurkat (immortalized line of T lymphocyte), HL-60 (acute myeloid leukemia), MCF-7 (human breast adenocarcinoma) and HCT-116 (colorectal carcinoma) tumor cell lines. Jurkat and HL-60 cells were more sensitive than MCF-7 and HCT-116 cells. Upon coordinating to the gold(I) metal centers in complexes (2) and (4), the cytotoxic activity of the H2Ac4Me and H2Bz4Ph ligands increased against the HL-60 and Jurkat tumor cell lines. 2 was more active than auranofin against both leukemia cells. Most of the studied compounds were less toxic than auranofin to peripheral blood mononuclear cells (PBMC). All compounds induced DNA fragmentation in HL-60 and Jurkat cells indicating their pro-apoptotic potential. Complex (2) strongly inhibited the activity of thioredoxin reductase (TrxR), which suggests inhibition of TrxR to be part of its mechanism of action. |
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Keywords: | Gold(I) complexes Thiosemicarbazones Cytotoxic activity Thioredoxin reductase |
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