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Metal complexes of 3-(4-bromophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone: cytotoxic activity and investigation on the mode of action of the gold(III) complex

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Abstract

Complexes [Au(PyCT4BrPh)Cl]Cl (1), [Pt(PyCT4BrPh)Cl]0.5KCl (2), and [Pd(PyCT4BrPh)Cl]KCl (3) were obtained with 3-(4-bromophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone (HPyCT4BrPh). Although complexes (2) and (3) did not exhibit potent cytotoxic activity, HPyCT4BrPh and its gold(III) complex (1) proved to be highly cytotoxic against HL-60 (human promyelocytic leukemia) and THP-1 (human monocytic leukemia) cells, and against MDA-MB 231 and MCF-7 (human breast adenocarcinoma) solid tumor cells. Except for HL-60 cells, upon coordination to gold(III) a 2- to 3-fold increase in the cytotoxic effect was observed. An investigation on the possible biological targets of the gold(III) complex was carried out. Complex (1) but not the free thiosemicarbazone inhibits the enzymatic activity of thioredoxin reductase (TrxR). The affinity of 1 for TrxR suggests metal binding to a selenol residue in the active site of the enzyme. While HPyCT4BrPh was inactive, 1 was able to inhibit topoisomerase IB (Topo IB) activity. Hence, inhibition of TrxR and Topo IB could contribute to the mechanism of cytotoxic action of complex (1).

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Acknowledgments

The authors are grateful to CNPq, INCT-INOFAR (Proc. CNPq 573.364/2008-6) and CAPES/PNPD.

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Authors and Affiliations

  1. Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil

    Luciana B. P. Sâmia, Gabrieli L. Parrilha & Heloisa Beraldo

  2. Departamento de Farmácia, Universidade Federal de Juiz de Fora (UFJF), Governador Valadares, MG, 35010-177, Brazil

    Jeferson G. Da Silva

  3. Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil

    Jonas P. Ramos & Elaine M. Souza-Fagundes

  4. Department of Biology, University of Rome “Tor Vergata”, Via della Ricerca Scientifica 1, 00133, Rome, Italy

    Silvia Castelli, Venn Vutey & Alessandro Desideri

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  1. Luciana B. P. Sâmia
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  2. Gabrieli L. Parrilha
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Sâmia, L.B.P., Parrilha, G.L., Da Silva, J.G. et al. Metal complexes of 3-(4-bromophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone: cytotoxic activity and investigation on the mode of action of the gold(III) complex. Biometals 29, 515–526 (2016). https://doi.org/10.1007/s10534-016-9933-5

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