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Gallium(III) complexes with 2-acetylpyridine-derived thiosemicarbazones: antimicrobial and cytotoxic effects and investigation on the interactions with tubulin

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Abstract

Complexes [Ga(2Ac4pFPh)2]NO3 (1), [Ga(2Ac4pClPh)2]NO3 (2), [Ga(2Ac4pIPh)2]NO3 (3), [Ga(2Ac4pNO2Ph)2]NO3·3H2O (4) and [Ga(2Ac4pT)2]NO3 (5) were obtained with 2-acetylpyridine N(4)-para-fluorophenyl-(H2Ac4pFPh), 2-acetylpyridine N(4)-para-chlorophenyl-(H2Ac4pClPh), 2-acetylpyridine N(4)-para-iodophenyl-(H2Ac4pIPh), 2-acetylpyridine N(4)-para-nitrophenyl-(H2Ac4pNO2Ph) and 2-acetylpyridine N(4)-para-tolyl-(H2Ac4pT) thiosemicarbazone. 1–5 presented antimicrobial and cytotoxic properties. Coordination to gallium(III) proved to be an effective strategy for activity improvement against Pseudomonas aeruginosa and Candida albicans. The complexes were highly cytotoxic against malignant glioblastoma and breast cancer cells at nanomolar concentrations. The compounds induced morphological changes characteristic of apoptotic death in tumor cells and showed no toxicity against erythrocytes. 2 partially inhibited tubulin assembly at high concentrations and induced cellular microtubule disorganization, but this does not appear to be the main mechanism of cytotoxic activity.

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Acknowledgments

This work was supported by CNPq and INCT-INOFAR (Proc. CNPq 573.364/2008-6). The authors express sincere thanks to LabCRI (UFMG), particularly to Professor Nilvado L. Speziali for the X-ray facilities and measurements.

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Authors and Affiliations

  1. Instituto de Química, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, 20550-013, Brazil

    Josane A. Lessa

  2. Centro de Desenvolvimento da Tecnologia Nuclear, CDTN, Belo Horizonte, MG, 31270-901, Brazil

    Marcella A. Soares & Raquel G. dos Santos

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

    Marcella A. Soares

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

    Isolda C. Mendes & Heloisa Beraldo

  5. Centro de Biotecnologia Molecular Estrutural, Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, SP, 13560-970, Brazil

    Lívia B. Salum & Adriano D. Andricopulo

  6. Department of Structural Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USA

    Hikmat N. Daghestani

  7. Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, 15261, USA

    Billy W. Day

  8. University of Pittsburgh Drug Discovery Institute, University of Pittsburgh, Pittsburgh, PA, 15261, USA

    Andreas Vogt

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  1. Josane A. Lessa
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  2. Marcella A. Soares
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  6. Hikmat N. Daghestani
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  7. Adriano D. Andricopulo
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  8. Billy W. Day
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  10. Heloisa Beraldo
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Correspondence to Heloisa Beraldo.

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Lessa, J.A., Soares, M.A., dos Santos, R.G. et al. Gallium(III) complexes with 2-acetylpyridine-derived thiosemicarbazones: antimicrobial and cytotoxic effects and investigation on the interactions with tubulin. Biometals 26, 151–165 (2013). https://doi.org/10.1007/s10534-012-9603-1

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