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Copper(II)–fluoroquinolone complexes with anti-Trypanosoma cruzi activity and DNA binding ability

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Abstract

Copper(II) complexes of fluoroquinolone antibacterial agents levofloxacin (LEV) and sparfloxacin (SPAR), containing or not a nitrogen donor heterocyclic ligand, 2,2′-bipyridine (bipy) or 1,10-phenathroline (phen), were prepared and characterized. The complexes are of the type [CuCl2(H2O)(L)], [CuCl(bipy)(L)]Cl and [CuCl2(phen)(L)], where L = LEV or SPAR. The data suggest that LEV and SPAR act as zwitterionic bidentade ligands coordinated to Cu(II) through the carboxylate and ketone oxygen atoms. The electron paramagnetic resonance spectra of the [CuCl(bipy)(L)]Cl and [CuCl2(phen)(L)] complexes (L = LEV and SPAR) in aqueous and DMSO solutions indicate mixture of mononuclear and binuclear forms. The Cu(II) complexes, together with the corresponding ligands, were evaluated for their trypanocidal activity in vitro against Trypanosoma cruzi, the causative agent of Chagas disease. The assays performed against bloodstream trypomastigotes showed that all complexes were more active than their corresponding ligands. Complexes [CuCl2(phen)(LEV)] and [CuCl2(phen)(SPAR)] were revealed, among all studied compounds, to be the most active with IC50 = 1.6 and 4.7 μM, respectively, both presenting a superior effect than benznidazole. The interactions of fluoroquinolones and their Cu(II) complexes with calf-thymus DNA were investigated. These compounds showed binding properties towards DNA, with moderated binding constants values, suggesting that this structure may represent a parasite target.

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Acknowledgments

The present study was supported by Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG), Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). The EPR spectrometer from Centro Brasileiro de Pesquisas Físicas (CBPF) was used in this research. We thank Dr. Eliane Wajnberg for skilful assistance and discussions.

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Authors and Affiliations

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

    Darliane A. Martins, Ligiane R. Gouvea & Letícia R. Teixeira

  2. Laboratório de Biologia Celular, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, 21040-360, Brazil

    Denise da Gama Jean Batista, Patrícia Bernardino da Silva & Maria de Nazaré C. Soeiro

  3. Departamento de Física, Pontifícia Universidade Católica do Rio de Janeiro, Rio de Janeiro, RJ, 22653-900, Brazil

    Sonia R. W. Louro

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  1. Darliane A. Martins
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  2. Ligiane R. Gouvea
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  3. Denise da Gama Jean Batista
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  4. Patrícia Bernardino da Silva
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  5. Sonia R. W. Louro
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  6. Maria de Nazaré C. Soeiro
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  7. Letícia R. Teixeira
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Correspondence to Letícia R. Teixeira.

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Martins, D.A., Gouvea, L.R., da Gama Jean Batista, D. et al. Copper(II)–fluoroquinolone complexes with anti-Trypanosoma cruzi activity and DNA binding ability. Biometals 25, 951–960 (2012). https://doi.org/10.1007/s10534-012-9565-3

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