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Norfloxacin Zn(II)-based complexes: acid base ionization constant determination, DNA and albumin binding properties and the biological effect against Trypanosoma cruzi

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Abstract

Zn(II) complexes with norfloxacin (NOR) in the absence or in the presence of 1,10-phenanthroline (phen) were obtained and characterized. In both complexes, the ligand NOR was coordinated through a keto and a carboxyl oxygen. Tetrahedral and octahedral geometries were proposed for [ZnCl2(NOR)]·H2O (1) and [ZnCl2(NOR)(phen)]·2H2O (2), respectively. Since the biological activity of the chemicals depends on the pH value, pH titrations of the Zn(II) complexes were performed. UV spectroscopic studies of the interaction of the complexes with calf-thymus DNA (CT DNA) have suggested that they can bind to CT DNA with moderate affinity in an intercalative mode. The interactions between the Zn(II) complexes and bovine serum albumin (BSA) were investigated by steady-state and time-resolved fluorescence spectroscopy at pH 7.4. The experimental data showed static quenching of BSA fluorescence, indicating that both complexes bind to BSA. A modified Stern–Volmer plot for the quenching by complex 2 demonstrated preferential binding near one of the two tryptophan residues of BSA. The binding constants obtained (K b ) showed that BSA had a two orders of magnitude higher affinity for complex 2 than for 1. The results also showed that the affinity of both complexes for BSA was much higher than for DNA. This preferential interaction with protein sites could be important to their biological mechanisms of action. The analysis in vitro of the Zn(II) complexes and corresponding ligand were assayed against Trypanosoma cruzi, the causative agent of Chagas disease and the data showed that complex 2 was the most active against bloodstream trypomastigotes.

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Acknowledgments

The present study was supported by Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG), Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and PDTIS/Fiocruz.

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Authors and Affiliations

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

    Ligiane R. Gouvea, Darliane A. Martins, Paulo J. S. Barbeira & Letícia R. Teixeira

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

    Denise da Gama Jean Batista & 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. Ligiane R. Gouvea
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  2. Darliane A. Martins
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  3. Denise da Gama Jean Batista
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  4. Maria de Nazaré C. Soeiro
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  5. Sonia R. W. Louro
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  6. Paulo J. S. Barbeira
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  7. Letícia R. Teixeira
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Correspondence to Letícia R. Teixeira.

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Gouvea, L.R., Martins, D.A., da Gama Jean Batista, D. et al. Norfloxacin Zn(II)-based complexes: acid base ionization constant determination, DNA and albumin binding properties and the biological effect against Trypanosoma cruzi . Biometals 26, 813–825 (2013). https://doi.org/10.1007/s10534-013-9661-z

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