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Increasing the activity of copper(II) complexes against Leishmania through lipophilicity and pro-oxidant ability

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Abstract

Copper complexes with fluorinated β-diketones were synthesized and characterized in terms of lipophilicity and peroxide-assisted oxidation of dihydrorhodamine as an indicator of redox activity. The biological activity of the complexes was tested against promastigotes of Leishmania amazonensis. Inhibition of trypanosomatid-specific trypanothione reductase was also tested. It was found that the highly lipophilic and redox-active bis(trifluoroacetylacetonate) derivative had increased toxicity towards promastigotes. These results indicate that it is possible to modulate the activity of metallodrugs based on redox-active metals through the appropriate choice of lipophilic chelators in order to design new antileishmanials. Further work will be necessary to improve selectivity of these compounds against the parasite.

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Acknowledgments

Raúl Hernández helped us with the statistical analysis. This project was funded by CNPq and FAPESP (Brazilian government agencies).

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Authors and Affiliations

  1. Instituto de Química, Universidade de São Paulo, Av Lineu Prestes 748, 05508-000, São Paulo, SP, Brazil

    Andressa dos Santos Portas & Breno Pannia Espósito

  2. Instituto de Ciências Biomédicas, Universidade de São Paulo, Av Lineu Prestes 1374, 05508-000, São Paulo, SP, Brazil

    Danilo Ciccone Miguel, Jenicer K. U. Yokoyama-Yasunaka & Silvia Reni Bortolin Uliana

Authors
  1. Andressa dos Santos Portas
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  2. Danilo Ciccone Miguel
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  3. Jenicer K. U. Yokoyama-Yasunaka
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  4. Silvia Reni Bortolin Uliana
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  5. Breno Pannia Espósito
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Correspondence to Breno Pannia Espósito.

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Portas, A.d.S., Miguel, D.C., Yokoyama-Yasunaka, J.K.U. et al. Increasing the activity of copper(II) complexes against Leishmania through lipophilicity and pro-oxidant ability. J Biol Inorg Chem 17, 107–112 (2012). https://doi.org/10.1007/s00775-011-0834-3

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  • DOI: https://doi.org/10.1007/s00775-011-0834-3

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