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BioMetals

, Volume 31, Issue 6, pp 961–974 | Cite as

Effect of a new anti-T. cruzi metallic compound based on palladium

  • M. Florencia Mosquillo
  • Lucía Bilbao
  • Fabricio Hernández
  • Ignacio Machado
  • Dinorah Gambino
  • Beatriz Garat
  • Leticia Pérez-DíazEmail author
Article
  • 73 Downloads

Abstract

Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. It is estimated that 6 million people are infected in Latin America. Current treatment is not effective due to the severe side effects and the limited efficacy towards the chronic phase of the disease. Considering the growing need for specific anti-Trypanosoma cruzi drugs, organometallic Pt and Pd based compounds were previously synthesized. Although the Pt-based compound effects on T. cruzi death have been reported, no mechanism of action has been proposed for the Pd-based analogous compound. In this work, we determined excellent to very good values of IC50 and SI. To analyze the compound mode of action, we measured Pd uptake and its association to the macromolecules of the parasite by electrothermal atomic absorption spectrometry. We found a poor uptake, which reaches only 16% after 24 h of incubation using 10× IC50, being the scarce incorporated metal preferentially associated to DNA. However, this compound has a trypanocidal effect, leading to morphological changes such as shortening of the parasite cell body and inducing necrosis after 24 h of treatment. Furthermore, this compound impairs the parasite development in the host both at the trypomastigote infection process and the intracellular amastigotes replication. In conclusion, our findings support that Pd-dppf-mpo compound constitutes a promising anti-T. cruzi compound effective against the chronic phase of the disease.

Keywords

Trypanosoma cruzi Pd-based compound Cell death mechanism Morphological changes 

Notes

Acknowledgements

This work was supported by Comisión Sectorial de Investigación Científica CSIC-Uruguay [Grant Number INI_2015_362]; Agencia Nacional de Investigación e Innovación ANII [Grant Number POS_FMV_2015_1_1005183]; and Programa de Desarrollo de Ciencias Básicas, Uruguay.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.

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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Laboratorio de Interacciones Moleculares, Facultad de CienciasUniversidad de la RepúblicaMontevideoUruguay
  2. 2.Área de Química Analítica, Facultad de QuímicaUniversidad de la RepúblicaMontevideoUruguay
  3. 3.Área de Química Inorgánica, Facultad de QuímicaUniversidad de la RepúblicaMontevideoUruguay

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