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Platinum(II) metal complexes as potential anti-Trypanosoma cruzi agents

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2008-05
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Vieites, Marisol
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Platinum(II) metal complexes as potential anti-Trypanosoma cruzi agents
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Author
  • Vieites, Marisol;
  • Otero, Lucía;
  • Santos, Diego;
  • Toloza, Jeannette;
  • Figueroa, Roberto;
  • Norambuena, Ester;
  • Olea Azar, Claudio;
  • Aguirre, Gabriela;
  • Cerecetto, Hugo;
  • González, Mercedes;
  • Morello Casté, Antonio;
  • Maya Arango, Juan;
  • Garat, Beatriz;
  • Gambino, Dinorah;
Abstract
In the search for new therapeutic tools against Chagas’ disease (American Trypanosomiasis) two series of new platinum(II) complexes with bioactive 5-nitrofuryl containing thiosemicarbazones as ligands were synthesized, characterized and in vitro evaluated. Most of the complexes showed IC50 values in the lMrange against two different strains of Trypanosoma cruzi, causative agent of the disease, being as active as the anti-trypanosomal drug Nifurtimox. In particular, the coordination of L3 (4-ethyl-1-(5-nitrofurfurylidene)thiosemicarbazide) to Pt(II) forming [Pt(L3)2] lead to almost a five-fold activity increase in respect to the free ligand. Trying to get an insight into the trypanocidal mechanism of action of these compounds, DNA and redox metabolism (intra-parasite free radical production) were evaluated as potential parasite targets. Results suggest that the complexes could inhibit parasite growth through a dual mechanism of action involving production of toxic free radicals by bioreduction and DNA interaction.
Patrocinador
This work was partially supported by PEDECIBA and Universidad de La Repu´ blica (CSIC project 364/06) of Uruguay, Prosul-CNPq project 490209/2005-0, SIBAS- 0807 UMCE, FONDECYT Chile 1061072 and CONICYT- PBCT Anillo ACT 29.
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URI: https://repositorio.uchile.cl/handle/2250/120867
ISSN: 0162-0134
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JOURNAL OF INORGANIC BIOCHEMISTRY, Volume: 102, Issue: 5-6, Pages: 1033-1043, 2008
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