Effect of the metal ion on the anti T. cruzi activity and mechanism of action of 5-nitrofuryl-containing thiosemicarbazone metal complexes
Author
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Cipriani, Micaella
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Toloza, Jeannette
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Bradford, Lara
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Putzu, Eugenia
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Vieites, Marisol
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Curbelo, Estela
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Tomaz, Ana
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Garat, Beatriz
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Guerrero, Juan
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Gancheff, Jorge
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Maya Arango, Juan
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Olea Azar, Claudio
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Gambino, Dinorah
Author
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Otero, Lucía
Admission date
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2018-12-20T15:13:22Z
Available date
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2018-12-20T15:13:22Z
Publication date
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2014
Cita de ítem
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European Journal of Inorganic Chemistry, Volumen 2014, Issue 27, 2014, Pages 4677-4689
Identifier
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10990682
Identifier
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14341948
Identifier
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10.1002/ejic.201402614
Identifier
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https://repositorio.uchile.cl/handle/2250/158601
Abstract
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Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major health problem worldwide. In this work, we report the development of palladium and platinum metal complexes with 5-nitrofuryl-containing thiosemicarbazones (L) as bioactive ligands against T. cruzi and PTA (1,3,5-triaza-7-phosphaadamantane) as co-ligand. Eight new complexes of the formula [MCl(L)(PTA)] with M = Pd or Pt were synthesized and fully characterized. Most complexes showed similar activities against T. cruzi to those of the corresponding free thiosemicarbazone ligands. No significant differences between palladium and platinum complexes were observed. Metal compounds with the phenylthiosemicarbazone derivative were the most active ones (IC50 = 9.84 +/- 0.32 and 4.94 +/- 0.24 mu M for Pd2+ and Pt2+, respectively). The prepared complexes were not toxic on mammalian cells, showing selective indexes of more than 10-20. The ability of the complexes to be reduced in the parasite, which leads to toxic free radical species, was confirmed by the detection of OH center dot and nitroanion free radical species by ESR spectroscopy experiments. Gel electrophoresis and fluorescence experiments were consistent with an intercalating-like mode of DNA interaction for the complexes, but DNA interaction does not seem to be the main mechanism of anti T. cruzi action for these compounds. The results obtained show that complexation of the bioactive ligands with the selected metals is a valid strategy to obtain improved metal-based antiparasitic compounds.