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In this work, we report the development of palladium and platinum metal complexes with 5\u2010nitrofuryl\u2010containing thiosemicarbazones (L) as bioactive ligands against <jats:italic>T. cruzi<\/jats:italic> and PTA (1,3,5\u2010triaza\u20107\u2010phosphaadamantane) as co\u2010ligand. 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 <jats:italic>T. cruzi<\/jats:italic> 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 (<jats:italic>IC<\/jats:italic><jats:sub>50<\/jats:sub> = 9.84\u2009\u00b1\u20090.32 and 4.94\u2009\u00b1\u20090.24 \u03bc<jats:sc>M<\/jats:sc> for Pd<jats:sup>2+<\/jats:sup> and Pt<jats:sup>2+<\/jats:sup>, respectively). The prepared complexes were not toxic on mammalian cells, showing selective indexes of more than 10\u201320. 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<jats:sup><jats:bold>\u00b7<\/jats:bold><\/jats:sup> and nitroanion free radical species by ESR spectroscopy experiments. Gel electrophoresis and fluorescence experiments were consistent with an intercalating\u2010like mode of DNA interaction for the complexes, but DNA interaction does not seem to be the main mechanism of anti <jats:italic>T. cruzi<\/jats:italic> 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\u2010based antiparasitic compounds.<\/jats:p>","DOI":"10.1002\/ejic.201402614","type":"journal-article","created":{"date-parts":[[2014,9,8]],"date-time":"2014-09-08T11:23:03Z","timestamp":1410175383000},"page":"4677-4689","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Effect of the Metal Ion on the anti <i>T. cruzi<\/i> Activity and Mechanism of Action of 5\u2010Nitrofuryl\u2010Containing Thiosemicarbazone Metal Complexes"],"prefix":"10.1002","volume":"2014","author":[{"given":"Micaella","family":"Cipriani","sequence":"first","affiliation":[]},{"given":"Jeannette","family":"Toloza","sequence":"additional","affiliation":[]},{"given":"Lara","family":"Bradford","sequence":"additional","affiliation":[]},{"given":"Eugenia","family":"Putzu","sequence":"additional","affiliation":[]},{"given":"Marisol","family":"Vieites","sequence":"additional","affiliation":[]},{"given":"Estela","family":"Curbelo","sequence":"additional","affiliation":[]},{"given":"Ana Isabel","family":"Tomaz","sequence":"additional","affiliation":[]},{"given":"Beatriz","family":"Garat","sequence":"additional","affiliation":[]},{"given":"Juan","family":"Guerrero","sequence":"additional","affiliation":[]},{"given":"Jorge S.","family":"Gancheff","sequence":"additional","affiliation":[]},{"given":"Juan Diego","family":"Maya","sequence":"additional","affiliation":[]},{"given":"Claudio","family":"Olea Azar","sequence":"additional","affiliation":[]},{"given":"Dinorah","family":"Gambino","sequence":"additional","affiliation":[]},{"given":"Luc\u00eda","family":"Otero","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2014,9,8]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1039\/c1dt10522a"},{"key":"e_1_2_6_2_2","first-page":"38","volume":"5","author":"Rafique S.","year":"2010","journal-title":"Biotechnol. 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