title: Platinum(II) metal complexes as potential anti-Trypanosoma cruzi agents.
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 muM range 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.
authors.affiliation: Cátedra de Química Inorgánica, Facultad de Química, Universidad de la República, Gral. Flores 2124, CC 1157, 11800 Montevideo, Uruguay.
authors.forename: Marisol
authors.initials: M
authors.lastname: Vieites
authors.forename: Lucía
authors.initials: L
authors.lastname: Otero
authors.forename: Diego
authors.initials: D
authors.lastname: Santos
authors.forename: Jeannette
authors.initials: J
authors.lastname: Toloza
authors.forename: Roberto
authors.initials: R
authors.lastname: Figueroa
authors.forename: Ester
authors.initials: E
authors.lastname: Norambuena
authors.forename: Claudio
authors.initials: C
authors.lastname: Olea-Azar
authors.forename: Gabriela
authors.initials: G
authors.lastname: Aguirre
authors.forename: Hugo
authors.initials: H
authors.lastname: Cerecetto
authors.forename: Mercedes
authors.initials: M
authors.lastname: González
authors.forename: Antonio
authors.initials: A
authors.lastname: Morello
authors.forename: Juan Diego
authors.initials: JD
authors.lastname: Maya
authors.forename: Beatriz
authors.initials: B
authors.lastname: Garat
authors.forename: Dinorah
authors.initials: D
authors.lastname: Gambino
mesh_terms: D000818:Animals; D004247:DNA / Q000737:chemistry; D005609:Free Radicals / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D013059:Spectrum Analysis, Raman; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D005609:Free Radicals; D009944:Organoplatinum Compounds; D013882:Thiosemicarbazones; D014344:Trypanocidal Agents; D004247:DNA