title: Platinum-based complexes of bioactive 3-(5-nitrofuryl)acroleine thiosemicarbazones showing anti-Trypanosoma cruzi activity.
abstract: Eight new platinum(II) complexes with 3-(5-nitrofuryl)acroleine thiosemicarbazones showing anti-trypanosomal activity were synthesized, characterized and in vitro evaluated. Most of the complexes showed IC(50) values in the micromolar range against two different strains of Trypanosoma cruzi, causative agent of Chagas disease (American Trypanosomiasis). In addition, most of the newly developed complexes, together with the analogous platinum 5-nitrofuraldehyde containing thiosemicarbazones previously reported, resulted more active than the reference trypanocidal drug nifurtimox on the infective trypomastigote form of the parasite. Their capacity to produce free radicals that could lead to parasite death was evaluated by ESR experiments in the parasite and by respiration measurements. Compounds were tested for their DNA interaction ability. Results showed that some of the compounds could act as dual inhibitors in the parasite, through production of toxic free radicals and interaction with DNA. All the results were compared with those previously reported for the free ligands, the analogous palladium(II) compounds and the previously reported series of platinum(II) compounds.
authors.affiliation: Cátedra de Química Inorgánica, Facultad de Química, Universidad de República, Gral. Flores 2124, C. C. 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: Claudio
authors.initials: C
authors.lastname: Olea-Azar
authors.forename: Ester
authors.initials: E
authors.lastname: Norambuena
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: Ulrike
authors.initials: U
authors.lastname: Kemmerling
authors.forename: Antonio
authors.initials: A
authors.lastname: Morello
authors.forename: Juan
authors.initials: J
authors.lastname: Diego Maya
authors.forename: Dinorah
authors.initials: D
authors.lastname: Gambino
mesh_terms: D000818:Animals; D004247:DNA / Q000187:drug effects; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D009944:Organoplatinum Compounds; D013882:Thiosemicarbazones; D014344:Trypanocidal Agents; D004247:DNA; C427203:calf thymus DNA