Platinum-based complexes of bioactive 3-(5-nitrofuryl)acroleine thiosemicarbazones showing anti-Trypanosoma cruzi activity |
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Authors: | Marisol Vieites Diego Santos Ester Norambuena Hugo Cerecetto Ulrike Kemmerling Juan Diego Maya |
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Institution: | a Cátedra de Química Inorgánica, Facultad de Química, Universidad de la República, Gral. Flores 2124, C. C. 1157, 11800 Montevideo, Uruguay b Departamento de Química Inorgánica y Analítica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Casilla 233, Santiago, Chile c Departamento de Química, Facultad de Ciencias Básicas, Universidad Metropolitana de Ciencias de la Educación, Santiago, Chile d Laboratorio de Química Orgánica, Facultad de Química - Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay e Programa de Farmacología Molecular y Clínica, ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile |
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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 IC50 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. |
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Keywords: | Chagas disease Platinum 5-Nitrofuryl containing thiosemicarbazones Trypanosoma cruzi |
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