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New heterobimetallic ferrocenyl derivatives are promising antitrypanosomal agents.
Rodríguez Arce, Esteban; Putzu, Eugenia; Lapier, Michel; Maya, Juan Diego; Olea Azar, Claudio; Echeverría, Gustavo A; Piro, Oscar E; Medeiros, Andrea; Sardi, Florencia; Comini, Marcelo; Risi, Gastón; Salinas, Gustavo; Correia, Isabel; Pessoa, João Costa; Otero, Lucía; Gambino, Dinorah.
Afiliación
  • Rodríguez Arce E; Química Inorgánica, Facultad de Química, Universidad de la República, Gral. Flores 2124, 11800 Montevideo, Uruguay. dgambino@fq.edu.uy luotero@fq.edu.uy.
Dalton Trans ; 48(22): 7644-7658, 2019 Jun 14.
Article en En | MEDLINE | ID: mdl-31049548
In the search for a more effective chemotherapy for the treatment of Chagas' disease and human African trypanosomiasis, caused by Trypanosoma cruzi and Trypanosoma brucei parasites, respectively, the use of organometallic compounds may be a promising strategy. In this work, eight new heterobimetallic compounds are described including four 5-nitrofuryl containing thiosemicarbazones as bioactive ligands (HL1-HL4) and dppf = 1,1'-bis(diphenylphosphino) ferrocene as an organometallic co-ligand. Complexes of the formula [MII(L)(dppf)](PF6) with M = Pd or Pt were synthesized and fully characterized in the solid state and in solution, including the determination of the molecular structure of four of them by single crystal X-ray diffraction methods. Most compounds showed activity in the low micromolar or submicromolar range against both parasites, with the platinum compounds being more active than the palladium analogues. Activity was significantly increased by generation of the M-dppf compounds (3-24 fold increase with respect to free ligands HL for T. cruzi and up to 99 fold increase with respect to HL for T. brucei). The inclusion of the organometallic co-ligand also led to lower toxicity in mammalian cells and higher selectivity towards both parasites when compared to the free HL compounds. The complexes interact with DNA and affect the redox metabolism of the parasites. Furthermore, the most active and selective compound of the new series showed no in vivo toxicity in zebrafish embryos.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos Organometálicos / Paladio / Platino (Metal) / Tripanocidas / Compuestos Ferrosos / Metalocenos Límite: Animals / Humans Idioma: En Revista: Dalton Trans Asunto de la revista: QUIMICA Año: 2019 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos Organometálicos / Paladio / Platino (Metal) / Tripanocidas / Compuestos Ferrosos / Metalocenos Límite: Animals / Humans Idioma: En Revista: Dalton Trans Asunto de la revista: QUIMICA Año: 2019 Tipo del documento: Article Pais de publicación: Reino Unido