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Pt-Fe ferrocenyl compounds with hydroxyquinoline ligands show selective cytotoxicity on highly proliferative cells.
Rivas, Feriannys; Medeiros, Andrea; Comini, Marcelo; Suescun, Leopoldo; Rodríguez Arce, Esteban; Martins, Marta; Pinheiro, Teresa; Marques, Fernanda; Gambino, Dinorah.
Afiliação
  • Rivas F; Área Química Inorgánica, Facultad de Química, Universidad de la República, Montevideo, Uruguay.
  • Medeiros A; Group Redox Biology of Trypanosomes, Institut Pasteur de Montevideo, Montevideo, Uruguay; Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
  • Comini M; Group Redox Biology of Trypanosomes, Institut Pasteur de Montevideo, Montevideo, Uruguay.
  • Suescun L; Laboratorio de Cristalografía, Química del Estado Sólido y Materiales, Cátedra de Física, DETEMA, Facultad de Química, Universidad de la República, Montevideo, Uruguay.
  • Rodríguez Arce E; Área Química Inorgánica, Facultad de Química, Universidad de la República, Montevideo, Uruguay.
  • Martins M; Instituto de Medicina Molecular- João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
  • Pinheiro T; Institute for Bioengineering and Biosciences, Departamento de Engenharia e Ciências Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Bobadela, Portugal.
  • Marques F; Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Bobadela, Portugal.
  • Gambino D; Área Química Inorgánica, Facultad de Química, Universidad de la República, Montevideo, Uruguay. Electronic address: dgambino@fq.edu.uy.
J Inorg Biochem ; 199: 110779, 2019 10.
Article em En | MEDLINE | ID: mdl-31351379
Searching for a more effective chemotherapy for the treatment of Human African trypanosomiasis, the disease caused by the parasite Trypanosoma brucei, and cancer, in the current work five new [PtII(L)(dppf)](PF6) compounds, with HL = 8-hydroxyquinoline derivatives and dppf = 1,1'-bis(diphenylphosphino)ferrocene, were synthesized and fully characterized. Crystal structures of three compounds were solved by XRD. The compounds displayed fairly good activity against bloodstream T. brucei, with IC50 values in the submicromolar range (IC50: 0.14-0.93 µM), and good selectivity towards the pathogen (SI: 11 - 48) with respect to mammalian macrophages (cell line J774). Coordination to the {Pt-dppf} moiety led, in most cases, to an enhancement of the activity in respect to the bioactive ligands (11 to 41 fold). Cytotoxicity was assessed against wildtype (A2780) and cisplatin-resistance (A2780cisR) ovarian cancer cell lines. Four [PtII(L)(dppf)](PF6) compounds were more active (IC50: 1.2-4.4 µM) than cisplatin (IC50: 26.0 µM) on A2780 cells and showed far superior activity than the reference drug against A2780cisR cells. Platinum levels in A2780 cells showed poor correlation between cellular uptake and the cytotoxic activity. All the complexes interacted with DNA and the most active ones induced reactive oxygen species (ROS) formation which suggested that the mechanism of action for these complexes may be mediated by oxidative stress and interaction with DNA that could act as a potential molecular target for this type of complexes. Some complexes of this series could be considered new hits for the development of prospective agents against trypanosomatid parasites and ovarian cancer.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Platina / Trypanosoma brucei brucei / Compostos Ferrosos / Hidroxiquinolinas / Ferro / Antineoplásicos Limite: Animals / Humans Idioma: En Revista: J Inorg Biochem Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Uruguai País de publicação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Platina / Trypanosoma brucei brucei / Compostos Ferrosos / Hidroxiquinolinas / Ferro / Antineoplásicos Limite: Animals / Humans Idioma: En Revista: J Inorg Biochem Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Uruguai País de publicação: Estados Unidos