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Multifunctional Pt(iv) prodrug candidates featuring the carboplatin core and deferoxamine.
Harringer, Sophia; Hejl, Michaela; Enyedy, Éva A; Jakupec, Michael A; Galanski, Mathea S; Keppler, Bernhard K; Dyson, Paul J; Varbanov, Hristo P.
Afiliación
  • Harringer S; Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, 1090 Vienna, Austria. hristo.varbanov@univie.ac.at.
Dalton Trans ; 50(23): 8167-8178, 2021 Jun 21.
Article en En | MEDLINE | ID: mdl-34031671
The synergistic combination of the anticancer drug carboplatin and the iron chelator deferoxamine (DFO) served as a foundation for the development of novel multifunctional prodrugs. Hence, five platinum(iv) complexes, featuring the equatorial coordination sphere of carboplatin, and one or two DFO units incorporated at axial positions, were synthesized and characterized using ESI-HRMS, multinuclear (1H, 13C, 15N, 195Pt) NMR spectroscopy and elemental analysis. Analytical studies demonstrated that the chelating properties of the DFO moiety were not compromised after coupling to the platinum(iv) core. The cytotoxic activity of the compounds was evaluated in monolayer (2D) and spheroid (3D) cancer cell models, derived from ovarian teratocarcinoma (CH1/PA-1), colon carcinoma (SW480) and non-small cell lung cancer (A549). The platinum(iv)-DFO prodrugs demonstrated moderate in vitro cytotoxicity (a consequence of their slow activation kinetics) but with less pronounced differences between intrinsically chemoresistant and chemosensitive cell lines as well as between 2D and 3D models than the clinically used platinum(ii) drug carboplatin.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos Organoplatinos / Profármacos / Carboplatino / Deferoxamina / Antineoplásicos Límite: Humans Idioma: En Revista: Dalton Trans Asunto de la revista: QUIMICA Año: 2021 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos Organoplatinos / Profármacos / Carboplatino / Deferoxamina / Antineoplásicos Límite: Humans Idioma: En Revista: Dalton Trans Asunto de la revista: QUIMICA Año: 2021 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Reino Unido