Experimental and theoretical studies of copper complexes with isomeric dipeptides as novel candidates against breast cancer

COBRE

NEOPLASMAS

COMPLEJOS DE COBRE

CANCER DE MAMA

BIBLIOGRAFIA NACIONAL QUIMICA

2016

In the search for new cytotoxic drugs, two copper complexes with isomeric dipeptides (Ala-Phe and Phe-Ala) were developed in order to determine the influence of their different structures in the modulation of the chemical, biochemical and biological properties. Spectroscopic, voltammetric and equilibrium studies were performed providing information about the chemical properties. The superoxide dismutase (SOD) activity was studied and showed differences of IC50 for both Cu-Ala-Phe (IC50 = 4.5) and Cu-Phe-Ala (IC50 = 45). The computational results permitted to explain this behavior proposing that it is feasible that the O2− anion is attracted straight to the positive zone in Cu-Ala-Phe whereas for Cu-Phe-Ala this phenomenon would happen to a smaller extent. Confirming our previous studies, both complexes interacted with DNA. Molecular docking studies showed that the position of the phenyl ring modulates the complex-DNA affinity and in Cu-Ala-Phe the docked conformation allows the copper ion to face the DNA basis, giving rise to a more stable complex-DNA adduct than for Cu-Phe-Ala. In spite of the fact that Atomic Force Microscopy showed plasmid compactation and aggregation for both complexes, the image showed softer changes in the case of Cu-Ala-Phe in comparison with those produced by Cu-Phe-Ala. In order to evaluate the effect of Cu-Ala-Phe and Cu-Phe-Ala complexes against tumor cells, we have employed three aggressive metastatic breast adenocarcinoma cellular models, derived from human (MDA-MB-231 and MCF-7) and mouse (4T1) spontaneous tumors. These experiments showed that both Cu-dipeptide complexes have a similar cytotoxic effect against breast cancer cells, and lower toxicity against BJ non-tumor cells in comparison to Cisplatin.

Journal of Inorganic Biochemistry 2016 Disponible ONLINE. http://dx.doi.org/10.1016/j.jinorgbio.2016.06.005

Elsevier

2016

Información sobre Derechos de Autor

(Por favor lea este aviso antes de abrir los documentos u objetos)

La legislación uruguaya protege el derecho de autor sobre toda creación literaria, científica o artística, tanto en lo que tiene que ver con sus derechos morales, como en lo referente a los derechos patrimoniales con sujeción a lo establecido por el derecho común y las siguientes leyes (LEY 9.739 DE 17 DE DICIEMBRE DE 1937 SOBRE PROPIEDAD LITERARIA Y ARTISTICA CON LAS MODIFICACIONES INTRODUCIDAS POR LA LEY DE DERECHO DE AUTOR Y DERECHOS CONEXOS No. 17.616 DE 10 DE ENERO DE 2003, LEY 17.805 DE 26 DE AGOSTO DE 2004, LEY 18.046 DE 24 DE OCTUBRE DE 2006 LEY 18.046 DE 24 DE OCTUBRE DE 2006)

ADVERTENCIA - La consulta de este documento queda condicionada a la aceptación de las siguientes condiciones de uso: Este documento es únicamente para usos privados enmarcados en actividades de investigación y docencia. No se autoriza su reproducción con fines de lucro. Esta reserva de derechos afecta tanto los datos del documento como a sus contenidos. En la utilización o cita de partes debe indicarse el nombre de la persona autora.

PDF

Inglés

Artículo

DOI: 10.1016/j.jinorgbio.2016.06.005

PDF