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001-es BibID:BIBFORM081458
035-os BibID:(WoS)000388059600006 (Scopus)84979656975
Első szerző:Facchin, Gianella
Cím:Experimental and theoretical studies of copper complexes with isomeric dipeptides as novel candidates against breast cancer / Gianella Facchin, Nicolás Veiga, M. Gabriela Kramer, Alzir A. Batista, Katalin Várnagy, Etelka Farkas, Virtudes Moreno, María H. Torre
Dátum:2016
ISSN:0162-0134
Megjegyzések: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.
Tárgyszavak:Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Copper dipeptide complexes
Antitumor agents
Docking
Spectroscopy
Stability
Atomic Force Microscopy
Megjelenés:Journal Of Inorganic Biochemistry. - 162 (2016), p. 52-61. -
További szerzők:Veiga, Nicolás Kramer, M. Gabriela Batista, Alzir A. Várnagy Katalin (1961-) (vegyész) Farkas Etelka (1948-) (vegyész) Moreno, Virtudes Torre, María H.
Pályázati támogatás:OTKA K 115480
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