Lanthanide complexes with phenanthroline-based ligands: insights into cell death mechanisms obtained by microscopy techniques

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Título

Lanthanide complexes with phenanthroline-based ligands: insights into cell death mechanisms obtained by microscopy techniques

Tema

LANTANIDOS
FENANTROLINA
MICROSCOPIA
BIBLIOGRAFIA NACIONAL QUIMICA
2019

Abstract

Herein we report the synthesis, characterization, and photophysical and biological evaluation of the complexes Ln(DBM)3(RPhen) (Ln = Sm, R = H; Ln = Sm, Eu, Tb, R = 5-NH2) stabilized by three β-diketonate units (DBM) and a phenanthroline (RPhen) derivative, with the aim of contributing to the development of lanthanide-based compounds with potential application as anticancer agents. The UV-vis spectra of [Sm(DBM)3(Phen)], [Sm(DBM)3(NH2Phen)], [Eu(DBM)3(NH2Phen)] and [Tb(DBM)3(NH2Phen)] measured in DMSO and PBS showed a strong absorption band centered at ca. 350 nm in both solvents. In DMSO, all lanthanide compounds except [Sm(DBM)3(Phen)] show a ligand centered emission band at ca. 520 nm. In PBS only sharp emission peaks are detected. The complexes show similar cytotoxic effects in A2780 ovarian cancer cells, presenting IC50 values at 24 h in the range 16–27 μM. The measurement of the cellular uptake of the complexes in the A2780 cells by inductively coupled plasma mass spectrometry (ICP-MS) revealed preferential accumulation at the membrane and cytoskeleton, with the exception of [Sm(DBM)3(Phen)] that presented higher accumulation in the cytosol than in the cell membranes. All the evaluated lanthanide complexes showed low nuclear uptake, although not negligible. Spectroscopic studies on the interaction of the complexes with calf thymus DNA (ctDNA) revealed a moderate affinity with apparent binding constants in the 104 M−1 range. Complexes bind DNA not by intercalation but probably by electrostatic interactions. A morphological evaluation of the cells treated with the different complexes by electron microscopy (TEM/SEM) proved that all of them induce mitochondrial alterations, which seemed more pronounced for the NH2Phen complexes. In addition, the complex [Eu(DBM)3(NH2Phen)] presented lysosomal uptake that might explain its augmented cytotoxicity.

Autor

Cabral Campello, María Paula
Palma, Elisa
Correia, Isabel
Paulo, Pedro M. R.
Matos António
Rino, José
Coimbra, Joana
Costa Pessoa, João
Paulo, António
Marques, Fernanda

Fuente

Dalton Transactions v. 48, no. 14, 2019. -- p. 4611-4624

Editor

Royal Society of Chemistry

Fecha

2019

Derechos

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PDF

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Tipo

Artículo

Identificador

DOI: 10.1039/C9DT00640K

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PDF
Fecha de agregación
August 15, 2019
Colección
Bibliografía Nacional Química
Tipo de Elemento
Document
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Citación
Cabral Campello, María Paula, “Lanthanide complexes with phenanthroline-based ligands: insights into cell death mechanisms obtained by microscopy techniques,” RIQUIM - Repositorio Institucional de la Facultad de Química - UdelaR, accessed December 9, 2019, http://riquim.fq.edu.uy/items/show/5837.
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