Publication Type Journal Article
Title Lanthanide complexes with phenanthroline-based ligands: insights into cell death mechanisms obtained by microscopy techniques
Authors Maria Paula C. Campello E Palma Isabel Correia Pedro M. R. Paulo Antonio Matos Jose Rino Joana Coimbra J.C. Pessoa Dinorah Gambino Antonio Paulo Fernanda M. Marques
Year 2019
Month April
Volume 48
Number 14
Pages 4611-4624
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 -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)(NH(2)Phen)], [Eu(DBM)(3)(NH(2)Phen)] and [Tb(DBM)(3)(NH(2)Phen)] 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 M. 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 10(4) 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 NH(2)Phen complexes. In addition, the complex [Eu(DBM)(3)(NH(2)Phen)] presented lysosomal uptake that might explain its augmented cytotoxicity.
Book Title
ISSN 1477-9226
EISSN 1477-9234
Conference Name
Bibtex ID ISI:000467173800019
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