TY - JOUR
T1 - Lanthanide complexes with phenanthroline-based ligands
T2 - insights into cell death mechanisms obtained by microscopy techniques
AU - Cabral Campello, Maria Paula
AU - Palma, Elisa
AU - Correia, Isabel
AU - Paulo, Pedro M.R.
AU - Matos, António
AU - Rino, José
AU - Coimbra, Joana
AU - Pessoa, João Costa
AU - Gambino, Dinorah
AU - Paulo, António
AU - Marques, Fernanda
N1 - Publisher Copyright:
© The Royal Society of Chemistry.
PY - 2019
Y1 - 2019
N2 - 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-NH 2 ) 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 (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 IC 50 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 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.
AB - 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-NH 2 ) 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 (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 IC 50 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 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.
UR - http://www.scopus.com/inward/record.url?scp=85063729981&partnerID=8YFLogxK
U2 - 10.1039/c9dt00640k
DO - 10.1039/c9dt00640k
M3 - Article
C2 - 30888352
AN - SCOPUS:85063729981
SN - 1477-9226
VL - 48
SP - 4611
EP - 4624
JO - Dalton Transactions
JF - Dalton Transactions
IS - 14
ER -
