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首页> 外文期刊>Dalton transactions: An international journal of inorganic chemistry >Lanthanide complexes with phenanthroline-based ligands: insights into cell death mechanisms obtained by microscopy techniques
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Lanthanide complexes with phenanthroline-based ligands: insights into cell death mechanisms obtained by microscopy techniques

机译:镧系有菲碱基配体的镧系元素:通过显微镜技术获得的细胞死亡机制见解

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摘要

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.
机译:本文我们报告的合成,表征,和(DBM)(3)(RPhen)(LN = SM,R = H; Ln为钐,铕,铽,R = 5-NH 2)LN络合物的光物理和生物学评价稳定化由三个二酮单元(DBM)和菲咯啉(RPhen)衍生物,与潜在的应用作为抗癌剂促进的镧系元素基化合物发展的目的。的UV-VIS [SM(DBM)(3)(phen)的]的光谱,[SM(DBM)(3)(NH(2)苯)],[铕(DBM)(3)(NH(2)苯)]和[Tb的(DBM)(3)(NH(2)phen)的在DMSO和PBS测量表现出强烈的吸收带在约中心在两种溶剂中350纳米。在DMSO中,除[SM(DBM)(3)(phen)的]示出了配体的所有镧系元素化合物在约中心发射带520纳米。在PBS中仅检测到尖锐的发射峰。该配合物显示在A2780卵巢癌细胞相似的细胞毒性效应,在16-27 M.通过电感耦合等离子体质谱法在A2780细胞的复合物的细胞摄取的测定范围内的24小时呈现IC 50个值(ICP-MS)揭示在膜和细胞骨架优先积累,与[SM(DBM)(3)(phen)的]在胞质中比在细胞膜呈现更高的积累的异常。所有评估稀土配合物呈低核摄取,但不可忽略的。与小牛胸腺DNA(小牛胸腺DNA)复合物的相互作用的光谱学研究揭示了与在图10(4)M-1的范围内的表观结合常数中等亲和力。配合绑定DNA不被插入,但可能通过静电相互作用。与由电子显微镜的不同复合物处理的细胞的形态学评价(TEM / SEM)证实了所有的他们的诱导线粒体的改变,这似乎更加显着的NH(2)Phen的复合物。此外,配合物[铕(DBM)(3)(NH(2)phen)的]提出溶酶体摄取可以解释其增强细胞毒性。

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    Univ Lisbon Inst Super Tecn Ctr Ciencias &

    Tecnol Nucl Estr Nacl 10 Km 139-7 P-2695066 Bobadela Lrs Portugal;

    Univ Lisbon Inst Super Tecn Ctr Ciencias &

    Tecnol Nucl Estr Nacl 10 Km 139-7 P-2695066 Bobadela Lrs Portugal;

    Univ Lisbon Inst Super Tecn Ctr Quim Estrutural Ave Rovisco Pais P-1049001 Lisbon Portugal;

    Univ Lisbon Inst Super Tecn Ctr Quim Estrutural Ave Rovisco Pais P-1049001 Lisbon Portugal;

    Ctr Invest Interdisciplinar Egas Moniz Campus Univ Monte De Caparica Almada Portugal;

    Univ Lisbon Fac Med Lisboa Inst Med Mol Fac Med Ave Prof Egas Moniz P-1649028 Lisbon Portugal;

    Univ Aveiro Lab Cent Anal P-3810193 Aveiro Portugal;

    Univ Lisbon Inst Super Tecn Ctr Quim Estrutural Ave Rovisco Pais P-1049001 Lisbon Portugal;

    Univ Republica Fac Quim Catedra Quim Inorgan Montevideo 11800 Uruguay;

    Univ Lisbon Inst Super Tecn Ctr Ciencias &

    Tecnol Nucl Estr Nacl 10 Km 139-7 P-2695066 Bobadela Lrs Portugal;

    Univ Lisbon Inst Super Tecn Ctr Ciencias &

    Tecnol Nucl Estr Nacl 10 Km 139-7 P-2695066 Bobadela Lrs Portugal;

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  • 中图分类 化学;无机化学;
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