Evaluation of cellular uptake, cytotoxicity and cellular ultrastructural effects of heteroleptic oxidovanadium(IV) complexes of salicylaldimines and polypyridyl ligands

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Título

Evaluation of cellular uptake, cytotoxicity and cellular ultrastructural effects of heteroleptic oxidovanadium(IV) complexes of salicylaldimines and polypyridyl ligands

Tema

ANTINEOPLASICOS
OXIDOVANADIO
COMPLEJOS
BIBLIOGRAFIA NACIONAL QUIMICA
2017

Abstract

Searching for prospective vanadium-based drugs for cancer treatment, a new series of structurally related [VIVO(L − 2H)(NN)] compounds (1–8) was developed. They include a double deprotonated salicylaldimine Schiff base ligand (L-2H) and different NN-polypyridyl co-ligands having DNA intercalating capacity. Compounds were characterized in solid state and in solution. EPR spectroscopy suggests that the NN ligands act as bidentate and bind through both nitrogen donor atoms in an axial-equatorial mode. The cytotoxicity was evaluated in human tumoral cells (ovarian A2780, breast MCF7, prostate PC3). The cytotoxic activity was dependent on type of cell and incubation time. At 24 h PC3 cells presented low sensitivity, but at 72 h all complexes showed high cytotoxic activity in all cells. Human kidney HEK293 and ovarian cisplatin resistant A2780cisR cells were also included to evaluate selectivity towards cancer cells and potency to overcome cisplatin resistance, respectively. Most complexes showed no detectable interaction with plasmid DNA, except 2 and 7 which depicted low ability to induce single strand breaks in supercoiled DNA. Based on the overall cytotoxic profile, complexes with 2,2´-bipyridine and 1,10-phenanthroline ligands (1 and 2) were selected for further studies, which consisted on cellular distribution and ultrastructural analyses. In the A2780 cells both depicted different distribution profiles; the former accumulates mostly at the membrane and the latter in the cytoskeleton. Morphology of treated cells showed nuclear atypia and membrane alterations, more severe for 1. Complexes induce different cell death pathways, predominantly necrosis for 1 and apoptosis for 2. Complexes alternative mode of cell death motivates the possibility for further developments.

Autor

Scalese, Gonzalo
Correia, Isabel
Benitez, Julio
Rostan, Sergio.
Marques, Fernanda
Mendes, Filipa
Matos, António Pedro
Costa Pessoa, João

Fuente

Journal of Inorganic Biochemistry v. 166, 2017. -- p. 162-172

Editor

Elsevier

Fecha

2017

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PDF

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Tipo

Artículo

Identificador

DOI: 10.1016/j.jinorgbio.2016.11.010

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Original Format

PDF
Fecha de agregación
December 12, 2017
Colección
Bibliografía Nacional Química
Tipo de Elemento
Document
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Citación
Scalese, Gonzalo, “Evaluation of cellular uptake, cytotoxicity and cellular ultrastructural effects of heteroleptic oxidovanadium(IV) complexes of salicylaldimines and polypyridyl ligands,” RIQUIM - Repositorio Institucional de la Facultad de Química - UdelaR, accessed April 21, 2018, http://riquim.fq.edu.uy/items/show/4803.
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