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Detalhes Referência

Tipo
Artigos em Revista

Tipo de Documento
Artigo Completo

Título
Unravelling the antitumoral potential of novel bis(thiosemicarbazonato) Zn(II) complexes: structural and cellular studies

Participantes na publicação
Elisa Palma (Author)
Hugo M. Botelho (Author)
Dep. Química e Bioquímica
BioISI
Goreti Ribeiro Morais (Author)
Inês Rodrigues (Author)
Isabel Cordeiro Santos (Author)
Maria Paula Cabral Campello (Author)
Paula Raposinho (Author)
Ana Belchior (Author)
Susana Sousa Gomes (Author)
Maria Fátima Araújo (Author)
Isabel Correia (Author)
Nadia Ribeiro (Author)
Sofia Gama (Author)
Filipa Mendes (Author)
António Paulo (Author)

Resumo
The development of pharmacologically active compounds based on bis(thiosemicarbazones) (BTSC) and on their coordination to metal centers constitutes a promising field of research. We have recently explored this class of ligands and their Cu(II) complexes for the design of cancer theranostics agents with enhanced uptake by tumoral cells. In the present work, we expand our focus to aliphatic and aromatic BTSC Zn(II) complexes bearing piperidine/morpholine pendant arms. The new complexes ZnL1-ZnL4 were characterized by a variety of analytical techniques, which included single-crystal X-ray crystallography for ZnL2 and ZnL3. Taking advantage of the fluorescent properties of the aromatic complexes, we investigated their cellular uptake kinetics and subcellular localization. Furthermore, we tried to elucidate the mechanism of action of the cytotoxic effect observed in human cancer cell line models. The results show that the aliphatic complexes (ZnL1 and ZnL2) have a symmetrical structure, while the aromatic counterparts (ZnL3 and ZnL4) have an asymmetrical nature. The cytotoxic activity was higher for the aromatic BTSC complexes, as well as the cellular uptake, evaluated by measurement of intracellular Zn accumulation. Among the most active complexes, ZnL3 presented the fastest uptake kinetics and lysosomal localization assessed by live-cell microscopy. Detailed studies of its impact on cellular production of reactive oxygen species and impairment of lysosomal membrane integrity reinforced the influence of the pendant piperidine in the biological performance of aromatic BTSC Zn(II) complexes.

Data de Submissão/Pedido
2018-08-27
Data de Aceitação
2018-11-07
Data de Publicação
2018-11-24

Instituição
BioISI - Biosystems & Integrative Sciences Institute

Suporte
JBIC Journal of Biological Inorganic Chemistry

Identificadores da Publicação
ISSN - 0949-8257
eISSN - 1432-1327

Editora
Springer Nature

Volume
24
Fascículo
1

Número de Páginas
18
Página Inicial
71
Página Final
89

Identificadores do Documento
DOI - https://doi.org/10.1007/s00775-018-1629-6
URL - http://dx.doi.org/10.1007/s00775-018-1629-6

Keywords
Zinc Bis(thiosemicarbazones) X-ray diffraction Fluorescence imaging Cellular studies


Exportar referência

APA
Elisa Palma, Hugo M. Botelho, Goreti Ribeiro Morais, Inês Rodrigues, Isabel Cordeiro Santos, Maria Paula Cabral Campello, Paula Raposinho, Ana Belchior, Susana Sousa Gomes, Maria Fátima Araújo, Isabel Correia, Nadia Ribeiro, Sofia Gama, Filipa Mendes, António Paulo, (2018). Unravelling the antitumoral potential of novel bis(thiosemicarbazonato) Zn(II) complexes: structural and cellular studies. JBIC Journal of Biological Inorganic Chemistry, 24, 71-89. ISSN 0949-8257. eISSN 1432-1327. http://dx.doi.org/10.1007/s00775-018-1629-6

IEEE
Elisa Palma, Hugo M. Botelho, Goreti Ribeiro Morais, Inês Rodrigues, Isabel Cordeiro Santos, Maria Paula Cabral Campello, Paula Raposinho, Ana Belchior, Susana Sousa Gomes, Maria Fátima Araújo, Isabel Correia, Nadia Ribeiro, Sofia Gama, Filipa Mendes, António Paulo, "Unravelling the antitumoral potential of novel bis(thiosemicarbazonato) Zn(II) complexes: structural and cellular studies" in JBIC Journal of Biological Inorganic Chemistry, vol. 24, pp. 71-89, 2018. 10.1007/s00775-018-1629-6

BIBTEX
@article{39283, author = {Elisa Palma and Hugo M. Botelho and Goreti Ribeiro Morais and Inês Rodrigues and Isabel Cordeiro Santos and Maria Paula Cabral Campello and Paula Raposinho and Ana Belchior and Susana Sousa Gomes and Maria Fátima Araújo and Isabel Correia and Nadia Ribeiro and Sofia Gama and Filipa Mendes and António Paulo}, title = {Unravelling the antitumoral potential of novel bis(thiosemicarbazonato) Zn(II) complexes: structural and cellular studies}, journal = {JBIC Journal of Biological Inorganic Chemistry}, year = 2018, pages = {71-89}, volume = 24 }