Artigo De: scopus, orcid, cienciavitae
Biophysical characterization and antineoplastic activity of new bis(thiosemicarbazonato) Cu(II) complexes
Journal of inorganic biochemistry
2017 — Elsevier
—Informações chave
Autores:
Publicado em
01/02/2017
Resumo
Aiming to explore alternative mechanisms of cellular uptake and cytotoxicity, we have studied a new family of copper(II) complexes (CuL1-CuL4) with bis(thiosemicarbazone) (BTSC) ligands containing pendant protonable cyclic amines (morpholine and piperidine). Herein, we report on the synthesis and characterization of these new complexes, as well as on their biological performance (cytotoxic activity, cellular uptake, protein and DNA binding), in comparison with the parental CuIIATSM (ATSM = diacetyl-bis(N4-methylthiosemicarbazonate) complex without pendant cyclic amines. The new compounds have been characterized by a range of analytical techniques including ESI-MS, IR spectroscopy, cyclic voltammetry, reverse-phase HPLC and X-ray spectroscopy. In vitro cytotoxicity studies revealed that the copper complexes are cytotoxic, unlike the corresponding ligands, with a similar potency to that of CuATSM. Unlike CuATSM, the new complexes were able to circumvent cisplatin cross-resistance. The presence of the protonable cyclic amines did not lead to an enhancement of the interaction of the complexes with human serum albumin or calf thymus DNA. However, CuL1–CuL4 showed a remarkably augmented cellular uptake compared with CuATSM, as proved by uptake, internalization and externalization studies that were performed using the radioactive congeners 64CuL1-64CuL4. The enhanced cellular uptake of CuL1-CuL4 indicates that this new family of CuIIBTSC complexes deserves to be further evaluated in the design of metallodrugs for cancer theranostics.
Detalhes da publicação
Autores da comunidade :
Elisa Vaz Morgado de Palma
ist423985
Filipa Fernandes Mendes
ist25493
Paula Dolores Galhofas Raposinho
ist25382
Maria Isabel Rodrigues Correia
ist135350
Ana Sofia Cavalheiro Gama
ist31580
Maria Dulce Jesus Pombo Belo
ist171949
Isabel da Graça Rego dos Santos
ist25348
António Manuel Rocha Paulo
ist126677
Versão da publicação
AO - Versão original do autor
Editora
Elsevier
Ligação para a versão da editora
https://www.sciencedirect.com/journal/journal-of-inorganic-biochemistry
Título do contentor da publicação
Journal of inorganic biochemistry
Primeira página ou número de artigo
68
Última página
79
Volume
167
ISSN
0162-0134
WoS (Web of Science)
Domínio Científico (FOS)
health-sciences - Ciências de Saúde
Palavras-chave
- charge transfer salts
- TTF donors
- dimercaptopyrazine bisdithiolate complexes
- crystal engineering
Idioma da publicação (código ISO)
eng - Inglês
Identificador alternativo (URI)
http://europepmc.org/abstract/med/27907865
Acesso à publicação:
Acesso apenas a metadados