Artigo De: scopus, orcid, cienciavitae

Anticancer Activity and Mode of Action of Copper(II)-Bis(thiosemicarbazonato) Complexes with Pendant Nitrogen Heterocycles

European Journal of Inorganic Chemistry

Elisa Palma; Paula Raposinho; Filipa Mendes2021European Chemical Societies Publishing

Informações chave

Autores:

Elisa Palma (Elisa Vaz Morgado de Palma); Paula Raposinho (Paula Dolores Galhofas Raposinho); Maria Paula Cabral Campello (Maria Paula Cordeiro Crespo Cabral Campello Aboim de Barros); Dulce Belo (Maria Dulce Jesus Pombo Belo); Joana F. Guerreiro; Vítor Alves; Alexandra Fonseca; Antero J. Abrunhosa; António Paulo (António Manuel Rocha Paulo); Filipa Mendes (Filipa Fernandes Mendes)

Publicado em

15/04/2021

Resumo

Exploring the potential of bis(thiosemicarbazones) (BTSC), a new family of BTSC ligands derived from GTSM (glyoxal-bis(N4-methylthiosemicarbazonato) and respective CuIIBTSC complexes were synthesized. These complexes, having pendant nitrogen heterocycles, exhibited increased water-solubility, lower lipophilicity at physiological pH and more negative Cu(II)/Cu(I) redox potential, when compared with the parental complex. The cytotoxic evaluation performed in a panel of cancer cells lines showed an important effect of the metal complexation, and furthermore correlated well with the cellular uptake of the compounds, which was determined using their 64Cu congeners. The radiolabelling of the complexes also allowed more detailed uptake studies, with the results suggesting an active transport or facilitated diffusion mechanism for the cellular uptake of 64CuGTSMpip and 64CuGTSMmor, with pendant piperidine and morpholine rings, respectively. Additionally, a comparative study with the corresponding Cu(II) complexes derived from ATSM (diacetyl-bis(N4-methylthiosemicarbazonato) that we have previously described, demonstrated a clear difference in their lysosomotropic properties in particular for the piperidine derivatives. From this study, CuGTSMpip emerged as the most promising compound to be further evaluated as an anticancer metallodrug.

Detalhes da publicação

Autores da comunidade :

Versão da publicação

AO - Versão original do autor

Editora

European Chemical Societies Publishing

Título do contentor da publicação

European Journal of Inorganic Chemistry

Primeira página ou número de artigo

1337

Última página

1348

Volume

2021

Fascículo

14

ISSN

1434-1948

WoS (Web of Science)

WOS:000630024700001

Domínio Científico (FOS)

chemical-sciences - Química

Idioma da publicação (código ISO)

eng - Inglês

Identificador alternativo (URI)

http://dx.doi.org/10.1002/ejic.202100168

Acesso à publicação:

Acesso apenas a metadados