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Ferreira, Helen Soares Valenca
;
Ramos, Luana Munique Sousa
;
Silva, Fernanda Cardoso
;
Alves, Daniel Lima
;
Pereira, Gabriele de Menezes
;
Santiago, Pedro Henrique de Oliveira
;
de Almeida, Angelina Maria
;
Ellena, Javier
;
Corbi, Pedro Paulo
;
Oliveira, Carolina Goncalves
;
de Almeida, Mauro Vieira
;
Furstenau, Cristina Ribas
;
Borges, Dayanne Silva
;
Siqueira, Raoni Pais
;
Guerra, Wendell
;
Araujo, Thaise Goncalves
Número total de Autores: 16
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Journal of Inorganic Biochemistry; v. 255, p. 10-pg., 2024-03-19. |
| Resumo | |
Copper can be opportunely complexed to modulate oncogenic pathways, being a promising strategy for cancer treatment. Herein, three new copper(II) complexes containing long -chain aliphatic hydrazides and 1,10-phenanthroline (1,10-phen), namely, [Cu(octh)(1,10-phen)(H2O)](NO3)2 1, [Cu(dech)(1,10-phen)(H2O)](NO3)2 2 and [Cu(dodh)(1,10-phen)(H2O)](NO3)2.H2O 3 (where octh = octanoic hydrazide, dech = decanoic hydrazide, dodh = dodecanoic hydrazide) were successfully prepared and characterized by several physical -chemical methods. Furthermore, X-ray structural analysis of complex 2 indicated that the geometry around the copper(II) ion is distorted square -pyramidal, in which hydrazide and 1,10-phenanthroline act as bidentate ligands. A water molecule in the apical position completes the coordination sphere of the metal ion. All new copper(II) complexes were cytotoxic to breast cancer cell lines (MCF7, MDA-MB-453, MDA-MB-231, and MDA-MB-157) and selective when compared to the non tumor lineage MCF-10A. In particular, complex 2 showed half -maximal inhibitory concentration (IC50) values ranging between 2.7 and 13.4 mu M in MDA-MB231 cells after 24 and 48 h of treatment, respectively. Furthermore, this complex proved to be more selective for tumor cell lines when compared to doxorubicin and docetaxel. Complex 2 inhibited the clonogenicity of MDA-MB231 cells, increasing adenosine diphosphate (ADP) hydrolysis and upregulating ecto-nucleoside triphosphate diphosphohydrolase 1 (ENTPD1) transcriptional levels. In this sense, we suggest that the inhibitory effect on cell proliferation may be related to the modulation of adenosine monophosphate (AMP) levels. Thus, a novel copper(II) complex with increased cytotoxic effects and selectivity against breast cancer cells was obtained, contributing to medicinal chemistry efforts toward the development of new chemotherapeutic agents. (AU) | |
| Processo FAPESP: | 21/10265-8 - Centro de Inovação Teranóstica em Câncer (CancerThera) |
| Beneficiário: | Carmino Antonio de Souza |
| Modalidade de apoio: | Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs |
| Processo FAPESP: | 19/12219-3 - Estudo da responsividade vascular em consequência da Síndrome Cardiorrenal: participação do sistema purinérgico |
| Beneficiário: | Cristina Ribas Fürstenau |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 21/08717-8 - Síntese de complexos de cobre, prata e ouro envolvendo análogos de nucleotídeos na busca por novas alternativas para o tratamento do câncer de ovário |
| Beneficiário: | Pedro Paulo Corbi |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |