Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Gold(III) complexes with thiosemicarbazonate ligands as potential anticancer agents: Cytotoxicity and interactions with biomolecular targets

Texto completo
Autor(es):
Mostrar menos -
Possato, Bruna [1] ; Dalmolin, Luciana Falcco [1] ; Pereira, Luiz Miguel [1] ; Alves, Jacqueline Querino [2] ; Silva, Raphael Tristao Cruvinel [3] ; Gelamo, Rogerio Valentim [4] ; Yatsuda, Ana Patricia [1] ; Lopez, Renata Fonseca Vianna [1] ; de Albuquerque, Sergio [1] ; Leite, Natalia Bueno [3] ; Maia, Pedro Ivo da Silva [3]
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Ribeirao Preto - Brazil
[2] Prefeitura Municipal Ribeirao Preto, Secretaria Educ, Ribeirao Preto - Brazil
[3] Univ Fed Triangulo Mineiro, Nucl Desenvolvimento Compostos Bioat NDCBio, Uberaba - Brazil
[4] Univ Fed Triangulo Mineiro, Inst Ciencias Tecnol & Exatas, Uberaba - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: European Journal of Pharmaceutical Sciences; v. 162, JUL 1 2021.
Citações Web of Science: 0
Resumo

Gold(III) complexes have been studied for the past years due to their anticancer properties and great affinity to biotargets, such as enzymes and proteins, which support their pharmacological applications. Within this scope, in this work the antiproliferative activities of two Au(III)-thiosemicarbazonate complexes, {[}AuClL1] (1, L1: (E,Z)-Nethyl-N'-(3-nitroso-kN)butan-2-ylidene)carbamohydrazonothioato-k2 N2,S) and {[}Au(Hdamp)L2]Cl (2, L2: N-(N{''}, N{''}-diethylaminothiocarbonyl)-N'(N{''}', N{''}'-dimethylcarbothioamide)benzamidineto-kN,k2S and Hdamp: 2-(N, N-dimethylaminomethyl)-phenyl-C1), and their affinities to possible biological targets were investigated. Three different tumor cell lines were used to perform the cytotoxicity assays, including one cisplatin-resistant model, and the results showed lower EC50 for 1 over 2 in every case: B16F10 (4.1 mu M and 15.6 mu M), A431 (4.0 mu M and >50 mu M) and OVCAR3 (4.2 mu M and 24.5 mu M). However, a lower toxicity to fibroblast 3T3 cell line was observed for 2 (30.58 mu M) when compared to 1 (7.17 mu M), resulting in comparable therapeutic indexes. Both complexes presented strong affinity to HSA: they distorted the secondary structure of the protein, as verified by circular dichroism, but 1 additionally presented the apparent fluorescence quenching constant (Kapp) ten times greater than 2, which was probably due to the fact of 1 being able to denature HSA. The ethidium bromide displacement assay showed that neither 1 nor 2 are strong DNA intercalators, which is in agreement with what was observed through the UV-vis titration. In both cases, the 260 nm band presented hyperchromism, which can indicate ionic interactions or DNA damage. In fact, 1 was able to damage the pGEM plasmid, similarly to cisplatin, as verified by agarose gel electrophoresis and Atomic Force Microscopy. Biophysical studies in cancer cells model membranes were also performed in order to investigate the interaction of the gold complexes to lipid bilayers and revealed that the compounds interact with the membranes by exhibiting partition coefficients of 103 order of magnitude. Overall, both complexes were found to be promising candidates for the development of a future anticancer drug against low sensitive or cisplatin resistant tumors. (AU)

Processo FAPESP: 18/21020-3 - Fator de despolimerização de actina (NcADF): oxidação como regulador da atividade de NcADF na morte celular programada de Neospora caninum
Beneficiário:Ana Patricia Yatsuda Natsui
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 18/10711-5 - Avaliação do potencial de corantes fenotiazínicos para o controle de Toxoplasma gondii
Beneficiário:Luiz Miguel Pereira
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 18/24544-3 - Avaliação de complexos metálicos coordenados a derivados de melatonina como candidatos a metalofármacos: síntese, caracterização e estudos de atividade tripanocida
Beneficiário:Sérgio de Albuquerque
Linha de fomento: Auxílio à Pesquisa - Regular