Complexo de prata(I) contendo a tiossemicarbazona derivada da vanilina: síntese, avaliação da atividade antiproliferativa e estudos de interação com o DNA
Carregando...
Data
2022-05-06
Autores
Vinhas, Manuela Alves
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
O câncer é termo genérico que abrange uma variedade de doenças, seu diagnostico representa em sua maioria um prognostico ruim, pois o câncer esta associado à uma das principais causas de morte em todo o mundo. Desse modo, o desenvolvimento de novos quimioterápicos para um tratamento mais adequado é de vital importância. Nesse contexto, foi desenvolvido um novo complexo de prata contendo ligantes de interesse biológico, de formula [AgCl(VMTSC)(PPh3)2], onde PPh3 = trifenilfosfina e VMTSC=(E)-N-etil-2-(3-metoxi-4-[2-(1-morfolinil)etóxi]benzadeíldo tiossemicarbazona. Os compostos foram caracterizados através das técnicas espectroscópicas de infravermelho com transformada de Fourier, ressonância magnética nuclear de 1H, 13C e 31P. As formulas mínimas e purezas dos compostos foram determinadas através de análise elementar e os cristais obtidos do complexo foram submetidos a experimentos de difração de raios X por monocristal o qual revelou sua estrutura cristalina. A citotoxicidade in vitro dos compostos foi determinada frente as linhagens tumorais A2780cis (tumoral de ovário com resistência a cisplatina), A549 (tumoral de pulmão), HepG2 (tumoral de fígado), MDA-MB-231 (tumoral de mama triplo-negativo) e MRC5 (não tumoral de pulmão de origem fetal). O complexo foi ativo contra todas as linhagens tumorais, sendo mais ativo contra a linhagem A2780cis, IC50 = 0,428 ± 0,008 μM, linhagem com resistência a cisplatina. Ensaios de interação com o ctDNA por titulação espectroscópica, dicroísmo circular e ensaios de ligação competitiva evidenciaram que o complexo [AgCl(VMTSC)(PPh3)2] consegue interagir com ctDNA, tornando o ctDNA um possível alvo.
Cancer is a generic term that covers a variety of diseases, its diagnosis represents mostly a bad prognosis, as cancer is associated with one of the main causes of death worldwide. Thus, the development of new chemotherapeutic agents for a more adequate treatment is of vital importance. In this context, a new silver complex containing ligands of biological interest was developed, with the formula [AgCl(VMTSC)(PPh3)2], where PPh3 = triphenylphosphine and VMTSC=(E)-N-ethyl-2-(3-methoxy-4-[2-(1-morpholinyl)ethoxy]benzadeyldo thiosemicarbazone. The compounds were characterized by infrared spectroscopic techniques with Fourier transform, 1H, 13C and 31P nuclear magnetic resonance. The minimum formulas and purities of the compounds were determined through elemental analysis and the crystals obtained from the complex were subjected to X-ray diffraction experiments by single crystal which revealed its crystalline structure. The in vitro cytotoxicity of the compounds was determined against the tumor lines A2780cis (cisplatin-resistant ovarian tumor), A549 (lung tumor), HepG2 (liver tumor), MDA-MB-231 (triple-negative breast tumor) and MRC5 (non-tumor lung of fetal origin). The complex was active against all tumor strains, being more active against the A2780cis strain, IC50 = 0.428 ± 0.008 μM, a strain with resistance to cisplatin. Interaction assays with ctDNA by spectroscopic titration, circular dichroism and competitive binding assays showed that the complex [AgCl(VMTSC)(PPh3)2] can interact with ctDNA, making ctDNA a possible target
Cancer is a generic term that covers a variety of diseases, its diagnosis represents mostly a bad prognosis, as cancer is associated with one of the main causes of death worldwide. Thus, the development of new chemotherapeutic agents for a more adequate treatment is of vital importance. In this context, a new silver complex containing ligands of biological interest was developed, with the formula [AgCl(VMTSC)(PPh3)2], where PPh3 = triphenylphosphine and VMTSC=(E)-N-ethyl-2-(3-methoxy-4-[2-(1-morpholinyl)ethoxy]benzadeyldo thiosemicarbazone. The compounds were characterized by infrared spectroscopic techniques with Fourier transform, 1H, 13C and 31P nuclear magnetic resonance. The minimum formulas and purities of the compounds were determined through elemental analysis and the crystals obtained from the complex were subjected to X-ray diffraction experiments by single crystal which revealed its crystalline structure. The in vitro cytotoxicity of the compounds was determined against the tumor lines A2780cis (cisplatin-resistant ovarian tumor), A549 (lung tumor), HepG2 (liver tumor), MDA-MB-231 (triple-negative breast tumor) and MRC5 (non-tumor lung of fetal origin). The complex was active against all tumor strains, being more active against the A2780cis strain, IC50 = 0.428 ± 0.008 μM, a strain with resistance to cisplatin. Interaction assays with ctDNA by spectroscopic titration, circular dichroism and competitive binding assays showed that the complex [AgCl(VMTSC)(PPh3)2] can interact with ctDNA, making ctDNA a possible target
Descrição
Palavras-chave
Compostos de prata, Tiossemicarbazonas, Citotoxicidade, Câncer, DNA