Síntese, avaliação da atividade antiproliferativa e estudo da interação frente ao DNA de um composto de prata contendo a tiossemicarbazona derivada da isatina
Carregando...
Data
2022-06-10
Autores
Lima, Andresa Alves de
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
O câncer é a segunda doença que mais causa mortes no mundo. O tratamento mais utilizado é a quimioterapia, sendo que os compostos à base de platina representam 50% dos tratamentos. No entanto, esses compostos apresentam algumas limitações devido a toxicidade e resistência celular. Visando o desenvolvimento de novos compostos biologicamente ativos, destaca-se Ag(I), por conta de suas vantagens em relação a outros íons metálicos. Nesse trabalho, foi sintetizado um complexo de Ag(I) contendo isatina-3-etil-tiossemicarbazona (ITSC-Et) e 1,10-fenantrolina (phen). Esse composto foi caracterizado pelas técnicas de espectroscopia vibracional na região do infravermelho (IV), ressonância magnética nuclear (RMN) de 1H e 13C, condutividade molar, análise elementar e espectrometria de massas com ionização por electrospray (ESI-MS). A atividade antiproliferativa in vitro do complexo foi avaliada frente as linhagens celulares tumorais A2780 cis (ovário resistente a cisplatina), A549 (pulmão), MCF-7 (mama) e não tumoral MRC-5 (fibroblasto de pulmão). O complexo apresentou atividade citotóxica elevada (IC50 = 1,69 – 8,58 μM) em relação ao fármaco de controle cisplatina (IC50 cisplatina = 8,63 – 21,61 μM) por meio do método colorimétrico MTT. A interação do complexo de Ag(I) com ct-DNA foi avaliada pelas técnicas de titulação espectrofotométrica e dicroísmo circular, que sugeriram que o mesmo interage fracamente com o DNA (Kb = 7,52 x 104 M-1) por meio do sulco menor ou por interações eletrostáticas. Além disso, foram realizados ensaios de ligação competitiva com Hoechst 33258 e laranja de tiazol, que exibiram uma supressão da fluorescência de 80% e 39%, respectivamente. Portanto, esses resultados sugerem que o complexo de Ag(I) interage com o DNA por meio do sulco menor, porém essa interação é mais fraca em comparação com a sonda Hoechst 33258
Cancer is the second leading cause of death in the world. The most used treatment is chemotherapy, with platinum-based compounds representing 50% of treatments. However, these compounds have some limitations due to their toxicity and cell resistance. Aiming at the development of new biologically active compounds, Ag(I) stands out, due to its advantages in relation to other metallic ions. In this work, an Ag(I) complex containing isatin-3-ethyl-thiosemicarbazone (ITSC-Et) and 1,10- phenanthroline (phen) was synthesized. This compound was characterized by infrared spectroscopic (IR), 1H and 13C NMR, molar conductivity, elemental analysis, and electrospray ionization mass spectrometry (ESI-MS). The in vitro antiproliferative activity of the complex was evaluated against tumor cell lines A2780 cis (cisplatin- resistant ovarian), A549 (lung), MCF-7 (breast) and non-tumoral MRC-5 (lung fibroblast). The complex showed higher cytotoxic activity (IC50 = 1.69 to 8.58 μM) than the control drug cisplatin (IC50 cisplatin = 8.63 – 21.61 μM) by the MTT colorimetric method. The interaction of the Ag(I) complex with ct-DNA was evaluated by spectroscopic titration and circular dichroism techniques, which suggested that it interacts weakly with DNA (Kb = 7.52 x 104 M-1) through minor groove or by electrostatic forces. In addition, competitive binding assays were performed with Hoechst 33258 and thiazole orange (TO), which exhibited 80% and 39% fluorescence suppression, respectively. Therefore, these results suggests that the Ag(I) complex interacts weakly with ct-DNA through minor groove, but this interaction is weaker than Hoechst 33258 probe.
Cancer is the second leading cause of death in the world. The most used treatment is chemotherapy, with platinum-based compounds representing 50% of treatments. However, these compounds have some limitations due to their toxicity and cell resistance. Aiming at the development of new biologically active compounds, Ag(I) stands out, due to its advantages in relation to other metallic ions. In this work, an Ag(I) complex containing isatin-3-ethyl-thiosemicarbazone (ITSC-Et) and 1,10- phenanthroline (phen) was synthesized. This compound was characterized by infrared spectroscopic (IR), 1H and 13C NMR, molar conductivity, elemental analysis, and electrospray ionization mass spectrometry (ESI-MS). The in vitro antiproliferative activity of the complex was evaluated against tumor cell lines A2780 cis (cisplatin- resistant ovarian), A549 (lung), MCF-7 (breast) and non-tumoral MRC-5 (lung fibroblast). The complex showed higher cytotoxic activity (IC50 = 1.69 to 8.58 μM) than the control drug cisplatin (IC50 cisplatin = 8.63 – 21.61 μM) by the MTT colorimetric method. The interaction of the Ag(I) complex with ct-DNA was evaluated by spectroscopic titration and circular dichroism techniques, which suggested that it interacts weakly with DNA (Kb = 7.52 x 104 M-1) through minor groove or by electrostatic forces. In addition, competitive binding assays were performed with Hoechst 33258 and thiazole orange (TO), which exhibited 80% and 39% fluorescence suppression, respectively. Therefore, these results suggests that the Ag(I) complex interacts weakly with ct-DNA through minor groove, but this interaction is weaker than Hoechst 33258 probe.
Descrição
Palavras-chave
Câncer, Compostos de prata, Fármacos, Tiossemicarbazonas, DNA