Novos complexos de prata (I) contendo tiosemicarbazonas derivados do cinamaldeído: síntese, caracterização e estudos biológicos preliminares
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Data
2023-01-13
Autores
Silva, Heitor Burim
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Universidade Estadual Paulista (Unesp)
Resumo
De acordo com a Organização Mundial da Saúde (OMS), o Câncer é a segunda doença que mais causa mortes no mundo, cuja estimativa baseia-se em 9,6 milhões de mortes por ano, podendo também ser explicado como 1 morte por Câncer a cada 6 registradas. Cirurgia, quimioterapia e radioterapia são as opções mais conhecidas para o tratamento da doença, podendo ser realizados sozinhos ou combinados. Particularmente, a quimioterapia tem como objetivo erradicar as células tumorais sem causar prejuízo às normais. Contudo, grande parte dos fármacos antitumorais exerce seus efeitos de modo não específico, provocando lesões tanto as células tumorais quanto as normais. Apesar da sua importância em diversos regimes quimioterápicos, a cisplatina também é conhecida pela sua baixa seletividade e efeitos colaterais. Neste sentido, esforços vêm sendo direcionados na busca por novos complexos metálicos, contendo platina ou não, capazes de exercer seus efeitos citotóxicos de forma mais seletiva. Estudos vêm apontando compostos de prata (I) como candidatos promissores para o desenvolvimento de novos metalofármacos antitumorais. A escolha adequada dos ligantes que compõem o complexo de prata é crucial para garantir propriedades importantes para a bioatividade como, por exemplo, lipofilicidade e estabilidade hidrolítica. Neste trabalho, foi sintetizado um complexo de prata de formula geral [Ag(cTSC)(Neo)]NO3, onde cTSC = Tiosemicarbazona derivada do cinamaldeido; neo = Neocuproína, com a finalidade de avaliar seus efeitos em células tumorais e sua capacidade de interação com o DNA. O complexo foi caracterizado pelas técnicas de análise elementar, espectroscopia no IV e de RMN-1H. Estudo de comportamento em solução demonstraram que o composto não sofre alterações significativas em sua estrutura quando dissolvido em DMSO, onde DMSO = dimetilsulfóxido. O índice de citotoxicidade (IC50) do complexo sobre células tumorais A549 foi de 4,0±0,2 M, sendo mais ativo que a cisplatina. Ensaios de competição entre o complexo e o aduto DNA-Hoescht sugerem que o complexo possui uma baixa afinidade pelo DNA.
According to the World Health Organization (WHO), Cancer is the second disease that causes the most deaths in the world, whose estimate is based on 9.6 million deaths, which can also be explained as 1 death from Cancer in every 6 recorded. Surgery, chemotherapy and radiotherapy are the best known options for treating the disease, and can be administered alone or combined. Chemotherapy aims to eradicate tumor cells without harming normal ones. However, most antitumor drugs exert their effects in a non-specific way, causing damage to both tumor and healthy cells. Despite its importance in several chemotherapy regimens, cisplatin is also known for its low selectivity and side effects. In this sense, efforts have been directed towards the search for new metallic complexes, containing platinum or not, capable of exerting their cytotoxic effects in a more selective way. Studies have pointed to silver (I) compounds as promising candidates for the development of new antitumor metallopharmaceuticals. The proper choice of ligands that make up the silver complex is crucial to ensure important properties for bioactivity, such as lipophilicity and hydrolytic stability. In this work, a silver complex with the general formula [Ag(cTSC)(Neo)]NO3 was synthesized, where cTSC = Thiosemicarbazone derived from cinnamaldehyde; neo = Neocuproin, in order to evaluate its effects on tumor cells and its ability to interact with DNA. The complex was characterized by elemental analysis, IR, and 1H-NMR spectroscopy. Behavior studies in solution showed that the compound does not undergo significant changes in its structure when dissolved in DMSO, where DMSO = dimethylsulfoxide. The cytotoxicity index (IC50) of the complex on tumor cells A549 was 4.0±0.2 M, being more active than cisplatin. Competition assays between the complex and the DNA-Hoescht adduct suggest that the complex has a low affinity for DNA.
According to the World Health Organization (WHO), Cancer is the second disease that causes the most deaths in the world, whose estimate is based on 9.6 million deaths, which can also be explained as 1 death from Cancer in every 6 recorded. Surgery, chemotherapy and radiotherapy are the best known options for treating the disease, and can be administered alone or combined. Chemotherapy aims to eradicate tumor cells without harming normal ones. However, most antitumor drugs exert their effects in a non-specific way, causing damage to both tumor and healthy cells. Despite its importance in several chemotherapy regimens, cisplatin is also known for its low selectivity and side effects. In this sense, efforts have been directed towards the search for new metallic complexes, containing platinum or not, capable of exerting their cytotoxic effects in a more selective way. Studies have pointed to silver (I) compounds as promising candidates for the development of new antitumor metallopharmaceuticals. The proper choice of ligands that make up the silver complex is crucial to ensure important properties for bioactivity, such as lipophilicity and hydrolytic stability. In this work, a silver complex with the general formula [Ag(cTSC)(Neo)]NO3 was synthesized, where cTSC = Thiosemicarbazone derived from cinnamaldehyde; neo = Neocuproin, in order to evaluate its effects on tumor cells and its ability to interact with DNA. The complex was characterized by elemental analysis, IR, and 1H-NMR spectroscopy. Behavior studies in solution showed that the compound does not undergo significant changes in its structure when dissolved in DMSO, where DMSO = dimethylsulfoxide. The cytotoxicity index (IC50) of the complex on tumor cells A549 was 4.0±0.2 M, being more active than cisplatin. Competition assays between the complex and the DNA-Hoescht adduct suggest that the complex has a low affinity for DNA.
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Palavras-chave
Complexos metálicos, Câncer, Agentes antineoplásicos, Prata, DNA