Investigação dos efeitos citotóxicos e mecanismos de ação de metalocomplexos em células tumorais: uma busca por novos quimioterápicos mais eficazes e seguros

• Autor(a) principal: Silva, Clara Maria Faria
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFU
• Texto Completo: https://repositorio.ufu.br/handle/123456789/40965; http://doi.org/10.14393/ufu.di.2023.659
• topic: Docking molecular; autofagia; espécies reativas de oxigênio; metais de transição; Molecular docking; autophagy; reactive oxygen species; antitumor; transition metals; antitumoral; CNPQ::CIENCIAS BIOLOGICAS::GENETICA; Genética; Dinâmica molecular; Marcadores biológicos de tumor; Câncer - Aspectos moleculares; ODS::ODS 3. Saúde e bem-estar - Assegurar uma vida saudável e promover o bem-estar para todos, em todas as idades.

Cancer has become one of the diseases that most affects people around the world. A widely used treatment alternative is the use of chemotherapy drugs, however, these medications have several side effects, which encourages the search for new molecules that are more effective and safer for the individual. Therefore, the use of metallocomplexes appears to be very promising, as well as unveiling their mechanisms of action. The objective of this work was to investigate the binding characteristics and cytotoxic effects of various metallocomplexes and analyze the mechanisms of action of the CUDOXPHEN complex. For this purpose, in silico tests such as molecular docking and in vitro tests such as cytotoxicity, cell cycle analysis, quantification of reactive oxygen species and autophagic pockets and apoptosis and necrosis assay were used. The results obtained showed a low cytotoxicity of several metallocomplexes and an undesirable selectivity index, however the CUDOXPHEN complex demonstrated moderate cytotoxicity for several tumor types. Furthermore, this compound shows a significant production rate of reactive oxygen species and autophagic pockets as the treatment concentration increases. It is also seen that CUDOXPHEN has the ability to reduce the growth of tumor cells and trap them in the G0-G1 phase of the cell cycle. The negative results of most of the compounds tested show the difficulty in finding molecules with antineoplastic capacity, however the results from CUDOXPHEN show promise for its use as a chemotherapy drug, although for future studies the selectivity of the metallocomplex must be improved or analyzed a possible form of delivery capable of helping to increase your selectivity.