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Síntese, caracterização e avaliação biológica de complexos de Prata (I) e Rénio (I) como potenciais agentes anticancerígenos

2025Dissertação de mestrado Acesso embargado
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dc.contributor.advisorValente,Andreia Marques
dc.contributor.authorLino,Daniela Alexandra Esteves Ferreira
dc.contributor.institutionFaculdade de Ciências
dc.contributor.institutionDepartamento de Química e Bioquímica
dc.date.accessioned2026-05-18T16:05:01Z
dc.date.available2026-05-18T16:05:01Z
dc.date.issued2025
dc.descriptionTese de Mestrado, Química, 2025, Universidade de Lisboa, Faculdade de Ciências
dc.description.abstractCancer remains one of the leading causes of mortality worldwide, making the search for new therapeutic agents with antitumor activity a central topic in Bioorganometallic Chemistry. Although platinum-based compounds such as cisplatin remain widely used in chemotherapy, their adverse effects and the development of resistance have driven the exploration of complexes involving other transition metals. In this context, this thesis focused on the synthesis and characterization of new silver(I) and rhenium(I) complexes, aiming at their application as potential anticancer agents due to their ability to modulate different biological targets. Initially, it was explored the stability of silver(I) complexes in biologically relevant media such as DMSO + H2O and DMSO + PBS. It was found that although stable in DMSO + H2O, the complexes exhibited low solubility and instability in PBS. Attempts at encapsulation using Kolliphor® HS 15 and the development of Metal-Organic Framework (MOF) did not result in significant improvements in either stability or solubility. These results highlight the challenges associated with the direct biological application of these complexes, underscoring the need for more effective synthetic strategies and novel approaches to improve their solubility and stability. In another approach, the research focused on the synthesis and characterization of new rhenium(I) complexes of the type fac-[Re(CO)3(N-N)(L)][CF3SO3], where N-N corresponds to 4,4’-dimethyl or 4,4’-dimethoxy-2,2’-bipyridine and L to the axial ligand 4-(4-nitrobenzyl)pyridine (complexes DL10 and DL12). The complexes were obtained with modest yields but with purity greater than 92%. Stability studies in DMSO and in cell culture medium (DMEM + DMSO 90%/10%) demonstrated adequate stability, enabling further biological testing. In biological assays, the complexes were tested in the MDA-MB-231 cell line, representative of triple-negative breast cancer. Cell viability (IC50) and colony formation capacity were evaluated. The complexes demonstrated relevant cytotoxic activity, with the final products (DL10 and DL12) showing higher efficacy than the intermediates (DL9 and DL11, with L = Br). In colony formation assays, DL9 and DL11 showed strong inhibition of cell proliferation, whereas DL10 and DL12 appeared to exert a more cytostatic than cytotoxic effect. This thesis contributed to the advancement of Bioorganometallic Chemistry by demonstrating the potential of silver(I) and rhenium(I) complexes as anticancer agents, particularly for the treatment of triple-negative breast cancer. While silver complexes face serious challenges in terms of stability and solubility, the rhenium(I) compounds proved more promising in a biological context, representing an interesting alternative to conventional chemotherapy.en
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dc.identifier.urihttp://hdl.handle.net/10400.5/118597
dc.identifier.urlhttp://hdl.handle.net/10400.5/118597
dc.language.isopor
dc.subjectSilve(I) complexes
dc.subjectRhenium(I) complexes
dc.subjectAnticancer agents
dc.subjectMetal-Organic Frameworks (MOFs)
dc.titleSíntese, caracterização e avaliação biológica de complexos de Prata (I) e Rénio (I) como potenciais agentes anticancerígenospt
dc.typemaster thesis
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