Complexos de rutênio funcionalizados como potenciais agentes fototerapêuticos

• Ano de defesa: 2024
• Autor(a) principal: Oliveira, Geângela de Fátima Sousa
• Orientador(a): Sousa, Eduardo Henrique Silva de
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Área do conhecimento CNPq: CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
• Link de acesso: http://repositorio.ufc.br/handle/riufc/80423

During the last decades, ruthenium metal complexes have been extensively investigated, with polypyridine compounds standing out for their potential applications as anticancer, antiviral and antibacterial agents. New strategies, including the use of light, have been developed to enhance cytotoxicity with increasead target selectivity and lower toxicity. In order to combine these properties, two polypyridine complexes of ruthenium containing conjugated anthracene were synthesized, GRBA = [Ru(bpy)2(bpy-anth)](PF6)2 and GRPA = [Ru(phen)2(bpy-anth)](PF6)2, linkers: (bpy-anth = 4'-methyl-N-(anthracen-2-yl)-[2,2'bipyridine]-4-carboxamide; bpy = 2,2'-bipyridine; phen = 1,10-phenanthroline). These complexes characterized by UV-vis and infrared spectroscopy, emission spectroscopy, nuclear magnetic resonance and cyclic voltammetry. The GRPA complex showed very high singlet oxygen photogeneration (blue light, Δ = 0.95) measured using the SOSG probe in water, while GRBA demonstrated 1.8 times higher efficiency in photogenerating superoxide radicals. Additionally, DNA interaction studies revealed that GRBA did not exhibit measurable binding to genomic DNA, whereas GRPA displayed an association constant of Kb = 4.51 × 104, suggesting intercalation with genomic DNA. Experiments with G-quadruplex DNA sequences, particularly hTel and 22AG, showed significant interactions and stabilization, with evident selectivity over duplex DNA. In addition, this complex was shown to be lipophilic (logP = +0.310) when compared to GRBA (logP = -0.018), showing promising characteristics for good cell permeability. In antimicrobial tests, the complexes exhibited notable antibacterial activity, including a synergistic effect when combined with commercial antibiotics. On the other hand, GRBA showed potent cytotoxic activity under blue light irradiation, with IC50 values of 43 nmol L⁻¹ and 13 nmol L⁻¹ for MDA-MB-231 (triple-negative breast cancer) and A2780 (ovarian cancer) cells, respectively. These promising findings illustrate an impressive 130-fold increase in biological activity under blue light for a simple modification in the ruthenium polypyridine complex, underscoring the need for further studies to explore their therapeutic potential.