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Piano-stool metal complexes as inhibitors of amyloid-β aggregation in vitro and in vivo Vigueras, Gloria Sabaté Lagunas, Raimon Barrios Moreno, Leoní Alejandra Caballero Hernández, Ana Belén Hernández García, Samanta Bayón Rueda, Joan Pau Gandía Herrero, Fernando Ruiz, José Gámez Enamorado, Patrick Metalls de transició Osmi Terapèutica Malaltia d'Alzheimer Transition metals Osmium Therapeutics Alzheimer's disease Alzheimer’s disease (AD) is the most common form of dementia worldwide. There is currently no cure for this neurodegenerative disorder, and the available therapies only temporarily lessen some symptoms rather than stopping the disease’s progression. One of the pathological hallmarks in AD brains is the formation of amyloid-β plaques. Transition-metal complexes have aroused great interest as potential chemical modulators of Aβ aggregation thanks to intrinsic features such as the metal oxidation state or the coordination geometry. Four related piano-stool complexes with different metal ions, namely Ru(II), Os(II), Ir(III) and Rh(III), were prepared and their inhibition properties of Aβ aggregation were investigated. It was found that all of them favour an alternative folding pathway, impeding the formation of mature fibres. Moreover, the metal centre seems to play a crucial role in their inhibiting activities. Ru(II) (1), Ir(III) (3) and Rh(III) (4) compounds were remarkable inhibitors of Aβ aggregation in vitro, most particularly 4, and they appear to share the inhibitory mechanism. However Os(II) complex 2 acts differently on the Aβ aggregation process. In vivo studies using a Caenorhabditis elegans animal model of AD revealed the potential of complexes 2 and 4, with 2 exhibiting better inhibition potential than 4, thus illustrating the possible occurrence of additional variables to the aggregation process when moving from in vitro experiments to a living organism. To the best of our knowledge, 2 is the first osmium complex reported as an effective inhibitor of amyloid-β aggregation both in vitro and in vivo. 2025-11-04T11:17:43Z 2025-11-04T11:17:43Z 2025-11-04 2025-11-04T11:17:44Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 2052-1553 https://hdl.handle.net/2445/224063 749902 eng Reproducció del document publicat a: https://doi.org/10.1039/D4QI01460J Inorganic Chemistry Frontiers, 2024, vol. 11, num. 18, p. 6089-6102 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess 14 p. application/pdf Royal Society of Chemistry Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)