info:eu-repo/semantics/article
2’-Hydroxy-4’,5’-dimethyl-4-dimethylaminochalcone, a novel fluorescent flavonoid with capacity to detect aluminium in cells and modulate Alzheimer's disease targets
Fecha
2021-03Registro en:
Kamecki González, Fabiola Elizabeth; Marcucci, Carolina; Ferreira Gomes, Mariela Soledad; Sabatier, Laureano Leonel; Miklavcic, Damijan; et al.; 2’-Hydroxy-4’,5’-dimethyl-4-dimethylaminochalcone, a novel fluorescent flavonoid with capacity to detect aluminium in cells and modulate Alzheimer's disease targets; Elsevier Science SA; Journal of Photochemistry and Photobiology A: Chemistry; 409; 3-2021; 1-10
1010-6030
CONICET Digital
CONICET
Autor
Kamecki González, Fabiola Elizabeth
Marcucci, Carolina
Ferreira Gomes, Mariela Soledad
Sabatier, Laureano Leonel
Miklavcic, Damijan
Makarchuk, Stanislav
Monti, José Luis Eugenio
Rademacher, Maria
Marcos, Alejandra Lucía
de Tezanos Pinto, Felicitas
Gavernet, Luciana
Colettis, Natalia Claudia
Marder, Nora Mariel
Resumen
Alzheimer's disease (AD) is a progressive multifactorial neurodegenerative disorder with several factors contributing to its aetiology such as abnormal protein aggregation (e.g., β-amyloid peptide), oxidative stress, alterations in neurotransmitter levels (e.g., acetylcholine, monoamines) and ion metal accumulation in the brain (e.g., aluminium), among others. Due to the complex nature of this disease, there is a critical need to develop multitarget-directed compounds to address the alternative pathways involved. In this context, the aim of this work was to synthesise a simple chalcone derivative with capacity to affect different key targets of AD neurodegeneration. Consequently, we report here a microwave-assisted synthesis of a new chalcone derivative, namely 2’-hydroxy-4’,5’-dimethyl-4-dimethylaminochalcone (1). Compound 1 selectively chelated aluminium, inhibited the aggregation of Aβ 1-42 peptide, behaved as a radical scavenger and inhibited acetylcholinesterase in vitro. An extensive spectral study (UV/visible, fluorescence and MS) of chalcone 1/Al3+ complex as well as a molecular modelling study of its 3D conformation confirmed the structure of the complex. Additionally, chalcone 1 was capable of interacting with aluminium in cell lines HEK293 T and SH-SY5Y. In conclusion, chalcone 1 is a novel probe for the detection of Al3+ in cells and, moreover, it can be regarded as a promising multifunctional ligand for AD treatment.