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Neurotox Res ; 37(4): 893-903, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31853730

RESUMO

The level of acetylcholine, a neurotransmitter essential for processing memory and learning, is lower in the brains of patients with Alzheimer's disease due to the higher concentration of the enzyme acetylcholinesterase. The main compounds used for Alzheimer's treatment are acetylcholinesterase inhibitors. Quercetin coordination complexes with the metal ions Cu+2, Zn+2, Ni+2, Co+2, and Fe+2 were synthesized to investigate their potential use against Alzheimer's disease, by evaluating the inhibition of acetylcholinesterase in vitro and in silico, as well as the antioxidant activity, toxicity, and anxiolytic action in the zebrafish (Danio rerio) model. The organic complexes were characterized by UV-Vis and FT-IR. The spectral information suggested that coordination of metals occurs with the carbonyl group and OH linked to the C-3 carbon of quercetin. The quercetin-Fe (QFe) complex presented the best antioxidant and antiacetylcholinesterase actions, and these results were confirmed by molecular docking. In the toxicity and locomotor evaluation, the quercetin molecules and the synthesized complexes, mainly QCu and QZn derivatives, showed the highest degree of inhibition of the fish's locomotor activity, suggesting a possible anxiolytic action. Then, quercetin complexes with metals, mainly with Fe+2, represent valuable compounds and deserve more investigation as promising agents against Alzheimer's disease.


Assuntos
Ansiolíticos/síntese química , Antioxidantes/síntese química , Inibidores da Colinesterase/síntese química , Simulação por Computador , Complexos de Coordenação/síntese química , Compostos de Ferro/síntese química , Animais , Ansiolíticos/toxicidade , Antioxidantes/toxicidade , Inibidores da Colinesterase/toxicidade , Complexos de Coordenação/toxicidade , Avaliação Pré-Clínica de Medicamentos/métodos , Compostos de Ferro/toxicidade , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Simulação de Acoplamento Molecular/métodos , Estrutura Secundária de Proteína , Quercetina , Peixe-Zebra
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