Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that involves different pathogenic mechanisms. In this regard, the goal of this study was the design and synthesis of new compounds with multifunctional pharmacological activity by molecular hybridization of structural fragments of curcumin and resveratrol connected by an N-acyl-hydrazone function linked to a 1,4-disubstituted triazole system. Among these hybrid compounds, derivative 3e showed the ability to inhibit acetylcholinesterase activity, the intracellular formation of reactive oxygen species as well as the neurotoxicity elicited by Aβ42 oligomers in neuronal SH-SY5Y cells. In parallel, compound 3e showed a good profile of safety and ADME parameters. Taken together, these results suggest that 3e could be considered a lead compound for the further development of AD therapeutics.

Design, Synthesis and Biological Evaluation of Novel Triazole N-acylhydrazone Hybrids for Alzheimer's Disease

Letizia Pruccoli;Andrea Tarozzi
;
2020

Abstract

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that involves different pathogenic mechanisms. In this regard, the goal of this study was the design and synthesis of new compounds with multifunctional pharmacological activity by molecular hybridization of structural fragments of curcumin and resveratrol connected by an N-acyl-hydrazone function linked to a 1,4-disubstituted triazole system. Among these hybrid compounds, derivative 3e showed the ability to inhibit acetylcholinesterase activity, the intracellular formation of reactive oxygen species as well as the neurotoxicity elicited by Aβ42 oligomers in neuronal SH-SY5Y cells. In parallel, compound 3e showed a good profile of safety and ADME parameters. Taken together, these results suggest that 3e could be considered a lead compound for the further development of AD therapeutics.
Matheus de Freitas Silva; Ellen Tardelli Lima; Letizia Pruccoli; Newton G Castro; Marcos Jorge R Guimarães; Fernanda M R da Silva; Nathalia Fonseca Nadur; Luciana Luiz de Azevedo; Arthur Eugen Kümmerle; Isabella Alvim Guedes; Laurent Emmanuel Dardenne; Vanessa Silva Gontijo; Andrea Tarozzi; Claudio Viegas
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/794733
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