Targeting the multifaceted neurotoxicity of Alzheimer's disease by tailored functionalisation of the curcumin scaffold
Articolo
Data di Pubblicazione:
2023
Citazione:
Targeting the multifaceted neurotoxicity of Alzheimer's disease by tailored functionalisation of the curcumin scaffold / E. De Lorenzi, F. Seghetti, A. Tarozzi, L. Pruccoli, C. Contardi, M. Serra, A. Bisi, S. Gobbi, G. Vistoli, S. Gervasoni, C. Argentini, G. Ghirardo, G. Guarato, G. Orso, F. Belluti, R.M.C. Di Martino, M. Zusso. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 1768-3254. - 252:(2023 Apr 05), pp. 115297.1-115297.15. [10.1016/j.ejmech.2023.115297]
Abstract:
Simultaneous modulation of multifaceted toxicity arising from neuroinflammation, oxidative stress, and mitochondrial dysfunction represents a valuable therapeutic strategy to tackle Alzheimer's disease. Among the significant hallmarks of the disorder, A beta protein and its aggregation products are well-recognised triggers of the neurotoxic cascade. In this study, by tailored modification of the curcumin-based lead compound 1, we aimed at developing a small library of hybrid compounds targeting A beta protein oligomerisation and the consequent neurotoxic events. Interestingly, from in vitro studies, analogues 3 and 4, bearing a substituted triazole moiety, emerged as multifunctional agents able to counteract A beta aggregation, neuroinflammation and oxidative stress. In vivo proof-of-concept evaluations, performed in a Drosophila oxidative stress model, allowed us to identify compound 4 as a promising lead candidate.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Alzheimer's disease; Amyloid beta oligomers; Curcumin analogues; Drosophila Melanogaster model; Natural products; Neuroinflammation; Oxidative stress;
Elenco autori:
E. De Lorenzi, F. Seghetti, A. Tarozzi, L. Pruccoli, C. Contardi, M. Serra, A. Bisi, S. Gobbi, G. Vistoli, S. Gervasoni, C. Argentini, G. Ghirardo, G. Guarato, G. Orso, F. Belluti, R.M.C. Di Martino, M. Zusso
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