The Antioxidant Additive Approach for Alzheimer's Disease Therapy: New Ferulic (Lipoic) Acid Plus Melatonin Modified Tacrines as Cholinesterases Inhibitors, Direct Antioxidants, and Nuclear Factor (Erythroid-Derived 2)-Like 2 Activators

Affiliation auteurs!!!! Error affiliation !!!!
TitreThe Antioxidant Additive Approach for Alzheimer's Disease Therapy: New Ferulic (Lipoic) Acid Plus Melatonin Modified Tacrines as Cholinesterases Inhibitors, Direct Antioxidants, and Nuclear Factor (Erythroid-Derived 2)-Like 2 Activators
Type de publicationJournal Article
Year of Publication2016
AuteursBenchekroun M, Romero A, Egea J, Leon R, Michalska P, Buendia I, Jimeno MLuisa, Jun D, Janockova J, Sepsova V, Soukup O, Bautista-Aguilera OM, Refouvelet B, Ouari O, Marco-Contelles J, Ismaili L
JournalJOURNAL OF MEDICINAL CHEMISTRY
Volume59
Pagination9967-9973
Date PublishedNOV 10
Type of ArticleArticle
ISSN0022-2623
Résumé

Novel multifunctional tacrines for Alzheimer's disease were obtained by Ugi-reaction between ferulic (or lipoic acid), a melatonin-like isocyanide, formaldehyde, and tacrine derivatives, according to the antioxidant additive approach in order to modulate the oxidative stress as therapeutic strategy. Compound 5c has been identified as a promising permeable agent showing excellent antioxidant properties, strong cholinesterase inhibitory activity, less hepatotoxicity than tacrine, and the best neuroprotective capacity, being able to significantly activate the Nrf2 transcriptional pathway.
DOI10.1021/acs.jmedchem.6b01178