RT Journal Article T1 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 A1 Benchekroun, Mohamed A1 Romero Hernández, Alejandro A1 Egea, Javier A1 León Martínez, Rafael A1 Michalska Dziama, Patrycja A1 Buendía, Izaskun A1 Jimeno, María Luisa A1 Jun, Daniel A1 Janockova, Jana A1 Sepsova, Vendula A1 Soukup, Ondrej A1 Bautista-Aguilera, Oscar M. A1 Refouvelet, Bernard A1 Ouari, Olivier A1 Marco Contelles, José Luis A1 Ismaili, Lhassane AB 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. YR 2016 FD 2016-10-13 LK https://hdl.handle.net/20.500.14352/97148 UL https://hdl.handle.net/20.500.14352/97148 LA eng NO Regional Council of Franche-Comté NO Instituto de Salud Carlos III NO Faculty of Military Health Sciences, University of Defence (Czech Republic) NO Bayer AG NO Fundación FIPSE NO Ministerio de Educación, Cultura y Deporte(España) DS Docta Complutense RD 23 ago 2024