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
2016
Abstrakt
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.