American Chemical Society, Journal of Medicinal Chemistry, 21(59), p. 9967-9973, 2016
DOI: 10.1021/acs.jmedchem.6b01178
Full text: Download
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.