Dehydroabietylamine derivatives as multifunctional agents for the treatment of Alzheimer's disease

Abstract

Dehydroabietylamine derivatives have been reported to eliminate the superoxide anion (O₂⁻˙) and 1,1-dipheny-2-picrylhydrazyl radicals. In this work, several dehydroabietylamine derivatives were shown to have potent anti-oxidative activity in SH-SY5Y cells and exhibited significant inhibition of Aβ₄₂ self-mediated aggregation and the disaggregation of Aβ₄₂ aging fibrils. In particular, the compound 12N,18N-bis(caffeoyl)-14-nitrodehydroabietylamine (3b) showed the most potent inhibitory activity against Aβ₄₂ self-mediated aggregation with an IC₅₀ value of 3.96 ± 0.33 μM. Compound 3b decreased the production of Aβ₄₂ in swAPP HEK293 cells and showed neuroprotective activity against Aβ₄₂-induced cytotoxicity. Through reducing the production of the Aβ₄₂ species, compound 3b alleviated Aβ₄₂-induced paralysis in transgenic Caenorhabditis elegans strain CL4176. Considering its multifunctional activity and low cytotoxicity, 3b is considered to be a potential multifunctional agent for the treatment of Alzheimer's disease.