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

MedChemComm Pub Date: 2014-08-27 DOI: 10.1039/C4MD00305E

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.

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