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Issue 11, 2014
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Dehydroabietylamine derivatives as multifunctional agents for the treatment of Alzheimer's disease

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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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Supplementary files

Article information


Submitted
13 Jul 2014
Accepted
26 Aug 2014
First published
27 Aug 2014

, 2014,5, 1736-1743
Article type
Concise Article

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

Y. Cao, L. Wang, Z. Lin, F. Liang, Z. Pei, J. Xu and Q. Gu, , 2014, 5, 1736
DOI: 10.1039/C4MD00305E

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