Issue 19, 2015

Design of a structural framework with potential use to develop balanced multifunctional agents against Alzheimer's disease

Abstract

A series of small molecules had been designed, synthesized, and evaluated as multifunctional ligands against Alzheimer's disease (AD). The results of biological activity tests showed that most of the molecules exhibited a significant ability to inhibit self-induced β-amyloid (Aβ1–42) aggregation, and to function as potential antioxidants and biometal chelators. Among these compounds, compound 3d was found to be highly potent and showed a balanced multifunctional profile covering inhibitory activity against self-induced Aβ1–42 aggregation (IC50 = 7.8 μM), strong free radical scavenging activities [IC50 (ABTS) = 1.82 μM; IC50 (DPPH) = 15.4 μM] and inhibitory activity against MAO-B (IC50 = 6.4 μM). Moreover, it showed excellent metal chelating properties and good inhibitory activity against Cu2+-induced Aβ1–42 aggregation, and was capable of decreasing reactive oxygen species (ROS) induced by Cu2+–Aβ1–42. Importantly, compound 3d was the most neuroprotective against neuronal death induced by oxidative stress and β-amyloid (Aβ1–42), and was able to cross the blood–brain barrier (BBB), according to a parallel artificial membrane permeation assay. These results indicated that compound 3d might be a promising lead compound for AD treatment.

Graphical abstract: Design of a structural framework with potential use to develop balanced multifunctional agents against Alzheimer's disease

Supplementary files

Article information

Article type
Paper
Submitted
18 Sept. 2014
Accepted
22 Janv. 2015
First published
28 Janv. 2015

RSC Adv., 2015,5, 14242-14255

Design of a structural framework with potential use to develop balanced multifunctional agents against Alzheimer's disease

N. Jiang, X. Wang, Z. Li, S. Li, S. Xie, M. Huang and L. Kong, RSC Adv., 2015, 5, 14242 DOI: 10.1039/C4RA10692J

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