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Issue 3, 2011
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Synthesis and characterization of IMPY derivatives that regulate metal-induced amyloid-β aggregation

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Abstract

Metal ions associated with amyloid-β (Aβ) species have been suggested to be involved in neurodegeneration leading to the progression of Alzheimer's disease (AD). The role of metal-involved Aβ species in AD neuropathogenesis, however, is not fully elucidated. In order to advance this understanding and contribute to the therapeutic development for AD, the rational structure-based design of small molecules that specifically target metal ions surrounded by Aβ species has recently received increased attention. To date, only a few compounds have been fashioned for this purpose. Herein, we report the design strategy, synthesis, characterization, and reactivity of new bifunctional IMPY derivatives K1 and K2. Using UV-vis and high-resolution two-dimensional (2D) NMR spectroscopy, the bifunctionality of K1 and K2 (metal chelation and Aβ interaction) was confirmed. These bifunctional IMPY derivatives showed preferential reactivity toward metal-induced Aβ aggregation over metal-free conditions in both in vitro inhibition and disaggregation experiments. Taken together, this study provides another example of a bifunctional small molecule framework that can target metal ions associated with Aβ species.

Graphical abstract: Synthesis and characterization of IMPY derivatives that regulate metal-induced amyloid-β aggregation

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Publication details

The article was received on 15 Nov 2010, accepted on 06 Dec 2010 and first published on 06 Jan 2011


Article type: Paper
DOI: 10.1039/C0MT00077A
Citation: Metallomics, 2011,3, 284-291
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    Synthesis and characterization of IMPY derivatives that regulate metal-induced amyloid-β aggregation

    J. Choi, J. J. Braymer, S. K. Park, S. Mustafa, J. Chae and M. H. Lim, Metallomics, 2011, 3, 284
    DOI: 10.1039/C0MT00077A

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