Design and Synthesis of Dimeric Inhibitors against β-Amyloid Aggregation
Date Issued
2011
Date
2011
Author(s)
Tsai, Ya-Ju
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder and it is associated with β-amyloid (Aβ) aggregation. Aβ peptides are prone to self-aggregation, in vivo and in vitro. Aggregation of Aβ in the brain is considered the primary influence on driving AD pathogenesis. Thus, design and synthesis of potent inhibitors against Aβ aggregation is a therapeutic strategy for AD.
In this study, homodimers of caffeic acid (CA) with different linkers, some rosmarinic acid (RA) analogues and 5-((2-aminoethyl)amino)naphthalene-1-sulfonic acid (EDANS) derivatives were synthesized. Inhibition of Aβ aggregation was evaluated by thioflavin T fluorescence assay. The results revealed that dimeric CA inhibitors are more efficient than CA molecule. The assay results also indicated that RA and its analogues have ability to inhibit Aβ aggregation. In addition, modified EDANS with benzyl and naphthylmethyl amines have better efficiency than EDANS. These findings suggest that the designed inhibitors could be used to inhibit Aβ aggregation. Further development of these compounds may promise a novel therapeutic intervention for AD and other neurodegeneration diseases.
Subjects
nerodegenerative disease
β-amyloid (Aβ)
inhibitor
Type
thesis
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