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Updated: Jun 10, 2026

A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis
Published on: May 22, 2018
Structural optimization and biological evaluation of substituted bisphenol A derivatives as beta-amyloid peptide
Yu Zhou1, Chunyi Jiang, Yaping Zhang
1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Abstract:
The aggregation of Abeta is a crucial step in the etiology of Alzheimer's disease. Our previous work showed that Abeta undergoes alpha-helix/beta-sheet intermediate structures during the conformational transition, and an Abeta aggregation inhibitor (1) was discovered by targeting the intermediates. Here, structure optimization toward compound 1 was performed and 34 novel derivatives were designed and synthesized. Nine compounds showed more effective inhibitory activity than the hit compound 1 in ThT fluorescence assay. Among them, compound 43 demonstrated more excellent inhibitory potency, which not only can suppress the aggregation of Abeta but also can dissolve the preformed fibrils as shown by CD spectroscopy, PICUP and AFM assays. Cellular assay indicated that 43 has no toxicity to neuronal cells, moreover, can effectively inhibit Abeta(1-42)-induced neutrotoxicity and increase the cell viability. Together, on the basis of these positive results, these novel chemical structures may provide a promising potential for therapeutic applications in AD and other types of neurodegenerative disorders.
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