Novel beta-amyloid aggregate inhibitors for Alzheimer’s disease
RMS Wong1, HW Li1, DWJ Kwong1, KKL Yung2, Y Ke3
1 Department of Chemistry, Hong Kong Baptist University
2 Department of Biology, Hong Kong Baptist University
3 School of Biomedical Sciences, The Chinese University of Hong Kong
1. Carbazole-based cyanines offer neuroprotection against amyloid-β-induced toxicity; thus, they have a potential role in the treatment of Alzheimer’s disease.
2. We designed, synthesised, and screened more than 30 carbazole-based cyanines for effective and potent amyloid-β peptide oligomerisation and aggregation inhibitors.
3. Of these, six carbazole-based cyanines that were non-toxic, brain penetrable, and neuroprotective against amyloid-β-induced toxicity were identified as potential candidates for further clinical development.
4. Mice treated with one neuroprotective carbazole-based cyanine, SLM, showed improvement in cognitive functions, decrease in oligomeric amyloid-β contents and t-tau and p-tau proteins, particularly in the cerebral hippocampal region.