A New Naphthalene Derivative With Anti-Amyloidogenic Activity As Potential Therapeutic Agent For Alzheimer'S Disease

The aggregation of beta-amyloid peptides is associated to neurodegeneration in Alzheimer's disease (AD) patients. Consequently, the inhibition of both oligomerization and fibrillation of beta-amyloid peptides is considered a plausible therapeutic approach for AD. Herein, the synthesis of new naphthalene derivatives and their evaluation as anti-beta-amyloidogenic agents are presented. Molecular dynamic simulations predicted the formation of thermodynamically stable complexes between the compounds, the A beta(1-42) peptide and fibrils. In human microglia cells, these compounds inhibited the aggregation of A beta(1-42) peptide. The lead compound 8 showed a high affinity to amyloid plaques in mice brain ex vivo assays and an adequate log P-oct/PBS value. Compound 8 also improved the cognitive function and decreased hippocampal beta-amyloid burden in the brain of 3xTg-AD female mice. Altogether, our results suggest that 8 could be a novel therapeutic agent for AD.