| First Author | Rivera-Marrero S | Year | 2020 |
| Journal | Bioorg Med Chem | Volume | 28 |
| Issue | 20 | Pages | 115700 |
| PubMed ID | 33069076 | Mgi Jnum | J:352648 |
| Mgi Id | MGI:7704313 | Doi | 10.1016/j.bmc.2020.115700 |
| Citation | Rivera-Marrero S, et al. (2020) A new naphthalene derivative with anti-amyloidogenic activity as potential therapeutic agent for Alzheimer's disease. Bioorg Med Chem 28(20):115700 |
| abstractText | 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 Abeta(1-42) peptide and fibrils. In human microglia cells, these compounds inhibited the aggregation of Abeta(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. |
