Dual Inhibitors of Amyloid-β and Tau Aggregation with Amyloid-β Disaggregating Properties: Extended In Cellulo, In Silico, and Kinetic Studies of Multifunctional Anti-Alzheimer's Agents.

ABSTRACT: In Alzheimer's disease, neurons slowly degenerate due to the accumulation of misfolded amyloid β and tau proteins. In our research, we performed extended studies directed at amyloid β and tau aggregation inhibition using in cellulo (Escherichia coli model of protein aggregation), in silico, and in vitro kinetic studies. We tested our library of 1-benzylamino-2-hydroxyalkyl multifunctional anti-Alzheimer's agents and identified very potent dual aggregation inhibitors. Among the tested derivatives, we selected compound 18, which exhibited a unique profile of biological activity. This compound was the most potent and balanced dual aggregation inhibitor (Aβ₄₂ inhibition (inh.) 80.0%, tau inh. 68.3% in 10 μM), with previously reported in vitro

SUBMITTER: Pasieka A 

PROVIDER: S-EPMC8291496 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature