New Tacrine Dimers Alleviate the Intracellular Amyloid-β-induced Cognitive Disturbance and Oxidative Stress in Mice.

Abstract

This study aimed to investigate <italic>in vivo</italic> and <italic>ex-vivo</italic> the effects of tacrine dimers (TD1, TD2, TD3 and TD4) in mice with Alzheimer's disease (AD) induced by amyloid peptide (A<italic>&#x3b2;</italic>42) and, respectively, evaluated in behavioral tests of cognition, oxidative stress and neuroinflammation. All dimers reduced the cognitive deficit caused by A<italic>&#x3b2;</italic>42, oxidative stress and neuroinflammation, especially the compound TD4. By ADMET analysis (SwissADME and pkCSM 2.10 platforms), TD4 exhibited favorable pharmacokinetic properties with the control drug. The results suggest a therapeutic potential for AD for these compounds, given their distinct cognitive and neuroprotective effects in AD models induced by A<italic>&#x3b2;</italic>42.