Landi_2025_Neurotox.Res_43_12

Aminopyrimidine compounds have been gaining traction in the field of drug discovery in recent years due to their emergence as multi-targeted molecules. This makes them perfect candidates as agents for cognitive improvement, as cognitive decline is a multifaceted condition. We aim to evaluate their potential for memory enhancement, specifically through their cholinergic properties. This work examines the properties of seven aminopyrimidine derivatives and their effects on memory acquisition and retention. These compounds were administered to NMRI mice after the induction of amnesia by scopolamine, and memory impairment and improvement were assessed using passive avoidance and spontaneous alternation tests with the drug donepezil as the positive control group. These compounds were also analyzed using docking and ADME prediction studies to determine potential affinity to the acetylcholinesterase enzyme, and characterize pharmacokinetic properties, respectively. Additionally, in vitro inhibition of cholinesterase was evaluated. Results showed that three of the seven compounds significantly increased cognition in both behavioral tests. Software analysis suggested allosteric inhibition or modulation of acetylcholinesterase, signifying the potential of these compounds for further optimization and eventual utilization for treatment of cognitive impairment cases.