DefinePK

Abstract

Alzheimer’s disease (AD) is advanced neurodegenerative complaint driven by pathological mechanisms, including acetyl cholinesterase over activity and beta-Amyloid plaque formation. Existing therapeutic strategies predominantly focus on single targets, offering only symptomatic relief without addressing the multifactorial countryside of the ailment. In this context, the present study aims to develop benzyl Piperazine-based results as promising multi-target-directed ligands (MTDLs) for AD management. A rational design is used to synthesize series of benzyl Piperazine derivatives, followed by extensive in silico evaluations comprising molecular docking and molecular dynamics simulation to examine their dual inhibitory possible against acetylcholinesterase (AChE) and beta-Amyloid (Aβ1–42) combination. The results revealed that several designed molecules exhibited superior binding affinities and stable interactions with both target proteins, surpassing the performance of standard inhibitors. ADMET predictions further confirmed their drug-like properties, favorable pharmacokinetic profiles, and low toxicity risks. This study is among the first to propose benzyl Piperazine-based compounds as dual-action inhibitors for AD, presenting a novel chemical scaffold with strong potential for multi-target therapeutic applications. These findings lay the groundwork for future experimental validation and open avenues in the expansion of effective disease-modifying actions for Alzheimer’s disease.