Computational Design of Azole Derivatives as Multifunctional Agents for Alzheimer's Disease

ABSTRACT Alzheimer's disease ( AD ) is the most common form of dementia, characterized by multifactorial factors including oxidative stress and metal ion dysregulation. In this scenario, metal chelators have been explored as an alternative strategy to mitigate this damage. This study focuses on the computational design of azole derivatives as potential multifunctional agents targeting these key aspects of AD . Using a combination of density functional theory (DFT) and bioinformatic methods, we evaluated a series of ligands for their drug‐likeness, blood–brain barrier permeation, and interaction with copper ions, a metal implicated in oxidative stress within AD pathology. Our analysis classified the ligands into three plausible mechanisms of action: antioxidants, which disrupt copper‐induced oxidative stress; distributors, which modulate copper transport and cellular redox processes; and suppressors, which stabilize copper ions in a redox‐inactive state. Computational results indicate that most ligands exhibit favorable pharmacokinetic properties and varying degrees of copper affinity and redox behavior, aligning with these mechanisms.