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Cholinesterase and Neurodegenerative Diseases · Journal article
Chemistryselect · July 1, 2026
Raises a question worth testing. It does not answer one.
This is a narrative review of triazole-based chemical structures and their in vitro inhibition of key Alzheimer's-related enzymes (acetylcholinesterase, butyrylcholinesterase, MAO, BACE-1). The authors propose that triazole scaffolds with specific substituents (electron-donating, halogen, methoxy groups) warrant further investigation as multitarget-directed ligands, but no clinical evidence, animal models, or direct demonstration of disease-modifying activity in humans is presented.
Journal article.
Triazole hybrids with electron-donating, halogen, or methoxy substituents exhibit marked inhibition of key AD-related enzymes. Current AD pharmacological therapies are mainly symptomatic relief, highlighting need for multitarget-directed ligands. Triazole derivatives are characterized by chemical stability, favorable bioavailability potential, and capacity for hydrogen bonds and π–π interactions in enzyme active sites.
Current AD pharmacological therapies are mainly symptomatic relief, highlighting need for multitarget-directed ligands.
The source did not state who this applies to in practice.
A review of chemical structures and in vitro enzyme inhibition data supporting triazole compounds as potential AD agents, without clinical trial evidence or in vivo efficacy demonstration.
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ABSTRACT Alzheimer's disease (AD) is a degenerative neurological disorder characterized by loss of memory, cognitive decline, and differences in behavior that mainly affects the elderly. The multifactorial etiology of AD includes the aggregation of amyloid‐β, tau hyperphosphorylation, oxidative stress, cholinergic dysfunction, and neurotransmitter imbalances resulting from monoamine oxidase activity. Current pharmacological therapies are mainly symptomatic relief, highlighting the need for multitarget‐directed ligands. Triazole derivatives, known as nitrogen‐containing heterocyclic compounds, are gaining attention as viable therapeutic agents in modern drug design because of their chemical stability, possibly favorable bioavailability, and their ability to participate in hydrogen bonds and π–π interactions in the active sites of all the enzymes. This review will attempt to highlight the most recent advancements in triazole‐based analogues that target key enzymes involved in AD, including acetylcholinesterase, butyrylcholinesterase, MAO, and β‐site amyloid precursor protein cleaving enzyme‐1. Most notable structure–activity relationship studies have demonstrated that triazole hybrids that have electron‐donating, halogen, or methoxy substituents exhibit marked inhibition and perceived neuroprotective activity. These findings support the use of triazole scaffolds as a unique and versatile framework for developing multifunctional anti‐Alzheimer agents with perceived disease‐modifying activity.
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