Quinoxaline-Based Monoamine Oxidase Inhibitors: Design Strategies, Synthesis, Structure-Activity Relationships, and Therapeutic Potential in Neurological Disorders: A Review From 1996 to 2026.

Publication date: Jul 14, 2026

Monoamine oxidases (MAOs) are key enzymes involved in the metabolism of neurotransmitters and play a significant role in the pathophysiology of neurological disorders such as depression, Parkinson’s disease, and Alzheimer’s disease. Inhibition of MAOs, particularly MAO-A and MAO-B, has emerged as a promising therapeutic strategy. Quinoxaline is an emerging scaffold with promising biological activities against various molecular targets, owing to its rich repertoire of bioactive molecules. Due to their favorable pharmacological profiles and structural versatility, quinoxaline derivatives have gained considerable attention among the various scaffolds explored. This review highlights rational design strategies for developing quinoxaline-based MAO inhibitors, focusing on structure-activity relationships (SARs) that govern their potency and selectivity. Modifications at specific positions of the quinoxaline ring system and the nature of substituents have demonstrated significant impacts on MAO-A versus MAO-B selectivity, metabolic stability, and blood-brain barrier permeability. This review primarily focuses on elucidating recent advancements in quinoxaline scaffolds targeting MAO inhibitors, including structural developments, structural-activity relationships (SAR), and potential therapeutic applications in neurological disorders, to help researchers develop a new generation of MAO inhibitors.

Concepts Keywords
Animals
Drug Design
Humans
MAO‐A
MAO‐B
Molecular Structure
Monoamine Oxidase
Monoamine Oxidase
Monoamine Oxidase Inhibitors
Monoamine Oxidase Inhibitors
Nervous System Diseases
neurological disorders
quinoxaline
Quinoxalines
Quinoxalines
Structure-Activity Relationship
structure–activity relationships
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Semantics

Type Source Name
disease MESH Neurological Disorders
pathway REACTOME Metabolism
disease MESH Parkinson’s disease
disease MESH Alzheimer’s disease

Original Article

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