Quinoxaline-Based Monoamine Oxidase Inhibitors: Design Strategies, Synthesis, Structure-Activity Relationships, and...

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.