Insights into the Structure-Activity Relationship of Alkynyl-Coumarinyl Ethers as Selective MAO-B Inhibitors Using Molecular Docking

Coumarins are considered a highly privileged and versatile scaffold by medicinal chemists. A considerable number of studies have highlighted the synthesis and the various pharmacological activities of coumarins as promising drug candidates for treating neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. A wide range of compounds based on the coumarin ring system have been found to possess biological activities such as anticonvulsant, antiviral, anti-inflammatory, antibacterial, antioxidant as well as monoamine oxidase inhibitory properties. Their promise as a novel drug for neurodegenerative diseases is demonstrated by many drug candidates that made it to clinical trials such as nodakenin that have been potent for demoting memory impairment. This study focuses on some synthesized alkynyl-coumarinyl ethers with promising MAO-B inhibitory activity and selectivity and aims to elucidates the molecular interactions of ether-connected coumarins behind obtaining remarkably high MAO-B selectivity using molecular docking. Structure-activity relationship analysis revealed a common interaction between the selective coumarin inhibitors consisting of hydrogen bonding with Tyr-188 and Cys-172. Our findings might open new opportunities to explore for developing novel highly selective MAO-B inhibitors for the treatment of neurodegenerative diseases.

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