Morpholine chalcones emerge as selective MAO-B inhibitor leads
- Alkoxy-substituted morpholine chalcones were made by a rapid microwave route and tested against MAO enzymes, cholinesterases and BACE1.
- Most analogues favored MAO-B; lead MBC21 was a competitive, reversible inhibitor, while MBC24 hit several targets.
- Docking and dynamics linked selectivity to hydrophobic contacts and stacking with Tyr326; microsomal stability and PAMPA-BBB suggested moderate brain permeability.
💡 Points Based on the abstract
Chalcones carry a Michael-acceptor enone, so a glutathione-trapping assay and a jump-dilution washout would test the reversibility claim for MBC21. The Tyr326 stacking story currently rests on modeling. A matched alkoxy-chain series benchmarked against reference MAO-B inhibitors such as safinamide would show whether this chemotype adds anything new.