Dual MAO-A and MAO-B Inhibition by Newly Synthesized Heterocyclic Acetamide Derivatives of Morpholine: In Vitro and In Silico Insights

Abstract

Monoamine oxidase (MAO) enzymes are important targets for the treatment of neurological disorders such as Parkinson's disease and depression. This study investigates a series of newly synthesized heterocyclic acetamide derivatives of morpholine (1a–1n) for their potential as neuroprotective agents through MAO-A and MAO-B inhibition. The compounds were evaluated in vitro for their inhibitory activity against both MAO isoforms. Results indicated that several compounds particularly 1e, 1i, and 1m exhibited significant inhibition, with 1f showing selectivity for MAO-A and 1l for MAO-B. Molecular docking studies were performed on human MAO-A and MAO-B to explore binding interactions. Compounds 1i and 1m demonstrated strong binding affinities, comparable or superior to reference inhibitors clorgyline and deprenyl. The findings suggest that these morpholine-based acetamide derivatives represent promising scaffolds for the development of novel MAO inhibitors with potential applications in the treatment of neurodegenerative and affective disorders.