Chromone-based monoamine oxidase B inhibitor with potential iron-chelating activity for the treatment of Alzheimer's disease.

Based on the multitarget-directed ligands (MTDLs) strategy, a series of chromone-hydroxypyridinone hybrids were designed, synthesised, and evaluated as potential multimodal anti-AD ligands. Prospective iron-chelating effects and favourable monoamine oxidase B (MAO-B) inhibitory activities were observed for most of the compounds. Pharmacological assays led to the identification of compound , which exhibited favourable iron-chelating potential (pFe = 18.52) and selective MAO-B inhibitory activity (IC = 67.02 ± 4.3 nM, SI = 11). Docking simulation showed that occupied both the substrate and the entrance cavity of MAO-B, and established several key interactions with the pocket residues. Moreover, was determined to cross the blood-brain barrier (BBB), and can significantly ameliorate scopolamine-induced cognitive impairment in AD mice. Despite its undesired pharmacokinetic property, remains a promising multifaceted agent that is worth further investigation.