ABSTRACT: Herein, a series of novel O-alkyl ferulamide derivatives were designed and synthesised through the multi-target-directed ligands (MTDLs) strategy. The biological activities in vitro showed that compounds 5a, 5d, 5e, 5f, and 5h indicated significantly selective MAO-B inhibitory potency (IC50 = 0.32, 0.56, 0.54, 0.73, and 0.86 μM, respectively) and moderate antioxidant activity. Moreover, compounds 5a, 5d, 5e, 5f, and 5h showed potent anti-inflammatory properties, remarkable effects on self-induced Aβ1-42 aggregation, and potent neuroprotective effect on Aβ1-42-induced PC12 cell injury. Furthermore, compounds 5a, 5d, 5e, 5f, and 5h<