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 (IC(50) = 0.32, 0.56, 0.54, 0.73, and 0.86 microM, respectively) and moderate antioxidant activity. Moreover, compounds 5a, 5d, 5e, 5f, and 5h showed potent anti-inflammatory properties, remarkable effects on self-induced Abeta(1-42) aggregation, and potent neuroprotective effect on Abeta(1-42)-induced PC12 cell injury. Furthermore, compounds 5a, 5d, 5e, 5f, and 5h presented good blood-brain barrier permeation in vitro and drug-like properties. More interesting, the PET/CT images with [(11)C]5f demonstrated that [(11)C]5f could penetrate the BBB with a high brain uptake and exhibited good brain clearance kinetic property. Therefore, compound 5f would be a promising multi-functional agent for the treatment of AD.
        
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Zhu G, Bai P, Wang K, Mi J, Yang J, Hu J, Ban Y, Xu R, Chen R, Wang C, Tang L, Sang Z (2022) Design, synthesis, and evaluation of novel O-alkyl ferulamide derivatives as multifunctional ligands for treating Alzheimer's disease J Enzyme Inhib Med Chem37: 1375-1388
Zhu G, Bai P, Wang K, Mi J, Yang J, Hu J, Ban Y, Xu R, Chen R, Wang C, Tang L, Sang Z (2022) J Enzyme Inhib Med Chem37: 1375-1388