Herein, a series of novel -alkyl ferulamide derivatives were designed and synthesised through the multi-target-directed ligands (MTDLs) strategy. The biological activities showed that compounds , , , , and indicated significantly selective MAO-B inhibitory potency (IC = 0.32, 0.56, 0.54, 0.73, and 0.86 μM, respectively) and moderate antioxidant activity. Moreover, compounds , , , , and showed potent anti-inflammatory properties, remarkable effects on self-induced A aggregation, and potent neuroprotective effect on A-induced PC12 cell injury. Furthermore, compounds , , , , and presented good blood-brain barrier permeation and drug-like properties. More interesting, the PET/CT images with [C] demonstrated that [C] could penetrate the BBB with a high brain uptake and exhibited good brain clearance kinetic property. Therefore, compound would be a promising multi-functional agent for the treatment of AD.
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| http://dx.doi.org/10.1080/14756366.2022.2073442 | DOI Listing |
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