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Abstract A series of resveratrol dimer derivatives against Alzheimer's disease (AD) was obtained by structural modification and transformation using resveratrol as substrate. Biological analysis revealed that these derivatives had moderate inhibitory activity against human monoamine oxidase B (h MAO-B). In particular, 3 and 7 showed the better inhibitory activity for h MAO-B (IC 50 = 3.91 ± 0.23 μ M, 0.90 ± 0.01 μ M) respectively. Compound 3 (IC 50 = 46.95 ± 0.21 μ M for DPPH, 1.43 and 1.74 trolox equivalent by ABTS and FRAP method respectively), and 7 (IC 50 = 35.33 ± 0.15 μ M for DPPH, 1.70 and 1.97 trolox equivalent by ABTS method and FRAP method respectively) have excellent antioxidant effects. Cellular assay shown that 3 and 7 had lower toxicity and were resistant to neurotoxicity induced by oxidative toxins (H 2 O 2 , rotenone and oligomycin-A). More importantly, the selected compounds have neuroprotective effects against ROS generation, H 2 O 2 -induced apoptosis and a significant in vitro anti-inflammatory activity. The results of the parallel artificial membrane permeability assay for blood-brain barrier indicated that 3 and 7 would be predominant to cross the blood-brain barrier. In this study, mouse microglia BV2 cells were used to establish cell oxidative stress injury model with H 2 O 2 and to explore the protective effect and mechanism of 3 and 7. In general, 3 and 7 can be considered candidates for potential treatment of AD. Graphical abstract Image 1 Highlights • A series of resveratrol dimer derivatives against Alzheimer's disease (AD) was obtained by structural modification and transformation using resveratrol as substrate. • Most of the compounds showed moderate to good inhibitory activities against MAO-B as well as remarkable antioxidant activities. • Compounds 3 and 7 displayed a balanced multifunctional profile having MAO-B inhibition, excellent antioxidant activity. • Compounds 3 and 7 possessed significant neuroprotection against H2O2-induced oxidative damage on PC12 cells and BV2 microglial cells and Lipopolysaccharides (LPS)-stimulated inflammation on BV2 microglial cells. • Compounds 3 and 7 have lower toxicity and could cross the blood-brain barrier. [ABSTRACT FROM AUTHOR]

A series of salicyladimine derivatives were designed, synthesized and evaluated as multi-target-directed ligands for the treatment of Alzheimer’s disease (AD). Biological activity results demonstrated that some derivatives possessed significant inhibitory activities against amyloid- β (A β ) aggregation and human monoamine oxidase B ( h MAO-B) as well as remarkable antioxidant effects and low cell toxicity. The optimal compound, 5 , exhibited excellent potency for inhibition of self-induced A β 1–42 aggregation (91.3 ± 2.1%, 25 μM), inhibition of h MAO-B (IC 50 , 1.73 ± 0.39 μM), antioxidant effects (43.4 ± 2.6 μM of IC 50 by DPPH method, 0.67 ± 0.06 trolox equivalent by ABTS method), metal chelation and BBB penetration. Furthermore, compound 5 had neuroprotective effects against ROS generation, H 2 O 2 -induced apoptosis, 6-OHDA-induced cell injury, and a significant in vitro anti-inflammatory activity. Collectively, these findings highlighted that compound 5 was a potential balanced multifunctional neuroprotective agent for the development of anti-AD drugs. [ABSTRACT FROM AUTHOR]