Background: Due to the complex etiology of AD, multi-target-directed ligands
(MTDLs), combining two or more distinct pharmacological moieties, have been developed in both
symptomatic and disease-modifying efficiencies and are considered as an effective way for the
treatment of AD.
Methods: To test their biological activities, including AChE/BChE inhibitory activity and MAOA/
MAO-B inhibitory activity. In addition, molecular modeling studies were performed to afford
insight into the binding mode.
Results and Discussions: The results displayed that compound 4c showed the best AChE inhibitory
activity with an IC50 value of 4.2 μM, which was supported by the kinetic study and docking study.
Compound 4c was also a selective MAO-B inhibitor (IC50 = 8.2 μM). Moreover, compound 4c
could cross the blood-brain barrier in vitro.
Conclusion: Compound 4c deserved to further study as a potential multifunctional agent for the
treatment of Alzheimer’s disease.