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 MAO-A/MAO-B inhibitory activity. In addition, molecular modeling studies
were performed to afford insight into the binding mode.
Results: The results displayed that compound 4c showed the best AChE inhibitory
activity with 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 blood-brain barrier in vitro.
Conclusion: Compound 4c deserved to further study as a potential multifunctional
agent for the treatment of Alzheimer’s disease.