Design, synthesis, and biological evaluation of novel 2-acetylphenol-rivastigmine hybrids as potential multifunctional agents for the treatment of Alzheimer's disease.

Herein, a series of 2-acetylphenol-rivastigmine hybrids were rationally designed as multifunctional agents for the treatment of AD through multi-target-directed ligands (MTDLs) strategy. The biological activity in vitro showed that compound 3c was a pseudo-irreversible and selective huAChE inhibitor (IC₅₀ = 8.7 μM). Compound 3c was also a significant antioxidant with ORAC value of 1.2 eq. Moreover, compound 3c showed potent MAO-B inhibitory activity with IC₅₀ values of 2.9 μM. In addition, compound 3c displayed selective metal chelation property. Furthermore, compound 3c showed significant neuroprotective effect on H₂O₂-induced PC12 cells injury. More importantly, compound 3c displayed favorable drug-like property and good blood brain barrier permeability in vitro. Thus, compound 3c was a promising multifunctional agent in vitro for the treatment of AD, deserving for further investigations. [ABSTRACT FROM AUTHOR]