Design, synthesis and evaluation of salicylic acid-donepezil hybrids as functional agents for the treatment of Alzheimer ’s disease

AbstractIn this work, a series of salicylic acid derivatives was designed through the multi-target-directed ligand strategy (MTDLs). The synthesized compounds were evaluated as multifunctional agents. The in vitro biological activity results revealed that compound3a was a selectiveeqBuChE inhibitor (IC50 = 0.29 μM), compound3k was a selectiveeeAChE inhibitor (IC50 = 0.77 μM), and compound3p was a selectiveeqBuChE inhibitor (IC50 = 0.82 μM). Compounds3a,3k and3p also showed good antioxidant activity and anti-inflammatory property. Furthermore, compounds3a,3k and3p were selective metal chelators. Moreover, compounds3a,3k and3p showed significant neuroprotective effects on H2O2-/Aβ25-35-induced PC12 cells injury. More importantly, compounds3a,3k and3p possessed favorable ADME properties. Taken together, compounds3a,3k and3p were promising multifunctional agents, deserving further investigations.

Source: Medicinal Chemistry Research - January 2, 2023 Category: Chemistry Source Type: research