Development of novel salicylic acid-donepezil-rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer's disease.

ABSTRACT: Alzheimer's disease (AD) is a chronic, progressive brain degenerative disease that is common in the elderly. So far, there is no effective treatment. The multi-target-directed ligands (MTDLs) strategy has been recognised as the most promising approach due to the complexity of the pathogenesis of AD. Herein, novel salicylic acid-donepezil-rivastigmine hybrids were designed and synthesised. The bioactivity results exhibited that 5a was a reversible and selective eqBChE inhibitor (IC₅₀ = 0.53 μM), and the docking provided the possible mechanism. Compound 5a also displayed potential anti-inflammatory effects and significant neuroprotective effect. Moreover, 5a exhibited favourable stabilities in artificial gastrointestinal solution and plasma. Finally,

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC10327518 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature