Title : Development of novel salicylic acid-donepezil-rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer's disease - Zhou_2023_J.Enzyme.Inhib.Med.Chem_38_2231661 |
Author(s) : Zhou Y , He Y , Teng X , Mi J , Yang J , Wei R , Liu W , Ma Q , Tan Z , Sang Z |
Ref : J Enzyme Inhib Med Chem , 38 :2231661 , 2023 |
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 (IC(50) = 0.53 microM), 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, 5a demonstrated potential cognitive improvement in scopolamine-induced cognitive dysfunction. Hence, 5a was a potential multifunctional lead compound against AD. |
PubMedSearch : Zhou_2023_J.Enzyme.Inhib.Med.Chem_38_2231661 |
PubMedID: 37414563 |
Inhibitor | Salicylic-donepezil-rivastigmine-5a |
Zhou Y, He Y, Teng X, Mi J, Yang J, Wei R, Liu W, Ma Q, Tan Z, Sang Z (2023)
Development of novel salicylic acid-donepezil-rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer's disease
J Enzyme Inhib Med Chem
38 :2231661
Zhou Y, He Y, Teng X, Mi J, Yang J, Wei R, Liu W, Ma Q, Tan Z, Sang Z (2023)
J Enzyme Inhib Med Chem
38 :2231661