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

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 o...

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Bibliographic Details
Published in:Journal of enzyme inhibition and medicinal chemistry 2023-12, Vol.38 (1), p.2231661-2231661
Main Authors: Zhou, Yi, He, Ying, Teng, Xue, Mi, Jing, Yang, Jing, Wei, Rongrui, Liu, Wenmin, Ma, Qinge, Tan, Zhenghuai, Sang, Zhipei
Format: Article
Language:English
Subjects:
Acids
Alzheimer's disease
Biological activity
Brain research
Chinese medicine
Cognitive ability
Donepezil
drug-likeness
Education
Enzymes
Hybrids
Hypotheses
Inflammation
Ligands
multi-functional agent
Neurodegenerative diseases
Neuroprotection
Pathogenesis
Pharmaceutical sciences
Research Paper
Rivastigmine
Salicylic acid
salicylic acid-donepezil-rivastigmine hybrids
Scopolamine
scopolamine-induced AD model
Toxicology
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Summary: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 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, 5a demonstrated potential cognitive improvement in scopolamine-induced cognitive dysfunction. Hence, 5a was a potential multifunctional lead compound against AD.
ISSN:1475-6366
1475-6374
DOI:10.1080/14756366.2023.2231661