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

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

  • J Enzyme Inhib Med Chem. 2023 Dec;38(1):2231661. doi: 10.1080/14756366.2023.2231661.
Yi Zhou 1,  Ying He 1,  Xue Teng 2,  Jing Mi 1,  Jing Yang 1,  Rongrui Wei 3,  Wenmin Liu 1,  Qinge Ma 3,  Zhenghuai Tan 4,  Zhipei Sang 1 2
Affiliations

Affiliations

  • 1 College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang, China.
  • 2 Key Laboratory of Tropical Biological Resources of Ministry of Education and One Health Institute, School of Pharmaceutical Sciences, Hainan University, Haikou, China.
  • 3 Key Laboratory of Modern Preparation of Traditional Chinese Medicine of Ministry of Education, Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
  • 4 Institute of Traditional Chinese Medicine Pharmacology and Toxicology, Sichuan Academy of Chinese Medicine Sciences, Chengdu, China.
PMID: 37414563 DOI: 10.1080/14756366.2023.2231661
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, 5a demonstrated potential cognitive improvement in scopolamine-induced cognitive dysfunction. Hence, 5a was a potential multifunctional lead compound against AD.

Keywords

Alzheimer’s disease; drug-likeness; multi-functional agent; salicylic acid–donepezil–rivastigmine hybrids; scopolamine-induced AD model.

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