Cited by 68Cholinesterase and Neurodegenerative DiseasesAlzheimer's disease research and treatmentsCurcumin's Biomedical Applications

Design, synthesis, and evaluation of multitarget-directed ligands against Alzheimer’s disease based on the fusion of donepezil and curcumin

Yan, Jun, Hu, Jinhui, Liu, Anqiu, He, Lin, Li, Xingshu, Wei, Hui·2017·Bioorganic & Medicinal Chemistry

Abstract

By fusing donepezil and curcumin, a novel series of compounds were obtained as multitarget-directed ligands against Alzheimer's disease. Among them, compound 11b displayed potent acetylcholinesterase (AChE) inhibition (IC 50=187nM) and the highest BuChE/AChE selectivity (66.3). Compound 11b also inhibited 45.3% Aβ 1-42 self-aggregation at 20μM and displayed remarkable antioxidant effects. The metal-chelating property of compound 11b was elucidated by determining the 1:1 stoichiometry for the 11b-Cu(II) complex. The excellent blood-brain barrier permeability of 11b also indicated the potential for the compound to penetrate the central nervous system.

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Crossref · 10.1016/j.bmc.2017.02.048

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27 of 27 references verified0 citation errors · 0 not checkable

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Authors
Yan, J., Hu, J., Liu, A., He, L., Li, X., & Wei, H.
Affiliations
  • Sun Yat-sen University (CN)
  • Guangdong Pharmaceutical University (CN)
Corresponding author
  • Li, Xingshu
  • Wei, Hui
Venue
Bioorganic & Medicinal Chemistry
Publisher
Elsevier BV
Published
2017-06
Volume
25
Issue
12
Pages
2946-2955
ISSN
0968-0896 (ISSN-L)
OpenAlex
W2605975439
Cited by
65
References
27
Citations by year
2026: 2 · 2025: 7 · 2024: 3 · 2023: 7 · 2022: 7 · 2021: 8 · 2020: 8 · 2019: 9 · 2018: 12 · 2017: 2
FWCI
5.92
Type
journal article
Language
en
Open access
closed
Locations
  • Bioorganic & Medicinal Chemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Guangdong Pharmaceutical University
  • U.S. Food and Drug Administration
Topics
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Curcumin's Biomedical Applications
Keywords
Alzheimer's disease, multi-target-directed ligands, donepezil, curcumin, acetylcholinesterase inhibition, butyrylcholinesterase selectivity, amyloid beta aggregation inhibition, antioxidant activity, metal chelation, copper(II) complexes, blood-brain barrier permeability, CNS penetration
MeSH terms
Donepezil, Acetylcholinesterase, Alzheimer Disease, Animals, Blood-Brain Barrier, Cholinesterase Inhibitors, Curcumin, Electrophorus, Humans, Indans, Ligands, Peptide Fragments, Piperidines, Swine, Drug Design, Amyloid beta-Peptides, Molecular Targeted Therapy, Molecular Docking Simulation, Protein Aggregates

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