Design, synthesis, and evaluation of multitarget-directed ligands against Alzheimer’s disease based on the fusion of donepezil and curcumin
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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Curcumin has good blood-brain barrier permeability.
“and good BBB permeability [274].”
From Indian Medicinal Herbs and Formulations for Alzheimer’s Disease, from Traditional Knowledge to Scientific Assessment (2020) · cites this paper as [274]
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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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