Synthesis of donepezil-based multifunctional agents for the treatment of Alzheimer's disease.

Abstract

Amyloid beta (Aβ) and cholinesterase enzymes (AChE, BuChE) are important biological targets for the effective treatment of Alzheimer's disease. In this study, the aim was to synthesize new donepezil-like secondary amide compounds that display a potent inhibition of cholinesterases and Aβ with antioxidant and metal chelation abilities. All test compounds showed activities against both ChEs and β1-42 inhibition. The most encouraging compound, 20, is an AChE inhibitor with high anti-aggregation activity (55.3%). Based on the results, compound 20 may be a promising structure in further research for new anti-Alzheimer's agents.

• Authors: Kadir Ozden Yerdelen, Mehmet Koca, Baris Anil, Handan Sevindik, Zeynep Kasap, Zekai Halici, Kubra Turkaydin, Gulsen Gunesacar
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 25 Issue 23 Pg. 5576-82 (Dec 01 2015) ISSN: 1464-3405 [Electronic] England
• PMID: 26514744 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Amides
• Amyloid beta-Peptides
• Cholinesterase Inhibitors
• Indans
• Piperidines
• Donepezil

Topics

• Alzheimer Disease (drug therapy)
• Amides (chemical synthesis, chemistry, pharmacology)
• Amyloid beta-Peptides (chemistry)
• Catalytic Domain
• Cholinesterase Inhibitors (chemical synthesis, chemistry)
• Donepezil
• Drug Design
• Indans (chemical synthesis, chemistry, therapeutic use)
• Inhibitory Concentration 50
• Models, Molecular
• Piperidines (chemical synthesis, chemistry, therapeutic use)
• Structure-Activity Relationship