Aurone Mannich base derivatives as promising multifunctional agents with acetylcholinesterase inhibition, anti-β-amyloid aggragation and neuroprotective properties for the treatment of Alzheimer's disease.

Abstract

A series of aurone Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. In vitro assays demonstrated that most of the derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compound 7d exhibited outstanding inhibitory activity for RatAChE, EeAChE and HuAChE (IC50 = 0.00878 ± 0.0002 μM, 0.0212 ± 0.006 μM and 0.0371 ± 0.004 μM, respectively). Moreover, 7d displayed high antioxidant activity and could confer significant neuroprotective effect against H2O2-induced PC-12 cell injury. In addition, 7d also showed biometal chelating abilities, good self- and Cu2+-induced Aβ1-42 aggregation inhibitory potency and high BBB permeability. These multifunctional properties highlight 7d as promising candidate for further studies directed to the development of novel drugs against AD.

• Authors: Yan Li, Xiaoming Qiang, Li Luo, Xia Yang, Ganyuan Xiao, Qi Liu, Jiachen Ai, Zhenghuai Tan, Yong Deng
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 126 Pg. 762-775 (Jan 27 2017) ISSN: 1768-3254 [Electronic] France
• PMID: 27951485 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Cholinesterase Inhibitors
• Mannich Bases
• Neuroprotective Agents

Topics

• Alzheimer Disease (drug therapy)
• Amyloid beta-Peptides (antagonists & inhibitors, metabolism)
• Animals
• Blood-Brain Barrier (drug effects)
• Cholinesterase Inhibitors (chemical synthesis, pharmacology)
• Drug Design
• Electrophorus
• Humans
• Mannich Bases (chemical synthesis, pharmacology)
• Neuroprotective Agents (chemical synthesis, pharmacology)
• PC12 Cells
• Rats