Synthesis and evaluation of 4-hydroxyl aurone derivatives as multifunctional agents for the treatment of Alzheimer's disease.

Abstract

A series of 4-hydroxyl aurone derivatives were designed synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease. The results demonstrated that most of the derivatives exhibited good multifunctional properties. Among them, compound 14e displayed good inhibitory activities of self- and Cu(2+)-induced Aβ1-42 aggregation with 99.2% and 84.0% at 25μM, respectively, and high antioxidant activity with a value 1.90-fold of Trolox. In addition, 14e also showed remarkable inhibitory activities of both monoamine oxidase A and B with IC50 values of 0.271μM and 0.393μM, respectively. However the 6-methoxyl aurones 15a-c revealed excellent selectivity toward MAO-B. Furthermore, the representative compounds 14e and 15b displayed good metal-chelating abilities and blood-brain barrier (BBB) permeabilities in vitro.

• Authors: Yan Li, Xiaoming Qiang, Li Luo, Yuxing Li, Ganyuan Xiao, Zhenghuai Tan, Yong Deng
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 24 Issue 10 Pg. 2342-51 (05 15 2016) ISSN: 1464-3391 [Electronic] England
• PMID: 27079124 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Antioxidants
• Benzofurans
• Chelating Agents
• Monoamine Oxidase Inhibitors
• Peptide Fragments
• Protein Aggregates
• amyloid beta-protein (1-42)
• aurone
• Copper
• Monoamine Oxidase

Topics

• Alzheimer Disease (drug therapy, metabolism)
• Amyloid beta-Peptides (antagonists & inhibitors, metabolism)
• Animals
• Antioxidants (chemical synthesis, chemistry, pharmacokinetics, pharmacology)
• Benzofurans (chemical synthesis, chemistry, pharmacokinetics, pharmacology)
• Blood-Brain Barrier (metabolism)
• Chelating Agents (chemical synthesis, chemistry, pharmacokinetics, pharmacology)
• Copper (metabolism)
• Humans
• Models, Molecular
• Monoamine Oxidase (metabolism)
• Monoamine Oxidase Inhibitors (chemical synthesis, chemistry, pharmacokinetics, pharmacology)
• Peptide Fragments (antagonists & inhibitors, metabolism)
• Protein Aggregates (drug effects)
• Swine