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

Yan Li; Xiaoming Qiang; Li Luo; Yuxing Li; Ganyuan Xiao; Zhenghuai Tan; Yong Deng

doi:10.1016/j.bmc.2016.04.012

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

Bioorg Med Chem. 2016 May 15;24(10):2342-51. doi: 10.1016/j.bmc.2016.04.012. Epub 2016 Apr 5.

Authors

Yan Li¹, Xiaoming Qiang¹, Li Luo¹, Yuxing Li¹, Ganyuan Xiao¹, Zhenghuai Tan², Yong Deng³

Affiliations

¹ Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
² Institute of Traditional Chinese Medicine Pharmacology and Toxicology, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, China. Electronic address: tanzhh616@163.com.
³ Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address: dengyong@scu.edu.cn.

PMID: 27079124
DOI: 10.1016/j.bmc.2016.04.012

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.

Keywords: Alzheimer’s disease; Aurone derivatives; Monoamine oxidase; Multifunctional agents; β-Amyloid aggregation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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