Resveratrol-maltol hybrids as multi-target-directed agents for Alzheimer's disease

Gang Cheng; Ping Xu; Minkui Zhang; Jing Chen; Rong Sheng; Yongmin Ma

doi:10.1016/j.bmc.2018.08.011

Resveratrol-maltol hybrids as multi-target-directed agents for Alzheimer's disease

Bioorg Med Chem. 2018 Dec 1;26(22):5759-5765. doi: 10.1016/j.bmc.2018.08.011. Epub 2018 Aug 9.

Authors

Gang Cheng¹, Ping Xu², Minkui Zhang³, Jing Chen², Rong Sheng⁴, Yongmin Ma⁵

Affiliations

¹ College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 311402, PR China; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, PR China. Electronic address: gangcheng@zcmu.edu.cn.
² College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 311402, PR China.
³ College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, PR China.
⁴ College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, PR China. Electronic address: shengr@zju.edu.cn.
⁵ College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 311402, PR China. Electronic address: yongmin.ma@zcmu.edu.cn.

PMID: 30360953
DOI: 10.1016/j.bmc.2018.08.011

Abstract

The 3-hydroxypyran-4-one moiety (maltol) was incorporated into the structure of resveratrol to achieve a series of resveratrol-maltol hybrids (8a-8k) as novel multi-target-directed ligands (MTDLs). In vitro biological evaluation of the MTDLs revealed these compounds to have a triple function, namely inhibition of self-induced Aβ_1-42 aggregation, antioxidation, and metal chelating activity. Among all the evaluated MTDLs, compounds 8i and 8j showed the most promise, demonstrating micromolar IC₅₀ values for Aβ_1-42 aggregation inhibition, more potent ABTS⁺ scavenging activity than Trolox, and good metal chelating activities.

Keywords: 3-Hydroxypyran-4-one; Alzheimer; Metal chelator; Resveratrol derivative; β-amyloid.

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
Antioxidants / chemical synthesis
Antioxidants / chemistry
Antioxidants / pharmacology*
Benzothiazoles / antagonists & inhibitors
Chelating Agents / chemical synthesis
Chelating Agents / chemistry
Chelating Agents / pharmacology*
Dose-Response Relationship, Drug
Humans
Ligands
Molecular Structure
Neuroprotective Agents / chemical synthesis
Neuroprotective Agents / chemistry
Neuroprotective Agents / pharmacology*
Peptide Fragments / antagonists & inhibitors
Peptide Fragments / metabolism
Protein Aggregates / drug effects
Pyrones / chemistry
Pyrones / pharmacology*
Resveratrol / chemistry
Resveratrol / pharmacology*
Structure-Activity Relationship
Sulfonic Acids / antagonists & inhibitors

Substances

Amyloid beta-Peptides
Antioxidants
Benzothiazoles
Chelating Agents
Ligands
Neuroprotective Agents
Peptide Fragments
Protein Aggregates
Pyrones
Sulfonic Acids
amyloid beta-protein (1-42)
2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid
maltol
Resveratrol