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Dual-target anti-Alzheimer's disease agents with both iron ion chelating and monoamine oxidase-B inhibitory activity.

ABSTRACT: MAO-B leads to an increase in the levels of hydrogen peroxide and oxidative free radicals, which contribute to the aetiology of the AD. Thus, both iron ion chelators and MAO-B inhibitors can be used to treat AD. Taking the coumarin derivatives and hydroxypyridinones as the lead compounds, a series of dual-target hybrids were designed and synthesised by Click Chemistry. The compounds were biologically evaluated for their iron ion chelating and MAO-B inhibitory activity. Most of the compounds displayed excellent iron ion chelating activity and moderate to good anti-MAO-B activity. Compounds 27b and 27j exhibited the most potent MAO-B inhibitory activity, with IC₅₀ values of 0.68 and 0.86??M, respectively. In summary, these dual-target compounds have the potential anti-AD activity.

SUBMITTER: Mi Z

PROVIDER: S-EPMC6713216 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Dual-target anti-Alzheimer's disease agents with both iron ion chelating and monoamine oxidase-B inhibitory activity.

Mi Zhisheng Z Gan Bing B Yu Sihang S Guo Jianan J Zhang Changjun C Jiang Xiaoying X Zhou Tao T Su Jing J Bai Renren R Xie Yuanyuan Y

Journal of enzyme inhibition and medicinal chemistry 20191201 1

MAO-B leads to an increase in the levels of hydrogen peroxide and oxidative free radicals, which contribute to the aetiology of the AD. Thus, both iron ion chelators and MAO-B inhibitors can be used to treat AD. Taking the coumarin derivatives and hydroxypyridinones as the lead compounds, a series of dual-target hybrids were designed and synthesised by Click Chemistry. The compounds were biologically evaluated for their iron ion chelating and MAO-B inhibitory activity. Most of the compounds disp ...[more]

PMID: 31416364

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