Discovery of phenylcarbamoyl xanthone derivatives as potent neuroprotective agents for treating ischemic stroke

被引：12

作者：

Chen, Yi-Li ^{[1
]}

Chen, Yu-Chen ^{[1
]}

Xiong, Lin-An ^{[1
]}

Huang, Qu-Yang ^{[1
]}

Gong, Ting-Ting ^{[1
]}

Chen, Yan ^{[1
]}

Ma, Lie-Feng ^{[1
]}

Fang, Luo ^{[2
]}

Zhan, Zha-Jun ^{[1
]}

机构：

[1] Zhejiang Univ Technol, Coll Pharmaceut Sci, Hangzhou 310014, Peoples R China

[2] Zhejiang Canc Hosp, Dept Pharm, Hangzhou, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2023年 / 251卷

基金：

中国国家自然科学基金;

关键词：

-mangostin; Ischemic stroke; Carbamate; Neuroprotection; ALPHA-MANGOSTIN; DESIGN;

D O I：

10.1016/j.ejmech.2023.115251

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Compounds of natural sources are widespread discovered in the treatment of ischemic stroke. Alpha-mangostin, a natural prenylated xanthone, has been found to display a therapeutic potential to treat ischemic stroke. However, the direct application of alpha-mangostin is limited due to its cytotoxicity and relatively low efficacy. Herein, structural modification of alpha-mangostin was necessary to improve its drug-ability. Currently, 34 alpha-mangostin phenylcarbamoyl derivatives were synthesized and evaluated for their neuroprotective activities by glutamate-induced excitotoxicity and H2O2-induced oxidative damage models in vitro. The results showed that compound 2 had the most therapeutic potential in both models. Whereafter, 2 has been proved to have powerful therapeutic effects by the MCAO ischemic stroke model in rats, which might be due to inhibition of inflammatory reaction and free radical accumulation. Besides, acute toxicity assay in rats showed that compound 2 had excellent safety. Overall, 2 could be a promising neuroprotective agent for the treatment of ischemic stroke deserving further investigations.

引用

页数：12

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