2. Academic Validation
  3. Discovery of phenylcarbamoyl xanthone derivatives as potent neuroprotective agents for treating ischemic stroke

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

  • Eur J Med Chem. 2023 May 5;251:115251. doi: 10.1016/j.ejmech.2023.115251.
Yi-Li Chen 1,  Yu-Chen Chen 1,  Lin-An Xiong 1,  Qu-Yang Huang 1,  Ting-Ting Gong 1,  Yan Chen 1,  Lie-Feng Ma 1,  Luo Fang 2,  Zha-Jun Zhan 3
Affiliations

Affiliations

  • 1 College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, PR China.
  • 2 Department of Pharmacy, Zhejiang Cancer Hospital, PR China. Electronic address: [email protected].
  • 3 College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, PR China. Electronic address: [email protected].
PMID: 36921528 DOI: 10.1016/j.ejmech.2023.115251
Abstract

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 α-mangostin is limited due to its cytotoxicity and relatively low efficacy. Herein, structural modification of α-mangostin was necessary to improve its drug-ability. Currently, 34 α-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.

Keywords

Carbamate; Ischemic stroke; Neuroprotection; α-mangostin.

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