Synthesis and bioactivity evaluation of glycosylated resveratrol derivatives as antioxidative neuroprotection agents against cerebral Ischemia-Reperfusion injury

  • Bioorg Chem. 2024 Sep 2:153:107791. doi: 10.1016/j.bioorg.2024.107791.
Yanning Xu  1 ,  Peiyun Yu  1 ,  Jiao Liang  1 ,  Yuting Chen  1 ,  Chunyan Yang  1 ,  Chen Xia  2 ,  Junlin Deng  2 ,  Li Hai  1 ,  Jian Chen  3 ,  Yong Wu  4
Affiliations
  • 1. Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
  • 2. Institute of Agro-Products Processing Science and Technology (Institute of Food Nutrition and Health), Sichuan Academy of Agricultural Sciences, Chengdu 610066, China.
  • 3. Institute of Agro-Products Processing Science and Technology (Institute of Food Nutrition and Health), Sichuan Academy of Agricultural Sciences, Chengdu 610066, China. Electronic address: [email protected].
  • 4. Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address: [email protected].
PMID: 39244974 DOI: 10.1016/j.bioorg.2024.107791
Abstract

Resveratrol (Res) has long been discovered to have antioxidant effects to prevent such as oxidation, inflammation, neurodegeneration and age-related diseases. However, its poor water solubility, low bioavailability and instability have become a barrier to its pharmaceutical application. In order to improve the neuroprotective effects and develop more potential usage of Res, three Res derivatives containing one or two glucose groups, i.e., Res-Glu1, Res-Glu2 and Res-Glu3, were designed and synthesized through click reaction. Res-Glu1, Res-Glu2 and Res-Glu3 were tested being better water solubility and stability compared to Res. Res derivatives reduced •OH radicals-induced DNA damage. PC12 assays indicated that glucosylated Res derivatives could alleviate H2O2-induced neurotoxicity and reduce intracellular ROS generation, demonstrating their neuroprotective effects. In addition, Res derivatives enhanced the protective effects on cerebral ischemia-reperfusion injury in rats. Res-Glu3 displayed the best neuroprotective effects among the three derivatives.

Keywords
Antioxidative; Cerebral ischemia–reperfusion injury; Glucosylation; Neuroprotection; Resveratrol.
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