数字农科院2.0

Screening Novel Furoxan Derivatives as Potential Inhibitors Targeting Thioredoxin Glutathione Reductase of Fasciola gigantica

文献类型： 外文期刊

作者： Yanhui Han;Yuting He;Qingqing Guo;Gongming Li;Huan Chen;Wenjiao Zhao;Yan Zhou;Zhiqiang Fu;Oyetunde T. Oyeyemi;Huili Zhu;Qiangqiang Wang;Dequn Sun;Yang Hong

作者机构：

关键词： enzymatic activity;Fasciola gigantica;furoxan;thioredoxin glutathione reductase

期刊名称： Pharmaceuticals

ISSN： 1424-8247

年卷期： 2025 年 18 卷 11 期

页码：

收录情况： SCIE（2025版）

摘要： Background: Fascioliasis, caused by Fasciola species, is a significant public health concern affecting over 250 million people globally and causing annual economic losses exceeding USD 6 billion. The sole FDA-approved treatment, triclabendazole (TCZ), faces increasing resistance due to extensive use, highlighting the urgent need for alternative therapeutic targets. A promising candidate is thioredoxin glutathione reductase (TGR), a multifunctional enzyme unique to platyhelminths, essential for redox balance and parasite survival. Methods: This study investigated the antioxidant and enzymatic activities of recombinant Fasciola gigantica TGR (FgTGR), its localization within the parasite, and its inhibition by furoxan derivatives. FgTGRsec (FgTGR containing selenocysteine) was expressed and purified, and its enzymatic activities, including thioredoxin reductase (TrxR), glutathione reductase (GR), and glutaredoxin (Grx), were characterized. Results: Immunolocalization studies revealed FgTGR’s presence in critical tissues, underscoring its functional significance. Antioxidant assays demonstrated the protein’s role in protecting against oxidative damage. Inhibition assays with furoxan derivatives identified potential inhibitors targeting TGR activity. Sequence and phylogenetic analyses showed FgTGR’s evolutionary conservation among trematodes, confirming its potential as a drug target. Conclusions: The study’s findings establish FgTGR as a critical enzyme for parasite survival and a promising target for developing novel therapeutics. These results pave the way for the further screening and optimization of TGR inhibitors, offering a strategic approach to overcoming TCZ resistance and improving fascioliasis control.

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