Screening Novel Furoxan Derivatives as Potential Inhibitors Targeting Thioredoxin Glutathione Reductase of .
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Pharmaceuticals (Basel, Switzerland)
2025
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| Online Access: | |
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| _version_ | 1868266119904624640 |
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| author | Han, Yanhui He, Yuting Guo, Qingqing Li, Gongming Chen, Huan Zhao, Wenjiao Zhou, Yan Fu, Zhiqiang Oyeyemi, Oyetunde T Zhu, Huili Wang, Qiangqiang Sun, Dequn Hong, Yang |
| author_facet | Han, Yanhui He, Yuting Guo, Qingqing Li, Gongming Chen, Huan Zhao, Wenjiao Zhou, Yan Fu, Zhiqiang Oyeyemi, Oyetunde T Zhu, Huili Wang, Qiangqiang Sun, Dequn Hong, Yang Han, Yanhui He, Yuting Guo, Qingqing Li, Gongming Chen, Huan Zhao, Wenjiao Zhou, Yan Fu, Zhiqiang Oyeyemi, Oyetunde T Zhu, Huili Wang, Qiangqiang Sun, Dequn Hong, Yang |
| collection | PubMed - marine biology |
| contents | Screening Novel Furoxan Derivatives as Potential Inhibitors Targeting Thioredoxin Glutathione Reductase of . Han, Yanhui He, Yuting Guo, Qingqing Li, Gongming Chen, Huan Zhao, Wenjiao Zhou, Yan Fu, Zhiqiang Oyeyemi, Oyetunde T Zhu, Huili Wang, Qiangqiang Sun, Dequn Hong, Yang Fascioliasis, caused by 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. This study investigated the antioxidant and enzymatic activities of recombinant 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. 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. 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. |
| format | Artículo científico |
| id | pubmed_41304851 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Pharmaceuticals (Basel, Switzerland) |
| record_format | pubmed |
| spellingShingle | Screening Novel Furoxan Derivatives as Potential Inhibitors Targeting Thioredoxin Glutathione Reductase of . Han, Yanhui He, Yuting Guo, Qingqing Li, Gongming Chen, Huan Zhao, Wenjiao Zhou, Yan Fu, Zhiqiang Oyeyemi, Oyetunde T Zhu, Huili Wang, Qiangqiang Sun, Dequn Hong, Yang Screening Novel Furoxan Derivatives as Potential Inhibitors Targeting Thioredoxin Glutathione Reductase of . Han, Yanhui He, Yuting Guo, Qingqing Li, Gongming Chen, Huan Zhao, Wenjiao Zhou, Yan Fu, Zhiqiang Oyeyemi, Oyetunde T Zhu, Huili Wang, Qiangqiang Sun, Dequn Hong, Yang Fascioliasis, caused by 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. This study investigated the antioxidant and enzymatic activities of recombinant 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. 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. 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. |
| title | Screening Novel Furoxan Derivatives as Potential Inhibitors Targeting Thioredoxin Glutathione Reductase of . |
| url | https://pubmed.ncbi.nlm.nih.gov/41304851/ |