{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T04:36:42Z","timestamp":1761367002091,"version":"build-2065373602"},"reference-count":60,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Research and Development Program in Hainan Province","award":["ZDYF2024SHFZ083"],"award-info":[{"award-number":["ZDYF2024SHFZ083"]}]},{"DOI":"10.13039\/501100008111","name":"Hainan Provincial Department of Science and Technology","doi-asserted-by":"crossref","award":["WSJK2024MS226"],"award-info":[{"award-number":["WSJK2024MS226"]}],"id":[{"id":"10.13039\/501100008111","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Guizhou Provincial Department of Science and Technology","award":["Qian Ke He (2023) General 183"],"award-info":[{"award-number":["Qian Ke He (2023) General 183"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>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\u2019s presence in critical tissues, underscoring its functional significance. Antioxidant assays demonstrated the protein\u2019s role in protecting against oxidative damage. Inhibition assays with furoxan derivatives identified potential inhibitors targeting TGR activity. Sequence and phylogenetic analyses showed FgTGR\u2019s evolutionary conservation among trematodes, confirming its potential as a drug target. Conclusions: The study\u2019s 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.<\/jats:p>","DOI":"10.3390\/ph18111603","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:47:36Z","timestamp":1761266856000},"page":"1603","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Screening Novel Furoxan Derivatives as Potential Inhibitors Targeting Thioredoxin Glutathione Reductase of Fasciola gigantica"],"prefix":"10.3390","volume":"18","author":[{"given":"Yanhui","family":"Han","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Henan Institute of Science and Technology, Xinxiang 453003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuting","family":"He","sequence":"additional","affiliation":[{"name":"National Reference Laboratory for Animal Schistosomiasis, Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingqing","family":"Guo","sequence":"additional","affiliation":[{"name":"National Reference Laboratory for Animal Schistosomiasis, Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gongming","family":"Li","sequence":"additional","affiliation":[{"name":"Marine College, Shandong University, Weihai 264209, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Chen","sequence":"additional","affiliation":[{"name":"Marine College, Shandong University, Weihai 264209, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjiao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Marine College, Shandong University, Weihai 264209, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Diseases Control and Prevention (Chinese Center for Tropical Diseases Research), National Health Commission of the People\u2019s Republic of China (NHC) Key Laboratory of Parasite and Vector Biology, World Health Organization (WHO) Collaborating Center for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6903-3308","authenticated-orcid":false,"given":"Zhiqiang","family":"Fu","sequence":"additional","affiliation":[{"name":"National Reference Laboratory for Animal Schistosomiasis, Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oyetunde T.","family":"Oyeyemi","sequence":"additional","affiliation":[{"name":"Tropical Medicine & Diagnostics Development (TMDD) Group, Department of Biosciences and Biotechnology, University of Medical Sciences, Ondo City 351001, Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huili","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Henan Institute of Science and Technology, Xinxiang 453003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiangqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Henan Institute of Science and Technology, Xinxiang 453003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dequn","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agri-Forestry, Southwest University of Science and Technology, Mianyang 621010, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Hong","sequence":"additional","affiliation":[{"name":"National Institute of Parasitic Diseases, Chinese Center for Diseases Control and Prevention (Chinese Center for Tropical Diseases Research), National Health Commission of the People\u2019s Republic of China (NHC) Key Laboratory of Parasite and Vector Biology, World Health Organization (WHO) Collaborating Center for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai 200025, China"},{"name":"Hainan Tropical Diseases Research Center, Haikou 571199, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nchembio837","article-title":"Drug discovery and development for neglected parasitic diseases","volume":"2","author":"Renslo","year":"2006","journal-title":"Nat. Chem. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1098\/rstb.2009.0089","article-title":"Zoonotic helminth infections with particular emphasis on fasciolosis and other trematodiases","volume":"364","author":"Robinson","year":"2009","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ferraro, F., Corvo, I., Bergalli, L., Ilarraz, A., Cabrera, M., Gil, J., Susuki, B.M., Caffrey, C.R., Timson, D.J., and Robert, X. (2020). Novel and selective inactivators of Triosephosphate isomerase with anti-trematode activity. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-59460-y"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.pt.2016.03.002","article-title":"Current Threat of Triclabendazole Resistance in Fasciola hepatica","volume":"32","author":"Kelley","year":"2016","journal-title":"Trends Parasitol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1358\/dot.2019.55.12.3058861","article-title":"Triclabendazole for the treatment of fascioliasis","volume":"55","author":"Thakare","year":"2019","journal-title":"Drugs Today"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.vetpar.2010.12.047","article-title":"Resistance of Fasciola hepatica against triclabendazole in cattle in Patagonia (Argentina)","volume":"178","author":"Olaechea","year":"2011","journal-title":"Vet. Parasitol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Cabada, M.M., Lopez, M., Cruz, M., Delgado, J.R., Hill, V., and White, A.C. (2016). Treatment Failure after Multiple Courses of Triclabendazole among Patients with Fascioliasis in Cusco, Peru: A Case Series. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004361"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.parint.2016.05.013","article-title":"Unusual thiol-based redox metabolism of parasitic flukes","volume":"66","author":"Tripathi","year":"2017","journal-title":"Parasitol. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4959","DOI":"10.1074\/jbc.M110.170761","article-title":"Linked thioredoxin-glutathione systems in platyhelminth parasites: Alternative pathways for glutathione reduction and deglutathionylation","volume":"286","author":"Bonilla","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.pt.2004.05.002","article-title":"Linked thioredoxin-glutathione systems in platyhelminths","volume":"20","author":"Salinas","year":"2004","journal-title":"Trends Parasitol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Song, L., Li, J., Xie, S., Qian, C., Wang, J., Zhang, W., Yin, X., Hua, Z., and Yu, C. (2012). Thioredoxin glutathione reductase as a novel drug target: Evidence from Schistosoma japonicum. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031456"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kuntz, A.N., Davioud-Charvet, E., Sayed, A.A., Califf, L.L., Dessolin, J., Arner, E.S., and Williams, D.L. (2007). Thioredoxin glutathione reductase from Schistosoma mansoni: An essential parasite enzyme and a key drug target. PLoS Med., 4.","DOI":"10.1371\/journal.pmed.0040264"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.parint.2012.03.005","article-title":"Characterization of thioredoxin glutathione reductase in Schiotosoma japonicum","volume":"61","author":"Han","year":"2012","journal-title":"Parasitol. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1186\/s13071-021-04634-4","article-title":"Synthesis of oxadiazole-2-oxide derivatives as potential drug candidates for schistosomiasis targeting SjTGR","volume":"14","author":"Li","year":"2021","journal-title":"Parasit. Vectors"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tang, W., Yue, Y., Shi, B., Zhao, X., and Hong, Y. (2025). Characterization and enzymatic function of thioredoxin glutathione reductase in Orientobilharzia turkestanicum isolated from Xizang. BMC Vet. Res., 21.","DOI":"10.1186\/s12917-025-04964-w"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1007\/s00436-015-4400-8","article-title":"Molecular cloning and characterization of Fasciola gigantica thioredoxin-glutathione reductase","volume":"114","author":"Changklungmoa","year":"2015","journal-title":"Parasitol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1645\/13-397.1","article-title":"Inhibitory effects and analysis of RNA interference on thioredoxin glutathione reductase expression in Schistosoma japonicum","volume":"100","author":"Han","year":"2014","journal-title":"J. Parasitol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"105621","DOI":"10.1016\/j.actatropica.2020.105621","article-title":"Characterization and in vitro functional analysis of thioredoxin glutathione reductase from the liver fluke Opisthorchis viverrini","volume":"210","author":"Prum","year":"2020","journal-title":"Acta Trop."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.bbrc.2011.12.009","article-title":"Investigation of a potential mechanism for the inhibition of SmTGR by Auranofin and its implications for Plasmodium falciparum inhibition","volume":"417","author":"Caroli","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Guevara-Flores, A., Martinez-Gonzalez, J.J., Herrera-Juarez, A.M., Rendon, J.L., Gonzalez-Andrade, M., Torres Duran, P.V., Enriquez-Habib, R.G., and Del Arenal Mena, I.P. (2019). Effect of curcuminoids and curcumin derivate products on thioredoxin-glutathione reductase from Taenia crassiceps cysticerci. Evidence suggesting a curcumin oxidation product as a suitable inhibitor. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0220098"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1002\/jcb.26444","article-title":"Structural insights into natural compounds as inhibitors of Fasciola gigantica thioredoxin glutathione reductase","volume":"119","author":"Shukla","year":"2018","journal-title":"J. Cell Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7075","DOI":"10.1021\/acs.jmedchem.5b02038","article-title":"Discovery of New Anti-Schistosomal Hits by Integration of QSAR-Based Virtual Screening and High Content Screening","volume":"59","author":"Neves","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s40249-015-0071-z","article-title":"High-throughput screening against thioredoxin glutathione reductase identifies novel inhibitors with potential therapeutic value for schistosomiasis","volume":"4","author":"Li","year":"2015","journal-title":"Infect. Dis. Poverty"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1021\/acsinfecdis.9b00354","article-title":"Characterization of Lead Compounds Targeting the Selenoprotein Thioredoxin Glutathione Reductase for Treatment of Schistosomiasis","volume":"6","author":"Lyu","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ross, F., Hernandez, P., Porcal, W., Lopez, G.V., Cerecetto, H., Gonzalez, M., Basika, T., Carmona, C., Flo, M., and Maggioli, G. (2012). Identification of thioredoxin glutathione reductase inhibitors that kill cestode and trematode parasites. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035033"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.parint.2011.01.005","article-title":"Hysteresis in thioredoxin-glutathione reductase (TGR) from the adult stage of the liver fluke Fasciola hepatica","volume":"60","author":"Pardo","year":"2011","journal-title":"Parasitol. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.yexmp.2007.01.009","article-title":"Understanding triclabendazole resistance","volume":"82","author":"Brennan","year":"2007","journal-title":"Exp. Mol. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.ijbiomac.2016.04.063","article-title":"Fasciola gigantica thioredoxin glutathione reductase: Biochemical properties and structural modeling","volume":"89","author":"Gupta","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1152\/physrev.1994.74.1.139","article-title":"Cellular defenses against damage from reactive oxygen species","volume":"74","author":"Yu","year":"1994","journal-title":"Physiol. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.fsi.2009.05.002","article-title":"Molecular cloning, characterization and expression analysis of peroxiredoxin 6 from disk abalone Haliotis discus discus and the antioxidant activity of its recombinant protein","volume":"27","author":"Nikapitiya","year":"2009","journal-title":"Fish Shellfish Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1084\/jem.189.11.1783","article-title":"Thioredoxin, a redox enzyme released in infection and inflammation, is a unique chemoattractant for neutrophils, monocytes, and T cells","volume":"189","author":"Bertini","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15143","DOI":"10.1073\/pnas.191498798","article-title":"Circulating thioredoxin suppresses lipopolysaccharide-induced neutrophil chemotaxis","volume":"98","author":"Nakamura","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1089\/ars.2006.8.229","article-title":"Peroxiredoxin 6 gene-targeted mice show increased lung injury with paraquat-induced oxidative stress","volume":"8","author":"Wang","year":"2006","journal-title":"Antioxid. Redox Signal"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.molbiopara.2008.04.010","article-title":"Characterization of the antioxidant enzyme, thioredoxin peroxidase, from the carcinogenic human liver fluke, Opisthorchis viverrini","volume":"160","author":"Suttiprapa","year":"2008","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_35","first-page":"17","article-title":"Superoxide Dismutase (SOD) Enzyme Activity Assay in Fasciola spp. Parasites and Liver Tissue Extract","volume":"6","author":"Assady","year":"2011","journal-title":"Iran. J. Parasitol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.exppara.2014.02.017","article-title":"Analysis of the expression and antioxidant activity of 2-Cys peroxiredoxin protein in Fasciola gigantica","volume":"140","author":"Sangpairoj","year":"2014","journal-title":"Exp. Parasitol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.exppara.2010.01.004","article-title":"Molecular cloning and characterization of two genes encoding 2-Cys peroxiredoxins from Fasciola gigantica","volume":"125","author":"Chaithirayanon","year":"2010","journal-title":"Exp. Parasitol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.exppara.2011.09.013","article-title":"A recombinant thioredoxin-glutathione reductase from Fasciola hepatica induces a protective response in rabbits","volume":"129","author":"Maggioli","year":"2011","journal-title":"Exp. Parasitol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/S0020-7519(02)00108-X","article-title":"Molecular and enzymatic characterisation of Schistosoma mansoni thioredoxin","volume":"32","author":"Alger","year":"2002","journal-title":"Int. J. Parasitol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1002\/prot.21986","article-title":"Glutathione reductase and thioredoxin reductase at the crossroad: The structure of Schistosoma mansoni thioredoxin glutathione reductase","volume":"72","author":"Angelucci","year":"2008","journal-title":"Proteins"},{"key":"ref_41","unstructured":"He, Y., Guo, Q., Yong, C., Jia, J., Han, Y., Zhou, Y., Lu, L., Tang, W., Hong, Y., and Fu, Z. (2024). Expression, Purification and Preparation of Polyclonal Antibodies of Thioredoxin Glutathione Reductase from Fasciola gigantica. Chin. J. Zoonotic Infect. Dis., 1\u201311. (in press)."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1016\/j.bbagen.2018.03.007","article-title":"Biochemical and thermodynamic comparison of the selenocysteine containing and non-containing thioredoxin glutathione reductase of Fasciola gigantica","volume":"1862","author":"Kalita","year":"2018","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"32557","DOI":"10.1074\/jbc.M110.141960","article-title":"Mapping the catalytic cycle of Schistosoma mansoni thioredoxin glutathione reductase by X-ray crystallography","volume":"285","author":"Angelucci","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1089\/ars.2012.4670","article-title":"Thioredoxin glutathione reductase-dependent redox networks in platyhelminth parasites","volume":"19","author":"Williams","year":"2013","journal-title":"Antioxid. Redox Signal"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/0020-7519(88)90101-4","article-title":"Antioxidant systems in Schistosoma mansoni correlation between susceptibility to oxidant killing and the levels of scavengers of hydrogen peroxide and oxygen free radicals","volume":"18","author":"Mkoji","year":"1988","journal-title":"Int. J. Parasitol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1645\/GE-3096.1","article-title":"Characterization and expression of the Schistosoma japonicum thioredoxin peroxidase-2 gene","volume":"99","author":"Hong","year":"2013","journal-title":"J. Parasitol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1006\/jmbi.1999.3085","article-title":"High-level expression in Escherichia coli of selenocysteine-containing rat thioredoxin reductase utilizing gene fusions with engineered bacterial-type SECIS elements and co-expression with the selA, selB and selC genes","volume":"292","author":"Arner","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5159","DOI":"10.1128\/AEM.70.9.5159-5167.2004","article-title":"Assessment of production conditions for efficient use of Escherichia coli in high-yield heterologous recombinant selenoprotein synthesis","volume":"70","author":"Rengby","year":"2004","journal-title":"Appl. Env. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8581","DOI":"10.1074\/jbc.273.15.8581","article-title":"Rat and calf thioredoxin reductase are homologous to glutathione reductase with a carboxyl-terminal elongation containing a conserved catalytically active penultimate selenocysteine residue","volume":"273","author":"Zhong","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"12920","DOI":"10.1074\/jbc.M209266200","article-title":"Alternative mRNAs arising from trans-splicing code for mitochondrial and cytosolic variants of Echinococcus granulosus thioredoxin Glutathione reductase","volume":"278","author":"Agorio","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_51","first-page":"719856","article-title":"Mitochondrial Thioredoxin-Glutathione Reductase from Larval Taenia crassiceps (Cysticerci)","volume":"2010","author":"Pardo","year":"2010","journal-title":"J Parasitol Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"28977","DOI":"10.1074\/jbc.M109.020701","article-title":"Inhibition of Schistosoma mansoni thioredoxin-glutathione reductase by auranofin: Structural and kinetic aspects","volume":"284","author":"Angelucci","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s00436-010-1867-1","article-title":"In vitro killing action of auranofin on Taenia crassiceps metacestode (cysticerci) and inactivation of thioredoxin-glutathione reductase (TGR)","volume":"107","author":"Alvarez","year":"2010","journal-title":"Parasitol. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6474","DOI":"10.1021\/jm901021k","article-title":"Structure mechanism insights and the role of nitric oxide donation guide the development of oxadiazole-2-oxides as therapeutic agents against schistosomiasis","volume":"52","author":"Rai","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13071-016-1301-3","article-title":"Oxadiazole-2-oxides may have other functional targets, in addition to SjTGR, through which they cause mortality in Schistosoma japonicum","volume":"9","author":"Song","year":"2016","journal-title":"Parasit. Vectors"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5787","DOI":"10.3892\/mmr.2015.4119","article-title":"Molecular docking to explore the possible binding mode of potential inhibitors of thioredoxin glutathione reductase","volume":"12","author":"Huang","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.molbiopara.2018.09.004","article-title":"Targeting thioredoxin glutathione reductase as a potential antischistosomal drug target","volume":"225","author":"Eweas","year":"2018","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nm1737","article-title":"Identification of oxadiazoles as new drug leads for the control of schistosomiasis","volume":"14","author":"Sayed","year":"2008","journal-title":"Nat. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1006\/bbrc.1993.1410","article-title":"Removals of hydrogen peroxide and hydroxyl radical by thiol-specific antioxidant protein as a possible role In Vivo","volume":"192","author":"Lim","year":"1993","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1006\/bbrc.1995.1428","article-title":"Antioxidant function of recombinant human natural killer enhancing factor","volume":"208","author":"Sauri","year":"1995","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/11\/1603\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T04:32:25Z","timestamp":1761366745000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/11\/1603"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":60,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ph18111603"],"URL":"https:\/\/doi.org\/10.3390\/ph18111603","relation":{},"ISSN":["1424-8247"],"issn-type":[{"type":"electronic","value":"1424-8247"}],"subject":[],"published":{"date-parts":[[2025,10,23]]}}}