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Because of the increasing drug resistance to praziquantel (PZQ), which is the primary drug for schistosomiasis, developing new drugs to treat schistosomiasis is crucial. Oxadiazole-2-oxides have been identified as potential anti-schistosomiasis reagents targeting thioredoxin glutathione reductase (TGR).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In this work, one of the oxadiazole-2-oxides derivatives furoxan was used as the lead compound to exploit a series of novel furoxan derivatives for studying inhibitory activity against both recombinant\n Schistosoma japonicum<\/jats:italic>\n TGR containing selenium (rS\n j<\/jats:italic>\n TGR-Sec) and soluble worm antigen protein (SWAP) containing wild-type\n Schistosoma japonicum<\/jats:italic>\n TGR (wtS\n j<\/jats:italic>\n TGR), in order to develop a new leading compound for schistosomiasis. Thirty-nine novel derivatives were prepared to test their activity toward both enzymes. The docking method was used to detect the binding site between the active molecule and S\n j<\/jats:italic>\n TGR. The structure\u2013activity relationship (SAR) of these novel furoxan derivatives was preliminarily analyzed.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n It was found that several new derivatives, including compounds\n 6a\u20136d<\/jats:bold>\n ,\n 9ab<\/jats:bold>\n ,\n 9bd<\/jats:bold>\n and\n 9be<\/jats:bold>\n , demonstrated greater activity toward rS\n j<\/jats:italic>\n TGR-Sec or SWAP containing wtS\n j<\/jats:italic>\n TGR than did furoxan. Interestingly, all intermediates bearing hydroxy (\n 6a\u20136d<\/jats:bold>\n ) showed excellent inhibitory activity against both enzymes. In particular, compound\n 6d<\/jats:bold>\n with trifluoromethyl on a pyridine ring was found to have much higher inhibition toward both rS\n j<\/jats:italic>\n TGR-Sec (half-maximal inhibitory concentration, IC\n 50<\/jats:sub>\n ,7.5nM) and SWAP containing wtS\n j<\/jats:italic>\n TGR (IC\n 50<\/jats:sub>\n 55.8nM) than furoxan. Additionally, the docking method identified the possible matching sites between\n 6d<\/jats:bold>\n and\n Schistosoma japonicum<\/jats:italic>\n TGR (S\n j<\/jats:italic>\n TGR), which theoretically lends support to the inhibitory activity of\n 6d<\/jats:bold>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The data obtained herein showed that\n 6d<\/jats:bold>\n with trifluoromethyl on a pyridine ring could be a valuable leading compound for further study.\n <\/jats:p>\n <\/jats:sec>\n \n Graphical Abstract<\/jats:title>\n <\/jats:sec>","DOI":"10.1186\/s13071-021-04634-4","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T04:03:33Z","timestamp":1619409813000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Synthesis of oxadiazole-2-oxide derivatives as potential drug candidates for schistosomiasis targeting SjTGR"],"prefix":"10.1186","volume":"14","author":[{"given":"Gongming","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjiao","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dequn","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,26]]},"reference":[{"key":"4634_CR1","doi-asserted-by":"publisher","first-page":"e31456","DOI":"10.1371\/journal.pone.0031456","volume":"7","author":"L Song","year":"2012","unstructured":"Song L, Li J, Xie S, Qian C, Wang J, Zhang W, et al. 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