BackgroundSchistosomiasis is one of the world’s major public health problems. Besides praziquantel (PZQ), there is currently no other effective treatment against schistosomiasis. The development of new antischistosomal agents to curb the emergence of PZQ resistance should be a high priority. Oxadiazole-2-oxides have been identified as potential antischistosomal reagents, with thioredoxin glutathione reductase (TGR) being one of their molecular targets.MethodsTo develop novel treatment reagents against Schistosoma japonicum, 30 novel oxadiazole-2-oxides were synthesised and their antischistosomal activities on juvenile and adult S. japonicum were evaluated in vitro and in vivo. Their inhibitory activities against S. japonicum thioredoxin glutathione reductase (SjTGR) were also analysed.ResultsMost of the oxadiazole-2-oxides showed good juvenile and adult S. japonica killing activities in vitro. However, the antischistosomal effects of these compounds were not positively correlated with either their inhibition of SjTGR, or with nitric oxide (NO) release. Compounds 4a, 4b, 7c, 13, 16 and 20 resulted in 87.7 %, 83.1 %, 87.1 %, 84.6 %, 90.8 % and 69.5 %, respectively, mortality in the adult worms, when used to treat infected mice at schistosomula stage. These mortality rates were similar to or higher than that of artemisinin. Furthermore, compounds 4a and 16 resulted in 66.7 % and 69.4 % reductions in the worm burdens, respectively, when infected mice were treated at the adult worm stage. These treatment effects were similar to PZQ. No differences in activity of the oxadiazole-2-oxides against female and male adult worms were observed. The toxicity of the oxadiazole-2-oxides on mammalian cells appeared to be similar to, or less than, that of PZQ.ConclusionsThe antischistosomal activity of the oxadiazole-2-oxides does not depend on NO production or the inhibition of SjTGR activity. There may be other functional targets of the oxadiazole-2-oxides in S. japonicum. Several of the novel oxadiazole-2-oxides synthesised in this study could be used to develop novel antischistosomal drugs and explore potential molecular targets.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1301-3) contains supplementary material, which is available to authorized users.

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Intestinal schistosomiasis caused by the Schistosoma japonicum is located mainly in the East Asian region. Schistosomiasis is part of the neglected tropical diseases that affects mostly the poor population; although its incidence has dropped in these years, schistosomiasis caused by S. japonicum still is a prevalent disease. Adult worms reside in the mesenteric veins and excrete eggs that migrate through the intestinal wall and pass out with the stool. The clinical manifestations depend on the stage of the disease, the intestinal schistosomiasis mostly affects the colon, but it can also affect the small intestine. This review's purpose is to highlight the background and importance of the intestinal manifestations caused by Schistosoma japonicum.