Oxadiazole-2-oxides may have other functional targets, in addition to SjTGR, through which they cause mortality in Schistosoma japonicum. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Song, Li-Jun; Luo, Huan; Fan, Wen-Hua; Wang, Gu-Ping; Yin, Xu-Ren; Shen, Shuang; Wang, Jie; Jin, Yi; Zhang, Wei; Gao, Hong; Liu, Qian; Wang, Wen-Long; Feng, Bainian; Yu, Chuan-Xin
• Is Part Of: Parasites & vectors. Volume 9:Issue 1(2016)
• Page Start: 1
• Page End: 12
• Publication Date: 2016-12
• Subjects: Schistosoma japonicum -- Oxadiazole-2-oxide -- Antischistosomal activity -- Structure-activity relationship (SAR); Parasitism -- Periodicals; Parasites -- Periodicals; Vector-pathogen relationships -- Periodicals; Animals as carriers of disease -- Periodicals; Insects as carriers of disease -- Periodicals; 616.96
• DOI: 10.1186/s13071-016-1301-3
• Languages: English
• ISSNs: 1756-3305

Abstract

Abstract Background Schistosomiasis 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. Methods To develop novel treatment reagents againstSchistosoma japonicum, 30 novel oxadiazole-2-oxides were synthesised and their antischistosomal activities on juvenile and adultS. japonicum were evaluatedin vitro andin vivo . Their inhibitory activities againstS. japonicum thioredoxin glutathione reductase (SjTGR) were also analysed. Results Most of the oxadiazole-2-oxides showed good juvenile and adultS. japonica killing activitiesin vitro . However, the antischistosomal effects of these compounds were not positively correlated with either their inhibition of SjTGR, or with nitric oxide (NO) release. Compounds4a, 4b, 7c, 13, 16 and20 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, compounds4a and16 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. Conclusions The 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 inS. 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.