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Oxadiazole-2-oxides may have other functional targets, in addition to SjTGR, through which they cause mortality in Schistosoma japonicum.
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.
Affiliation
  • Song LJ; Key Laboratory on Technology for Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key laboratory of Parasite Molecular Biology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu, 214064, China. songlijun1025@163.com.
  • Luo H; Public Health Research Center, Jiangnan University, Wuxi, 214122, China. songlijun1025@163.com.
  • Fan WH; School of Pharmaceutical Science, Jiangnan University, Wuxi, 214122, China. 1464371728@qq.com.
  • Wang GP; School of Pharmaceutical Science, Jiangnan University, Wuxi, 214122, China. fanwenhua1987@163.com.
  • Yin XR; School of Pharmaceutical Science, Jiangnan University, Wuxi, 214122, China. p85615822@yeah.net.
  • Shen S; Key Laboratory on Technology for Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key laboratory of Parasite Molecular Biology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu, 214064, China. yinxuren@sohu.com.
  • Wang J; Public Health Research Center, Jiangnan University, Wuxi, 214122, China. yinxuren@sohu.com.
  • Jin Y; Key Laboratory on Technology for Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key laboratory of Parasite Molecular Biology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu, 214064, China. 2496049650@163.com.
  • Zhang W; Public Health Research Center, Jiangnan University, Wuxi, 214122, China. 2496049650@163.com.
  • Gao H; Key Laboratory on Technology for Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key laboratory of Parasite Molecular Biology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu, 214064, China. sunflower1230@163.com.
  • Liu Q; Public Health Research Center, Jiangnan University, Wuxi, 214122, China. sunflower1230@163.com.
  • Wang WL; Key Laboratory on Technology for Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key laboratory of Parasite Molecular Biology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu, 214064, China. 502240773@qq.com.
  • Feng B; Public Health Research Center, Jiangnan University, Wuxi, 214122, China. 502240773@qq.com.
  • Yu CX; Key Laboratory on Technology for Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key laboratory of Parasite Molecular Biology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu, 214064, China. 543608268@qq.com.
Parasit Vectors ; 9: 26, 2016 Jan 20.
Article in En | MEDLINE | ID: mdl-26791563
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 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.

RESULTS:

Most 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.

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 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.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Oxadiazoles / Oxides / Praziquantel / Schistosoma japonicum / Schistosomicides / Schistosomiasis japonica Limits: Animals / Female / Humans / Male Language: En Journal: Parasit Vectors Year: 2016 Document type: Article Affiliation country: China

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Oxadiazoles / Oxides / Praziquantel / Schistosoma japonicum / Schistosomicides / Schistosomiasis japonica Limits: Animals / Female / Humans / Male Language: En Journal: Parasit Vectors Year: 2016 Document type: Article Affiliation country: China