Synthesis of oxadiazole-2-oxide analogues as potential antischistosomal agents

doi:10.1016/j.tetlet.2009.01.120

Tetrahedron Letters

Volume 50, Issue 15, 15 April 2009, Pages 1710-1713

https://doi.org/10.1016/j.tetlet.2009.01.120 Get rights and content

Abstract

The synthesis of several 1,2,5-oxadiazole-2-oxide (Furoxan) analogues is described herein. These compounds were prepared in an effort to probe the SAR around the phenyl substituent and oxadiazole core for our studies toward thioredoxin-glutathione reductase (TGR) inhibition and antischistosomal activity.

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Acknowledgments

The authors thank Jeremy Smith and Paul Shinn for assistance with compound management. This research was supported by the Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research.

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The antioxidant defenses of vertebrates are dependent on two enzymes: glutathione reductase and thioredoxinareductase. The schistosomes only contain a single enzyme, multifunctional aselenocysteine, thioredoxin glutathione reductase (TGR) (Cioli et al., 2014; Rai et al., 2009). This enzyme is essential for the survival of the parasite and has been the subject of intense studies to increase the capacity of identification of oxadiazole-2-oxides as a class of potential schistosomicidal agents (Cioli et al., 2014; Rai et al., 2009).
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Synthesis of oxadiazole-2-oxide analogues as potential antischistosomal agents

Abstract

Graphical abstract

Section snippets

Acknowledgments

Acta Trop.

Biomed. Pharmacother.

Mol. Biochem. Parasitol.

Adv. Heterocycl. Chem.

Bioorg. Med. Chem.

Bioorg. Med. Chem.

Nat. Med.

PLos Negl. Trop. Dis.

Proc. Natl. Acad. Sci. U.S.A.

Science

Clin. Infect. Dis.

Med. J. Aust.