1147334-80-2Relevant academic research and scientific papers
Synthesis of oxadiazole-2-oxide analogues as potential antischistosomal agents
Rai, Ganesha,Thomas, Craig J.,Leister, William,Maloney, David J.
supporting information; experimental part, p. 1710 - 1713 (2009/07/05)
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.
Structure mechanism insights and the role of nitric oxide donation guide the development of oxadiazole-2-oxides as therapeutic agents against schistosomiasis
Rai, Ganesha,Sayed, Ahmed A.,Lea, Wendy A.,Luecke, Hans F.,Chakrapani, Harinath,Prast-Nielsen, Stefanie,Jadhav, Ajit,Leister, William,Shen, Min,Inglese, James,Austin, Christopher P.,Keefer, Larry,Arnér, Elias S. J.,Simeonov, Anton,Maloney, David J.,Williams, David L.,Thomas, Craig J.
supporting information; experimental part, p. 6474 - 6483 (2010/03/31)
Schistosomiasis is a chronic parasitic disease affecting hundreds of millions of individuals worldwide. Current treatment depends on a single agent, praziquantel, raising concerns of emergence of resistant parasites. Here, we continue our explorations of an oxadiazole-2-oxide class of compounds we recently identified as inhibitors of thioredoxin glutathione reductase (TGR), a selenocysteine-containing flavoenzyme required by the parasite to maintain proper cellular redox balance. Through systematic evaluation of the core molecular structure of this chemotype, we define the essential pharmacophore, establish a link between the nitric oxide donation and TGR inhibition, determine the selectivity for this chemotype versus related reductase enzymes, and present evidence that these agents can be modified to possess appropriate drug metabolism and pharmacokinetic properties. The mechanistic link between exogenous NO donation and parasite injury is expanded and better defined. The results of these studies verify the utility of oxadiazole-2-oxides as novel inhibitors of TGR and as efficacious antischistosomal agents. 2009 American Chemical Society.
