Design, Synthesis, and Characterization of Novel Small Molecules as Broad Range Antischistosomal Agents.
Publication Type:Journal Article
Source:ACS Med Chem Lett, Volume 9, Issue 10, p.967-973 (2018)
<p>Schistosomiasis is a major human parasitic disease afflicting more than 250 million people, historically treated with chemotherapies praziquantel or oxamniquine. Since oxamniquine is species-specific, killing but not other schistosome species ( or ) and evidence for drug resistant strains is growing, research efforts have focused on identifying novel approaches. Guided by data from X-ray crystallographic studies and worm killing assays on oxamniquine, our structure-based drug design approach produced a robust structure-activity relationship (SAR) program that identified several new lead compounds with effective worm killing. These studies culminated in the discovery of compound , which demonstrated broad-species activity in killing (75%), (40%), and (83%).</p>