Design, Synthesis, and Characterization of Novel Small Molecules as Broad Range Antischistosomal Agents [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 540.2 Chemistry and allied sciences
• Thông tin xuất bản: Bethesda, Md. : Oak Ridge, Tenn. : National Institutes of Health (U.S.) ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2018
• Mô tả vật lý: Size: p. 967-973 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 260196
• Chủ đề: 1. 37 inorganic, organic, physical, and analytical chemistry; 2. 60 applied life sciences; 3. Aminopiperidine; 4. Aminopyrrolidine; 5. Oxamniquine; 6. Schistosomiasis; 7. Structure?activity relationships; 8. X-ray crystallographic studies

Tóm tắt

 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 <
 i>
 Schistosoma mansoni<
 /i>
  but not other schistosome species (<
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 S. haematobium<
 /i>
  or <
 i>
 S. japonicum<
 /i>
 ) 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 <
 i>
 Schistosoma<
 /i>
  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. We report these studies culminated in the discovery of compound <
 b>
 12a<
 /b>
 , which demonstrated broad-species activity in killing <
 i>
 S. mansoni<
 /i>
  (75%), <
 i>
 S. haematobium<
 /i>
  (40%), and <
 i>
 S. japonicum<
 /i>
  (83%).