Design, Synthesis, and Characterization of Novel Small Molecules as Broad Range Antischistosomal Agents
- University of Texas Health Science Center at San Antonio, TX (United States)
- Univ. of Texas at San Antonio, TX (United States). Center for Innovative Drug Discovery
- Texas BioMedical Research Inst., San Antonio, TX (United States)
- University of Texas Health Science Center at San Antonio, TX (United States); South Texas Veterans Health Care System, San Antonio, TX (United States)
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 Schistosoma mansoni but not other schistosome species (S. haematobium or S. japonicum) 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 Schistosoma 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 12a, which demonstrated broad-species activity in killing S. mansoni (75%), S. haematobium (40%), and S. japonicum (83%).
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- National Institutes of Health (NIH); National Institute of Allergy and Infectious Diseases (NIAID); The Welch Foundation; National Institute of General Medical Sciences (NIGMS); USDOE Office of Science (SC)
- Grant/Contract Number:
- NIAID R01 AI115691; AC02-06CH11357; HHSN272201000005I
- OSTI ID:
- 1481298
- Journal Information:
- ACS Medicinal Chemistry Letters, Vol. 9, Issue 10; ISSN 1948-5875
- Publisher:
- American Chemical Society (ACS)Copyright Statement
- Country of Publication:
- United States
- Language:
- ENGLISH
Web of Science
Oxamniquine resistance alleles are widespread in Old World Schistosoma mansoni and predate drug deployment
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journal | October 2019 |
Non-sedating benzodiazepines cause paralysis and tissue damage in the parasitic blood fluke Schistosoma mansoni
|
journal | November 2019 |
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