Schistosomiasis is a major human parasitic disease and a major cause of morbidity in 76 countries of the world where it afflicts more than 208 million people. Existing therapies such as Praziquantel (PZQ) or Oxamniquine (OXA) although efficacious, are showing reduced cure rates, while evidence for drug resistant strains is being established. Previous work at UTHSCSA identified a sulfotransferase as the gene responsible for OXA drug resistance and thus the hitherto unknown mode of OXA action. With this information X-ray structural studies helped establish the protein-drug interactions and paved a path for rational design of improved OXA derivatives that kill the three most prevalent species S. mansoni, S. haematobium and S. japonicum. Guided by X-ray crystallographic studies, the OXA structure and mechanism of action, structure-based drug design efforts are focused on the design of OXA-like analogs targeting S. mansoni, S. haematobium and S. japonicum. The design of new analogs, compound synthesis, structure-activity relationships, protein-drug interactions and in vitro assay results will be presented.

Center for innovative in drug discovery collaborative programs: Structure based drug design, synthesis and evaluation of new antischistosomal agents

253rd National Meeting (2017)

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