Fig. 6.

Iterative process of identifying novel drugs. We soaked OXA into S. mansoni sulfotransferase (SmSULT) and determined the structural relationships. We then designed and synthesized new derivatives based on the structural information. The OXA derivatives are tested for killing activity using worm motility assays or direct observation in cultured parasites. Those derivatives that showed the best cidal activity were soaked into new crystals and the process repeated. This innovative approach has produced highly efficacious OXA derivatives that will kill the three major species of Schistosoma where OXA would only kill S. mansoni. The very best cidal derivatives are tested in in vivo Schistosoma models.