Naturally occurring cardenolides affecting Schistosoma mansoni

Schistosomiasis is a neglected tropical disease of considerable public health burden. We recently discovered a micromolar activity of several cardenolides against newly transformed schistosomula (NTS) of the parasitic flatworm; Schistosoma mansoni; in a small compound screen including different substance classes of both natural products as well as synthetic molecules. In further experiments, a focused library of naturally occurring and synthetic steroids was explored against NTS and adult; S. mansoni; , revealing seven cardenolides with comparable activities as known anthelminthics such as praziquantel. Of these, gomphoside monoacetate and uscharin showed suitable therapeutic indices. In a first; in vivo; study, at a dose of 10 mg/kg, only minor activity in mice harboring a chronic; S. mansoni; infection could be shown, which will be further investigated by structure-activity relationship studies as well as pharmacodynamic and pharmacokinetic approaches.