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.