Open AccessNaturally Occurring Cardenolides Affecting Schistosoma mansoni
Author(s) -
Jennifer Keiser,
Vanessa Koch,
Anke Deckers,
H. T. Andrew Cheung,
Nicole Jung,
Stefan Bräse
Publication year - 2020
Publication title -
acs infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.324
H-Index - 39
ISSN - 2373-8227
DOI - 10.1021/acsinfecdis.0c00175
Subject(s) - schistosoma mansoni , praziquantel , schistosomiasis , in vivo , biology , schistosoma , pharmacodynamics , flatworm , pharmacology , pharmacokinetics , toxicology , immunology , helminths , zoology , microbiology and biotechnology
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.