New evidence fortamoxifen as an antischistosomal agent: in vitro, in vivo and target fishing studies.

Abstract

Background: Praziquantel is the only drug available to treat schistosomiasis, and there is an urgent demand for new anthelmintic agents. Methodology & results: We conducted in-depth in vitro and in vivostudies and report a target fishing investigation. In vitro, tamoxifen was active against adult and immature worms at low concentrations (<5μM). Tamoxifen at a single dose (400mg/kg) or once daily for five consecutive days (100mg/kg/day) in mice harboring either adult (patent infection) or juvenile (prepatent infection) significantly reduced worm burden (30-70%) and egg production (70-90%). Target fishing studies revealed propionyl-CoA carboxylase as a potential target for tamoxifen in Schistosomamansoni and glucose uptake by S. mansoni was also significantly reduced. Conclusion: Our results provide news evidence of antiparasitic effect of tamoxifen and reveal propionyl-CoA carboxylase as a potential target.