New Evidence for Tamoxifen as an Antischistosomal Agent:<i>In Vitro</i>,<i>In Vivo</i>and Target Fishing Studies

Abstract

<b>Background:</b> Praziquantel is the only drug available to treat schistosomiasis, and there is an urgent demand for new anthelmintic agents. <b>Methodology & results:</b> We conducted in-depth <i>in vitro</i> and <i>in vivo</i> studies and report a target fishing investigation. <i>In vitro</i>, tamoxifen was active against adult and immature worms at low concentrations (<5 μM). Tamoxifen at a single dose (400 mg/kg) or once daily for five consecutive days (100 mg/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 <i>Schistosoma</i> <i>mansoni</i> and glucose uptake by <i>S. mansoni</i> was also significantly reduced. <b>Conclusion:</b> Our results provide news evidence of antiparasitic effect of tamoxifen and reveal propionyl-CoA carboxylase as a potential target.