The treatment and control of schistosomiasis virtually relies on a single drug, praziquantel. The pressing need to develop new antischistosomal compounds has been emphasized [8]�C[11], sellekchem particularly in view of blanket application of praziquantel within the frame of ��preventive chemotherapy�� [12], a strategy that might select for drug-resistant parasites. Additionally, there is an important deficiency in the therapeutic profile of praziquantel. The drug targets the adult worm, but has only minor activity against the young developing stages (i.e., schistosomula); hence, retreatment is necessary to kill those parasites that have since matured. There is no dedicated drug discovery and development program pursued for schistosomiasis, either by the pharmaceutical industry or through public-private partnerships.

However, despite the paucity of a concerted effort to develop novel antischistosomal drugs, a number of compounds with promising antischistosomal properties have been identified by academia, such as the synthetic trioxolanes [13], the cysteine protease inhibitor K11777 [14], alkylaminoalkanethiosulfuric acids [15], praziquantel analogs [16] and, most recently, the oxadiazoles [10]. Nonetheless, to develop a new antischistosomal drug from lead drug candidates will take at least another decade. Underlying reasons are the scarce resources available for schistosomiasis and other neglected tropical diseases and the high failure rates of compounds during preclinical and clinical testing [17]. Interestingly, the artemisinins (e.g.

, artemether and artesunate), which are essential components of malaria treatment and control [18], also possess antischistosomal properties [19],[20]. Detailed in vivo studies revealed that schistosomula are particularly susceptible to the artemisinins, whereas moderate worm burden reductions are still apparent for adult worms [21]. A number of clinical trials carried out in different African settings confirmed that both artemether and artesunate have an effect against patent infections with S. haematobium and S. mansoni [20],[22]. Artemisinin-based combination therapies (ACTs) have been adopted as first-line drugs for uncomplicated Plasmodium falciparum malaria in most malaria-endemic countries as a strategy to avoid the selection of parasite drug resistance [18].

Since large parts of Africa are co-endemic for malaria and schistosomiasis [22] and both Plasmodium and Schistosoma parasites degrade hemoglobin, a putative target for several antimalarial drugs, we were motivated to test other antimalarials that are commonly employed in combination with an artemisinin derivative for their potential Entinostat antischistosomal activities. We then followed up on the promising in vivo activity of mefloquine, first to elucidate the dose-response relationships of single-dose mefloquine against juvenile and adult S. mansoni and S. japonicum and, second, to assess the stage-specific susceptibility of both parasites to mefloquine.