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We discovered tetrahydro- gamma -carboline sulfonamides as a new antischistosomal chemotype. The aryl sulfonamide and tetrahydro- gamma-carboline substructures were required for high antischistosomal activity. Increasing polarity improved solubility and metabolic stability but decreased antischistosomal activity. We identified two compounds with IC50 values < 5 microM against ex vivo Schistosoma mansoni.
