Anti-schistosomal Biarylalkyl Carboxylic Acids Amides: Development and Target-Identification

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Schistosomiasis represents one of the „neglegted tropical infectious diseases (NTDs)“ of worldwide importance and is caused by worm parasites of the genus Schistosoma. Because there is no vaccine available and only one commonly used drug (Praziquantel), fighting NTDs like schistosomiasis has been prioritized by the WHO and the G7-nations. Starting with the identification of aldose reductases in Schistosoma mansoni we tested some inhibitors of human aldose reductase available from previous studies against cultured worm pairs and identified one active compound. Based on this „hit“, we made structural modifications leading us to the biarylcarboxylic acid amides with promising activity, which led to phenotypes hitherto not observed. Next we intend to further develop the class of biarylalkyl carboxylic acid amides to obtain a lead structure by extensive structural modifications flanked by in vitro and in vivo-assays evaluation. The second aim of this project is the identification and characterisation of further potential target proteins of these compounds through comprehensive biochemical investigations.