Fungal metabolites as novel anthelmintics against soil-transmitted helminthes

It is estimated that over 2 billion people worldwide are suffering from complications due to infections with soil transmitted helminthes (STHs), but very little research is being conducted by human health pharmaceutical companies. In the USA, it is estimated that in distressed areas of poverty, just under 4 million people harbor undiagnosed STH infections.Anthelmintic resistance to broad spectrum compounds has become a worldwide issue. Our initial goal was to screen a unique collection of filamentous fungi and pure isolated fungus metabolites against Brugia malayi microfilaria, Haemonchus contortus L1 and Strongyloides stercoralis L3. We confirmed a number of active fungi against all three targets. Many of these active extracts were produced by cultures not previously shown to produce anthelmintic metabolites. De-replication procedures demonstrated metabolite novelty. Of the 90 pure compounds tested, we identified active metabolites against all three target species. One of the active pure compounds identified was enniatin D which belongs to a structure class known to have anthelmintic activity, thereby validating the approach.