Drugstore in the forest: New anthelmintic compounds isolated from fungi.
More than 1.7 billion people worldwide are affected by infections with roundworms, whipworms and hookworms. These neglected tropical diseases are controlled by the widespread application of anthelmintic drugs regardless of the infection status of the treated individuals. This mass medication and the fact that only a few active substances are currently in use lead to increasing resistance of the parasites to the anthelmintic drugs. New therapeutic approaches are therefore needed to effectively combat worm diseases.
IPB chemists, together with Swiss and MLU scientists, have isolated new anthelmintic agents from fungi. To do this, they studied eleven different species of fungi that are not naturally eaten by insect larvae, which led to the assumption that these species produce active substances against maggots and, in the best case, are also active against worms. One of the selected species, Albatrellus confluens, proved to be a hit. The Halle scientists were able to isolate the promising compounds grifolin and neogrifolin from its fruiting body. In the bioassay, both substances proved to be highly effective against the nematode Caenorhabditis elegans.
Since anthelmintic agents do not yield high economic profits, the development of cost-effective syntheses is essential for launching these substances on the market. The Halle scientists succeeded in synthesizing various analogues of the compounds, which they subsequently tested not only for their activity against C. elegans, but also against five different worm parasites of humans and animals. Two of the compounds tested showed high activity against the activated laboratory strain of Schistosoma mansoni, the causative agent of schistosomiasis. One compound also showed antiproliferative activity against human prostate and colorectal cancer cell lines.
Fungi are increasingly proving to be a promising source of new agents against various diseases. However, their suitability for providing new lead structures for anthelmintics remains largely unexplored. About half of their biomass in the soil is consumed by nematodes. Therefore, they possess appropriate protective and defensive compounds. Recent studies showed various anthelmintic effects especially in edible mushrooms. Grifolin and neogrifolin are known for their diverse antioxidant, antimicrobial and antiproliferative activities. Now, they have also been shown to be useful in combating worm diseases.
