| Summary: | Parasitic nematodes cause diseases in livestock animals and major economic losses to the agricultural industry worldwide. Nematodes of the order Strongylida, including <i>Haemonchus contortus</i>, are particularly important. The excessive use of anthelmintic compounds to treat infections and disease has led to widespread resistance to these compounds in nematodes, such that there is a need for new anthelmintics with distinctive mechanisms of action. With a focus on discovering new anthelmintic entities, we screened 400 chemically diverse compounds within the ‘<i>Pandemic Response Box</i>’ (from Medicines for Malaria Venture, MMV) for activity against <i>H. contortus</i> and its free-living relative, <i>Caenorhabditis elegans</i>—a model organism. Using established phenotypic assays, test compounds were evaluated in vitro for their ability to inhibit the motility and/or development of <i>H. contortus</i> and <i>C. elegans</i>. Dose-response evaluations identified a compound, MMV1581032, that significantly the motility of <i>H. contortus</i> larvae (IC<sub>50</sub> = 3.4 ± 1.1 μM) and young adults of <i>C. elegans</i> (IC<sub>50</sub> = 7.1 ± 4.6 μM), and the development of <i>H. contortus</i> larvae (IC<sub>50</sub> = 2.2 ± 0.7 μM). The favourable characteristics of MMV1581032, such as suitable physicochemical properties and an efficient, cost-effective pathway to analogue synthesis, indicates a promising candidate for further evaluation as a nematocide. Future work will focus on a structure-activity relationship investigation of this chemical scaffold, a toxicity assessment of potent analogues and a mechanism/mode of action investigation.
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