Authors

Akrachalanont¹;  Lawrence¹;  Carter¹;  ¹ University Of Strathclyde

Discussion

Anthelmintic resistance in humans and livestock has been spreading in prevalence and severity and has encouraged the research for new treatments. Conventional screens that rely on parasitic helminths are costly, labor intensive and low in high throughput. Caenorhabditis elegans has been demonstrated to be a valuable model organism for studying molecular and cellular properties of numerous human diseases. Recently, C. elegans has been used as a tool for drug discovery. The objective of this study is to establish a C. elegans based in vitro method for screening anthelminthic bioactivity of natural compounds and minor groove binder compounds. We evaluated the colorimetric Alamar Blue method for high throughput screening for anthelminthic activity of novel compounds. As C. elegans was maintained on Escherichia coli, we needed to remove this from the culture. We found that treatment with 0.09 mg/ml chloramphenicol could ablate the activity of E. coli without compromising the viability of C. elegans. Screening of novel compounds showed that high concentrations of the solvent, dimethylsulfoxide, was not toxic to C. elegans. Although, the current anthelminthics, ivermectin, levamizole and nitaxozanide were ineffective at killing the nematode we identified 2 novel compounds, which displayed activity against the helminth in vitro. This research determines C. elegans as an effective and low-priced model system for anthelmintic drug discovery.