Practical High-Throughput Method to Screen Compounds for Anthelmintic Activity against Caenorhabditis elegans

Area of Science:

• Biochemistry
• Pharmacology
• Parasitology

Background:

• Drug resistance in parasitic worms necessitates novel anthelmintic discovery.
• Existing screening methods for anthelmintics can be time-consuming and costly.
• Caenorhabditis elegans is a widely used model organism in parasitic nematode research.

Purpose of the Study:

• To establish a practical, cost-effective, and high throughput screening assay for identifying motility inhibitors.
• To screen a library of small molecules for compounds affecting C. elegans motility.
• To assess the potential of identified compounds as candidates for nematocides or anthelmintics.

Main Methods:

• Development of a high throughput screening assay measuring Caenorhabditis elegans motility using infrared light-interference.
• Screening of 14,400 small molecules from the Maybridge HitFinder library.
• Identification of compounds that reproducibly inhibit C. elegans motility and assessment of dose-response relationships.

Main Results:

• A hit rate of 0.3% was achieved, identifying small molecules that inhibit C. elegans motility.
• Dose-response relationships were established for a subset of identified compounds.
• The assay demonstrated high throughput (~10,000 compounds/week) and cost-effectiveness.

Conclusions:

• The developed assay is efficient and suitable for screening large compound libraries for anthelmintic discovery.
• Identified hits warrant further evaluation for optimization or repurposing as nematocides/nematostats.
• The assay is adaptable for screening parasitic nematodes, addressing the critical need for new anthelmintics due to widespread drug resistance.