Development of microscale assays to screen for novel anthelmintic drugs

Abstract

Parasitic nematodes are beginning to show resistance to the most commonly used classes of anthelmintic drugs at an alarming rate. As the number of documented cases of resistance increases, people are becoming more interested in identifying new sources of anthelmintic drugs. Since the emergence of popular anthelmintics in the 1980s, there has been little effort put into the development of new drugs for use against helminths. Recently, a few studies have investigated new sources for anthelmintics, including one that discovered a whole new class of compounds that showed anthelmintic activity against resistant nematode species. Previous studies used high volume assays which require milliliter amounts of the compounds being screened for anthelmintic abilities. The goal of this study was to develop new screening processes for identifying anthelmintic activity in naturally derived compounds using microliter volumes of the test compound solutions. Two microscale assays were developed using the nematode Caenorhabditis elegans as a model system: one looking for the immediate effects on motility and the other investigating the effects of each compound on development and fecundity of the worms. The assays developed in this project were used to identify several compounds of interest that could be further investigated as potential anthelmintic drugs.