Identification and Profiling of Nematicidal Compounds in Veterinary Parasitology

• Published in: Parasitic Helminths pp. 135 - 157
• Main Authors: Rohwer, Andreas, Lutz, Jürgen, Chassaing, Christophe, Uphoff, Manfred, Heckeroth, Anja R, Selzer, Paul M
• Format: Book Chapter
• Language: English
• Published: Weinheim, Germany Wiley‐VCH Verlag GmbH & Co. KGaA 18.07.2012
• Subjects: anthelmintic drug; bioassay; mode of action; nematode; phenotype; veterinary parasitology
• ISBN: 3527330593; 9783527330591
• DOI: 10.1002/9783527652969.ch9

Infections with parasitic nematodes are responsible for a significant part of the parasitic burden in humans, animals, and plants. They cause devastating diseases and drastic economic losses in agriculture. Several anthelmintic drugs are on the market to combat the parasites and to treat the respective diseases. Although those drugs have been effective in eliminating nematodes, increasing drug resistance makes their continued use of less value. Therefore, the development of novel anthelmintic drugs is essential. Here, we review several physiology‐based nematode assays, which are important for the identification and profiling of novel nematicidal compounds in veterinary medicine. Using these bioassays, we screened approximately 160 000 compounds, and identified 61 structural compound classes and 171 singleton hits that were active against gastrointestinal nematodes. Many of these compounds cause distinct phenotypic changes with respect to morphology and locomotion of the treated nematodes. By discovering the specific mode of action (MoA) of several compounds, we were able to link the compound's activity to the related phenotype and consider this a genotype‐to‐compound‐to‐phenotype correlation. One compound class and its MoA is linked to a specific phenotype and has now been transferred via our lead optimization process to a nematicidal drug candidate. From our experience, we conclude that a combination of physiology‐ and target‐based approaches will increase drug discovery output.