pyrazole-5-carboxamide and Mitochondrial-Diseases

In this study, we tested five series of pyrazole-5-carboxamide compounds (n = 55) for activity against parasitic stages of the nematode Haemonchus contortus (barber's pole worm), one of the most pathogenic parasites of ruminants.. In an optimised, whole-organism screening assay, using exsheathed third-stage (xL3) and fourth-stage (L4) larvae, we measured the inhibition of larval motility and development of H. contortus.. Amongst the 55 compounds, we identified two compounds (designated a-15 and a-17) that reproducibly inhibit xL3 motility as well as L4 motility and development, with IC. The present findings provide a sound basis for future work, aimed at identifying the targets of compounds a-15 and a-17 and establishing the modes of action of these chemicals in H. contortus.

Topics: Animals; Anthelmintics; Biological Assay; Drug Evaluation, Preclinical; Haemonchiasis; Haemonchus; Larva; Mitochondria; Mitochondrial Diseases; Oxygen Consumption; Parasitic Sensitivity Tests; Pyrazoles; Quaternary Ammonium Compounds; Reproducibility of Results; Ruminants; Toxicity Tests