Assessing the anthelmintic activity of pyrazole-5-carboxamide derivatives against Haemonchus contortus.
Parasit Vectors
; 10(1): 272, 2017 May 31.
Article
in En
| MEDLINE
| ID: mdl-28569174
ABSTRACT
BACKGROUND:
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.METHODS:
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.RESULTS:
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 IC50 values ranging between ~3.4 and 55.6 µM. We studied the effect of these two 'hit' compounds on mitochondrial function by measuring oxygen consumption. This assessment showed that xL3s exposed to each of these compounds consumed significantly less oxygen and had less mitochondrial activity than untreated xL3s, which was consistent with specific inhibition of complex I of the respiratory electron transport chain in arthropods.CONCLUSIONS:
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrazoles
/
Haemonchus
/
Anthelmintics
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Parasit Vectors
Year:
2017
Type:
Article
Affiliation country:
Australia