- Title
- Assessing the anthelmintic activity of pyrazole-5-carboxamide derivatives against Haemonchus contortus
- Creator
- Jiao, Yaqing; Preston, Sarah; Song, Hongjian; Jabbar, Abdul; Liu, Yuxiu; Baell, Jonathan; Hofmann, Andreas; Hutchinson, Dana; Wang, Tao; Koehler, Anson; Fisher, Gillian; Andrews, Katherine; Laleu, Benoit; Palmer, Michael; Burrows, Jeremy; Wells, Timothy; Wang, Qingmin; Gasser, Robin
- Date
- 2017
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/158374
- Identifier
- vital:11768
- Identifier
-
https://doi.org/10.1186/s13071-017-2191-8
- Identifier
- ISSN:1756-3305
- 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. © 2017 The Author(s).
- Publisher
- BioMed Central Ltd.
- Relation
- Parasites and Vectors Vol. 10, no. 1 (2017), p. 1-7
- Rights
- http://creativecommons.org/licenses/by/4.0/
- Rights
- Copyright © 2017 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Rights
- Open Access
- Rights
- This metadata is freely available under a CCO license
- Subject
- 1108 Medical Microbiology; 1117 Public Health and Health Services; Haemonchus contortus; Mitochondrial respiratory chain; Phenotypic screening; Synthetic pyrazole-5-carboxamide derivatives; Tolfenpyrad
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