Title |
Assessing the anthelmintic activity of pyrazole-5-carboxamide derivatives against Haemonchus contortus
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Published in |
Parasites & Vectors, May 2017
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DOI | 10.1186/s13071-017-2191-8 |
Pubmed ID | |
Authors |
Yaqing Jiao, Sarah Preston, Hongjian Song, Abdul Jabbar, Yuxiu Liu, Jonathan Baell, Andreas Hofmann, Dana Hutchinson, Tao Wang, Anson V. Koehler, Gillian M. Fisher, Katherine T. Andrews, Benoît Laleu, Michael J. Palmer, Jeremy N. Burrows, Timothy N. C. Wells, Qingmin Wang, Robin B. Gasser |
Abstract |
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 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. 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. |
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Country | Count | As % |
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United Kingdom | 2 | 25% |
United States | 1 | 13% |
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Members of the public | 5 | 63% |
Science communicators (journalists, bloggers, editors) | 3 | 38% |
Mendeley readers
Geographical breakdown
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Unknown | 28 | 100% |
Demographic breakdown
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Student > Ph. D. Student | 5 | 18% |
Researcher | 3 | 11% |
Student > Bachelor | 3 | 11% |
Student > Master | 2 | 7% |
Lecturer | 1 | 4% |
Other | 3 | 11% |
Unknown | 11 | 39% |
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Medicine and Dentistry | 3 | 11% |
Veterinary Science and Veterinary Medicine | 2 | 7% |
Biochemistry, Genetics and Molecular Biology | 1 | 4% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
Other | 1 | 4% |
Unknown | 15 | 54% |