- Title
- Phenotypic screening of the 'Kurz-box' of chemicals identifies two compounds (BLK127 and HBK4) with anthelmintic activity in vitro against parasitic larval stages of Haemonchus contortus
- Creator
- Nguyen, Linh; Kurz, Thomas; Preston, Sarah; Brueckmann, Hjoerdis; Lungerich, Beate; Herath, Dilrukshi; Koehler, Anson; Wang, Tao; Skalova, Lenka; Jabbar, Abdul; Gasser, Robin
- Date
- 2019
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/169196
- Identifier
- vital:13986
- Identifier
-
https://doi.org/10.1186/s13071-019-3426-7
- Identifier
- ISBN:1756-3305
- Abstract
- BackgroundDue to anthelmintic resistance problems, there is a need to discover and develop new drugs for the treatment and control of economically important and pathogenic nematodes of livestock animals. With this focus in mind, we screened 236 compounds from a library (called the Kurz-box') representing chemically diverse classes such as heterocyclic compounds (e.g. thiazoles, pyrroles, quinolines, pyrimidines, benzo[1,4]diazepines), hydoxamic acid-based metalloenzyme inhibitors, peptidomimetics (bis- and tris-pyrimidoneamides, alkoxyamides) and various intermediates on Haemonchus contortus, one of the most important parasitic nematodes of ruminants.MethodsIn the present study, we tested these compounds, and measured the inhibition of larval motility and development of exsheathed third-stage (xL3) and fourth-stage (L4) larvae of H. contortus using an optimised, whole-organism phenotypic screening assay.ResultsOf the 236 compounds, we identified two active compounds (called BLK127 and HBK4) that induced marked phenotypic changes in the worm in vitro. Compound BLK127 induced an eviscerated' phenotype in the xL3 stage and also inhibited L4 development. Compound HBK4 exerted a curved' phenotype in both xL3s and L4s.ConclusionsThe findings from this study provide a basis for future work on the chemical optimisation of these compounds, on assessing the activity of optimised compounds on adult stages of H. contortus both in vitro and in vivo (in the host animal) and against other parasitic worms of veterinary and medical importance.
- Publisher
- BMC
- Relation
- Parasites & Vectors Vol. 12, no. (2019), p. 1-9
- Rights
- http://creativecommons.org/licenses/by/4.0/
- Rights
- Copyright © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), 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; Phenotypic screening; Anthelmintic; Larval motility and development in vitro
- Full Text
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