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dc.contributor.authorPreston, Sarah
dc.contributor.authorLuo, Junjie
dc.contributor.authorZhang, Yuezhou
dc.contributor.authorJabbar, Abdul
dc.contributor.authorCrawford, Simon
dc.contributor.authorBaell, Jonathan
dc.contributor.authorHofmann, Andreas
dc.contributor.authorHu, Min
dc.contributor.authorZhou, Hai-Bing
dc.contributor.authorGasser, Robin B
dc.date.accessioned2017-07-17T23:39:33Z
dc.date.available2017-07-17T23:39:33Z
dc.date.issued2016
dc.identifier.issn1756-3305
dc.identifier.doi10.1186/s13071-016-1612-4
dc.identifier.urihttp://hdl.handle.net/10072/100695
dc.description.abstractBackground: Parasitic worms represent a substantial disease burden in animals and humans worldwide. The control of parasitic roundworms (nematodes) relies heavily on the use of anthelmintic drugs. However, widespread drug resistance in nematodes seriously compromises the effectiveness of many anthelmintics around the world. Thus, there is a need to discover new drugs, with unique modes of action, against parasites. Methods: Here, we synthesised and tested 74 selective estrogen receptor modulators (SERMs) for in vitro-activity on parasitic larvae of Haemonchus contortus (barber’s pole worm), one of the most important nematode pathogens of small ruminants (including sheep and goats) and a key representative of one of the largest groups of parasitic nematodes (the Strongylida) of animals. We also studied the morphology of treated and untreated larvae using scanning electron microscopy (SEM), and assessed the agonistic/antagonistic activity of SERMs in a human embryonic kidney cell line using a luciferase reporter assay system. Results: We identified three SERMs (one selenophene and two thiophene-core compounds) with potent inhibitory activities (at 3–25 μM) on the motility and development of parasitic stages of H. contortus. An SEM examination of treated H. contortus revealed considerable damage to the cuticle of fourth- but not exsheathed, third-stage larvae; this damage appeared to be consistent with that observed upon treatment with monepantel but not moxidectin (control compounds). Conclusion: The potency of the three SERMs compared favourably with commercially available anthelmintics, such that they warrant further assessment as nematocides. Future studies could focus on assessing the selectivity of these SERMs to parasites, characterising their target(s) and/or designing analogs that are parasite-specific.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherBioMed Central
dc.relation.ispartofpagefrom346-1
dc.relation.ispartofpageto346-11
dc.relation.ispartofjournalParasites & Vectors
dc.relation.ispartofvolume9
dc.subject.fieldofresearchMedical microbiology
dc.subject.fieldofresearchMedical parasitology
dc.subject.fieldofresearchHealth services and systems
dc.subject.fieldofresearchPublic health
dc.subject.fieldofresearchcode3207
dc.subject.fieldofresearchcode320704
dc.subject.fieldofresearchcode4203
dc.subject.fieldofresearchcode4206
dc.titleSelenophene and thiophene-core estrogen receptor ligands that inhibit motility and development of parasitic stages of Haemonchus contortus
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© The Author(s) 2016. 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.
gro.hasfulltextFull Text
gro.griffith.authorHofmann, Andreas


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