Show simple item record

dc.contributor.authorJiao, Y
dc.contributor.authorPreston, S
dc.contributor.authorHofmann, A
dc.contributor.authorTaki, A
dc.contributor.authorBaell, J
dc.contributor.authorChang, BCH
dc.contributor.authorJabbar, A
dc.contributor.authorGasser, RB
dc.contributor.editorRollinson, David
dc.contributor.editorStothard, Russell
dc.date.accessioned2020-12-07T00:03:55Z
dc.date.available2020-12-07T00:03:55Z
dc.date.issued2020
dc.identifier.isbn9780128207505
dc.identifier.doi10.1016/bs.apar.2019.12.003
dc.identifier.urihttp://hdl.handle.net/10072/399986
dc.description.abstractParasitic roundworms (nematodes) cause substantial morbidity and mortality in animals worldwide. Anthelmintic treatment is central to controlling these worms, but widespread resistance to most of the commercially available anthelmintics for veterinary and agricultural use is compromising control, such that there is an urgency to discover new and effective drugs. The purpose of this article is to review information on parasitic nematodes, the treatment and control of parasitic nematode infections and aspects of discovering new anthelmintics in the context of anthelmintic resistance problems, and then to discuss some progress that our group has made in identifying selected compounds with activity against nematodes. The focus of our recent work has been on discovering new chemical entities and known drugs with anthelmintic activities against Haemonchus contortus as well as other socioeconomically important parasitic nematodes for subsequent development. Using whole worm-based phenotypic assays, we have been screening compound collections obtained via product-development-partnerships and/or collaborators, and active compounds have been assessed for their potential as anthelmintic candidates. Following the screening of 15,333 chemicals from five distinct compound collections against H. contortus, we have discovered one new chemical entity (designated SN00797439), two human kinase inhibitors (SNS-032 and AG-1295), 14 tetrahydroquinoxaline analogues, one insecticide (tolfenpyrad) and two tolfenpyrad (pyrazole-5-carboxamide) derivatives (a-15 and a-17) with anthelmintic activity in vitro. Some of these 20 ‘hit’ compounds have selectivity against H. contortus in vitro when compared to particular human cell lines. In our opinion, some of these compounds could represent starting points for ‘lead’ development. Accordingly, the next research steps to be pursued include: (i) chemical optimisation of representative chemicals via structure-activity relationship (SAR) evaluations; (ii) assessment of the breadth of spectrum of anthelmintic activity on a range of other parasitic nematodes, such as strongyloids, ascaridoids, enoplids and filarioids; (iii) detailed investigations of the absorption, distribution, metabolism, excretion and toxicity (ADMET) of optimised chemicals with broad nematocidal or nematostatic activity; and (iv) establishment of the modes of action of lead candidates.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.publisher.placeUnited Kingdom
dc.relation.ispartofbooktitleAdvances in Parasitology
dc.relation.ispartofchapter1
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto45
dc.relation.ispartofvolume108
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchVeterinary sciences
dc.subject.fieldofresearchMedical microbiology
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode3107
dc.subject.fieldofresearchcode3009
dc.subject.fieldofresearchcode3207
dc.subject.keywordsAnthelmintics
dc.subject.keywordsDrug discovery
dc.subject.keywordsHaemonchus contortus
dc.subject.keywordsNovel chemical entities
dc.subject.keywordsPhenotypic screening
dc.titleA perspective on the discovery of selected compounds with anthelmintic activity against the barber's pole worm—Where to from here?
dc.typeBook chapter
dc.type.descriptionB1 - Chapters
dcterms.bibliographicCitationJiao, Y; Preston, S; Hofmann, A; Taki, A; Baell, J; Chang, BCH; Jabbar, A; Gasser, RB, A perspective on the discovery of selected compounds with anthelmintic activity against the barber's pole worm—Where to from here?, Advances in Parasitology, 2020, 108, pp. 1-45
dc.date.updated2020-12-07T00:01:41Z
gro.rights.copyrightSelf-archiving is not yet supported by this publisher. Please refer to the publisher's website or contact the author(s) for more information.
gro.hasfulltextNo Full Text
gro.griffith.authorHofmann, Andreas


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

  • Book chapters
    Contains book chapters authored by Griffith authors.

Show simple item record