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dc.contributor.authorGould, Eoin R.
dc.contributor.authorKing, Elizabeth F. B.
dc.contributor.authorMenzies, Stefanie K.
dc.contributor.authorFraser, Andrew L.
dc.contributor.authorTulloch, Lindsay B.
dc.contributor.authorZacharova, Marija K.
dc.contributor.authorSmith, Terry K.
dc.contributor.authorFlorence, Gordon J.
dc.date.accessioned2018-01-29T00:31:37Z
dc.date.available2018-01-29T00:31:37Z
dc.date.issued2017-11-15
dc.identifier.citationGould , E R , King , E F B , Menzies , S K , Fraser , A L , Tulloch , L B , Zacharova , M K , Smith , T K & Florence , G J 2017 , ' Simplifying nature : towards the design of broad spectrum kinetoplastid inhibitors, inspired by acetogenins ' Bioorganic & Medicinal Chemistry , vol. 25 , no. 22 , pp. 6126-6136 . https://doi.org/10.1016/j.bmc.2017.01.021en
dc.identifier.issn0968-0896
dc.identifier.otherPURE: 247264273
dc.identifier.otherPURE UUID: b05f98d0-3ad9-41f7-b8b8-31c9831397b4
dc.identifier.otherScopus: 85011592200
dc.identifier.otherORCID: /0000-0002-8987-5561/work/29949157
dc.identifier.otherORCID: /0000-0001-7223-5106/work/42522365
dc.identifier.otherORCID: /0000-0001-9921-4399/work/56638888
dc.identifier.urihttp://hdl.handle.net/10023/12625
dc.descriptionThis work was funded by the Leverhulme Trust. The research data supporting this publication can be accessed at http://dx.doi.org/10.17630/1dd8b881-17c2-48e4-a72f-53af938f4537.en
dc.description.abstractThe need for new treatments for the neglected tropical diseases African sleeping sickness, Chagas disease and Leishmaniasis remains urgent with the diseases widespread in tropical regions, affecting the worlds very poorest. We have previously reported bis-tetrahydropyran 1,4-triazole analogues designed as mimics of the annonaceous acetogenin natural product chamuvarinin, which maintained trypanocidal activity. Building upon these studies, we here report related triazole compounds with pendant heterocycles, mimicking the original butenolide of the natural product. Analogues were active against T. brucei, with a nitrofuran compound displaying nanomolar trypanocidal activity- several analogues also showed strong activity against T. cruzi and L. major. Importantly, select compounds gave excellent selectivity over mammalian cells with a furan-based analogue highly selective while remaining active against all three cell lines, thus representing a potential lead for a new broad spectrum kinetoplastid inhibitor.
dc.language.isoeng
dc.relation.ispartofBioorganic & Medicinal Chemistryen
dc.rights© 2017 Elsevier Ltd. All rights reserved. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at: https://doi.org/10.1016/j.bmc.2017.01.021en
dc.subjectTetrahydropyranen
dc.subjectNeglected tropical diseasesen
dc.subjectAcetogeninsen
dc.subjectNatural productsen
dc.subjectQD Chemistryen
dc.subjectR Medicine (General)en
dc.subjectDASen
dc.subject.lccQDen
dc.subject.lccR1en
dc.titleSimplifying nature : towards the design of broad spectrum kinetoplastid inhibitors, inspired by acetogeninsen
dc.typeJournal articleen
dc.description.versionPostprinten
dc.contributor.institutionUniversity of St Andrews.School of Chemistryen
dc.contributor.institutionUniversity of St Andrews.EaSTCHEMen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.identifier.doihttps://doi.org/10.1016/j.bmc.2017.01.021
dc.description.statusPeer revieweden
dc.date.embargoedUntil2018-01-28


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