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dc.contributor.authorZhou, Linna
dc.contributor.authorStewart, Gavin
dc.contributor.authorRideau, Emeline
dc.contributor.authorWestwood, Nicholas James
dc.contributor.authorSmith, Terry K
dc.date.accessioned2013-02-18T12:31:03Z
dc.date.available2013-02-18T12:31:03Z
dc.date.issued2013-02-14
dc.identifier.citationZhou , L , Stewart , G , Rideau , E , Westwood , N J & Smith , T K 2013 , ' A class of 5-nitro-2-furancarboxylamides with potent trypanocidal activity against Trypanosoma brucei in vitro ' , Journal of Medicinal Chemistry , vol. 56 , no. 3 , pp. 796–806 . https://doi.org/10.1021/jm301215een
dc.identifier.issn0022-2623
dc.identifier.otherPURE: 45940624
dc.identifier.otherPURE UUID: 859259e8-3c9e-465a-97ba-763f2081392e
dc.identifier.otherPubMed: 23281892
dc.identifier.otherScopus: 84873904852
dc.identifier.otherWOS: 000315182100015
dc.identifier.otherORCID: /0000-0003-0630-0138/work/56424206
dc.identifier.urihttps://hdl.handle.net/10023/3359
dc.description.abstractRecently, the World Health Organization approved the nifurtimox–eflornithine combination therapy for the treatment of human African trypanosomiasis, renewing interest in nitroheterocycle therapies for this and associated diseases. In this study, we have synthesized a series of novel 5-nitro-2-furancarboxylamides that show potent trypanocidal activity, 1000-fold more potent than nifurtimox against in vitro Trypanosoma brucei with very low cytotoxicity against human HeLa cells. More importantly, the most potent analogue showed very limited cross-resistance to nifurtimox-resistant cells and vice versa. This implies that our novel, relatively easy to synthesize and therefore cheap, 5-nitro-2-furancarboxylamides are targeting a different, but still essential, biochemical process to those targeted by nifurtimox or its metabolites in the parasites. The significant increase in potency (smaller dose probably required) has the potential for greatly reducing unwanted side effects and also reducing the likelihood of drug resistance. Collectively, these findings have important implications for the future therapeutic treatment of African sleeping sickness.
dc.format.extent11
dc.language.isoeng
dc.relation.ispartofJournal of Medicinal Chemistryen
dc.rightsThis is an open access article copyright © 2013 American Chemical Societyen
dc.subjectQD Chemistryen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.subject.lccQDen
dc.titleA class of 5-nitro-2-furancarboxylamides with potent trypanocidal activity against Trypanosoma brucei in vitroen
dc.typeJournal articleen
dc.contributor.sponsorCancer Research UKen
dc.contributor.sponsorThe Wellcome Trusten
dc.contributor.sponsorThe Wellcome Trusten
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Chemistryen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. EaSTCHEMen
dc.identifier.doihttps://doi.org/10.1021/jm301215e
dc.description.statusPeer revieweden
dc.identifier.urlhttp://europepmc.org/abstract/MED/23281892en
dc.identifier.grantnumberen
dc.identifier.grantnumber093228/Z/10/Zen
dc.identifier.grantnumber086658 Z 08 Zen


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