Synthesis of novel quinine analogs and evaluation of their effects on Trypanosoma cruzi

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dc.contributor.authorCeole, Ligia F.
dc.contributor.authorGandhi, Hirenkumar
dc.contributor.authorVillamizar, Luz H.
dc.contributor.authorSoares, Maurilio J.
dc.contributor.authorO'Sullivan, Timothy P.
dc.contributor.funderIrish Research Councilen
dc.contributor.funderConselho Nacional de Desenvolvimento Científico e Tecnológicoen
dc.contributor.funderFundação Oswaldo Cruzen
dc.date.accessioned2018-12-03T15:58:32Z
dc.date.available2018-12-03T15:58:32Z
dc.date.copyright2019-01-30
dc.date.issued2018-02
dc.date.updated2018-11-27T17:08:09Z
dc.description.abstractAim: Chagas disease is a tropical disease caused by the hemoflagellate protozoan Trypanosoma cruzi. There is no vaccine for Chagas disease and available drugs (e.g., benznidazole) are effective only during the acute phase, displaying a variable curative activity in the established chronic form of the disease. New leads with high efficacy and better toxicity profiles are urgently required. Materials & methods: A library of novel quinine derivatives was synthesized using Heck chemistry and evaluated against the various developmental forms of T. cruzi. Results and Conclusion: Several novel quinine analogs with trypanocidal activity have been identified with the para-nitro-substituted derivative displaying a submicromolar IC50, which is 83-times lower than quinine and three-times lower than benznidazole. Transmission electron microscopy analysis demonstrated that these compounds induced a marked vacuolization of the kinetoplast of intracellular amastigotes and cell-derived trypomastigotes.en
dc.description.sponsorshipIrish Research Council (Government of Ireland PhD Scholarship GOIPG/2013/113);en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationCeole, L. F., Gandhi, H., Villamizar, L. H., Soares, M. J. and O'Sullivan, T. P. (2018) 'Synthesis of novel quinine analogs and evaluation of their effects on Trypanosoma cruzi', Future Medicinal Chemistry, 10(4), pp. 391-408. doi: 10.4155/fmc-2017-0184en
dc.identifier.doi10.4155/fmc-2017-0184
dc.identifier.endpage408en
dc.identifier.issn1756-8919
dc.identifier.issn1756-8927
dc.identifier.journaltitleFuture Medicinal Chemistryen
dc.identifier.startpage391en
dc.identifier.urihttps://hdl.handle.net/10468/7168
dc.identifier.volume10en
dc.language.isoenen
dc.publisherFuture Science: Newlands Pressen
dc.relation.urihttps://www.future-science.com/doi/abs/10.4155/fmc-2017-0184
dc.rights© 2018 Newlands Press. For full bibliographic citation, please refer to the version available at www.future-science.comen
dc.subjectChagas diseaseen
dc.subjectHeck couplingen
dc.subjectKinetoplast vacuolizationen
dc.subjectQuinineen
dc.subjectTrypanocidesen
dc.subjectTrypanosoma cruzien
dc.subjectUltrastructureen
dc.titleSynthesis of novel quinine analogs and evaluation of their effects on Trypanosoma cruzien
dc.typeArticle (peer-reviewed)en
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