Please use this identifier to cite or link to this item: https://repositorio.unifesp.br/handle/11600/32417
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dc.contributor.authorCarvalho, Ivone
dc.contributor.authorAndrade, Peterson
dc.contributor.authorCampo, Vanessa L.
dc.contributor.authorGuedes, Paulo M. M.
dc.contributor.authorSesti-Costa, Renata
dc.contributor.authorSilva, Joao S.
dc.contributor.authorSchenkman, Sergio [UNIFESP]
dc.contributor.authorDedola, Simone
dc.contributor.authorHill, Lionel
dc.contributor.authorRejzek, Martin
dc.contributor.authorNepogodiev, Sergey A.
dc.contributor.authorField, Robert A.
dc.date.accessioned2016-01-24T13:59:31Z-
dc.date.available2016-01-24T13:59:31Z-
dc.date.issued2010-04-01
dc.identifierhttp://dx.doi.org/10.1016/j.bmc.2010.02.053
dc.identifier.citationBioorganic & Medicinal Chemistry. Oxford: Pergamon-Elsevier B.V., v. 18, n. 7, p. 2412-2427, 2010.
dc.identifier.issn0968-0896
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/32417-
dc.description.abstractTrypanosoma cruzi trans-sialidase (TcTS) plays a key role in the recognition and invasion of host cells and in enabling the parasite to escape the human immune response. To explore this potential drug target, we have synthesized a small library of substrate analogues based on 1,4-disubstituted 1,2,3-triazole derivatives of galactose modified at either the C-1 or C-6 positions. This was achieved by coupling the appropriate azido-sugars with a panel of 23 structurally diverse terminal alkynes by using the copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction, giving a library of 46 derivatives in good to excellent yield and with complete regioselectivity. the sugar triazoles showed weak inhibition towards TcTS-catalyzed hydrolysis of 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid in vitro (<40% inhibition at 1 mM concentration); many of the compounds assessed proved to be acceptor substrates for the enzyme. Despite this modest inhibitory activity, in vitro trypanocidal activity assays against the trypomastigote form of T. cruzi Y strain revealed several compounds active in the low 100s of mu M range. Further assessment of these compounds against cultured mouse spleen cells suggests a specific mode of anti-parasite action rather than a generic cytotoxic effect. (C) 2010 Elsevier B.V. All rights reserved.en
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipBBSRC (UK Biotehcnology and Biological Sciences Research Council)
dc.format.extent2412-2427
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofBioorganic & Medicinal Chemistry
dc.rightsAcesso restrito
dc.subjectTrypanosoma cruzien
dc.subjectTrans-sialidaseen
dc.subjectGalactoseen
dc.subjectTriazoleen
dc.subject'Click chemistry'en
dc.title'Click chemistry' synthesis of a library of 1,2,3-triazole-substituted galactose derivatives and their evaluation against Trypanosoma cruzi and its cell surface trans-sialidaseen
dc.typeArtigo
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionJohn Innes Ctr
dc.description.affiliationUSP, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP, Brazil
dc.description.affiliationUSP, Fac Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, Brazil
dc.description.affiliationJohn Innes Ctr, Dept Biol Chem, Norwich NR4 7UH, Norfolk, England
dc.description.affiliationJohn Innes Ctr, Dept Metab Biol, Norwich NR4 7UH, Norfolk, England
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, Brazil
dc.identifier.doi10.1016/j.bmc.2010.02.053
dc.description.sourceWeb of Science
dc.identifier.wosWOS:000276258700006
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