Synthetic organotelluride compounds induce the reversal of Pdr5p mediated fluconazole resistance in Saccharomyces cerevisiae

Página do item simplificado
dc.contributor.authorReis de Sa, Leandro Figueira
dc.contributor.authorToledo, Fabiano Travanca
dc.contributor.authorSousa, Bruno Artur de
dc.contributor.authorGoncalves, Augusto Cesar
dc.contributor.authorTessis, Ana Claudia
dc.contributor.authorWendler, Edison P.
dc.contributor.authorComasseto, Joao V. [UNIFESP]
dc.contributor.authorDos Santos, Alcindo A.
dc.contributor.authorFerreira-Pereira, Antonio
dc.contributor.institutionUniversidade Federal do Rio de Janeiro (UFRJ)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionInst Fed Educ Ciencia & Tecnol Rio de Janeiro IFR
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:37:36Z
dc.date.available2016-01-24T14:37:36Z
dc.date.issued2014-07-26
dc.description.abstractBackground: Resistance to fluconazole, a commonly used azole antifungal, is a challenge for the treatment of fungal infections. Resistance can be mediated by overexpression of ABC transporters, which promote drug efflux that requires ATP hydrolysis. the Pdr5p ABC transporter of Saccharomyces cerevisiae is a well-known model used to study this mechanism of antifungal resistance. the present study investigated the effects of 13 synthetic compounds on Pdr5p.Results: Among the tested compounds, four contained a tellurium-butane group and shared structural similarities that were absent in the other tested compounds: a lateral hydrocarbon chain and an amide group. These four compounds were capable of inhibiting Pdr5p ATPase activity by more than 90%, they demonstrated IC50 values less than 2 M and had an uncompetitive pattern of Pdr5p ATPase activity inhibition. These organotellurides did not demonstrate cytotoxicity against human erythrocytes or S. cerevisiae mutant strains (a strain that overexpress Pdr5p and a null mutant strain) even in concentrations above 100 mu M. When tested at 100 mu M, they could reverse the fluconazole resistance expressed by both the S. cerevisiae mutant strain that overexpress Pdr5p and a clinical isolate of Candida albicans.Conclusions: We have identified four organotellurides that are promising candidates for the reversal of drug resistance mediated by drug efflux pumps. These molecules will act as scaffolds for the development of more efficient and effective efflux pump inhibitors that can be used in combination therapy with available antifungals.en
dc.description.affiliationUniv Fed Rio de Janeiro, CCS, Inst Microbiol Paulo Goes, Dept Microbiol Geral,Lab Bioquim Microbiana, Rio de Janeiro, RJ, Brazil
dc.description.affiliationUniv São Paulo, Inst Quim, Dept Quim Fundamental, São Paulo, Brazil
dc.description.affiliationInst Fed Educ Ciencia & Tecnol Rio de Janeiro IFR, Rio de Janeiro, RJ, Brazil
dc.description.affiliationUniversidade Federal de São Paulo UNIFESP, Inst Ciencias Ambientais Quim & Farmaceut, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo UNIFESP, Inst Ciencias Ambientais Quim & Farmaceut, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipUniversity of São Paulo through the NAP-CatSinQ (Research Core in Catalysis and Chemical Synthesis)
dc.description.sponsorshipIDFAPERJ: E-26/111.338/2013
dc.description.sponsorshipIDFAPESP: 2005/59572-7
dc.description.sponsorshipIDFAPESP: 2008/55401-1
dc.description.sponsorshipIDFAPESP: 2010/17228-6
dc.description.sponsorshipIDFAPESP: 2011/03244-2
dc.description.sponsorshipIDFAPESP: 2011/11613-8
dc.description.sponsorshipIDFAPESP: 2012/17093-9
dc.description.sponsorshipIDCNPq: 470360/2012-7
dc.format.extent9
dc.identifierhttp://dx.doi.org/10.1186/s12866-014-0201-y
dc.identifier.citationBmc Microbiology. London: Biomed Central Ltd, v. 14, 9 p., 2014.
dc.identifier.doi10.1186/s12866-014-0201-y
dc.identifier.fileWOS000339838500001.pdf
dc.identifier.issn1471-2180
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/38000
dc.identifier.wosWOS:000339838500001
dc.language.isoeng
dc.publisherBiomed Central Ltd
dc.relation.ispartofBmc Microbiology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectOrganotelluridesen
dc.subjectPdr5pen
dc.subjectFluconazole resistanceen
dc.subjectSaccharomyces cerevisiaeen
dc.titleSynthetic organotelluride compounds induce the reversal of Pdr5p mediated fluconazole resistance in Saccharomyces cerevisiaeen
dc.typeinfo:eu-repo/semantics/article
Arquivos
Pacote Original
Agora exibindo 1 - 1 de 1
Imagem de Miniatura
Nome:
WOS000339838500001.pdf
Tamanho:
1.36 MB
Formato:
Adobe Portable Document Format
Descrição:
Baixar
Coleções
Em verificação - Geral