Show simple item record

dc.contributor.authorBastos, Tanira Matutino
dc.contributor.authorSoares, Milena Botelho Pereira
dc.contributor.authorFranco, Caio Haddad
dc.contributor.authorAlcântara, Laura
dc.contributor.authorAntonini, Lorenzo
dc.contributor.authorSabatino, Manuela
dc.contributor.authorMautone, Nicola
dc.contributor.authorFreitas-Junior, Lucio Holanda
dc.contributor.authorMoraes, Carolina Borsoi
dc.contributor.authorRagno, Rino
dc.contributor.authorRotili, Dante
dc.contributor.authorSchenkman, Sergio [UNIFESP]
dc.contributor.authorMai, Antonello
dc.contributor.authorMoretti, Nilmar Silvio [UNIFESP]
dc.date.accessioned2021-11-26T21:41:15Z
dc.date.available2021-11-26T21:41:15Z
dc.date.issued2020
dc.identifier.urihttps://repositorio.unifesp.br/xmlui/handle/11600/62314
dc.description.abstractChagas disease is an illness caused by the protozoan parasite Trypanosoma cruzi, a↵ecting more than 7 million people in the world. Benznidazole and nifurtimox are the only drugs available for treatment and in addition to causing several side e↵ects, are only satisfactory in the acute phase of the disease. Sirtuins are NAD+-dependent deacetylases involved in several biological processes, which have become drug target candidates in various disease settings. T. cruzi presents two sirtuins, one cytosolic (TcSir2rp1) and the latter mitochondrial (TcSir2rp3). Here, we characterized the e↵ects of human sirtuin inhibitors against T. cruzi sirtuins as an initial approach to develop specific parasite inhibitors. We found that, of 33 compounds tested, two inhibited TcSir2rp1 (15 and 17), while other five inhibited TcSir2rp3 (8, 12, 13, 30, and 32), indicating that specific inhibitors can be devised for each one of the enzymes. Furthermore, all inhibiting compounds prevented parasite proliferation in cultured mammalian cells. When combining the most efective inhibitors with benznidazole at least two compounds, 17 and 32, demonstrated synergistic effects. Altogether, these results support the importance of exploring T. cruzi sirtuins as drug targets and provide key elements to develop specific inhibitors for these enzymes as potential targets for Chagas disease treatment.pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.languageengpt_BR
dc.publisherMDPIpt_BR
dc.relation.ispartofInternational Journal of Molecular Sciencespt_BR
dc.rightsAcesso abertopt_BR
dc.subjectSirtuinspt_BR
dc.subjectTrypanosoma cruzipt_BR
dc.subjectSirtuin inhibitorspt_BR
dc.subjectDeacetylationpt_BR
dc.titleIdentification of inhibitors to Trypanosoma cruzi Sirtuins based on compounds developed to human enzymespt_BR
dc.typeArtigopt_BR
dc.description.sponsorshipIDFAPESP: 2018/09948-0pt_BR
dc.identifier.doidoi:10.3390/ijms21103659pt_BR
unifesp.campusEscola Paulista de Medicina (EPM)pt_BR
unifesp.graduateProgramMicrobiologia e Imunologiapt_BR
unifesp.knowledgeAreaOutrapt_BR
dc.contributor.authorLatteshttp://lattes.cnpq.br/2131472726202687pt_BR
unifesp.departamentoMicrobiologia, Imunologia e Parasitologiapt_BR


Files in this item

This item appears in the following Collection(s)

Show simple item record