Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/340073
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dc.contributor.CRUESPUNIVERSIDADE ESTADUAL DE CAMPINASpt_BR
dc.contributor.authorunicampFerreira, Rafael Augusto Alves-
dc.contributor.authorunicampRezende Júnior, Celso de Oliveira-
dc.contributor.authorunicampDias, Luiz Carlos-
dc.typeArtigopt_BR
dc.titleStructure-based and molecular modeling studies for the discovery of cyclic imides as reversible cruzain inhibitors with potent anti-Trypanosoma cruzi activitypt_BR
dc.contributor.authorFerreira, Rafael A. A.-
dc.contributor.authorPauli, Ivani-
dc.contributor.authorSampaio, Thiago S.-
dc.contributor.authorde Souza, Mariana L.-
dc.contributor.authorFerreira, Leonardo L. G.-
dc.contributor.authorMagalhaes, Luma G.-
dc.contributor.authorRezende Jr, Celso de O.-
dc.contributor.authorFerreira, Rafaela S.-
dc.contributor.authorKrogh, Renata-
dc.contributor.authorDias, Luiz C.-
dc.contributor.authorAndricopulo, Adriano D.-
dc.subjectDoença de Chagaspt_BR
dc.subjectTrypanosoma cruzipt_BR
dc.subject.otherlanguageChagas Diseasept_BR
dc.subject.otherlanguageTrypanosoma cruzipt_BR
dc.description.abstractChagas disease causes 10,000 deaths each year, mainly in Latin America, where it is endemic. The currently available chemotherapeutic agents are ineffective in the chronic stage of the disease, and the lack of pharmaceutical innovation for Chagas disease highlights the urgent need for the development of new drugs. The enzyme cruzain, the main cysteine protease of Trypanosoma cruzi, has been explored as a validated molecular target for drug discovery. Herein, the design, molecular modeling studies, synthesis, and biological evaluation of cyclic imides as cruzain inhibitors are described. Starting with a micromolar-range cruzain inhibitor (3a, IC50 = 2.2 mu M), this molecular optimization strategy resulted in the nanomolar-range inhibitor 10j (IC50 = 0.6 mu M), which is highly active against T. cruzi intracellular amastigotes (IC50 = 1.0 mu M). Moreover, most compounds were selective toward T. cruzi over human fibroblasts, which were used as host cells, and are less toxic to hepatic cells than the marketed drug benznidazole. This study enabled the discovery of novel chemical diversity and established robust structure-activity relationships to guide the design of optimized cruzain inhibitors as new trypanocidal agents.pt_BR
dc.relation.ispartofFrontiers in chemistrypt_BR
dc.publisher.cityLausannept_BR
dc.publisher.countrySuíçapt_BR
dc.publisherFrontiers Mediapt_BR
dc.date.issued2019-
dc.date.monthofcirculationNov.pt_BR
dc.language.isoengpt_BR
dc.description.volume7pt_BR
dc.rightsAbertopt_BR
dc.sourceWOSpt_BR
dc.identifier.eissn2296-2646pt_BR
dc.identifier.doi10.3389/fchem.2019.00798pt_BR
dc.identifier.urlhttps://www.frontiersin.org/articles/10.3389/fchem.2019.00798/fullpt_BR
dc.description.sponsorshipCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQpt_BR
dc.description.sponsorshipCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESpt_BR
dc.description.sponsorshipFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPpt_BR
dc.description.sponsordocumentnumber158926/2014-5pt_BR
dc.description.sponsordocumentnumberSem informaçãopt_BR
dc.description.sponsordocumentnumber2013/07600-3; 2011/137896pt_BR
dc.date.available2020-05-04T19:14:58Z-
dc.date.accessioned2020-05-04T19:14:58Z-
dc.description.provenanceSubmitted by Bruna Maria Campos da Cunha (bcampos@unicamp.br) on 2020-05-04T19:14:58Z No. of bitstreams: 0. Added 1 bitstream(s) on 2020-08-27T19:17:29Z : No. of bitstreams: 1 000501610400001.pdf: 3019659 bytes, checksum: 8b2d03b8f9ca3962a773b76a2e7a512c (MD5)en
dc.description.provenanceMade available in DSpace on 2020-05-04T19:14:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2019en
dc.identifier.urihttp://repositorio.unicamp.br/jspui/handle/REPOSIP/340073-
dc.contributor.departmentSem informaçãopt_BR
dc.contributor.departmentSem informaçãopt_BR
dc.contributor.departmentDepartamento de Química Orgânicapt_BR
dc.contributor.unidadeInstituto de Químicapt_BR
dc.contributor.unidadeInstituto de Químicapt_BR
dc.contributor.unidadeInstituto de Químicapt_BR
dc.subject.keywordCruzainpt_BR
dc.subject.keywordSARpt_BR
dc.subject.keywordMedicinal chemistrypt_BR
dc.subject.keywordSynthesispt_BR
dc.subject.keywordInhibitorspt_BR
dc.subject.keywordMolecular dockingpt_BR
dc.identifier.source000501610400001pt_BR
dc.creator.orcidSem informaçãopt_BR
dc.creator.orcidorcid.org/0000-0003-1402-2035pt_BR
dc.creator.orcidorcid.org/0000-0003-0628-9928pt_BR
dc.type.formArtigo de pesquisapt_BR
dc.identifier.articleid798pt_BR
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