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dc.contributor.authordo Espírito Santo, Rafael Dias [UNESP]
dc.contributor.authorVelásquez, Ángela María Arenas [UNESP]
dc.contributor.authorPassianoto, Luana Vitorino Gushiken [UNESP]
dc.contributor.authorSepulveda, Alex Arbey Lopera [UNESP]
dc.contributor.authorda Costa Clementino, Leandro [UNESP]
dc.contributor.authorAssis, Renata Pires [UNESP]
dc.contributor.authorBaviera, Amanda Martins [UNESP]
dc.contributor.authorKalaba, Predrag
dc.contributor.authordos Santos, Fábio Neves
dc.contributor.authorÉberlin, Marcos Nogueira
dc.contributor.authorda Silva, Gil Valdo José
dc.contributor.authorZehl, Martin
dc.contributor.authorLubec, Gert
dc.contributor.authorGraminha, Márcia Aparecida Silva [UNESP]
dc.contributor.authorGonzález, Eduardo René Pérez [UNESP]
dc.date.accessioned2019-10-06T16:21:23Z
dc.date.available2019-10-06T16:21:23Z
dc.date.issued2019-06-01
dc.identifierhttp://dx.doi.org/10.1016/j.ejmech.2019.03.032
dc.identifier.citationEuropean Journal of Medicinal Chemistry, v. 171, p. 116-128.
dc.identifier.issn1768-3254
dc.identifier.issn0223-5234
dc.identifier.urihttp://hdl.handle.net/11449/188857
dc.description.abstractLeishmaniasis is a group of diseases caused by protozoan parasites from the genus Leishmania. There are estimated 1.3 million new cases annually with a mortality of 20,000–30,000 per year, when patients are left untreated. Current chemotherapeutic drugs available present high toxicity and low efficacy, the latter mainly due to the emergence of drug-resistant parasites, which makes discovery of novel, safe, and efficacious antileishmanial drugs mandatory. The present work reports the synthesis, characterization by ESI-MS, 1H and 13C NMR, and FTIR techniques as well as in vitro and in vivo evaluation of leishmanicidal activity of guanidines derivatives presenting lower toxicity. Among ten investigated compounds, all being guanidines containing a benzoyl, a benzyl, and a substituted phenyl moiety, LQOF-G2 (IC50-ama 5.6 μM; SI = 131.8) and LQOF-G7 (IC50-ama 7.1 μM; SI = 87.1) were the most active against L. amazonensis intracellular amastigote, showing low cytotoxicity to the host cells according to their selectivity index. The most promising compound, LQOF-G2, was further evaluated in an in vivo model and was able to decrease 60% of the parasite load in foot lesions at a dose of 0.25 mg/kg/day. Moreover, this guanidine derivative demonstrated reduced hepatotoxicity compared to other leishmanicidal compounds and did not show nephrotoxicity, as determined by the analyses of biomarkers of hepatic damage and renal function, which make this compound a potential new hit for therapy against leishmaniasis.en
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.format.extent116-128
dc.language.isoeng
dc.relation.ispartofEuropean Journal of Medicinal Chemistry
dc.sourceScopus
dc.subjectHepatoprotective effect
dc.subjectIn vivo leishmanicidal activity
dc.subjectLeishmania amazonensis
dc.subjectLeishmaniasis
dc.subjectN, N′ N″-trisubstituted guanidine derivatives
dc.titleN, N′ N″-trisubstituted guanidines: Synthesis, characterization and evaluation of their leishmanicidal activityen
dc.typeArtigo
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversity of Vienna
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionParacelsus Medical University
dc.description.affiliationLaboratório de Química Orgânica Fina Departamento de Química e Biologia Faculdade de Ciências e Tecnologia Universidade Estadual Paulista – UNESP, Campus de Presidente Prudente, Rua Roberto Simonsen, 305
dc.description.affiliationPrograma de Pós-Graduação em Ciência e Tecnologia de Materiais (POSMAT) Universidade Estadual Paulista – UNESP
dc.description.affiliationDepartamento de Análises Clínicas Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista – UNESP Campus de Araraquara, Rodovia Araraquara-Jaú km1
dc.description.affiliationDepartment of Pharmaceutical Chemistry Faculty of Life Sciences University of Vienna, Althanstraße 14
dc.description.affiliationLaboratório ThoMSon de Espectrometria de Massas Instituto de Química Universidade de Campinas – UNICAMP
dc.description.affiliationDepartamento de Química Faculdade de Filosofia Ciências e Letras de Ribeirão Preto Universidade de São Paulo – USP, Avenida dos Bandeirantes, 3900
dc.description.affiliationDepartment of Analytical Chemistry Faculty of Chemistry University of Vienna, Währinger Straße 38
dc.description.affiliationDepartment of Neuroproteomics Paracelsus Medical University
dc.description.affiliationUnespLaboratório de Química Orgânica Fina Departamento de Química e Biologia Faculdade de Ciências e Tecnologia Universidade Estadual Paulista – UNESP, Campus de Presidente Prudente, Rua Roberto Simonsen, 305
dc.description.affiliationUnespPrograma de Pós-Graduação em Ciência e Tecnologia de Materiais (POSMAT) Universidade Estadual Paulista – UNESP
dc.description.affiliationUnespDepartamento de Análises Clínicas Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista – UNESP Campus de Araraquara, Rodovia Araraquara-Jaú km1
dc.identifier.doi10.1016/j.ejmech.2019.03.032
dc.rights.accessRightsAcesso aberto
dc.description.sponsorshipIdFAPESP: 2013/08248-1
dc.description.sponsorshipIdFAPESP: 2013/24487-6
dc.description.sponsorshipIdFAPESP: 2016/19289-9
dc.description.sponsorshipIdFAPESP: 2017/03552-5
dc.identifier.scopus2-s2.0-85063150817
unesp.author.lattes3736475025187750[7]
unesp.author.orcid0000-0003-0987-5295[7]
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