In vitro anti-Trypanosoma cruzi activity of ternary copper(II) complexes and in vivo evaluation of the most promising complex

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dc.contributor.authorPaixão, Drielly A.
dc.contributor.authorLopes, Carla D.
dc.contributor.authorCarneiro, Zumira A.
dc.contributor.authorSousa, Luana M.
dc.contributor.authorde Oliveira, Leticia P.
dc.contributor.authorLopes, Norberto P.
dc.contributor.authorPivatto, Marcos
dc.contributor.authorChaves, Joana Darc S.
dc.contributor.authorde Almeida, Mauro V.
dc.contributor.authorEllena, Javier
dc.contributor.authorMoreira, Mariete B. [UNESP]
dc.contributor.authorNetto, Adelino V.G. [UNESP]
dc.contributor.authorde Oliveira, Ronaldo J.
dc.contributor.authorGuilardi, Silvana
dc.contributor.authorde Albuquerque, Sérgio
dc.contributor.authorGuerra, Wendell
dc.contributor.institutionUniversidade Federal de Uberlândia (UFU)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionJuiz de Fora-MG
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade Federal do Triângulo Mineiro
dc.date.accessioned2019-10-06T16:48:23Z
dc.date.available2019-10-06T16:48:23Z
dc.date.issued2019-01-01
dc.description.abstractIn order to improve the previously observed antichagasic activity of Cu(II) complexes containing 2-chlorobenzhydrazide (2-CH), we report herein the synthesis and anti-Trypanosoma cruzi activity of novel copper complexes containing 2-methoxybenzhydrazide (2-MH), 4-methoxybenzhydrazide (4-MH) and three α-diimine ligands, namely, 1,10-phenanthroline (phen), 2,2-bipyridine (bipy) and 4-4′-dimethoxy-2-2′-bipyridine (dmb). Two of these complexes showed higher in vitro anti-Trypanosoma cruzi activity when compared to benznidazole, the main drug used in Chagas disease treatment. One of them, the copper complex with 4-MH and dmb, [Cu(4-MH)(dmb)(ClO 4 ) 2 ], exhibited a higher selectivity index than that recommended for preclinical studies. Considering this observation, complex [Cu(4-MH)(dmb)(ClO 4 ) 2 ] was selected for preliminary in vivo assays, which verified that this compound was able to reduce parasitemia by 64% at the peak of infection. Further investigations were performed on all compounds. The Cu(II) complexes bind to ct-DNA with K b values in the range of 10 3 –10 4 M –1 , with [Cu(4-MH)(dmb)(ClO 4 ) 2 ] showing the highest K b value (1.45 × 10 4 M –1 ). Molecular docking simulations predicted that [Cu(4-MH)(dmb)(ClO 4 ) 2 ] binds in the minor groove of the double helix of ct-DNA and forms one hydrogen bond.en
dc.description.affiliationInstituto de Química Universidade Federal de Uberlândia, Campus Santa Mônica
dc.description.affiliationDepartamento de Análises Clínicas Toxicológicas e Bromatológicas Faculdade de Ciências Farmacêuticas de Ribeirão Preto Universidade de São Paulo
dc.description.affiliationNúcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS) Faculdade de Ciências Farmacêuticas de Ribeirão Preto Universidade de São Paulo
dc.description.affiliationDepartamento de Química Universidade Federal de Juiz de Fora Juiz de Fora-MG
dc.description.affiliationInstituto de Física de São Carlos Universidade de São Paulo
dc.description.affiliationUNESP - Universidade Estadual Paulista Instituto de Química
dc.description.affiliationDepartamento de Física Instituto de Ciências Exatas Naturais e Educação Universidade Federal do Triângulo Mineiro
dc.description.affiliationUnespUNESP - Universidade Estadual Paulista Instituto de Química
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)
dc.description.sponsorshipIdFAPEMIG: APQ-00330-14
dc.format.extent157-166
dc.identifierhttp://dx.doi.org/10.1016/j.biopha.2018.10.057
dc.identifier.citationBiomedicine and Pharmacotherapy, v. 109, p. 157-166.
dc.identifier.doi10.1016/j.biopha.2018.10.057
dc.identifier.issn1950-6007
dc.identifier.issn0753-3322
dc.identifier.scopus2-s2.0-85055895361
dc.identifier.urihttp://hdl.handle.net/11449/189671
dc.language.isoeng
dc.relation.ispartofBiomedicine and Pharmacotherapy
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectChagas disease
dc.subjectCu(II) complexes
dc.subjectDNA binding
dc.subjectHydrazides
dc.subjectMolecular docking
dc.subjectT. cruzi
dc.titleIn vitro anti-Trypanosoma cruzi activity of ternary copper(II) complexes and in vivo evaluation of the most promising complexen
dc.typeArtigo

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