New quinoline derivatives demonstrate a promising antimalarial activity against Plasmodium falciparum in vitro and Plasmodium berghei in vivo

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dc.contributor.authorSoares, Roberta Reis
dc.contributor.authorSilva, José Marcio Fernandes da
dc.contributor.authorCarlos, Bianca Cechetto [UNESP]
dc.contributor.authorFonseca, Camila Campos da
dc.contributor.authorSouza, Laila Salomé Araújo de
dc.contributor.authorLopes, Fernanda Valério
dc.contributor.authorDias, Rafael Mafra de Paula
dc.contributor.authorMoreira, Paulo Otávio Lourenço
dc.contributor.authorAbramo, Clarice
dc.contributor.authorViana, Gustavo Henrique Ribeiro
dc.contributor.authorVarotti, Fernando de Pila
dc.contributor.authorSilva, Adilson David da
dc.contributor.authorScopel, Kezia Katiani Gorza
dc.contributor.institutionUniversidade Federal de Juiz de Fora (UFJF)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade de São João del-Rei (UFSJ)
dc.contributor.institutionUniversity of South Florida
dc.date.accessioned2015-10-22T07:08:57Z
dc.date.available2015-10-22T07:08:57Z
dc.date.issued2015-06-01
dc.description.abstractMalaria continues to be an important public health problem in the world. Nowadays, the widespread parasite resistance to many drugs used in antimalarial therapy has made the effective treatment of cases and control of the disease a constant challenge. Therefore, the discovery of new molecules with good antimalarial activity and tolerance to human use can be really important in the further treatment of the disease. In this study we have investigated the antiplasmodial activity of 10 synthetic compounds derived from quinoline, five of them combined to sulfonamide and five to the hydrazine or hydrazide group. The compounds were evaluated according to their cytotoxicity against HepG2 and HeLa cell lines, their antimalarial activity against CQ-sensitive and CQ-resistant Plasmodium falciparum strains and, finally, their schizonticide blood action in mice infected with Plasmodium berghei NK65. The compounds exhibited no cytotoxic action in HepG2 and HeLa cell lines when tested up to a concentration of 100 mu g/mL. In addition, the hydrazine or hydrazide derivative compounds were less cytotoxic against cell lines and more active against CQ-sensitive and CQ-resistant P. falciparum strains, showing high SI (> 1000 when SI was calculated using the CC50 from the 3D7 strain as reference). When tested in vivo, the hydrazine derivative 1f compound showed activity against the development of blood parasites similar to that observed with CQ, the reference drug. Interestingly, the 1f compound demonstrated the best LipE value (4.84) among all those tested in vivo. Considering the in vitro and in vivo activities of the compounds studied here and the LipE values, we believe the 1f compound to be the most promising molecule for further studies in antimalarial chemotherapy.en
dc.description.affiliationUniversidade Federal de Juiz de Fora, Departamento de Parasitologia, Microbiologia e Imunologia
dc.description.affiliationUniversidade Federal de Juiz de Fora, Departamento de Química, Instituto de Ciências Exatas
dc.description.affiliationUniversidade de São Paulo, Instituto de Química de São Carlos
dc.description.affiliationUniversidade de São João del-Rei, Núcleo de Pesquisa em Química Biológic
dc.description.affiliationUniversity of South Florida, Department of Global Health
dc.description.affiliationUnespUniversidade Estadual Paulista, Instituto de Biotecnologia de Botucatu
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdFAPEMIG: 769/12
dc.description.sponsorshipIdFAPEMIG: 20/12
dc.format.extent2308-2313
dc.identifierhttp://www.sciencedirect.com/science/article/pii/S0960894X1500325X
dc.identifier.citationBioorganic & Medicinal Chemistry Letters. Oxford: Pergamon-elsevier Science Ltd, v. 25, n. 11, p. 2308-2313, 2015.
dc.identifier.doi10.1016/j.bmcl.2015.04.014
dc.identifier.issn0960-894X
dc.identifier.urihttp://hdl.handle.net/11449/129791
dc.identifier.wosWOS:000354115400009
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofBioorganic & Medicinal Chemistry Letters
dc.relation.ispartofjcr2.442
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.subjectPlasmodium falciparumen
dc.subjectMalariaen
dc.subjectAntimalarial chemotherapyen
dc.subjectCytotoxicityen
dc.subjectQuinoline derivativesen
dc.titleNew quinoline derivatives demonstrate a promising antimalarial activity against Plasmodium falciparum in vitro and Plasmodium berghei in vivoen
dc.typeArtigo
dcterms.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dcterms.rightsHolderElsevier B.V.
unesp.author.orcid0000-0002-2939-7780[11]
unesp.author.orcid0000-0002-7995-8152[10]
unesp.author.orcid0000-0002-1521-7486[10]
unesp.author.orcid0000-0002-0780-8382[7]

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