| spelling |
Eduardo Antonio Ferraz Coelhohttp://lattes.cnpq.br/8176944320967545Luciana Maria Ribeiro AntinarelliLuísa Helena Perin de MeloLourena Emanuele CostaAna Thereza Chaveshttp://lattes.cnpq.br/4495540443593407Tauane Gonçalves Soyer2019-11-26T10:44:23Z2019-11-26T10:44:23Z2019-07-11http://hdl.handle.net/1843/31261O tratamento contra a leishmaniose apresenta problemas, uma vez que os medicamentos atualmente utilizados são tóxicos e / ou têm altos custos. Além disso, a resistência do parasita aumentou. Como conseqüência, neste estudo, um derivado da cloroquinolina, ou seja, 2- (7-cloroquinolin-4- il) oxi) -3- (3-metilbut-2- en-1-il) naftaleno-1,4-diona ou GF1059, foi testado in vitroe in vivo contra parasitos de Leishmania. Experimentos foram realizados para avaliar a atividade antileishmanial in vitro e citotoxicidade, bem como o tratamento de macrófagos infectados e a inibição da infecção usando parasitos pré-tratados. Este estudo também investigou o mecanismo de ação GF1059 em L. amazonensis. Os resultados mostraram que o composto foi altamente eficaz contra L. infantum e L. amazonensis, apresentando um índice de seletividade de 154,6 e 86,4, respectivamente, contra promastigotas e de 137,6 e 74,3, respectivamente, contra amastigotas. O GF1059 também foi eficaz no tratamento de macrófagos infectados e inibiu a infecção dessas células quando os parasitos foram pré-incubados com ele. A molécula também induziu alterações no potencial de membrana mitocondrial e integridade celular dos parasitos, e causou um aumento na produção de espécies reativas de oxigênio em L. amazonensis. Experimentos realizados em camundongos BALB / c, que haviam sido previamente infectados com promastigotas de L. amazonensis e tratados com GF1059, mostraram que esses animais apresentaram reduções significativas na carga do parasitária quando o tecido infectado, baço, fígado e linfonodo drenado foram avaliados. Camundongos tratados com GF1059 apresentaram menor parasitismo e baixos níveis de marcadores enzimáticos, em comparação com aqueles recebendo anfotericina B, que foi usada como controle. Em conclusão, os dados sugeriram que o GF1059 pode ser considerado um possível alvo terapêutico a ser testado contra a leishmaniose.The treatment against leishmaniasis presents problems, since the currently used drugs are toxic and/or have high costs. In addition, parasite resistance has increased. As a consequence, in this study, a chloroquinolin derivative, namely 2-(7-chloroquinolin-4- yl)oxy)-3-(3-methylbut-2- en- 1-yl)naphthalene-1,4- diona or GF1059, was in vitro and in vivo tested against Leishmania parasites. Experiments were performed to evaluate in vitro antileishmanial activity and cytotoxicity, as well as the treatment of infected macrophages and the inhibition of infection using pre-treated parasites. This study also investigated the GF1059 mechanism of action in L. amazonensis. Results showed that the compound was highly effective against L. infantum and L. amazonensis, presenting a selectivity index of 154.6 and 86.4, respectively, against promastigotes and of 137.6 and 74.3, respectively, against amastigotes. GF1059 was also effective in the treatment of infected macrophages and inhibited the infection of these cells when parasites were pre-incubated with it. The molecule also induced changes in the parasites’ mitochondrial membrane potential and cell integrity, and caused an increase in the reactive oxygen species production in L. amazonensis. Experiments performed in BALB/c mice, which had been previously infected with L. amazonensis promastigotes, and thus treated with GF1059, showed that these animals presented significant reductions in the parasite load when the infected tissue, spleen, liver, and draining lymph node were evaluated. GF1059-treated mice presented both lower parasitism and low levels of enzymatic markers, as compared to those receiving amphotericin B, which was used as control. In conclusion, data suggested that GF1059 can be considered a possible therapeutic target to be tested against leishmaniasis.FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisporUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em Ciências da Saúde - Infectologia e Medicina TropicalUFMGBrasilMEDICINA - FACULDADE DE MEDICINALeishmanioseTratamento farmacológicoToxicidadeCloroquinolinóisLeishmanioseTratamento FarmacológicoToxicidadeAvaliação da atividade antileishmanial in vitro e in vivo de um derivado de Cloroquinolina contra espécies de Leishmania capazes de causar Leishmaniose Tegumentar e VisceralEvaluation of the in vitro and in vivo antileishmanial activity of a chloroquinolin derivative against Leishmania species capable of causing tegumentary and visceral leishmaniasisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINALDissertação de Mestrado Tauane G Soyer.pdfDissertação de Mestrado Tauane G Soyer.pdfDissertação de Mestrado Tauane G Soyer.pdfapplication/pdf1283077https://repositorio.ufmg.br/bitstream/1843/31261/1/Disserta%c3%a7%c3%a3o%20de%20Mestrado%20Tauane%20G%20Soyer.pdf2afbea60d28037568aba7c50f2ae28a4MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-82119https://repositorio.ufmg.br/bitstream/1843/31261/2/license.txt34badce4be7e31e3adb4575ae96af679MD52TEXTDissertação de Mestrado Tauane G Soyer.pdf.txtDissertação de Mestrado Tauane G Soyer.pdf.txtExtracted texttext/plain108101https://repositorio.ufmg.br/bitstream/1843/31261/3/Disserta%c3%a7%c3%a3o%20de%20Mestrado%20Tauane%20G%20Soyer.pdf.txtcc73dbd8f861a5beda246365fe8d6f63MD531843/312612019-11-27 03:28:09.465oai:repositorio.ufmg.br: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Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oaiopendoar:2019-11-27T06:28:09Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
|