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Susana Johannhttp://lattes.cnpq.br/7244522592099497http://lattes.cnpq.br/3424012509486763Lana Ivone Barreto Cruz2020-03-05T19:19:04Z2020-03-05T19:19:04Z2019-03-11http://hdl.handle.net/1843/32714A candidíase é uma infecção fúngica oportunista, sendo Candida albicans a espécie mais frequentemente isolada. O tratamento dessas infecções é desafiador devido à resistência que pode se desenvolver durante a terapia e ao número limitado de compostos antifúngicos disponíveis. O objetivo deste estudo foi avaliar, por meio de testes in vitro e in vivo, a atividade antifúngica de quatro substâncias de derivados hidrazino-tiazólicos (1, 2, 3 e 4) e estudar os possíveis efeitos destas nos fatores de virulência de C. albicans. As substâncias hidrazino-tiazólicas 1, 2, 3 e 4 mostraram atividade antifúngica, apresentando CIMs de 0,125 - 16,0 μg / mL contra C. albicans. A toxicidade das substâncias foi avaliada usando eritrócitos humanos e produziu LC50> 64 μg/mL. Quando avaliada a capacidade de inibir alguns fatores de virulência de C. albicans, a substância 1 foi capaz de inibir a filamentação em concentração igual ao CIM, as substâncias 1, 2, e 3 inibiram a adesão em concentração referente ao valor de CIM e as substâncias 1 e 2 desintegraram o biofilme de C. albicans. As substâncias foram avaliadas adicionalmente utilizando a larva Galleria mellonella como um modelo in vivo. A sobrevida das larvas foi aumentada quando testadas concentrações entre 5 e 15 mg/kg, com desempenho comparável ao fluconazol. A substância 2 foi avaliada em modelo murino de candidíase oral e sistêmica. No modelo oral, a substância 2 reduziu a carga fúngica na língua do rato; e no modelo sistêmico reduziu a carga fúngica encontrada no rim quando testada a 10 mg/kg. Estes resultados mostram que os derivados hidrazino-tiazólicos apresentam potencial antifúngico contra C. albicans com eficácia in vivo.Candidiasis is an opportunistic fungal infection, being Candida albicans the most frequently isolated specie. Treatment of this infection is challenging because of the development of resistance during therapy and the limited number of antifungal compounds available. The aim of this study was to evaluate the antifungal activity of four thiazolylhydrazone-derived substances (1, 2, 3 and 4) by in vitro and in vivo tests and to study the possible effects of these on the virulence factors of C. albicans. Thiazolylhydrazone 1, 2, 3 and 4 showed antifungal activity, presenting MICs of 0.125 - 16.0 μg / mL against C. albicans. Toxicity of the substances was assessed using human erythrocytes and produced LC50> 64 μg / mL. When the ability to inhibit some virulence factors of C. albicans was evaluated, substance 1 was able to inhibit filamentation in a concentration equal to MIC; substances 1, 2 and 3 inhibited adhesion at a concentration related to MIC value and substances 1 and 2 disintegrated C. albicans biofilm. Substances were further evaluated using Galleria mellonella larva as an in vivo model. The survival of the larvae was increased when tested concentrations between 5 and 15 mg / kg, with as good as fluconazole performance. Substance 2 was evaluated in murine model of oral and systemic candidacy. In the oral model, substance 2 reduced the fungal load on rat tongue; and in the systemic model it reduced the fungal load found in the kidney when tested at 10 mg / kg. These results show that thiazolylhydrazones are an antifungal agent for C. albicans with in vivo efficacy.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoporUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em MicrobiologiaUFMGBrasilICB - INSTITUTO DE CIÊNCIAS BIOLOGICASMicrobiologiaCandida albicansTiazóisToxicidadeVirulênciaCandida spp.Tiazóisin vivoToxicidadeVirulênciaAtividade antifúngica de derivados hidrazino-tiazólicos contra Candida albicansinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINALTese para pos 2.pdfTese para pos 2.pdfapplication/pdf2077055https://repositorio.ufmg.br/bitstream/1843/32714/1/Tese%20para%20pos%202.pdf72e165263c585f60b31d28e9b7ab14c2MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-82119https://repositorio.ufmg.br/bitstream/1843/32714/2/license.txt34badce4be7e31e3adb4575ae96af679MD52TEXTTese para pos 2.pdf.txtTese para pos 2.pdf.txtExtracted texttext/plain202911https://repositorio.ufmg.br/bitstream/1843/32714/3/Tese%20para%20pos%202.pdf.txtb9f999306fcc614195d44ba05d88049cMD531843/327142020-03-06 03:36:05.25oai:repositorio.ufmg.br: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Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oaiopendoar:2020-03-06T06:36:05Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
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