Atividade antimicrobiana e efeito sinérgico entre o derivado sintético 4-Hidroxicumarina e anfotericina B frente cepas de Candida albicans

Fungal infections have become a major challenge in view of the impact of resistance to usual antifungal agents on therapeutic management, in addition to the lack of implementation of more advanced diagnostic techniques in public health units. Concomitantly, a greater number of cases is observed,...

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Autor principal: Souza, Monalisa Silva de
Outros Autores: Andrade, Vânia Sousa
Formato: Dissertação
Idioma:pt_BR
Publicado em: Universidade Federal do Rio Grande do Norte
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Endereço do item:https://repositorio.ufrn.br/handle/123456789/50005
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id ri-123456789-50005
record_format dspace
institution Repositório Institucional
collection RI - UFRN
language pt_BR
topic Candida albicans
Cumarinas
4-Hidroxicumarina
Atividade antifúngica
Sinergismo
CNPQ::CIENCIAS BIOLOGICAS
spellingShingle Candida albicans
Cumarinas
4-Hidroxicumarina
Atividade antifúngica
Sinergismo
CNPQ::CIENCIAS BIOLOGICAS
Souza, Monalisa Silva de
Atividade antimicrobiana e efeito sinérgico entre o derivado sintético 4-Hidroxicumarina e anfotericina B frente cepas de Candida albicans
description Fungal infections have become a major challenge in view of the impact of resistance to usual antifungal agents on therapeutic management, in addition to the lack of implementation of more advanced diagnostic techniques in public health units. Concomitantly, a greater number of cases is observed, reflecting an increase in the incidence of fungal diseases, both in immunosuppression conditions and in immunologically healthy patients in exogenously acquired infectious processes. Species of the genus Candida continue to be the most implicated in invasive fungal infections, which notoriously trigger high mortality rates. Given this scenario, there was an increase in the search for the development of new antifungal agents, as well as the implementation of strategies to prevent candidemia. Studies with bioactive products derived from plants, which historically have well-established biological properties and which demonstrate safety in terms of toxicity, have been evaluated for a more concrete application. Among the compounds under study, coumarins and their derivatives, such as 4-Hydroxycoumarin, stand out, which has important attributes, including antiviral, antitumor and anticoagulant properties. In this context, the present study aimed to evaluate the antifungal activity of the synthetic phenolic compound 4- Hydroxycoumarin on Candida albicans strains, as well as to analyze the synergistic effects between this compound and the antifungal Amphotericin B. The biological activity of 4- hydroxycoumarin was investigated in 17 strains of Candida albicans, from the determination of the Minimum Inhibitory Concentration (MIC) by the broth microdilution technique and by the Minimum Fungicide Concentration (MFC) method. To verify the synergistic effect, through the Checkerboard method, 5 strains of the C. albicans species were selected, considering pathogenicity criteria among the 17 strains and the MIC values found. Antifungal activity was found for 15 of the 17 strains tested with MIC ranging from 5.0 to 0.625 mg/mL, and CFM ranging from 5.0 to 1.25 mg/mL. Regarding the evaluation of the synergistic effect between the synthetic compound and the antifungal, it was observed that this combination presented an additive and indifferent character against some strains. It was concluded that 4-Hydroxycoumarin has antifungal potential, mostly of a fungistatic nature, that is, it reduces the yeast load, but it was not very effective in relation to the synergistic effect when associated with amphotericin B, an antifungal recognized as a fungicide, suggesting that 4-Hydroxycoumarin may be a promising strategy in antifungal therapy.
author2 Andrade, Vânia Sousa
author_facet Andrade, Vânia Sousa
Souza, Monalisa Silva de
format masterThesis
author Souza, Monalisa Silva de
author_sort Souza, Monalisa Silva de
title Atividade antimicrobiana e efeito sinérgico entre o derivado sintético 4-Hidroxicumarina e anfotericina B frente cepas de Candida albicans
title_short Atividade antimicrobiana e efeito sinérgico entre o derivado sintético 4-Hidroxicumarina e anfotericina B frente cepas de Candida albicans
title_full Atividade antimicrobiana e efeito sinérgico entre o derivado sintético 4-Hidroxicumarina e anfotericina B frente cepas de Candida albicans
title_fullStr Atividade antimicrobiana e efeito sinérgico entre o derivado sintético 4-Hidroxicumarina e anfotericina B frente cepas de Candida albicans
title_full_unstemmed Atividade antimicrobiana e efeito sinérgico entre o derivado sintético 4-Hidroxicumarina e anfotericina B frente cepas de Candida albicans
title_sort atividade antimicrobiana e efeito sinérgico entre o derivado sintético 4-hidroxicumarina e anfotericina b frente cepas de candida albicans
publisher Universidade Federal do Rio Grande do Norte
publishDate 2022
url https://repositorio.ufrn.br/handle/123456789/50005
work_keys_str_mv AT souzamonalisasilvade atividadeantimicrobianaeefeitosinergicoentreoderivadosintetico4hidroxicumarinaeanfotericinabfrentecepasdecandidaalbicans
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spelling ri-123456789-500052022-12-07T00:09:58Z Atividade antimicrobiana e efeito sinérgico entre o derivado sintético 4-Hidroxicumarina e anfotericina B frente cepas de Candida albicans Souza, Monalisa Silva de Andrade, Vânia Sousa http://lattes.cnpq.br/9355901092568662 https://orcid.org/0000-0003-4138-4373 http://lattes.cnpq.br/9327124853897215 Luz, Jefferson Romáryo Duarte da Stoianoff, Maria Aparecida Resende Melo, Maria Celeste Nunes de Candida albicans Cumarinas 4-Hidroxicumarina Atividade antifúngica Sinergismo CNPQ::CIENCIAS BIOLOGICAS Fungal infections have become a major challenge in view of the impact of resistance to usual antifungal agents on therapeutic management, in addition to the lack of implementation of more advanced diagnostic techniques in public health units. Concomitantly, a greater number of cases is observed, reflecting an increase in the incidence of fungal diseases, both in immunosuppression conditions and in immunologically healthy patients in exogenously acquired infectious processes. Species of the genus Candida continue to be the most implicated in invasive fungal infections, which notoriously trigger high mortality rates. Given this scenario, there was an increase in the search for the development of new antifungal agents, as well as the implementation of strategies to prevent candidemia. Studies with bioactive products derived from plants, which historically have well-established biological properties and which demonstrate safety in terms of toxicity, have been evaluated for a more concrete application. Among the compounds under study, coumarins and their derivatives, such as 4-Hydroxycoumarin, stand out, which has important attributes, including antiviral, antitumor and anticoagulant properties. In this context, the present study aimed to evaluate the antifungal activity of the synthetic phenolic compound 4- Hydroxycoumarin on Candida albicans strains, as well as to analyze the synergistic effects between this compound and the antifungal Amphotericin B. The biological activity of 4- hydroxycoumarin was investigated in 17 strains of Candida albicans, from the determination of the Minimum Inhibitory Concentration (MIC) by the broth microdilution technique and by the Minimum Fungicide Concentration (MFC) method. To verify the synergistic effect, through the Checkerboard method, 5 strains of the C. albicans species were selected, considering pathogenicity criteria among the 17 strains and the MIC values found. Antifungal activity was found for 15 of the 17 strains tested with MIC ranging from 5.0 to 0.625 mg/mL, and CFM ranging from 5.0 to 1.25 mg/mL. Regarding the evaluation of the synergistic effect between the synthetic compound and the antifungal, it was observed that this combination presented an additive and indifferent character against some strains. It was concluded that 4-Hydroxycoumarin has antifungal potential, mostly of a fungistatic nature, that is, it reduces the yeast load, but it was not very effective in relation to the synergistic effect when associated with amphotericin B, an antifungal recognized as a fungicide, suggesting that 4-Hydroxycoumarin may be a promising strategy in antifungal therapy. As infecções fúngicas tornaram-se um grande desafio diante do impacto da resistência aos antifúngicos usuais na conduta terapêutica, além da falta de implementação de técnicas de diagnóstico mais avançadas nas unidades públicas de saúde. Concomitantemente, observa-se um maior número de casos, refletindo em aumento da incidência das doenças fúngicas, tanto em condições de imunossupressão como em pacientes imunologicamente hígidos em processos infecciosos adquiridos por via exógena. As espécies do gênero Candida continuam sendo as mais implicadas nas infecções fúngicas invasivas, as quais notoriamente desencadeiam altos índices de mortalidade. Diante desse cenário, houve um aumento na busca pelo desenvolvimento de novos agentes antifúngicos, assim como a implementação de estratégias para prevenir a candidemia. Estudos com produtos bioativos derivados de plantas, que historicamente apresentam propriedades biológicas bem consolidadas e que demonstram segurança quanto a toxicidade, vêm sendo avaliados para uma aplicação mais concreta. Dentre os compostos em estudo, ressalta-se as cumarinas e seus derivados, como a 4-Hidroxicumarina, o qual possui atributos importantes, incluindo propriedades antiviral, antitumoral e anticoagulante. Diante desse contexto, o presente trabalho teve como objetivo avaliar a atividade antifúngica do composto fenólico sintético 4- Hidroxicumarina sobre cepas de Candida albicans, bem como analisar os efeitos sinérgicos entre esse composto e o antifúngico anfotericina B. A atividade biológica da 4–Hidroxicumarina foi averiguada em 17 cepas de Candida albicans, a partir da determinação da Concentração Inibitória Mínima (CIM) pela técnica de microdiluição em caldo e pelo método da Concentração Fungicida Mínima (CFM). Para a verificar o efeito sinérgico, através do método de Checkerboard, foram selecionadas 5 cepas da espécie C. albicans, considerando critérios de patogenicidade entre as 17 cepas e os valores de CIM encontrados. Constatou-se atividade antifúngica, para 15 das 17 cepas testadas com CIM variando entre 5,0 e 0,625 mg/mL, e CFM variando entre 5,0 a 1,25 mg/mL. Com relação a avaliação do efeito sinérgico entre o composto sintético e o antifúngico, observouse que essa combinação apresentou caráter aditivo e indiferente frente algumas cepas. Concluiuse que a 4 - Hidroxicumarina apresenta potencial antifúngico, em sua maioria de natureza fungistática, ou seja, reduz a carga leveduriforme, porém mostrou-se pouco eficaz com relação ao efeito sinérgico quando associada a Anfotericina B, um antifúngico reconhecido como fungicida, sugerindo que a 4 - Hidroxicumarina poderá constituir uma estratégia promissora na terapêutica antifúngica. 2022-12-07T00:09:18Z 2022-12-07T00:09:18Z 2022-08-26 masterThesis SOUZA, Monalisa Silva de. Atividade antimicrobiana e efeito sinérgico entre o derivado sintético 4-Hidroxicumarina e anfotericina B frente cepas de Candida albicans. Orientador: Vânia Souza Andrade. 2022. 88f. Dissertação (Mestrado em Biologia Parasitária) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2022. https://repositorio.ufrn.br/handle/123456789/50005 pt_BR Acesso Aberto application/pdf Universidade Federal do Rio Grande do Norte Brasil UFRN PROGRAMA DE PÓS-GRADUAÇÃO EM BIOLOGIA PARASITÁRIA