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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Resumo: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.