Synergistic effect of pedalitin and amphotericin B against Cryptococcus neoformans by in vitro and in vivo evaluation

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Sangalli-Leite, Fernanda ; Scorzoni, Liliana ; Alves de Paula e Silva, Ana Carolina ; da Silva, Julhiany de Fatima ; de Oliveira, Haroldo Cesar ; Singulani, Junya de Lacorte ; Gullo, Fernanda Patricia ; da Silva, Rosangela Moraes ; Regasini, Luis Octavio ; Siqueira da Silva, Dulce Helena ; Bolzani, Vanderlan da Silva ; Fusco-Almeida, Ana Marisa ; Soares Mendes-Giannini, Maria Jose

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS; v. 48, n. 5, p. 504-511, NOV 2016.
• Citações Web of Science: 9

Resumo

Cryptococcosis is an opportunistic fungal infection responsible for high morbidity and mortality in immunocompromised patients. Combination of antifungal substances is a promising way to increase the percentage of successful treatment. Pedalitin (PED) is a natural substance obtained from Pterogyne nitens. The aim of this study was to verify the efficacy of PED alone and in combination with amphotericin B (AmB) in vitro and in vivo against Cryptococcus spp. In the in vitro assay, minimum inhibitory concentrations (MICs) of 0.125 mg/L for AmB and 3.9 mg/L for PED were found when the substances were tested alone, whilst in the combination treatment the active concentration of both decreased, with MICs of 0.03 mg/L for AmB and 1 mg/L for PED. In the survival assay, fungal burden study and histopathological assays it was possible to study the efficacy of the substances alone and in combination. The efficacy of combination therapy was considered better than monotherapy as evaluated in a Galleria mellonella model and amurine model. Thus, the combination of PED and AmB is an interesting alternative for anticryptococcal fungal treatment. Moreover, a correlation was observed between the invertebrate and murine models for this antifungal treatment combination. (C) 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved. (AU)

• Processo FAPESP: 14/10446-9 - Pesquisa de novas terapias e de biomarcadores na paracoccidioidomicose: estudo da atividade antifúngica de galatos de alquila em modelos alternativos e camundongos e identificação de microRNAs circulantes
• Beneficiário: Junya de Lacorte Singulani
• Modalidade de apoio: Bolsas no Brasil - Doutorado
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• Processo FAPESP: 15/14023-8 - Uso de peptídeos com atividade anti-adesiva em Paracoccidoides spp. na terapêutica e profilaxia da paracoccidioidomicose
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