Identification of off-patent drugs that show synergism with amphotericin B or that present antifungal action against Cryptococcus neoformans and Candida spp.

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Autor(es): dc.contributorInstituto de Salud Carlos III-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorFundação Oswaldo Cruz (Fiocruz)-
Autor(es): dc.contributorSpanish Agency of Medicines and Medical Devices-
Autor(es): dc.creatorRossi, Suélen Andreia-
Autor(es): dc.creatorDe Oliveira, Haroldo Cesar [UNESP]-
Autor(es): dc.creatorAgreda-Mellon, Daniel-
Autor(es): dc.creatorLucio, José-
Autor(es): dc.creatorSoares Mendes-Giannini, Maria José [UNESP]-
Autor(es): dc.creatorGarcía-Cambero, Jesús Pablo-
Autor(es): dc.creatorZaragoza, Oscar-
Data de aceite: dc.date.accessioned2022-02-22T00:29:47Z-
Data de disponibilização: dc.date.available2022-02-22T00:29:47Z-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2019-12-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1128/AAC.01921-19-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/200209-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/200209-
Descrição: dc.descriptionAmphotericin B (AmB) is the antifungal with the strongest fungicidal activity, but its use has several limitations, mainly associated with its toxicity. Although some lipidic and liposomal formulations that present reduced toxicity are available, their price limits their application in developing countries. Flucytosine (5FC) has shown synergistic effect with AmB for treatment of some fungal infections, such as cryptococcosis, but again, its price is a limitation for its use in many regions. In the present work, we aimed to identify new drugs that have a minor effect on Cryptococcus neoformans, reducing its growth in the presence of subinhibitory concentrations of AmB. In the initial screening, we found fourteen drugs that had this pattern. Later, checkerboard assays of selected compounds, such as erythromycin, riluzole, nortriptyline, chenodiol, nisoldipine, promazine, chlorcyclizine, cloperastine, and glimepiride, were performed and all of them confirmed for their synergistic effect (fractional inhibitory concentration index [FICI] < 0.5). Additionally, toxicity of these drugs in combination with AmB was tested in mammalian cells and in zebrafish embryos. Harmless compounds, such as the antibiotic erythromycin, were found to have synergic activity with AmB, not only against C. neoformans but also against some Candida spp., in particular against Candida albicans. In parallel, we identified drugs that had antifungal activity against C. neoformans and found 43 drugs that completely inhibited the growth of this fungus, such as ciclopirox and auranofin. Our results expand our knowledge about antifungal compounds and open new perspectives in the treatment of invasive mycosis based on repurposing off-patent drugs.-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionMinisterio de Economía, Industria y Competitividad, Gobierno de España-
Descrição: dc.descriptionMycology Reference Laboratory National Centre for Microbiology Instituto de Salud Carlos III-
Descrição: dc.descriptionUniversidade Estadual Paulista (UNESP) Faculdade de Ciências Farmacêuticas Câmpus Araraquara Departamento de Análises Clínicas-
Descrição: dc.descriptionToxicology Area National Centre for Environmental Health Instituto de Salud Carlos III-
Descrição: dc.descriptionUniversidade de São Paulo (USP) Instituto de Ciências Biomédicas II (ICBII)-
Descrição: dc.descriptionInstituto Carlos Chagas Fundação Oswaldo Cruz (Fiocruz)-
Descrição: dc.descriptionDepartment of Medicines for Human Use Spanish Agency of Medicines and Medical Devices-
Descrição: dc.descriptionUniversidade Estadual Paulista (UNESP) Faculdade de Ciências Farmacêuticas Câmpus Araraquara Departamento de Análises Clínicas-
Descrição: dc.descriptionFAPESP: 2016/20631-3-
Descrição: dc.descriptionCNPq: 202436/2015-2-
Descrição: dc.descriptionMinisterio de Economía, Industria y Competitividad, Gobierno de España: SAF2014-54336-R-
Descrição: dc.descriptionMinisterio de Economía, Industria y Competitividad, Gobierno de España: SAF2017-86192-R-
Idioma: dc.languageen-
Relação: dc.relationAntimicrobial Agents and Chemotherapy-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectAmphotericin B-
Palavras-chave: dc.subjectCandida-
Palavras-chave: dc.subjectCryptococcus neoformans-
Palavras-chave: dc.subjectDrug repurposing-
Palavras-chave: dc.subjectSynergism-
Título: dc.titleIdentification of off-patent drugs that show synergism with amphotericin B or that present antifungal action against Cryptococcus neoformans and Candida spp.-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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