A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | por |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/41359 |
Resumo: | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório Micologia. Rio de Janeiro, RJ, Brasil. |
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Coelho, Rowena AlvesJoffe, Luna SobrinoAlves, Gabriela MachadoFigueiredo-Carvalho, Maria Helena GaldinoBrito-Santos, FábioAmaral, Ana Claudia FernandesRodrigues, Marcio LourençoAlmeida-Paes, Rodrigo2020-05-22T14:48:29Z2020-05-22T14:48:29Z2020COELHO, Rowena Alves et al. A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis. Plos One, v. 15, n. 5, p. 1-13, 2020.1932-6203https://www.arca.fiocruz.br/handle/icict/4135910.1371/journal.pone.0229630porPublic Library of ScienceMMV021013ChromoblastomycosisAntifungal AgentsMycosesAuranofinLodoquinolCromoblastomicosisAntifúngicosMicosisAuranofinaYodoquinolCromoblastomicoseAntifúngicosMicosesAuranofinaA screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório Micologia. Rio de Janeiro, RJ, Brasil.Department of Microbiology and Immunology. Stony Brook University. New York, NY, United States of America.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório Micologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório Micologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório Micologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Farmanguinhos. Laboratório de Produtos Químicos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório Micologia. Rio de Janeiro, RJ, Brasil.Chromoblastomycosis (CBM) is a chronic subcutaneous mycosis caused by traumatic implantation of many species of black fungi. Due to the refractoriness of some cases and common recurrence of CBM, a more effective and less time-consuming treatment is mandatory. The aim of this study was to identify compounds with in vitro antifungal activity in the Pathogen Box® compound collection against different CBM agents. Synergism of these compounds with drugs currently used to treat CBM was also assessed. An initial screening of the drugs present in this collection at 1 μM was performed with a Fonsecaea pedrosoi clinical strain according to the EUCAST protocol. The compounds with activity against this fungus were also tested against other seven etiologic agents of CBM (Cladophialophora carrionii, Phialophora verrucosa, Exophiala jeanselmei, Exophiala dermatitidis, Fonsecaea monophora, Fonsecaea nubica, and Rhinocladiella similis) at concentrations ranging from 0.039 to 10 μM. The analysis of potential synergism of these compounds with itraconazole and terbinafine was performed by the checkerboard method. Eight compounds inhibited more than 60% of the F. pedrosoi growth: difenoconazole, bitertanol, iodoquinol, azoxystrobin, MMV688179, MMV021013, trifloxystrobin, and auranofin. Iodoquinol produced the lowest MIC values (1.25-2.5 μM) and MMV688179 showed MICs that were higher than all compounds tested (5 - >10 μM). When auranofin and itraconazole were tested in combination, a synergistic interaction (FICI = 0.37) was observed against the C. carrionii isolate. Toxicity analysis revealed that MMV021013 showed high selectivity indices (SI ≥ 10) against the fungi tested. In summary, auranofin, iodoquinol, and MMV021013 were identified as promising compounds to be tested in CBM models of infection.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83084https://www.arca.fiocruz.br/bitstream/icict/41359/1/license.txt783568c2893d2e25a99990b126be1772MD51ORIGINALjournal.pone.022963.pdfjournal.pone.022963.pdfapplication/pdf1069101https://www.arca.fiocruz.br/bitstream/icict/41359/2/journal.pone.022963.pdff96159267f32ef47d3f6deebc6c319a0MD52TEXTjournal.pone.022963.pdf.txtjournal.pone.022963.pdf.txtExtracted texttext/plain46885https://www.arca.fiocruz.br/bitstream/icict/41359/3/journal.pone.022963.pdf.txtd998237a59cb9232b102373c467c61fdMD53icict/413592020-05-25 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| dc.title.pt_BR.fl_str_mv |
A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis |
| title |
A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis |
| spellingShingle |
A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis Coelho, Rowena Alves MMV021013 Chromoblastomycosis Antifungal Agents Mycoses Auranofin Lodoquinol Cromoblastomicosis Antifúngicos Micosis Auranofina Yodoquinol Cromoblastomicose Antifúngicos Micoses Auranofina |
| title_short |
A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis |
| title_full |
A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis |
| title_fullStr |
A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis |
| title_full_unstemmed |
A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis |
| title_sort |
A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis |
| author |
Coelho, Rowena Alves |
| author_facet |
Coelho, Rowena Alves Joffe, Luna Sobrino Alves, Gabriela Machado Figueiredo-Carvalho, Maria Helena Galdino Brito-Santos, Fábio Amaral, Ana Claudia Fernandes Rodrigues, Marcio Lourenço Almeida-Paes, Rodrigo |
| author_role |
author |
| author2 |
Joffe, Luna Sobrino Alves, Gabriela Machado Figueiredo-Carvalho, Maria Helena Galdino Brito-Santos, Fábio Amaral, Ana Claudia Fernandes Rodrigues, Marcio Lourenço Almeida-Paes, Rodrigo |
| author2_role |
author author author author author author author |
| dc.contributor.author.fl_str_mv |
Coelho, Rowena Alves Joffe, Luna Sobrino Alves, Gabriela Machado Figueiredo-Carvalho, Maria Helena Galdino Brito-Santos, Fábio Amaral, Ana Claudia Fernandes Rodrigues, Marcio Lourenço Almeida-Paes, Rodrigo |
| dc.subject.other.pt_BR.fl_str_mv |
MMV021013 |
| topic |
MMV021013 Chromoblastomycosis Antifungal Agents Mycoses Auranofin Lodoquinol Cromoblastomicosis Antifúngicos Micosis Auranofina Yodoquinol Cromoblastomicose Antifúngicos Micoses Auranofina |
| dc.subject.en.pt_BR.fl_str_mv |
Chromoblastomycosis Antifungal Agents Mycoses Auranofin Lodoquinol |
| dc.subject.es.pt_BR.fl_str_mv |
Cromoblastomicosis Antifúngicos Micosis Auranofina Yodoquinol |
| dc.subject.decs.pt_BR.fl_str_mv |
Cromoblastomicose Antifúngicos Micoses Auranofina |
| description |
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório Micologia. Rio de Janeiro, RJ, Brasil. |
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2020 |
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2020-05-22T14:48:29Z |
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2020-05-22T14:48:29Z |
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2020 |
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COELHO, Rowena Alves et al. A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis. Plos One, v. 15, n. 5, p. 1-13, 2020. |
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https://www.arca.fiocruz.br/handle/icict/41359 |
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1932-6203 |
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10.1371/journal.pone.0229630 |
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COELHO, Rowena Alves et al. A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis. Plos One, v. 15, n. 5, p. 1-13, 2020. 1932-6203 10.1371/journal.pone.0229630 |
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