Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/41359
Title: A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis
Authors: 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
Affilliation: Fundação 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.
Abstract: 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.
Keywords: Chromoblastomycosis
Antifungal Agents
Mycoses
Auranofin
Lodoquinol
Keywords in spanish: Cromoblastomicosis
Antifúngicos
Micosis
Auranofina
Yodoquinol
keywords: MMV021013
DeCS: Cromoblastomicose
Antifúngicos
Micoses
Auranofina
Issue Date: 2020
Publisher: Public Library of Science
Citation: 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.
DOI: 10.1371/journal.pone.0229630
ISSN: 1932-6203
Copyright: open access
Appears in Collections:PR - ICC - Artigos de Periódicos
INI - Artigos de Periódicos
Farmanguinhos - Artigos de Periódicos

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