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A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis.
PLoS One. 2020; 15(5):e0229630.Plos

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.

Authors+Show Affiliations

Mycology Laboratory at the Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil.Department of Microbiology and Immunology, Stony Brook University, New York, NY, United States of America.Mycology Laboratory at the Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil.Mycology Laboratory at the Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil.Mycology Laboratory at the Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil.Laboratory of Natural Products Chemistry, Farmanguinhos, Fiocruz, Rio de Janeiro, Brazil.Carlos Chagas Institute, Fiocruz, Paraná, Brazil. Microbiology Institute, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.Mycology Laboratory at the Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32401759

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, vol. 15, no. 5, 2020, pp. e0229630.
Coelho RA, Joffe LS, Alves GM, et al. A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis. PLoS ONE. 2020;15(5):e0229630.
Coelho, R. A., Joffe, L. S., Alves, G. M., Figueiredo-Carvalho, M. H. G., Brito-Santos, F., Amaral, A. C. F., Rodrigues, M. L., & Almeida-Paes, R. (2020). A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis. PloS One, 15(5), e0229630. https://doi.org/10.1371/journal.pone.0229630
Coelho RA, et al. A Screening of the MMV Pathogen Box® Reveals New Potential Antifungal Drugs Against the Etiologic Agents of Chromoblastomycosis. PLoS ONE. 2020;15(5):e0229630. PubMed PMID: 32401759.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis. AU - Coelho,Rowena Alves, AU - Joffe,Luna Sobrino, AU - Alves,Gabriela Machado, AU - Figueiredo-Carvalho,Maria Helena Galdino, AU - Brito-Santos,Fábio, AU - Amaral,Ana Claudia Fernandes, AU - Rodrigues,Marcio L, AU - Almeida-Paes,Rodrigo, Y1 - 2020/05/13/ PY - 2020/02/07/received PY - 2020/04/27/accepted PY - 2020/5/14/entrez PY - 2020/5/14/pubmed PY - 2020/7/24/medline SP - e0229630 EP - e0229630 JF - PloS one JO - PLoS ONE VL - 15 IS - 5 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/32401759/A_screening_of_the_MMV_Pathogen_Box®_reveals_new_potential_antifungal_drugs_against_the_etiologic_agents_of_chromoblastomycosis L2 - http://dx.plos.org/10.1371/journal.pone.0229630 DB - PRIME DP - Unbound Medicine ER -