Screening the pandemic response box identified benzimidazole carbamates, Olorofim and ravuconazole as promising drug candidates for the treatment of eumycetoma.
Eumycetoma is a chronic subcutaneous neglected tropical disease that can be caused by more than 40 different fungal causative agents. The most common causative agents produce black grains and belong to the fungal orders Sordariales and Pleosporales. The current antifungal agents used to treat eumyce...
Published in: | PLOS Neglected Tropical Diseases |
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ftdoajarticles:oai:doaj.org/article:d88552da4647484ea2d7458681c54041 2023-05-15T15:08:34+02:00 Screening the pandemic response box identified benzimidazole carbamates, Olorofim and ravuconazole as promising drug candidates for the treatment of eumycetoma. Wilson Lim Bertrand Nyuykonge Kimberly Eadie Mickey Konings Juli Smeets Ahmed Fahal Alexandro Bonifaz Matthew Todd Benjamin Perry Kirandeep Samby Jeremy Burrows Annelies Verbon Wendy van de Sande 2022-02-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0010159 https://doaj.org/article/d88552da4647484ea2d7458681c54041 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0010159 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010159 https://doaj.org/article/d88552da4647484ea2d7458681c54041 PLoS Neglected Tropical Diseases, Vol 16, Iss 2, p e0010159 (2022) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2022 ftdoajarticles https://doi.org/10.1371/journal.pntd.0010159 2022-12-31T16:06:15Z Eumycetoma is a chronic subcutaneous neglected tropical disease that can be caused by more than 40 different fungal causative agents. The most common causative agents produce black grains and belong to the fungal orders Sordariales and Pleosporales. The current antifungal agents used to treat eumycetoma are itraconazole or terbinafine, however, their cure rates are low. To find novel drugs for eumycetoma, we screened 400 diverse drug-like molecules from the Pandemic Response Box against common eumycetoma causative agents as part of the Open Source Mycetoma initiative (MycetOS). 26 compounds were able to inhibit the growth of Madurella mycetomatis, Madurella pseudomycetomatis and Madurella tropicana, 26 compounds inhibited Falciformispora senegalensis and seven inhibited growth of Medicopsis romeroi in vitro. Four compounds were able to inhibit the growth of all five species of fungi tested. They are the benzimidazole carbamates fenbendazole and carbendazim, the 8-aminoquinolone derivative tafenoquine and MMV1578570. Minimal inhibitory concentrations were then determined for the compounds active against M. mycetomatis. Compounds showing potent activity in vitro were further tested in vivo. Fenbendazole, MMV1782387, ravuconazole and olorofim were able to significantly prolong Galleria mellonella larvae survival and are promising candidates to explore in mycetoma treatment and to also serve as scaffolds for medicinal chemistry optimisation in the search for novel antifungals to treat eumycetoma. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 16 2 e0010159 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Wilson Lim Bertrand Nyuykonge Kimberly Eadie Mickey Konings Juli Smeets Ahmed Fahal Alexandro Bonifaz Matthew Todd Benjamin Perry Kirandeep Samby Jeremy Burrows Annelies Verbon Wendy van de Sande Screening the pandemic response box identified benzimidazole carbamates, Olorofim and ravuconazole as promising drug candidates for the treatment of eumycetoma. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Eumycetoma is a chronic subcutaneous neglected tropical disease that can be caused by more than 40 different fungal causative agents. The most common causative agents produce black grains and belong to the fungal orders Sordariales and Pleosporales. The current antifungal agents used to treat eumycetoma are itraconazole or terbinafine, however, their cure rates are low. To find novel drugs for eumycetoma, we screened 400 diverse drug-like molecules from the Pandemic Response Box against common eumycetoma causative agents as part of the Open Source Mycetoma initiative (MycetOS). 26 compounds were able to inhibit the growth of Madurella mycetomatis, Madurella pseudomycetomatis and Madurella tropicana, 26 compounds inhibited Falciformispora senegalensis and seven inhibited growth of Medicopsis romeroi in vitro. Four compounds were able to inhibit the growth of all five species of fungi tested. They are the benzimidazole carbamates fenbendazole and carbendazim, the 8-aminoquinolone derivative tafenoquine and MMV1578570. Minimal inhibitory concentrations were then determined for the compounds active against M. mycetomatis. Compounds showing potent activity in vitro were further tested in vivo. Fenbendazole, MMV1782387, ravuconazole and olorofim were able to significantly prolong Galleria mellonella larvae survival and are promising candidates to explore in mycetoma treatment and to also serve as scaffolds for medicinal chemistry optimisation in the search for novel antifungals to treat eumycetoma. |
format |
Article in Journal/Newspaper |
author |
Wilson Lim Bertrand Nyuykonge Kimberly Eadie Mickey Konings Juli Smeets Ahmed Fahal Alexandro Bonifaz Matthew Todd Benjamin Perry Kirandeep Samby Jeremy Burrows Annelies Verbon Wendy van de Sande |
author_facet |
Wilson Lim Bertrand Nyuykonge Kimberly Eadie Mickey Konings Juli Smeets Ahmed Fahal Alexandro Bonifaz Matthew Todd Benjamin Perry Kirandeep Samby Jeremy Burrows Annelies Verbon Wendy van de Sande |
author_sort |
Wilson Lim |
title |
Screening the pandemic response box identified benzimidazole carbamates, Olorofim and ravuconazole as promising drug candidates for the treatment of eumycetoma. |
title_short |
Screening the pandemic response box identified benzimidazole carbamates, Olorofim and ravuconazole as promising drug candidates for the treatment of eumycetoma. |
title_full |
Screening the pandemic response box identified benzimidazole carbamates, Olorofim and ravuconazole as promising drug candidates for the treatment of eumycetoma. |
title_fullStr |
Screening the pandemic response box identified benzimidazole carbamates, Olorofim and ravuconazole as promising drug candidates for the treatment of eumycetoma. |
title_full_unstemmed |
Screening the pandemic response box identified benzimidazole carbamates, Olorofim and ravuconazole as promising drug candidates for the treatment of eumycetoma. |
title_sort |
screening the pandemic response box identified benzimidazole carbamates, olorofim and ravuconazole as promising drug candidates for the treatment of eumycetoma. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2022 |
url |
https://doi.org/10.1371/journal.pntd.0010159 https://doaj.org/article/d88552da4647484ea2d7458681c54041 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 16, Iss 2, p e0010159 (2022) |
op_relation |
https://doi.org/10.1371/journal.pntd.0010159 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0010159 https://doaj.org/article/d88552da4647484ea2d7458681c54041 |
op_doi |
https://doi.org/10.1371/journal.pntd.0010159 |
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PLOS Neglected Tropical Diseases |
container_volume |
16 |
container_issue |
2 |
container_start_page |
e0010159 |
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