Addressing the most neglected diseases through an open research model: The discovery of fenarimols as novel drug candidates for eumycetoma.
Eumycetoma is a chronic infectious disease characterized by a large subcutaneous mass, often caused by the fungus Madurella mycetomatis. A combination of surgery and prolonged medication is needed to treat this infection with a success rate of only 30%. There is, therefore, an urgent need to find mo...
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ftdoajarticles:oai:doaj.org/article:bc3b4ad960864546b8afa606fed0e6cb 2023-05-15T15:10:48+02:00 Addressing the most neglected diseases through an open research model: The discovery of fenarimols as novel drug candidates for eumycetoma. Wilson Lim Youri Melse Mickey Konings Hung Phat Duong Kimberly Eadie Benoît Laleu Benjamin Perry Matthew H Todd Jean-Robert Ioset Wendy W J van de Sande 2018-04-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0006437 https://doaj.org/article/bc3b4ad960864546b8afa606fed0e6cb EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5940239?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006437 https://doaj.org/article/bc3b4ad960864546b8afa606fed0e6cb PLoS Neglected Tropical Diseases, Vol 12, Iss 4, p e0006437 (2018) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2018 ftdoajarticles https://doi.org/10.1371/journal.pntd.0006437 2022-12-31T01:04:09Z Eumycetoma is a chronic infectious disease characterized by a large subcutaneous mass, often caused by the fungus Madurella mycetomatis. A combination of surgery and prolonged medication is needed to treat this infection with a success rate of only 30%. There is, therefore, an urgent need to find more effective drugs for the treatment of this disease. In this study, we screened 800 diverse drug-like molecules and identified 215 molecules that were active in vitro. Minimal inhibitory concentrations were determined for the 13 most active compounds. One of the most potent compounds, a fenarimol analogue for which a large analogue library is available, led to the screening of an additional 35 compounds for their in vitro activity against M. mycetomatis hyphae, rendering four further hit compounds. To assess the in vivo potency of these hit compounds, a Galleria mellonella larvae model infected with M. mycetomatis was used. Several of the compounds identified in vitro demonstrated promising efficacy in vivo in terms of prolonged larval survival and/or reduced fungal burden. The results presented in this paper are the starting point of an Open Source Mycetoma (MycetOS) approach in which members of the global scientific community are invited to participate and contribute as equal partners. We hope that this initiative, coupled with the promising new hits we have reported, will lead to progress in drug discovery for this most neglected of neglected tropical diseases. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 12 4 e0006437 |
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Open Polar |
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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 Youri Melse Mickey Konings Hung Phat Duong Kimberly Eadie Benoît Laleu Benjamin Perry Matthew H Todd Jean-Robert Ioset Wendy W J van de Sande Addressing the most neglected diseases through an open research model: The discovery of fenarimols as novel drug candidates for eumycetoma. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Eumycetoma is a chronic infectious disease characterized by a large subcutaneous mass, often caused by the fungus Madurella mycetomatis. A combination of surgery and prolonged medication is needed to treat this infection with a success rate of only 30%. There is, therefore, an urgent need to find more effective drugs for the treatment of this disease. In this study, we screened 800 diverse drug-like molecules and identified 215 molecules that were active in vitro. Minimal inhibitory concentrations were determined for the 13 most active compounds. One of the most potent compounds, a fenarimol analogue for which a large analogue library is available, led to the screening of an additional 35 compounds for their in vitro activity against M. mycetomatis hyphae, rendering four further hit compounds. To assess the in vivo potency of these hit compounds, a Galleria mellonella larvae model infected with M. mycetomatis was used. Several of the compounds identified in vitro demonstrated promising efficacy in vivo in terms of prolonged larval survival and/or reduced fungal burden. The results presented in this paper are the starting point of an Open Source Mycetoma (MycetOS) approach in which members of the global scientific community are invited to participate and contribute as equal partners. We hope that this initiative, coupled with the promising new hits we have reported, will lead to progress in drug discovery for this most neglected of neglected tropical diseases. |
format |
Article in Journal/Newspaper |
author |
Wilson Lim Youri Melse Mickey Konings Hung Phat Duong Kimberly Eadie Benoît Laleu Benjamin Perry Matthew H Todd Jean-Robert Ioset Wendy W J van de Sande |
author_facet |
Wilson Lim Youri Melse Mickey Konings Hung Phat Duong Kimberly Eadie Benoît Laleu Benjamin Perry Matthew H Todd Jean-Robert Ioset Wendy W J van de Sande |
author_sort |
Wilson Lim |
title |
Addressing the most neglected diseases through an open research model: The discovery of fenarimols as novel drug candidates for eumycetoma. |
title_short |
Addressing the most neglected diseases through an open research model: The discovery of fenarimols as novel drug candidates for eumycetoma. |
title_full |
Addressing the most neglected diseases through an open research model: The discovery of fenarimols as novel drug candidates for eumycetoma. |
title_fullStr |
Addressing the most neglected diseases through an open research model: The discovery of fenarimols as novel drug candidates for eumycetoma. |
title_full_unstemmed |
Addressing the most neglected diseases through an open research model: The discovery of fenarimols as novel drug candidates for eumycetoma. |
title_sort |
addressing the most neglected diseases through an open research model: the discovery of fenarimols as novel drug candidates for eumycetoma. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2018 |
url |
https://doi.org/10.1371/journal.pntd.0006437 https://doaj.org/article/bc3b4ad960864546b8afa606fed0e6cb |
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Arctic |
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Arctic |
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Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 12, Iss 4, p e0006437 (2018) |
op_relation |
http://europepmc.org/articles/PMC5940239?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006437 https://doaj.org/article/bc3b4ad960864546b8afa606fed0e6cb |
op_doi |
https://doi.org/10.1371/journal.pntd.0006437 |
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PLOS Neglected Tropical Diseases |
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12 |
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4 |
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e0006437 |
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