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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.

Addressing the most neglected diseases through an open research model: The discovery of fenarimols as novel drug candidates for eumycetoma