Abstract
Sporotrichosis is a neglected endemic mycosis with a high incidence in Latin America, mainly in Brazil. Sporothrix schenckii is the most frequent species in Latin America, whereas Sporothrix brasiliensis is the predominant species observed in Brazil and is associated with both human and animal sporotrichosis. Sporotrichosis treatment remains restricted to a few options, itraconazole being the first choice for human and animal therapy. In this work, we screened the molecular library Pathogen Box (Medicines for Malaria Venture [MMV], Switzerland) in search of compounds with anti-Sporothrix activity. Our initial screen of the 400 compounds identified five compounds that inhibited more than 80% of S. brasiliensis and S. schenkii growth. Among those, three compounds (MMV675968, MMV102872, and MMV002817 (known as iodoquinol)) not previously described as antifungals or agrochemicals, were selected for further evaluation. MMV102872 and iodoquinol showed the most promising combination of antifungal activity (lower inhibitory concentration) and fungal selectivity (lower cytotoxicity in LLC-MK2 cells). Scanning electron microscopy and flow cytometry analyses revealed that MMV102872 and iodoquinol induced changes in cell morphology, membrane integrity, and the presence of neutral lipids, impairing fungal survival. Our results indicate that MMV102872 and iodoquinol are promising molecules for use as scaffolds for the development of new antifungal agents.
Highlights
ObjectivesThe purpose of this study was to screen this collection in search of compounds with potential anti-S. brasiliensis and S. schenckii activity
Data Availability Statement: All relevant data are within the manuscript
The initial screen of the 400 compounds in the Pathogen Box identified 12 compounds that inhibited S. brasiliensis CBS 133006 growth by more than 80% (Fig 1A)
Summary
The purpose of this study was to screen this collection in search of compounds with potential anti-S. brasiliensis and S. schenckii activity. As our goal is to treat humans and animals, we decided to exclude those agrochemical molecules from our pool of candidates for the development of new human and/or animal antifungal agents
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