Identification of repositionable drugs with novel antimycotic activity by screening the Prestwick Chemical Library against emerging invasive moulds

Abstract

Objectives: The incidence of severe filamentous fungal infections has increased over the past decade. Some of these filamentous fungi are resistant to available antifungals; it is thus urgent to find new compounds that are active against such life-threatening pathogens. Methods: In this study, 1280 drugs (Prestwick Chemical Library) were tested against six multidrug-resistant (MDR) filamentous fungi, includingAspergillus, Fusarium, Scedosporium/Lomentospora, Rhizopus and Lichtheimia species. Results: Several hits were identified that induced fungal growth inhibition ≥70%. Among the non-antifungal compounds that were effective against the clinical moulds tested in this study, clioquinol, alexidine dihydrochloride, hexachlorophene and thonzonium bromide displayed a broad activity against all strains tested. Conclusion: This study enriches the potential antifungal options that can be used against MDR invasive fungal diseases.

Keywords

• Drug repurposing
• Prestwick Chemical Library
• Emerging fungi
• Multidrug-resistant mould
• Alternative therapeutics