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

•1280 FDA-approved compounds were screened against six multidrug-resistant moulds.•Four non-antifungal compounds were effective against the clinical moulds tested.•These included clioquinol, alexidine dihydrochloride, hexachlorophene and thonzonium bromide. 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. 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. 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. This study enriches the potential antifungal options that can be used against MDR invasive fungal diseases.