Antifungal application of non-antifungal drugs.
Antimicrob Agents Chemother. 2013 Nov 25;
Authors: Stylianou M, Kulesskiy E, Lopes JP, Granlund M, Wennerberg K, Urban CF
Candida species are the cause of 60% of all mycoses in immunosuppressed individuals leading to ∼150000 annual deaths due to systemic infections, whereas the current antifungal therapies either have toxic side effects or are insufficiently efficient. We performed a screening of two compound libraries, the ENZO and the FIMM oncology collection library, for anti-Candida activity based on the European committee on antimicrobial susceptibility testing (EUCAST) guidelines. From a total of 844 drugs, 26 agents showed activity against Candida albicans. Of those 12 were standard antifungal drugs (SADs) and 7 were off-target drugs, previously reported to be active against Candida spp. The remaining 7 off-target drugs amonafide, tosedostat, megestrol acetate, melengestrol acetate, stanozolol, triflurperidol and haloperidol were identified with this screen. Anti-Candida activity of the new agents was investigated by three individual assays using optical density, ATP levels as well as microscopy. The antifungal activity of these drugs was comparable to the SADs found in the screen. The aminopeptidase inhibitor tosedostat, currently in a clinical trial phase for anticancer therapy, displayed a broad antifungal activity against different Candida spp., including Candida glabrata. Thus, this screen reveals previously unknown anti-Candida agents allowing for the design of novel therapies against invasive candidiasis.
PMID: 24277040 [PubMed - as supplied by publisher]