2026-07-16T10:48:50Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/271342026-01-14T11:18:09Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Rossi, Suelen Andreia
author
de Oliveira, Haroldo Cesar
author
Agreda-Mellon, Daniel
author
Lucio, Jose
author
Mendes-Giannini, Maria José Soares
author
Garcia-Cambero, Jesus Pablo
author
Zaragoza, Oscar
2026-01-12T09:55:04Z
2026-01-12T09:55:04Z
2020-03-24
Rossi SAde Oliveira HCAgreda-Mellon D, Lucio J, Mendes-Giannini MJS, García-Cambero JP, Zaragoza O. 2020. Identification of Off-Patent Drugs That Show Synergism with Amphotericin B or That Present Antifungal Action against Cryptococcus neoformans and Candida spp. Antimicrob Agents Chemother 64:10.1128/aac.01921-19. https://doi.org/10.1128/aac.01921-19.
10.1128/AAC.01921-19
Antimicrobial Agents and Chemotherapy
31988099
https://hdl.handle.net/20.500.12105/27134
Amphotericin B (AmB) is the antifungal with the strongest fungicidal activity, but its use has several limitations, mainly associated with its toxicity. Although some lipidic and liposomal formulations that present reduced toxicity are available, their price limits their application in developing countries. Flucytosine (5FC) has shown synergistic effect with AmB for treatment of some fungal infections, such as cryptococcosis, but again, its price is a limitation for its use in many regions. In the present work, we aimed to identify new drugs that have a minor effect on , reducing its growth in the presence of subinhibitory concentrations of AmB. In the initial screening, we found fourteen drugs that had this pattern. Later, checkerboard assays of selected compounds, such as erythromycin, riluzole, nortriptyline, chenodiol, nisoldipine, promazine, chlorcyclizine, cloperastine, and glimepiride, were performed and all of them confirmed for their synergistic effect (fractional inhibitory concentration index [FICI] < 0.5). Additionally, toxicity of these drugs in combination with AmB was tested in mammalian cells and in zebrafish embryos. Harmless compounds, such as the antibiotic erythromycin, were found to have synergic activity with AmB, not only against but also against some spp., in particular against In parallel, we identified drugs that had antifungal activity against and found 43 drugs that completely inhibited the growth of this fungus, such as ciclopirox and auranofin. Our results expand our knowledge about antifungal compounds and open new perspectives in the treatment of invasive mycosis based on repurposing off-patent drugs.
eng
Candida
Cryptococcus neoformans
Amphotericin B
Drug repurposing
Synergism
Identification of Off-Patent Drugs That Show Synergism with Amphotericin B or That Present Antifungal Action against Cryptococcus neoformans and spp.
research article
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URL
https://repisalud.isciii.es/bitstreams/2d9bf7d6-0972-4bbe-841e-7b06c20006f1/download
File
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IdentificationOff-PatentDrugsShow_2020.pdf
URL
https://repisalud.isciii.es/bitstreams/28004a95-1bee-43e0-a1b0-e33f854b238c/download
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Supplementary_IdentificationOff-PatentDrugsShow_2020.pdf