Repurposing FDA approved drugs against the human fungal pathogen, Candida albicans
Open accessAbstract
BACKGROUND: The high cost and prolonged timeline of new drug discovery and development are major roadblocks to creating therapies for infectious diseases. Candida albicans is an opportunistic fungal pathogen that is the most common cause of fatal fungal infections in humans and costs $2-4 billion dollars to treat in the US alone. METHODS: To accelerate drug discovery, we screened a library of 1581 existing FDA approved drugs, as well as drugs approved abroad, for inhibitors of C. albicans. The screen was done on YPD yeast growth media as well as on the serum plate assay developed in this study. RESULTS: We discovered that fifteen drugs, all which were originally approved for treating various infectious and non-infectious diseases, were able to kill Candida albicans. Additionally, one of those drugs, Octodrine, displays wide-spectrum anti-microbial activity. Compared to other selected anti-Candida drugs, Octodrine was shown to be one of the most effective drugs in killing serum-grown Candida albicans without significantly affecting the survival of host macrophages and skin cells. CONCLUSIONS: This approach is useful for the discovery of economically viable new therapies against infectious diseases.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
DIS's antifungal effects arise from inactivating key enzymes, including ALDH, urease, and carbamate kinase.
“DIS’s antifungal effects arise from inactivating key enzymes, including ALDH, urease (URE), and carbamate kinase (CK).”
From Off-label and repurposed use of disulfiram beyond alcohol dependence: A systematic review of clinical and preclinical evidence (2026) · cites this paper as [111]
The Results section (page not provided) reports moderate-to-weak anti-Candida activity for disulfiram. It does not establish that this effect arises from inactivation of ALDH, urease, or carbamate kinase; searches for those enzymes and the proposed mechanism found no supporting passage. (LLM, conf=0.86)
Experimental — accuracy not yet measuredDIS disrupts key fungal cell processes and exhibits potent antifungal activity against Candida and Cryptococcus species by inhibiting both growth and biofilm formation.
“DIS disrupts key fungal cell processes (metabolism, replication, and membrane transport), exhibiting potent antifungal activity against Candida and Cryptococcus species by inhibiting both growth and biofilm formation.111,112,113”
From Off-label and repurposed use of disulfiram beyond alcohol dependence: A systematic review of clinical and preclinical evidence (2026) · cites this paper as [111]
The Results section (Screening of inhibitors of Candida albicans lawn formation) reports that disulfiram inhibited C. albicans growth, but describes its activity as moderate to weak, not potent. The Discussion distinguishes this study's non-biofilm growth screen from another group's biofilm screen. Our copy does not establish disulfiram's effects on Cryptococcus, biofilm formation, or the specified cellular processes. (LLM, conf=0.91)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 44 · Cited by 48
Research works printed but not linked: 40
- [3]Perlroth J Choi B Spellberg B Nosocomial fungal infections: epidemiology, diagnosis, and treatment Med Mycol 2007 45 4 321 46 10.1080/13693780701218689 17510856 · DOI · Paper page
- [4]DiNubile MJ Hille D Sable CA Kartsonis NA Invasive candidiasis in cancer patients: observations from a randomized clinical trial J Infect 2005 50 5 443 9 10.1016/j.jinf.2005.01.016 15907554 · DOI
- [5]Fujitani S Ricardo-Dukelow M Kamiya T Sullivan L Low L Ethnicity and other possible risk factors for candidemia at 3 tertiary care university hospitals in Hawaii Infect Control Hosp Epidemiol 2006 27 11 1261 3 10.1086/508831 17080389 · DOI
- [6]Fisher JF Sobel JD Kauffman CA Newman CA Candida urinary tract infections--treatment Clin Infect Dis 2011 6 S457 66 10.1093/cid/cir112 21498839 · DOI
- [7]Berman J Sudbery PE Candida Albicans: a molecular revolution built on lessons from budding yeast Nat Rev Gen 2002 3 12 918 30 10.1038/nrg948 12459722 · DOI · Paper page
- [8]Paderu P Garcia-Effron G Balashov S Delmas G Park S Perlin DS Serum differentially alters the antifungal properties of echinocandin drugs Antimicrob Agents Chemother 2007 51 6 2253 6 10.1128/AAC.01536-06 17420211 PMC1891414 · DOI
- [9]Vandeputte P Ferrari S Coste AT Antifungal resistance and new strategies to control fungal infections Int J Microbiol 2012 2012 713687 10.1155/2012/713687 22187560 PMC3236459 · DOI
- [10]Odds FC Brown AJ Gow NA Antifungal agents: mechanisms of action Trends Microbio 2003 11 6 272 9 10.1016/S0966-842X(03)00117-3 12823944 · DOI · Paper page
- [11]Behrman REWJ FDA regulations for drug development Science 2010 329 33 10.1126/science.329.5987.33-b 20595600 · DOI · Paper page
- [13]Chong CR Chen X Shi L Liu JO Sullivan DJ Jr A clinical drug library screen identifies astemizole as an antimalarial agent Nat Chem Biol 2006 2 8 415 6 10.1038/nchembio806 16816845 · DOI
- [14]Gillum AM Tsay EY Kirsch DR Isolation of the Candida albicans gene for orotidine-5′-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations MGG 1984 198 1 179 82 10.1007/BF00328721 6394964 · DOI
- [16]Rauceo JM Blankenship JR Fanning S Hamaker JJ Deneault JS Smith FJ Regulation of the Candida albicans cell wall damage response by transcription factor Sko1 and PAS kinase Psk1 Mol Biol Cel 2008 19 7 2741 51 10.1091/mbc.E08-02-0191 PMC2441657 18434592 · DOI
- [18]nstitute CaLS M44-A2 Method for antifungal disk diffusion susceptibility testing of yeasts; approved guideline 2009 2 Wayne, PA Clinical and Laboratory Standards Institute 31339681
- [19]Arendrup MC Park S Brown S Pfaller M Perlin DS Evaluation of CLSI M44-A2 disk diffusion and associated breakpoint testing of caspofungin and micafungin using a well-characterized panel of wild-type and fks hot spot mutant Candida isolates Antimicrob Agents Chemother 2011 55 5 1891 5 10.1128/AAC.01373-10 21357293 PMC3088242 · DOI
- [21]Lu Q Wei W Kowalski PE Chang AC Cohen SN EST-based genome-wide gene inactivation identifies ARAP3 as a host protein affecting cellular susceptibility to anthrax toxin Proc Natl Acad Sci U S A 2004 101 49 17246 51 10.1073/pnas.0407794101 15569923 PMC534609 · DOI
- [22]Hendry AT Bakerspigel A Factors affecting serum inhibited growth of Candida albicans and Cryptococcus neoformans Sabouraudia 1969 7 3 219 29 10.1080/00362177085190391 5385158 · DOI
- [23]Elin RJ Wolff SM Effect of pH and iron concentration on growth of Candida albicans in human serum J Infect Dis 1973 127 6 705 8 10.1093/infdis/127.6.705 4575002 · DOI
- [24]King RD Khan HA Foye JC Greenberg JH Jones HE Transferrin, iron, and dermatophytes. I. Serum dematophyte inhibitory component definitively identified as unsaturated transferrin J Lab Clin Med 1975 86 2 204 12 1151148
- [25]Andes D Nett J Oschel P Albrecht R Marchillo K Pitula A Development and characterization of an in vivo central venous catheter Candida albicans biofilm model Infect Immun 2004 72 10 6023 31 10.1128/IAI.72.10.6023-6031.2004 15385506 PMC517581 · DOI · Paper page
- [26]Kot EJ Olson VL Rolewic LJ McClary DO An alternate respiratory pathway in Candida albicans Antonie Van Leeuwenhoek 1976 42 1–2 33 48 10.1007/BF00399447 821392 · DOI
- [27]Gale GR Smith AB Atkins LM Walker EM Jr Gadsden RH Pharmacology of captan: biochemical effects with special reference to macromolecular synthesis Toxicol Appl Pharmacol 1971 18 2 426 41 10.1016/0041-008X(71)90135-9 5569381 · DOI
- [28]Lovgren T Salmela I In vitro sensitivity of Trichomonas vaginalis and Candida albicans to chemotherapeutic agents Acta Pathol Microbiol Scand B 1978 86B 3 155 8 102108
- [29]Wachtler B Wilson D Hube B Candida albicans adhesion to and invasion and damage of vaginal epithelial cells: stage-specific inhibition by clotrimazole and bifonazole Antimicrob Agents Chemother 2011 55 9 4436 9 10.1128/AAC.00144-11 21746947 PMC3165311 · DOI
- [30]Shukla S Sauna ZE Prasad R Ambudkar SV Disulfiram is a potent modulator of multidrug transporter Cdr1p of Candida albicans Biochem Biophys Res Commun 2004 322 (2 520 5 10.1016/j.bbrc.2004.07.151 15325261 · DOI
- [31]Molepo J Musenge E Clade-related phenotypic switching among fluconazole resistant Candida albicans isolates SADJ 2012 67 7 326 8 23951786
- [33]Ichikawa T Yano Y Fujita Y Kashiwabara T Nagao K The enhancement effect of three sugar alcohols on the fungicidal effect of benzethonium chloride toward Candida albicans J Dent 2008 36 11 965 8 10.1016/j.jdent.2008.07.013 18778883 · DOI
- [34]Vandenbosch D Bink A Govaert G Cammue BP Nelis HJ Thevissen K Phytosphingosine-1-phosphate is a signaling molecule involved in miconazole resistance in sessile Candida albicans cells Antimicrob Agents Chemother 2012 56 5 2290 4 10.1128/AAC.05106-11 22354293 PMC3346612 · DOI
- [35]Kohler GA Gong X Bentink S Theiss S Pagani GM Agabian N The functional basis of mycophenolic acid resistance in Candida albicans IMP dehydrogenase J Biol Chem 2005 280 (12 11295 302 10.1074/jbc.M409847200 15665003 · DOI
- [36]Grossman LI Evaluation of antifungal agents for endodontic use J Dent Res 1967 46 1 215 7 10.1177/00220345670460011301 5226388 · DOI
- [37]Hernandez Molina JM Llosa J Ventosa A In vitro activity of nitroxoline against clinical isolates of Candida species Mycoses 1991 34 7–8 323 5 1803236
- [38]Omura Y O’Young B Jones M Pallos A Duvvi H Shimotsuura Y Caprylic acid in the effective treatment of intractable medical problems of frequent urination, incontinence, chronic upper respiratory infection, root canalled tooth infection, ALS, etc., caused by asbestos & mixed infections of Candida albicans, Helicobacter pylori & cytomegalovirus with or without other microorganisms & mercury Acupunct Electrother Res 2011 36 1–2 19 64 10.3727/036012911803860886 21830350 · DOI
- [39]De Prijck K De Smet N Honraet K Christiaen S Coenye T Schacht E Inhibition of Candida albicans biofilm formation by antimycotics released from modified polydimethyl siloxane Mycopathologia 2010 169 3 167 74 10.1007/s11046-009-9242-4 19774486 · DOI
- [41]PubChem-Octodrine. http://pubchem.ncbi.nlm.nih.gov/compound/10982. Accessed 28 April 2015.
- [42]Norice CT Smith FJ Jr Solis N Filler SG Mitchell AP Requirement for Candida albicans Sun41 in biofilm formation and virulence Eukaryot Cell 2007 6 11 2046 55 10.1128/EC.00314-07 17873081 PMC2168420 · DOI
- [43]Nobile CJ Mitchell AP Regulation of cell-surface genes and biofilm formation by the C. albicans transcription factor Bcr1p Curr Biol 2005 15 12 1150 5 10.1016/j.cub.2005.05.047 15964282 · DOI · Paper page
- [44]Hanahan D Studies on transformation of Escherichia coli with plasmids J Mol Biol 1983 166 4 557 80 10.1016/S0022-2836(83)80284-8 6345791 · DOI
- [45]Rasko DA Ravel J Okstad OA Helgason E Cer RZ Jiang L The genome sequence of Bacillus cereus ATCC 10987 reveals metabolic adaptations and a large plasmid related to Bacillus anthracis pXO1 Nucleic Acids Res 2004 32 3 977 88 10.1093/nar/gkh258 14960714 PMC373394 · DOI
- [46]Jeong SY Martchenko M Cohen SN Calpain-dependent cytoskeletal rearrangement exploited for anthrax toxin endocytosis Proc Natl Acad Sci U S A 2013 110 42 E4007 15 10.1073/pnas.1316852110 24085852 PMC3801034 · DOI
- [47]PubChem-BioAssay. http://pubchem.ncbi.nlm.nih.gov/assay/assay.cgi?aid=743079. Accessed 28 April 2015.
- [48]Fellows EJ The pharmacology of 2-amino-6-methylheptane J Pharmacol Exp Ther 1947 90 4 351 8 20265812
- Authors
- Kim, K., Zilbermintz, L., & Martchenko, M.
- Affiliations
- Keck Graduate Institute (US)
- Corresponding author
- Martchenko, Mikhail
- ORCID
- Kim, Kevin
- Venue
- Annals of Clinical Microbiology and Antimicrobials
- Published
- 2015-06-09
- Volume
- 14
- Issue
- 1
- Pages
- 32-32
- ISSN
- 1476-0711 (ISSN-L)
- PMC
- PMC4462072
- OpenAlex
- W1581877192
- Cited by
- 48
- References
- 44
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 5 · 2020: 10 · 2019: 6 · 2018: 3 · 2017: 1 · 2016: 6 · 2015: 1
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Annals of Clinical Microbiology and Antimicrobials (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Johns Hopkins University
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- Candida albicans, drug repurposing, FDA-approved drugs, antifungal drug discovery, opportunistic fungal infection
- MeSH terms
- Antifungal Agents, Candida albicans, Microbial Sensitivity Tests, Microbial Viability, Drug Repositioning
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review