Artemisinins, New Miconazole Potentiators Resulting in Increased Activity against Candida albicans Biofilms
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Mucosal biofilm-related fungal infections are very common, and the incidence of recurrent oral and vulvovaginal candidiasis is significant. As resistance to azoles (the preferred treatment) is occurring, we aimed at identifying compounds that increase the activity of miconazole against Candida albicans biofilms. We screened 1,600 compounds of a drug-repositioning library in combination with a subinhibitory concentration of miconazole. Synergy between the best identified potentiators and miconazole was characterized by checkerboard analyses and fractional inhibitory concentration indices. Hexachlorophene, pyrvinium pamoate, and artesunate act synergistically with miconazole in affecting C. albicans biofilms. Synergy was most pronounced for artesunate and structural homologues thereof. No synergistic effect could be observed between artesunate and fluconazole, caspofungin, or amphotericin B. Our data reveal enhancement of the antibiofilm activity of miconazole by artesunate, pointing to potential combination therapy consisting of miconazole and artesunate to treat C. albicans biofilm-related infections.
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The primary screen identified several drugs with known fluconazole chemosensitizing activities, including simvastatin, atorvastatin, lovastatin, artemisinin, amiodarone, sulfamethoxazole, doxycycline, nisoldipine, and tamoxifen.
“In addition and as expected, the primary screen identified several drugs with known fluconazole chemosensitizing activities, such as the cholesterol-lowering agents; simvastatin, atorvastatin, and lovastatin, artemisinin, amiodarone, sulfamethoxazole, doxycycline, and the calcineurin inhibitors nisoldipine and tamoxifen19–25.”
From Repurposing approach identifies pitavastatin as a potent azole chemosensitizing agent effective against azole-resistant Candida species (2020) · cites this paper as [23]
The Thevissen group identified artemisinins as new potentiators of miconazole activity against C. albicans biofilms.
“Likewise, the Thevissen group identified artemisinins as new potentiators of miconazole activity against C. albicans biofilms [56].”
From Antifungal therapy of Candida biofilms: Past, present and future (2023) · cites this paper as [56]
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- Authors
- De Cremer, K., Lanckacker, E., Cools, T. L., Bax, M., De Brucker, K., Cos, P., Cammue, B. P. A., & Thevissen, K.
- Affiliations
- Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Leuven, Belgium
- University of Antwerp (BE)
- KU Leuven (BE)
- VIB-UGent Center for Plant Systems Biology (BE)
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2015-01
- Volume
- 59
- Issue
- 1
- Pages
- 421-426
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC4291436
- OpenAlex
- W2157257162
- Cited by
- 77
- References
- 44
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 9 · 2023: 2 · 2022: 3 · 2021: 14 · 2020: 14 · 2019: 9 · 2018: 5 · 2017: 7 · 2016: 3 · 2015: 3
- FWCI
- 3.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- Candida albicans biofilm, miconazole, artesunate, artemisinin, drug repurposing, antifungal synergy, azole resistance, hexachlorophene, pyrvinium pamoate, combination therapy, oral candidiasis, vaginal candidiasis
- MeSH terms
- Artesunate, Caspofungin, Amphotericin B, Antifungal Agents, Candida albicans, Candidiasis, Drug Synergism, Hexachlorophene, Miconazole, Microbial Sensitivity Tests, Pyrvinium Compounds, Fluconazole, Reactive Oxygen Species, Biofilms, Artemisinins, Echinocandins, Lipopeptides
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