Aripiprazole repurposed as an inhibitor of biofilm formation and sterol biosynthesis in multidrug-resistant Candida albicans
Abstract
Drug repurposing is an anticipative chemotherapeutic strategy that accentuates the inadequacy of antifungal drugs. The study identifies an antipsychotic drug, aripiprazole, as a biofilm and hyphal inhibitor of Candida albicans. Microtitre plate biofilm inhibition, metabolic activity and hyphal inhibitory assays were used to assess the potency of aripiprazole; and filipin staining, reactive oxygen species staining, cAMP rescue, propidium iodide staining, computational studies and qRT-PCR assays were used to elucidate its mode of action. The study revealed aripiprazole functioned in a manner similar to standard azoles, particularly the imidazole, ketoconazole, by inhibiting pseudohyphal formation during the early stages of hyphal development. The action of aripiprazole on C. albicans was dose-dependent and it exhibited varied mechanisms of action at low and high dosages. At low dosage, aripiprazole outperformed ketoconazole in terms of inhibiting biofilm formation, hyphal filamentations, and yeast flocculation, whereas at higher dosage it mimicked ketoconazole. This study illustrates the anti-candidal potential and mechanistic activities of aripiprazole, and indicates the future use of this drug as an anti-biofilm agent.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
It has been suggested that neuroleptics such as aripiprazole can interfere with Lanosterol 14 alpha-demethylase or CYP51, similarly to azoles, disrupting lipid rafts and inducing membrane damage.
“It has been suggested that neuroleptics such as aripiprazole can interfere with Lanosterol 14 alpha-demethylase or CYP51, similarly to azoles, disrupting lipid rafts and inducing membrane damage [74].”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [74]
Cites
<i>Candida albicans</i> Biofilms and Human Disease
Nobile, C. J., & Johnson, A. D. (2015) · Annual Review of Microbiology · doi:10.1146/annurev-micro-091014-104330 · Cited by 1,057 · see citing works
Flocculation, adhesion and biofilm formation in yeasts
Verstrepen, K. J., & Klis, F. M. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05072.x · Cited by 589 · see citing works
Azole antifungal agents: Emphasis on new triazoles
Saag, M. S., & Dismukes, W. E. (1988) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.32.1.1 · Cited by 474 · see citing works
Ji, H., Zhang, W., Zhou, Y., Zhang, M., Zhu, J. S., Song, Y., Lü, J., & Zhu, J. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm990589g · Cited by 213 · see citing works
The Ras/cAMP/PKA signaling pathway and virulence in <i>Candida albicans</i>
Hogan, D. A., & Sundstrom, P. (2009) · Future Microbiology · doi:10.2217/fmb.09.106 · Cited by 186 · see citing works
Antifungals: Mechanism of Action and Drug Resistance
Prasad, R., Shah, A. H., & Rawal, M. K. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-25304-6_14 · Cited by 185 · see citing works
Dumitru, ., Hornby, J. M., & Nickerson, K. W. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.48.7.2350-2354.2004 · Cited by 143 · see citing works
Molecular basis of antifungal drug resistance in yeasts
Morio, F., Jensen, R. H., Le Pape, P., & Arendrup, M. C. (2017) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2017.05.012 · Cited by 114 · see citing works
Vale-Silva, L. A., Coste, A. T., Ischer, F., Parker, J. E., Kelly, S. L., Pinto, E., & Sanglard, D. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.05720-11 · Cited by 96 · see citing works
Nehme, H., Saulnier, P., Ramadan, A. A., Cassisa, V., Guillet, C., Eveillard, M., & Umerska, A. M. (2018) · PLoS ONE · doi:10.1371/journal.pone.0189950 · Cited by 93 · see citing works
Biofilms 2012: New Discoveries and Significant Wrinkles in a Dynamic Field
Häußler, S., & Fuqua, C. (2013) · Journal of Bacteriology · doi:10.1128/jb.00239-13 · Cited by 70 · see citing works
van Leeuwen, M. R., Smant, W., de Boer, W., & Dijksterhuis, J. (2008) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2008.04.001 · Cited by 63 · see citing works
Cell permeability and nuclear DNA staining by propidium iodide in basidiomycetous yeasts
Zhang, N., Fan, Y., Li, C., Wang, Q., Leksawasdi, N., Li, F., & Wang, S. (2018) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-018-8906-8 · Cited by 57 · see citing works
Lee, J., Kim, Y., Gupta, V. K., Manoharan, R. K., & Lee, J. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.02641 · Cited by 45 · see citing works
Self-citationAnti-Candida albicans biofilm effect of novel heterocyclic compounds
Kagan, S. A., Jabbour, A. R., Sionov, E., Al-Quntar, A., Steinberg, D., Srebnik, M., Nir‐Paz, R., Weiss, A. M., & Polacheck, I. (2013) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkt365 · Cited by 37 · see citing works
Lemos, J. D. A., Costa, C. R., de Araújo, C. R., Souza, L. K. H. E., & Silva, M. D. R. R. (2009) · Brazilian Journal of Microbiology · doi:10.1590/s1517-83822009000100028 · Cited by 33 · see citing works
Tricyclic antidepressants inhibit Candida albicans growth and biofilm formation
Caldara, M., & Marmiroli, N. (2018) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2018.06.023 · Cited by 31 · see citing works
Inhibitory effects of deoxynivalenol on pathogenesis of Candida albicans
Rajasekharan, S. K., Byun, J., & Lee, J. (2018) · Journal of Applied Microbiology · doi:10.1111/jam.14032 · Cited by 25 · see citing works
Self-citationZuo, R., Garrison, A. T., Basak, A. K., Zhang, P., Huigens, R. W., & Ding, Y. (2016) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2016.04.019 · Cited by 23 · see citing works
Proper Sterol Distribution Is Required for Candida albicans Hyphal Formation and Virulence
McCourt, P. C., Liu, H., Parker, J. E., Ebert, C., Donigan, M., Bata, A., Giordano, C., Kelly, S. L., & Nickels, J. T. (2016) · G3 Genes Genomes Genetics · doi:10.1534/g3.116.033969 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mechanistic Understanding of Candida albicans Biofilm Formation and Approaches for Its Inhibition
Atriwal, T., Azeem, K., Husain, F. M., Hussain, A., Khan, M. N., Alajmi, M. F., & Abid, M. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.638609 · Cited by 210 · see citing works
Kim, J. H., Cheng, L. W., Chan, K. L., Tam, C. C., Mahoney, N., Friedman, M., Shilman, M. M., & Land, K. M. (2020) · Antibiotics · doi:10.3390/antibiotics9110812 · Cited by 71 · see citing works
Peyclit, L., Yousfi, H., Rolain, J., & Bittar, F. (2021) · Pharmaceuticals · doi:10.3390/ph14050488 · Cited by 56 · see citing works
Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications
Caldara, M., & Marmiroli, N. (2021) · Pharmaceuticals · doi:10.3390/ph14090915 · Cited by 54 · see citing works
Srivastava, G. N., Malwe, A. S., Sharma, A. K., Shastri, V., Hibare, K., & Sharma, V. K. (2020) · Genomics · doi:10.1016/j.ygeno.2020.03.020 · Cited by 41 · see citing works
Antifungal activity of vitamin D3 against Candida albicans in vitro and in vivo
Lei, J., Xiao, W., Zhang, J., Liu, F., Xin, C., Zhou, B., Chen, W., & Song, Z. (2022) · Microbiological Research · doi:10.1016/j.micres.2022.127200 · Cited by 39 · see citing works
Suppression of hyphal formation and virulence of Candida albicans by natural and synthetic compounds
Khan, F., Bamunuarachchi, N. I., Tabassum, N., Jo, D., Khan, P. D. M. M., & Kim, Y. (2021) · Biofouling · doi:10.1080/08927014.2021.1948538 · Cited by 37 · see citing works
Cao, Y., Song, X., Xu, G., Zhang, X., Yan, H., Feng, J., Ma, Z., Liu, X., & Wang, Y. (2023) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.3c05154 · Cited by 36 · see citing works
The evolution of antifungal therapy: Traditional agents, current challenges and future perspectives
de Souza, C. M., Bezerra, B. T., Mellon, D. A., & de Oliveira, H. C. (2025) · Current Research in Microbial Sciences · doi:10.1016/j.crmicr.2025.100341 · Cited by 35 · see citing works
Singh, S. V., Fatima, Z., Ahmad, K., & Hameed, S. (2020) · Journal of Applied Microbiology · doi:10.1111/jam.14669 · Cited by 24 · see citing works
Rajasekharan, S. K., & Shemesh, M. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14050962 · Cited by 21 · see citing works
Self-citationNovel avenues for identification of new antifungal drugs and current challenges
Jampílek, J. (2022) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2022.2097659 · Cited by 19 · see citing works
Beattie, S. R., & Krysan, D. J. (2021) · mSphere · doi:10.1128/msphere.00539-21 · Cited by 16 · see citing works
Spatiotemporal bio-shielding of bacteria through consolidated geometrical structuring
Rajasekharan, S. K., & Shemesh, M. (2022) · npj Biofilms and Microbiomes · doi:10.1038/s41522-022-00302-2 · Cited by 16 · see citing works
Self-citationCeballos-Garzón, A., Amado, D., Robert, E., Parra‐Giraldo, C. M., & Pape, P. L. (2020) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkz565 · Cited by 15 · see citing works
Chilamakuri, S. N., Kumar, A., Nath, A. G., Gupta, A., Selvaraju, S., Basrani, S. T., Jadhav, A. K., & Gulbake, A. (2023) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2023.11.031 · Cited by 13 · see citing works
Small molecule based anti-virulence approaches against Candida albicans infections
Kalimuthu, S., Alshanta, O. A., Krishnamoorthy, A. L., Pudipeddi, A., Solomon, A. P., McLean, W., Leung, Y. Y., Ramage, G., & Neelakantan, P. (2022) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2021.2025337 · Cited by 13 · see citing works
Rajasekharan, S. K., Angelini, L. L., Kroupitski, Y., Mwangi, E. W., Chai, Y., & Shemesh, M. (2024) · Biofilm · doi:10.1016/j.bioflm.2024.100244 · Cited by 10 · see citing works
Self-citationPEGylated Terpesome-Loaded 3D-Printed Aripiprazole Ocuserts for the Treatment of Ocular Candidiasis
Albash, R., Hassan, M., Agiba, A. M., Abd-Elsalam, W. H., Aziz, D. E., Hassan, Y. R., Kassem, A. B., Saleh, A., & Eltabeeb, M. A. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17121616 · Cited by 9 · see citing works
Zhang, L., Ding, Y., Ran, J.-N., Long, Y., Huang, H.-Y., Meng, J., Li, M., Zhou, X., & Yang, S. (2026) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.5c10117 · Cited by 9 · see citing works
Drug Repurposing Strategy against Fungal Biofilms
de Mello, T. P., Silva, L. N., Ramos, L. S., Frota, H. F., Branquinha, M. H., & dos Santos, A. L. S. (2020) · Current Topics in Medicinal Chemistry · doi:10.2174/156802662007200316142626 · Cited by 9 · see citing works
Wang, Y., He, Y., Cai, T., Lei, Z., Lei, W., Cao, Y., & Wu, J. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e27346 · Cited by 7 · see citing works
Korade, Ž., Anderson, A. C., Balog, M., Tallman, K. A., Porter, N. A., & Mirnics, K. (2023) · Biomolecules · doi:10.3390/biom13091321 · Cited by 6 · see citing works
Heterocyclic Antidepressants with Antimicrobial and Fungicide Activity
Zolotareva, D., Zazybin, A., Belyankova, Y., Bayazit, S., Dauletbakov, A., Сейлханов, Т. М., Kemelbekov, U., & Aydemir, M. (2025) · Molecules · doi:10.3390/molecules30051102 · Cited by 6 · see citing works
Singh, N., Kumari, V., Agrawal, K., & Kulshreshtha, M. (2024) · Central Nervous System Agents in Medicinal Chemistry · doi:10.2174/0118715249274215231205062701 · Cited by 5 · see citing works
Chen, T., Yao, J., Quan, K., Xu, J., Hang, X., Tong, Q., Liu, G., Luo, P., Zeng, L., Feng, G., et al. (2023) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01131-23 · Cited by 5 · see citing works
Li, X., Kong, B., Sun, Y., Sun, F., Yang, H., & Zheng, S. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1282320 · Cited by 4 · see citing works
A Paradigm Shift in the Development of Anti-Candida Drugs
Gowda, D. V., Moin, A., Meenakshi, S. S., Manohar, M., Hemalatha, S., Siddaramaiah, H., Paranthaman, S., Rizvi, S. M. D., Hussain, T., & Kamal, M. A. (2019) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026619666191029145209 · Cited by 3 · see citing works
Repurposing of Linagliptin Similar FDA Approved Drugs as Antidiabetic Agents
(2021) · Letters in Applied NanoBioScience · doi:10.33263/lianbs104.27662776 · Cited by 3 · see citing works
Wang, M., Song, Z., Wen, Y., Li, Y., Jia, Y., Zhai, G., & Feng, R. (2023) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2023.104884 · Cited by 3 · see citing works
Albash, R., Nair, A. B., Morsy, M. A., Venugopala, K. N., Shinu, P., Hassan, M., El‐Sheikh, A. A. K., & Kassem, A. B. (2026) · Pharmaceuticals · doi:10.3390/ph19081135 · Cited by 1 · see citing works
Finally, successful interventions to ameliorate cutaneous infestations
Tausk, F. (2024) · Journal of Dermatological Treatment · doi:10.1080/09546634.2024.2326655 · Cited by 1 · see citing works
Drug Repurposing and Virtual Screening
Sharma, R., Roy, S., & Kumar, A. (2025) · Springer eBooks · doi:10.1007/978-981-97-9230-6_16 · Cited by 1 · see citing works
Antibiofilm and anti-hyphal activity of a valencene-enriched fraction against Candida albicans
Saravanan, T. S., Raorane, C. J., Pranaveer, R., Gopikuttan, M., Sarwar, M. T., Vaidyanathan, V. K., Ravichandran, V., & Rajasekharan, S. K. (2026) · Archives of Microbiology · doi:10.1007/s00203-026-05106-y
Self-citationPsychotropic Drugs: A Promising Non‐Antibiotic Agent to Combat Multi‐Drug‐Resistant Microorganisms
Singh, I. P., Singh, H., Sharma, D., Keshri, A., Gaurav, N., Dhakad, M. S., & Beg, M. M. A. (2026) · Drug Development Research · doi:10.1002/ddr.70380
Monazea, R. S., E.Aziz, D., Albash, R., Hassan, M., Abdelbary, G. A., & Alaa-Eldin, A. A. (2026) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2026.127470
- Authors
- Rajasekharan, S. K., Lee, J.-H., & Lee, J.
- Affiliations
- Yeungnam University (KR)
- Corresponding author
- Lee, Jintae
- Venue
- International Journal of Antimicrobial Agents
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 54
- Issue
- 4
- Pages
- 518-523
- ISSN
- 0924-8579 (ISSN-L)
- OpenAlex
- W2948297403
- Cited by
- 36
- References
- 20
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 1
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Antimicrobial Agents (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education (2014R1A6A1031189, 2018R1D1A1B07044288)
- National Research Foundation of Korea
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Keywords
- aripiprazole, drug repurposing, Candida albicans, biofilm inhibition, hyphal development, sterol biosynthesis, multidrug resistance, antifungal activity, ketoconazole, yeast flocculation, reactive oxygen species, cAMP signaling, antipsychotic drugs
- MeSH terms
- Aripiprazole, Antifungal Agents, Candida albicans, Cell Adhesion, Dose-Response Relationship, Drug, Microbial Sensitivity Tests, Sterols, Biofilms, Hyphae, 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
