{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T12:15:38Z","timestamp":1773663338102,"version":"3.50.1"},"reference-count":23,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:00:00Z","timestamp":1773446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"the Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["306358\/2021-2"],"award-info":[{"award-number":["306358\/2021-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundac\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","award":["E-26\/200.510\/2025"],"award-info":[{"award-number":["E-26\/200.510\/2025"]}]},{"name":"Fundac\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","award":["E-26\/200.438\/2023"],"award-info":[{"award-number":["E-26\/200.438\/2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Species of the Sporothrix genus were used as a biological model to identify potential antifungal compounds within the NIH Clinical Collection library. Methods: A total of 707 compounds were screened for antifungal activity using in vitro susceptibility assays. Compounds exhibiting significant inhibitory effects (growth inhibitions greater than 80%) were further evaluated by determining their minimum inhibitory concentrations (MICs). As cerivastatin demonstrated the highest activity after itraconazole, it was selected for further evaluation, either alone or in combination with itraconazole, using susceptibility assays, electron microscopy, and flow cytometry analyses. Results: Among the screened compounds, twenty-six showed significant inhibition of yeast growth (\u226580%). Compounds with previously reported antifungal activity or not used as oral treatment were excluded from further analysis. MIC determination of eleven selected compounds revealed that cerivastatin inhibited the growth of Sporothrix brasiliensis, Sporothrix schenckii, and Sporothrix globosa at concentrations of 1.25 \u00b5M and 0.6 \u00b5M. Combination treatment with cerivastatin and itraconazole resulted in greater inhibition of Sporothrix growth than either agent alone. Flow cytometry and microscopic analyses revealed more pronounced morphophysiological alterations in yeast cells following combination treatment. Conclusions: These findings highlight the potential of cerivastatin as an antifungal agent when used in combination with itraconazole. Furthermore, the chemical scaffold of cerivastatin warrants further investigation as a basis for the development of novel statins with antifungal activity.<\/jats:p>","DOI":"10.3390\/ph19030479","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:13:14Z","timestamp":1773659594000},"page":"479","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Something Old Brings New Insights: Activity of Cerivastatin Against Thermally Dimorphic Fungi and Its Potential as an Antifungal Scaffold"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6576-6646","authenticated-orcid":false,"given":"Luana P.","family":"Borba-Santos","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular de Fungos, Centro de Pesquisa em Medicina de Precis\u00e3o, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-599, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3659-5945","authenticated-orcid":false,"given":"Sonia","family":"Rozental","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular de Fungos, Centro de Pesquisa em Medicina de Precis\u00e3o, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-599, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bongomin, F., Gago, S., Oladele, R.O., and Denning, D.W. (2017). Global and Multi-National Prevalence of Fungal Diseases-Estimate Precision. J. Fungi, 3.","DOI":"10.3390\/jof3040057"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e428","DOI":"10.1016\/S1473-3099(23)00692-8","article-title":"Global incidence and mortality of severe fungal disease","volume":"24","author":"Denning","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"ofaa016","DOI":"10.1093\/ofid\/ofaa016","article-title":"Hope on the Horizon: Novel Fungal Treatments in Development","volume":"7","author":"Rauseo","year":"2020","journal-title":"Open Forum Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.4155\/fmc-2016-0020","article-title":"Strategies in the discovery of novel antifungal scaffolds","volume":"8","author":"Liu","year":"2016","journal-title":"Future Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Rodrigues, A.M., Gon\u00e7alves, S.S., de Carvalho, J.A., Borba-Santos, L.P., Rozental, S., and de Camargo, Z.P. (2022). Current Progress on Epidemiology, Diagnosis, and Treatment of Sporotrichosis and Their Future Trends. J. Fungi, 8.","DOI":"10.3390\/jof8080776"},{"key":"ref_6","unstructured":"World Health Organization (2022). WHO Fungal Priority Pathogens List to Guide Research, Development and Public Health Action."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.3389\/fmicb.2017.01759","article-title":"Tacrolimus Increases the Effectiveness of Itraconazole and Fluconazole against Sporothrix spp.","volume":"8","author":"Ramos","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1093\/mmy\/myaa115","article-title":"Ebselen and diphenyl diselenide against fungal pathogens: A systematic review","volume":"59","author":"Benelli","year":"2021","journal-title":"Med. Mycol."},{"key":"ref_9","unstructured":"(2026, February 09). Cortellis Drug Discovery Intelligence Database. Available online: https:\/\/www.cortellis.com\/drugdiscovery\/."},{"key":"ref_10","unstructured":"(2026, March 02). PUBCHEM National Center for Biotechnology Information, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s44259-025-00093-4","article-title":"Targeting fungal lipid synthesis for antifungal drug development and potentiation of contemporary antifungals","volume":"3","author":"Cramer","year":"2025","journal-title":"npj Antimicrob. Resist."},{"key":"ref_12","unstructured":"(2026, February 09). Cerivastatin. Available online: https:\/\/www.cortellis.com\/drugdiscovery\/entity\/drug\/189237."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"107483","DOI":"10.1016\/j.pharmthera.2020.107483","article-title":"Antifungal effects of statins","volume":"208","author":"Tavakkoli","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s41577-018-0094-3","article-title":"Statins: A viable candidate for host-directed therapy against infectious diseases","volume":"19","author":"Parihar","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sun, W., Park, Y., Sugui, J.A., Fothergill, A., Southall, N., Shinn, P., McKew, J.C., Kwon-Chung, K.J., Zheng, W., and Williamson, P.R. (2013). Rapid identification of antifungal compounds against Exserohilum rostratum using high throughput drug repurposing screens. PLoS ONE, 8.","DOI":"10.1371\/annotation\/1d0f9e65-e7a3-41ba-960e-c4274334f436"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1093\/ofid\/ofv133.505","article-title":"Growth Inhibitory Effect of Cerivastatin Against Yeasts and Aspergillus fumigatus","volume":"2","author":"Custodio","year":"2015","journal-title":"Open Forum Infect. Dis."},{"key":"ref_17","unstructured":"Abdel-Rahman, S., Preuett, B.L., and Leeder, J.L. (2021). Dermatophytosis Prophylaxis and Treatment. (US20190380990A1), U.S. Patent, Available online: https:\/\/patents.google.com\/patent\/US20190380990A1\/en."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5259","DOI":"10.1007\/s00253-021-11407-7","article-title":"Drug repurposing strategies in the development of potential antifungal agents","volume":"105","author":"Zhang","year":"2021","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"641","DOI":"10.3390\/stresses4040041","article-title":"Ergosterol Biosynthesis and Regulation Impact the Antifungal Resistance and Virulence of Candida spp.","volume":"4","year":"2024","journal-title":"Stresses"},{"key":"ref_20","unstructured":"(2026, February 09). BLAST Program, Available online: https:\/\/blast.ncbi.nlm.nih.gov\/Blast.cgi."},{"key":"ref_21","unstructured":"EUCAST-AFST (2023). Method for the Determination of Broth Dilution Minimum Inhibitory Concentrations of Antifungal Agents for Yeasts, European Committee on Antimicrobial Susceptibility Testing. Document E.DEF 7.4."},{"key":"ref_22","unstructured":"Pillai, S.K., Moellering, R.C., and Eliopoulos, G.M. (2005). Antibiotics in Laboratory Medicine, Lippincott Williams & Wilkins Co."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jac\/dkg301","article-title":"Synergy, antagonism, and what the chequerboard puts between them","volume":"52","author":"Odds","year":"2003","journal-title":"J. Antimicrob. Chemother."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/3\/479\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:23:42Z","timestamp":1773660222000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/3\/479"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,14]]},"references-count":23,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ph19030479"],"URL":"https:\/\/doi.org\/10.3390\/ph19030479","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,14]]}}}