{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:59:06Z","timestamp":1785473946815,"version":"3.56.0"},"reference-count":69,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Cryptococcosis is a severe fungal infection affecting immunocompromised individuals, with treatment limited to FLZ, AMB, and FC. This study investigated the antifungal potential of fluconazole (FLZ)-, amphotericin B (AMB)-, 8-hydroxyquinoline (8HQ)-, and clioquinol (CQ)-based combinations against Cryptococcus neoformans and C. gattii. Drug interactions were assessed by checkerboard assay, followed by time\u2013kill curves, irritability, toxicity, and virulence factors inhibition tests. The FLZ + AMB combination showed weak synergism, whereas FLZ combined with CQ or 8HQ exhibited strong synergistic effects (p &lt; 0.001) at low concentrations (0.125\u20130.25 \u00b5g\/mL), up to three times greater than those of FLZ + AMB. This effect persisted across other strains, including less FLZ-susceptible isolates. Moreover, FLZ + CQ inhibited melanin production in both species without causing significant irritability or toxicity in the tested models. These results indicate that combining drugs with distinct mechanisms of action can enhance antifungal efficacy while potentially reducing treatment doses. The FLZ + CQ\/8HQ combinations represent promising candidates for future in vivo models for therapeutic evaluation.<\/jats:p>","DOI":"10.3390\/microorganisms14081654","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T08:16:52Z","timestamp":1785313012000},"page":"1654","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergic Effect of Fluconazole and Quinoline Derivatives Combination Against Cryptococcus spp., Mechanisms of Action and Toxicity"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3495-094X","authenticated-orcid":false,"given":"Luana Candice","family":"Genz Bazana","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Micologia Aplicada, Universidade Federal do Rio Grande do Sul, Porto Alegre 90620-170, RS, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Federal do Rio Grande do Sul, Porto Alegre 90160-093, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3879-9650","authenticated-orcid":false,"given":"\u00c2nderson Ramos","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Micologia Aplicada, Universidade Federal do Rio Grande do Sul, Porto Alegre 90620-170, RS, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Federal do Rio Grande do Sul, Porto Alegre 90160-093, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Foss da Silva","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Federal do Rio Grande do Sul, Porto Alegre 90160-093, RS, Brazil"},{"name":"Laborat\u00f3rio de Toxicologia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90620-170, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3752-5751","authenticated-orcid":false,"given":"Solange Cristina","family":"Garcia","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Federal do Rio Grande do Sul, Porto Alegre 90160-093, RS, Brazil"},{"name":"Laborat\u00f3rio de Toxicologia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90620-170, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0434-1553","authenticated-orcid":false,"given":"Marcelo Dutra","family":"Arbo","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Federal do Rio Grande do Sul, Porto Alegre 90160-093, RS, Brazil"},{"name":"Laborat\u00f3rio de Toxicologia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90620-170, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4546-5584","authenticated-orcid":false,"given":"Mario","family":"Lettieri Teixeira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Toxicologia e Farmacologia, Instituto Federal Catarinense, Conc\u00f3rdia 89703-720, SC, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2979-4417","authenticated-orcid":false,"given":"Alexandre Meneghello","family":"Fuentefria","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Micologia Aplicada, Universidade Federal do Rio Grande do Sul, Porto Alegre 90620-170, RS, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Federal do Rio Grande do Sul, Porto Alegre 90160-093, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1111\/mmi.14565","article-title":"Combatting the evolution of antifungal resistance in Cryptococcus neoformans","volume":"114","author":"Bermas","year":"2020","journal-title":"Mol. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5484","DOI":"10.1016\/j.radcr.2025.07.011","article-title":"Cryptococcus gattii infection in an immunocompetent patient","volume":"20","author":"Fegahli","year":"2025","journal-title":"Radiol. Case Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrmicro.2015.6","article-title":"Cryptococcus: From environmental saprophyte to global pathogen","volume":"14","author":"May","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1146\/annurev-micro-020518-120210","article-title":"Life cycle of Cryptococcus neoformans","volume":"73","author":"Zhao","year":"2019","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1093\/mmy\/myy086","article-title":"Pulmonary cryptococcosis: A review of pathobiology and clinical aspects","volume":"57","author":"Setianingrum","year":"2019","journal-title":"Med. Mycol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/S1473-3099(17)30243-8","article-title":"Global burden of disease of HIV-associated cryptococcal meningitis: An updated analysis","volume":"17","author":"Rajasingham","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e495","DOI":"10.1016\/S1473-3099(23)00731-4","article-title":"Global guideline for the diagnosis and management of cryptococcosis: An initiative of the ECMM and ISHAM in cooperation with the ASM","volume":"24","author":"Chang","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"myae043","DOI":"10.1093\/mmy\/myae043","article-title":"Cryptococcosis\u2014A systematic review to inform the World Health Organization fungal priority pathogens list","volume":"62","author":"Dao","year":"2024","journal-title":"Med. Mycol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e00200-2025","DOI":"10.1590\/0037-8682-0328-2024","article-title":"Fluconazole resistance and heteroresistance in Cryptococcus spp.: Mechanisms and implications","volume":"58","author":"Moreira","year":"2025","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1128\/AAC.00295-09","article-title":"Heteroresistance to fluconazole in Cryptococcus neoformans is intrinsic and associated with virulence","volume":"53","author":"Sionov","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_11","first-page":"49","article-title":"SMON: Toxicity of clioquinol and the status quo","volume":"67","author":"Konagaya","year":"2015","journal-title":"Brain Nerve"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.pharmthera.2019.03.009","article-title":"Clioquinol: To harm or heal","volume":"199","author":"Perez","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1001\/archneur.60.12.1685","article-title":"Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: A pilot phase 2 clinical trial","volume":"60","author":"Ritchie","year":"2003","journal-title":"Arch. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.clml.2012.05.005","article-title":"A phase I study of the metal ionophore clioquinol in patients with advanced hematologic malignancies","volume":"12","author":"Schimmer","year":"2012","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1002\/ddr.21531","article-title":"8-hydroxyquinolines are bactericidal against Mycobacterium tuberculosis","volume":"80","author":"Odingo","year":"2019","journal-title":"Drug Dev. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"170","DOI":"10.3923\/ijp.2013.170.175","article-title":"Antimicrobial activity of 8-hydroxyquinoline and transition metal complexes","volume":"9","author":"Srisung","year":"2013","journal-title":"Int. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1111\/jam.15105","article-title":"Investigating surface binding effects: Antibacterial efficacy of bound 8-hydroxyquinoline against Staphylococcus aureus and Escherichia coli","volume":"131","author":"Richards","year":"2021","journal-title":"J. Appl. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4582","DOI":"10.1002\/slct.201900873","article-title":"8-hydroxyquinoline-2-carboxanilides as antiviral agents against avian influenza virus","volume":"4","author":"Kos","year":"2019","journal-title":"ChemistrySelect"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.antiviral.2012.10.009","article-title":"Characterization of 8-hydroxyquinoline derivatives containing aminobenzothiazole as inhibitors of dengue virus type 2 protease in vitro","volume":"97","author":"Lai","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lima, S.K.S., Jesus, J.A., Raminelli, C., Laurenti, M.D., and Passero, L.F.D. (2023). High selectivity of 8-hydroxyquinoline on Leishmania (Leishmania) and Leishmania (Viannia) species correlates with a potent therapeutic activity in vivo. Pharmaceuticals, 16.","DOI":"10.3390\/ph16050707"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.vetpar.2016.01.002","article-title":"An effective in vitro and in vivo antileishmanial activity and mechanism of action of 8-hydroxyquinoline against Leishmania species causing visceral and tegumentary leishmaniasis","volume":"217","author":"Duarte","year":"2016","journal-title":"Vet. Parasitol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"16364","DOI":"10.1021\/acs.jmedchem.3c01771","article-title":"Discovery of novel 8-hydroxyquinoline derivatives with potent in vitro and in vivo antifungal activity","volume":"66","author":"Li","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"18158","DOI":"10.1039\/D0NJ06188C","article-title":"New 8-hydroxyquinoline derivatives highlight the potential of this class for treatment of fungal infections","volume":"45","author":"Joaquim","year":"2021","journal-title":"New J. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e03182","DOI":"10.1002\/slct.202503182","article-title":"Synthesis of 8-hydroxyquinoline derivatives: A revolutionary target in medicinal chemistry (2020\u20132025)","volume":"10","author":"Sharma","year":"2025","journal-title":"ChemistrySelect"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1093\/infdis\/103.2.142","article-title":"The effect of chemotherapeutic agents upon the growth of Cryptococcus neoformans","volume":"103","author":"Schmidt","year":"1958","journal-title":"J. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1039\/C6MT00172F","article-title":"Chemical and functional properties of metal chelators that mobilize copper to elicit fungal killing of Cryptococcus neoformans","volume":"9","author":"Helsel","year":"2017","journal-title":"Metallomics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1128\/jb.150.3.1212-1220.1982","article-title":"Biochemical studies of phenoloxidase and utilization of catecholamines in Cryptococcus neoformans","volume":"150","author":"Polacheck","year":"1982","journal-title":"J. Bacteriol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e01921-19","DOI":"10.1128\/AAC.01921-19","article-title":"Identification of off-patent drugs that show synergism with amphotericin B or that present antifungal action against Cryptococcus neoformans and Candida spp","volume":"64","author":"Rossi","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1093\/jac\/dkh434","article-title":"Combinations of antifungal agents in therapy\u2014What value are they?","volume":"54","year":"2004","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S678","DOI":"10.1093\/cid\/civ819","article-title":"The regulatory pathway for antifungal drugs: A US perspective","volume":"61","author":"Tillotson","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_31","unstructured":"European Committee on Antimicrobial Susceptibility Testing (2021, November 20). Method for the Determination of Broth Dilution Minimum Inhibitory Concentrations of Antifungal Agents for Yeasts. EUCAST E.DEF 7.3.2. Available online: https:\/\/www.eucast.org\/astoffungi\/methodsinantifungalsusceptibilitytesting\/susceptibility_testing_of_yeasts\/."},{"key":"ref_32","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."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"101543","DOI":"10.1016\/j.mex.2021.101543","article-title":"New and simplified method for drug combination studies by checkerboard assay","volume":"8","author":"Bellio","year":"2021","journal-title":"MethodsX"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.1093\/bioinformatics\/btw230","article-title":"Combenefit: An interactive platform for the analysis and visualization of drug combinations","volume":"32","author":"Fornari","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1007\/s11094-018-1852-z","article-title":"Synthesis, spectroscopic studies, antibacterial activity, and colorimetric evaluation of the time-killing assay for newly synthesized chalcones using resazurin","volume":"52","author":"Prasad","year":"2018","journal-title":"Pharm. Chem. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101519","DOI":"10.1016\/j.jbc.2021.101519","article-title":"Cryptococcus neoformans melanization incorporates multiple catecholamines to produce polytypic melanin","volume":"298","author":"Baker","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e02646-25","DOI":"10.1128\/mbio.02646-25","article-title":"Cryptococcus neoformans serotype A virulence and pathogenicity are capsular glucuronoxylomannan (GXM) motif composition dependent","volume":"16","author":"Stempinski","year":"2025","journal-title":"mBio"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"105354","DOI":"10.1016\/j.chemolab.2025.105354","article-title":"Quantification of antibiotics in multicomponent drug formulations using UV\u2013Vis spectrometer with PLS and MCR-ALS","volume":"260","author":"Ramos","year":"2025","journal-title":"Chemom. Intell. Lab. Syst."},{"key":"ref_39","unstructured":"Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) (2010). The Hen\u2019s Egg Test\u2013Chorioallantoic Membrane (HET-CAM) Test Method, Research Triangle Park. National Toxicology Program."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Giordani, C.F.A., Campanharo, S., Wingert, N.R., Bueno, L.M., Manoel, J.W., Costa, B., Cattani, S., Arbo, M.D., Garcia, S.C., and Garcia, C.V. (2019). In vitro toxic evaluation of two gliptins and their main impurities of synthesis. BMC Pharmacol. Toxicol., 20.","DOI":"10.1186\/s40360-019-0354-2"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.mimet.2015.10.004","article-title":"Tenebrio molitor (Coleoptera: Tenebrionidae) as an alternative host to study fungal infections","volume":"118","author":"Morey","year":"2015","journal-title":"J. Microbiol. Methods"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"57","DOI":"10.5582\/ddt.2016.01025","article-title":"Acute oral toxicity test of chemical compounds in silkworms","volume":"10","author":"Usui","year":"2016","journal-title":"Drug Discov. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1056\/NEJMoa1710922","article-title":"Antifungal combinations for treatment of cryptococcal meningitis in Africa","volume":"378","author":"Molloy","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1016\/S1473-3099(22)00499-6","article-title":"The global burden of HIV-associated cryptococcal infection in adults in 2020: A modelling analysis","volume":"22","author":"Rajasingham","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Miot, J., Leong, T., Takuva, S., Parrish, A., and Dawood, H. (2021). Cost-effectiveness analysis of flucytosine as induction therapy in the treatment of cryptococcal meningitis in HIV-infected adults in South Africa. BMC Health Serv. Res., 21.","DOI":"10.1186\/s12913-021-06268-9"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/nm0409-356","article-title":"The curious case of clioquinol","volume":"15","author":"Cahoon","year":"2009","journal-title":"Nat. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/BF00267879","article-title":"8-hydroxyquinoline inhibition of DNA synthesis and intragenic recombination during yeast meiosis","volume":"162","author":"Mills","year":"1978","journal-title":"Mol. Gen. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"You, Z., Zhang, C., and Ran, Y. (2020). The effects of clioquinol in morphogenesis, cell membrane and ion homeostasis in Candida albicans. BMC Microbiol., 20.","DOI":"10.1186\/s12866-020-01850-3"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1099\/jmm.0.000850","article-title":"Clioquinol is a promising preventive morphological switching compound in the treatment of Candida infections linked to the use of intrauterine devices","volume":"67","author":"Pippi","year":"2018","journal-title":"J. Med. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.mycmed.2018.03.007","article-title":"Clioquinol, an alternative antimicrobial agent against common pathogenic microbes","volume":"28","author":"You","year":"2018","journal-title":"J. Mycol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1111\/myc.12510","article-title":"Evaluation of antifungal combination against Cryptococcus spp","volume":"59","author":"Lyra","year":"2016","journal-title":"Mycoses"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3312","DOI":"10.1128\/AAC.48.9.3312-3316.2004","article-title":"Posaconazole and amphotericin B combination therapy against Cryptococcus neoformans infection","volume":"48","author":"Barchiesi","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1128\/AAC.49.7.2994-2996.2005","article-title":"In vitro interactions of micafungin with other antifungal drugs against clinical isolates of four species of Cryptococcus","volume":"49","author":"Serena","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1111\/j.1462-5822.2008.01186.x","article-title":"Capsule enlargement in Cryptococcus neoformans confers resistance to oxidative stress suggesting a mechanism for intracellular survival","volume":"10","author":"Zaragoza","year":"2008","journal-title":"Cell Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Garcia-Rubio, R., de Oliveira, H.C., Rivera, J., and Trevijano-Contador, N. (2020). The fungal cell wall: Candida, Cryptococcus, and Aspergillus species. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.02993"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jsps.2018.07.017","article-title":"New insights into the mechanism of antifungal action of 8-hydroxyquinolines","volume":"27","author":"Pippi","year":"2019","journal-title":"Saudi Pharm. J."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Silva, M.G., Schrank, A., Bail\u00e3o, E.F.L.C., Bail\u00e3o, A.M., Borges, C.L., Staats, C.C., Parente, J.A., Pereira, M., Salem-Izacc, S.M., and Mendes-Giannini, M.J.S. (2011). The homeostasis of iron, copper, and zinc in Paracoccidioides brasiliensis, Cryptococcus neoformans var. grubii, and Cryptococcus gattii: A comparative analysis. Front. Microbiol., 2.","DOI":"10.3389\/fmicb.2011.00049"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.fgb.2012.08.006","article-title":"A defect in iron uptake enhances the susceptibility of Cryptococcus neoformans to azole antifungal drugs","volume":"49","author":"Kim","year":"2012","journal-title":"Fungal Genet. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.3233\/JAD-2010-100024","article-title":"The metal chelating and chaperoning effects of clioquinol: Insights from yeast studies","volume":"21","author":"Li","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"13582","DOI":"10.1039\/C5CP01615K","article-title":"Coordination properties of a metal chelator clioquinol to Zn(2+) studied by static DFT and ab initio molecular dynamics","volume":"17","author":"Vidossich","year":"2015","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1007\/s11745-008-3225-y","article-title":"CYP51: A major drug target in the cytochrome P450 superfamily","volume":"43","author":"Lepesheva","year":"2008","journal-title":"Lipids"},{"key":"ref_62","first-page":"1659","article-title":"Molecular simulations of fluconazole-mediated inhibition of sterol biosynthesis","volume":"38","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"36543","DOI":"10.1074\/jbc.M706770200","article-title":"Regulation of iron homeostasis mediated by the heme-binding protein Dap1 via the P450 protein Erg11\/Cyp51","volume":"282","author":"Craven","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1128\/AAC.06098-11","article-title":"Dynamic interaction between fluconazole and amphotericin B against Cryptococcus gattii","volume":"56","author":"Santos","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"509","DOI":"10.3233\/JAD-2010-1390","article-title":"PBT2 rapidly improves cognition in Alzheimer\u2019s disease: Additional phase II analyses","volume":"20","author":"Faux","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_66","first-page":"622","article-title":"A randomized, exploratory molecular imaging study targeting amyloid \u03b2 with a novel 8-OH quinoline in Alzheimer\u2019s disease: The PBT2-204 IMAGINE study","volume":"3","author":"Villemagne","year":"2017","journal-title":"Alzheimers Dement."},{"key":"ref_67","first-page":"001377","article-title":"8-hydroxyquinoline-5-(N-4-chlorophenyl)sulfonamide and fluconazole combination as a preventive strategy for Candida biofilm in haemodialysis devices","volume":"70","author":"Pippi","year":"2021","journal-title":"J. Med. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Demidenko, E., and Miller, T.W. (2019). Statistical determination of synergy based on Bliss definition of drugs independence. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0224137"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S0031-6997(25)06847-4","article-title":"The search for synergy: A critical review from a response surface perspective","volume":"47","author":"Greco","year":"1995","journal-title":"Pharmacol. Rev."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/8\/1654\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:22:53Z","timestamp":1785471773000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/8\/1654"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,29]]},"references-count":69,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["microorganisms14081654"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms14081654","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,29]]}}}