{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T16:47:14Z","timestamp":1780591634810,"version":"3.54.1"},"reference-count":57,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,23]],"date-time":"2020-08-23T00:00:00Z","timestamp":1598140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004263","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio Grande do Sul","doi-asserted-by":"publisher","award":["16\/2551\u20100000517\u20106"],"award-info":[{"award-number":["16\/2551\u20100000517\u20106"]}],"id":[{"id":"10.13039\/501100004263","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mycoses"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The influence of biofilm on the complexity of fungal diseases has been reported in recent years, especially in non\u2010invasive mycoses such as keratitis and onychomycosis. The difficulty in treating cases of fusariosis in the human medical clinic exemplifies this situation, because when <jats:italic>Fusarium<\/jats:italic> spp. are present in the form of biofilm, the permeation of antifungal agents is compromised.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>This study proposes an association of clioquinol, an inhibitor of fungal cells with antifungal drugs prescribed to combat fusariosis in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Susceptibility was assessed by microdilution in broth. Formation of biofilm by staining with violet crystal. Inhibition and removal of biofilm using the MTT colorimetric reagent. Time\u2010kill combination, hypoallergenicity test, cytotoxicity test and toxicity prediction by computer analysis were also performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Clioquinol associated with voriconazole and ciclopirox inhibited biofilm formation. Possibly, clioquinol acts in the germination and elongation of hyphae, while voriconazole prevents cell adhesion and ciclopirox the formation of the extracellular polymeric matrix. The CLIO\u2010VRC association reduced the biofilm formation by more than 90%, while the CLIO\u2010CPX association prevented over 95%. None of the association was irritating, and over 90% of the leucocytes remained viable. Computational analysis does not reveal toxicity relevant to CLIO, whereas VRC and CPX showed some risks for systemic use, but suitable for topical formulations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The combination of CLIO\u2010VRC or CLIO\u2010CPX proved to be a promising association strategy in the medical clinic, both in combating fungal keratitis and onychomycosis, since they prevent the initial process of establishing an infection, the formation of biofilm.<\/jats:p><\/jats:sec>","DOI":"10.1111\/myc.13142","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T09:25:57Z","timestamp":1594718757000},"page":"1069-1082","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Synergistic association of clioquinol with antifungal drugs against biofilm forms of clinical <i>Fusarium<\/i> isolates"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4472-1443","authenticated-orcid":false,"given":"Magda Antunes","family":"de Chaves","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Microbiologia Agr\u00edcola e do Ambiente Universidade Federal do Rio Grande do Sul Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6821-932X","authenticated-orcid":false,"given":"Tha\u00eds","family":"Ferreira do Amaral","sequence":"additional","affiliation":[{"name":"Faculdade de Farm\u00e1cia Universidade Federal do Rio Grande do Sul Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6788-7238","authenticated-orcid":false,"given":"Nat\u00e1lia","family":"Monteiro da Silva Rodrigues Coutinho","sequence":"additional","affiliation":[{"name":"Faculdade de Farm\u00e1cia Universidade Federal do Rio Grande do Sul Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6023-814X","authenticated-orcid":false,"given":"Ta\u00eds","family":"Fernanda Andrzejewski Kaminski","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas Universidade Federal do Rio Grande do Sul Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4546-5584","authenticated-orcid":false,"given":"M\u00e1rio Lettieri","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica e Toxicologia Instituto Federal de Santa Catarina Conc\u00f3rdia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5548-6576","authenticated-orcid":false,"given":"Lu\u00eds","family":"Flavio Souza de Oliveira","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas Universidade Federal do Pampa Uruguaiana Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2873-7939","authenticated-orcid":false,"given":"Saulo Fernandes","family":"de Andrade","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Microbiologia Agr\u00edcola e do Ambiente Universidade Federal do Rio Grande do Sul Porto Alegre Brazil"},{"name":"Faculdade de Farm\u00e1cia Universidade Federal do Rio Grande do Sul Porto Alegre Brazil"},{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas Universidade Federal do Rio Grande do Sul Porto Alegre 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":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Microbiologia Agr\u00edcola e do Ambiente Universidade Federal do Rio Grande do Sul Porto Alegre Brazil"},{"name":"Faculdade de Farm\u00e1cia Universidade Federal do Rio Grande do Sul Porto Alegre Brazil"},{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas Universidade Federal do Rio Grande do Sul Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12275-019-8637-2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.000175"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/528521"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sajb.2015.03.192"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2217\/fmb-2017-0052"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2019.03.001"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00387-07"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-9848"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/myc.12638"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2217\/fmb-2018-0245"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1590\/0037-8682-0175-2020"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000000008"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/emi.2016.126"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005464"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00020-09"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2017.06.017"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2016.05.006"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof4010016"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/myc.12706"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.5582\/bst.2020.03072"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2008.08.015"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsps.2018.07.017"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofw172.1345"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mycmed.2018.05.001"},{"key":"e_1_2_9_26_1","volume-title":"Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi; Aproved Standard \u2013 Second Edition","author":"Clinical and Laboratory Standards Institute (CLSI)","year":"2008"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/lam.12488"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/md16080274"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.3.693-715.2004"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg301"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/jam.12746"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2007.10.015"},{"key":"e_1_2_9_33_1","volume-title":"The Hen's Egg Test\u2010Chorioallantoic Membrane (HET\u2010MAC) Test Method","author":"Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVMA)","year":"2010"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2010.04.010"},{"key":"e_1_2_9_35_1","first-page":"4940","article-title":"Differences in susceptibility to tumour necrosis fator alpha\u2010induced apoptosis among MCF\u20107 breast cancer cell variants","volume":"58","author":"Burow ME","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_9_36_1","unstructured":"OECD.Guidance Document on the Validation of (Quantitative) Structure\u2010Activity Relationship [(Q) SAR] Models.2007.https:\/\/www.oecd\u2010ilibrary.org\/docserver\/9789264085442\u2010en.pdf?expires=1594151718&id=id&accname=ocid54025470&checksum=619CF74010F85CA56FEB63A80BD5D454. Accessed March 15 2020"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/1574-6968.12310"},{"key":"e_1_2_9_38_1","first-page":"28","article-title":"Adherence and biofilm formation of Fusarium oxysporum isolated from a corneal ulcer","volume":"4","author":"Tamura NK","year":"2015","journal-title":"GARJMMS"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2020.01.002"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mycmed.2018.03.007"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2018.05.006"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02456-15"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2230.2009.03698.x"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkh228"},{"issue":"8","key":"e_1_2_9_45_1","first-page":"e02669","article-title":"In vitro activity of chlorhexidine compared with seven antifungal agents against 98 Fusarium isolates recovered from fungal keratitis patients","volume":"63","author":"Santos CO","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.000850"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-5949.2010.00231.x"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01484-12"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/jam.13513"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv421"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.000301"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2017.09.012"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12990"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5RA00248F"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-009-0473-3"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5DT00634A"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1586\/17469872.2.2.233"},{"issue":"8","key":"e_1_2_9_58_1","first-page":"1328","article-title":"Studies on the pharmacology and toxicology of ciclopiroxolamine (author's transl)","volume":"31","author":"Alpermann HG","year":"1981","journal-title":"Arzneimittelforschung"}],"container-title":["Mycoses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fmyc.13142","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/myc.13142","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/myc.13142","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/myc.13142","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T19:14:36Z","timestamp":1693768476000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/myc.13142"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,23]]},"references-count":57,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1111\/myc.13142"],"URL":"https:\/\/doi.org\/10.1111\/myc.13142","archive":["Portico"],"relation":{},"ISSN":["0933-7407","1439-0507"],"issn-type":[{"value":"0933-7407","type":"print"},{"value":"1439-0507","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,23]]},"assertion":[{"value":"2020-05-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}