{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T07:21:16Z","timestamp":1793085676520,"version":"4.5.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T00:00:00Z","timestamp":1597968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"FAPEMIG","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UFSJ"},{"DOI":"10.13039\/501100002322","name":"CAPES","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Drug repositioning has been an important ally in the search for new antifungal drugs. Statins are drugs that act to prevent sterol synthesis in both humans and fungi and for this reason they are promissory candidates to be repositioned to treat mycoses. In this study we evaluated the antifungal activity of atorvastatin by in vitro tests to determine the minimum inhibitory concentration against azole resistant Candida albicans and its mechanisms of action. Moreover, the efficacy of both atorvastatin-loaded oral and vaginal emulgels (0.75%, 1.5% and 3% w\/w) was evaluated by means of in vivo experimental models of oral and vulvovaginal candidiasis, respectively. The results showed that atorvastatin minimal inhibitory concentration against C. albicans was 31.25\u00a0\u03bcg\/ml. In oral candidiasis experiments, the group treated with oral emulgel containing 3.0% atorvastatin showcased total reduction in fungal load after nine days of treatment. Intravaginal delivery atorvastatin emulgel showed considerable effectiveness at the concentration of 3% (65% of fungal burden reduction) after nine days of treatment. From these findings, it is possible to assert that atorvastatin may be promising for drug repositioning towards the treatment of these opportunistic mycoses.<\/jats:p>","DOI":"10.1093\/mmy\/myaa071","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T19:12:15Z","timestamp":1596222735000},"page":"476-485","source":"Crossref","is-referenced-by-count":21,"title":["Antifungal efficacy of atorvastatin-containing emulgel in the treatment of oral and vulvovaginal candidiasis"],"prefix":"10.1093","volume":"59","author":[{"given":"Ari Soares","family":"de Oliveira Neto","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacology, Federal University of S\u00e3o Jo\u00e3o Del-Rei, Campus Centro Oeste Dona Lindu, Divin\u00f3polis, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israel Lucas Antunes","family":"Souza","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Federal University of S\u00e3o Jo\u00e3o Del-Rei, Campus Centro Oeste Dona Lindu, Divin\u00f3polis, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eliza Samuel","family":"Amorim","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Development, Federal University of S\u00e3o Jo\u00e3o Del-Rei, Campus Centro Oeste Dona Lindu, Divin\u00f3polis, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thalita","family":"de Freitas Souza","sequence":"additional","affiliation":[{"name":"Bioactive Natural Products Laboratory, Department of Biochemistry, Institute of Biological Sciences, Federal University of Juiz de Fora, Campus, Juiz de Fora, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius Novaes","family":"Rocha","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Faculty of Medicine, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3748-3427","authenticated-orcid":false,"given":"Rene Oliveira","family":"do Couto","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Development, Federal University of S\u00e3o Jo\u00e3o Del-Rei, Campus Centro Oeste Dona Lindu, Divin\u00f3polis, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo Luiz","family":"Fabri","sequence":"additional","affiliation":[{"name":"Bioactive Natural Products Laboratory, Department of Biochemistry, Institute of Biological Sciences, Federal University of Juiz de Fora, Campus, Juiz de Fora, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6320-3185","authenticated-orcid":false,"given":"Marcelo Gonzaga","family":"de Freitas Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Federal University of S\u00e3o Jo\u00e3o Del-Rei, Campus Centro Oeste Dona Lindu, Divin\u00f3polis, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,8,21]]},"reference":[{"key":"2021050323561840400_bib1","doi-asserted-by":"crossref","first-page":"100496","DOI":"10.1016\/j.nmni.2018.11.004","article-title":"Social, environmental and microbiologic aspects of endemic mycoses in Brazil","volume":"29","author":"Costa","year":"2019","journal-title":"New Microbes New Infect"},{"key":"2021050323561840400_bib2","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1007\/s42770-019-00096-0","article-title":"Mycoses in northeastern Brazil: epidemiology and prevalence of fungal species in 8 years of retrospective analysis in Alagoas","volume":"50","author":"Maranh\u00e3o","year":"2020","journal-title":"Braz J Microbiol"},{"key":"2021050323561840400_bib3","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/jac\/dkz400","article-title":"Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungus Candida albicans","volume":"75","author":"Nishimoto","year":"2020","journal-title":"J Antimicrob Chemother"},{"key":"2021050323561840400_bib4","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12879-019-4736-2","article-title":"Prevalence and antifungal susceptibility of Candida albicans causing vaginal discharge among pregnant women in Lebanon","volume":"20","author":"Ghaddar","year":"2020","journal-title":"BMC Infect Dis"},{"key":"2021050323561840400_bib5","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1080\/14787210.2016.1199272","article-title":"Antifungal agents and liver toxicity: a complex interaction","volume":"14","author":"Tverdek","year":"2016","journal-title":"Expert Rev Anti Infect Ther"},{"key":"2021050323561840400_bib6","doi-asserted-by":"crossref","first-page":"249","DOI":"10.2147\/IDR.S124918","article-title":"Antifungal resistance: current trends and future strategies to combat","volume":"10","author":"Wiederhold","year":"2017","journal-title":"Infect Drug Resist"},{"key":"2021050323561840400_bib7","article-title":"Structure-based drug repositioning: potential and limits","author":"Adasme","year":"2020","journal-title":"Semin Cancer Biol"},{"key":"2021050323561840400_bib8","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.3389\/fmicb.2015.01474","article-title":"Atorvastatin reduces the survival of Candida albicans-infected BALB\/c mice","volume":"6","author":"Rahal","year":"2015","journal-title":"Front Microbiol"},{"key":"2021050323561840400_bib9","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.bjid.2015.06.001","article-title":"Simvastatin inhibits planktonic cells and biofilms of Candida and Cryptococcus species","volume":"19","author":"Brilhante","year":"2015","journal-title":"Braz J Infect Dis"},{"key":"2021050323561840400_bib10","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 Therapeut."},{"key":"2021050323561840400_bib11","first-page":"7","article-title":"Statin associated myopathy in clinical practice: results of DAMA study","volume":"29","author":"Mill\u00e1n","year":"2017","journal-title":"Clin Investig Arterioscler"},{"key":"2021050323561840400_bib12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphar.2017.00500","article-title":"Risk of myopathy in patients in therapy with statins: identification of biological markers in a pilot study","volume":"8","author":"Camerino","year":"2017","journal-title":"Front Pharmacol"},{"key":"2021050323561840400_bib13","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.ijantimicag.2017.04.005","article-title":"Atorvastatin as a promising anticryptococcal agent","volume":"49","author":"Ribeiro","year":"2017","journal-title":"Int J Antimic Agents"},{"key":"2021050323561840400_bib14","doi-asserted-by":"crossref","first-page":"5255","DOI":"10.1007\/s00253-018-8959-8","article-title":"Lovastatin synergizes with itraconazole against planktonic cells and biofilms of Candida albicans through the regulation on ergosterol biosynthesis pathway","volume":"102","author":"Zhou","year":"2018","journal-title":"Appl Microbiol Biotechnol"},{"key":"2021050323561840400_bib15","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1902\/jop.2016.150706","article-title":"1.2% rosuvastatin versus 1.2% atorvastatin gel local drug delivery and redelivery in treatment of intrabony defects in chronic periodontitis: a randomized placebo-controlled clinical trial","volume":"87","author":"Pradeep","year":"2016","journal-title":"J Periodontol."},{"key":"2021050323561840400_bib16","doi-asserted-by":"crossref","first-page":"31","DOI":"10.5530\/srp.2017.1.7","article-title":"Buccal Mucoadhesive films: a review","volume":"8","author":"Rajaram","year":"2017","journal-title":"Sys Rev Pharm"},{"key":"2021050323561840400_bib17","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.jconrel.2013.06.030","article-title":"Recent expansions in an emergent novel drug delivery technology: emulgel","volume":"171","author":"Ajazuddin","year":"2013","journal-title":"J Control Release"},{"key":"2021050323561840400_bib18","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1080\/09546630701247971","article-title":"Short-duration topical treatment of tinea pedis using terbinafine emulsion gel: results of a dose-ranging clinical trial","volume":"18","author":"James","year":"2007","journal-title":"J Dermatolog Treat"},{"key":"2021050323561840400_bib19","volume-title":"Candida albicans drug resistance panel (CaDR Panel). Microbial characterization data. American Type Culture Collection","author":"American Type Culture Collection (ATCC)","year":"2008"},{"key":"2021050323561840400_bib20","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1111\/myc.12762","article-title":"Formulation, stability study, and pre-clinical evaluation of a vaginal cream containing curcumin in a rat model of vulvovaginal candidiasis","volume":"61","author":"Fernandes","year":"2018","journal-title":"Mycoses"},{"key":"2021050323561840400_bib21","volume-title":"Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts","author":"Clinical and Laboratory Standards Institute (CLSI)","year":"2017","edition":"4th ed"},{"key":"2021050323561840400_bib22","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1021\/np070660i","article-title":"Evidence for the mechanism of action of the antifungal phytolaccoside B isolated from Phytolacca tetramera Hauman","volume":"71","author":"Escalante","year":"2008","journal-title":"J Nat Prod"},{"key":"2021050323561840400_bib23","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.jpba.2008.09.006","article-title":"Insertion mode of a novel anionic antimicrobial peptide MDpep5 (Val-Glu-Ser-Trp-Val) from Chinese traditional edible larvae of housefly and its effect on surface potential of bacterial membrane","volume":"48","author":"Tang","year":"2008","journal-title":"J Pharm Biomed Anal"},{"key":"2021050323561840400_bib24","doi-asserted-by":"crossref","first-page":"306","DOI":"10.7164\/antibiotics.48.306","article-title":"Whole-cell Candida albicans assay for the detection of inhibitors towards fungal cell wall synthesis and assembly","volume":"48","author":"Frost","year":"1995","journal-title":"J Antibiot"},{"key":"2021050323561840400_bib25","article-title":"Evaluation of antifungal activity and mechanism of action of citral against Candida albicans","volume":"378280","author":"Leite","year":"2014","journal-title":"Evid Based Complement Altern Med"},{"key":"2021050323561840400_bib26","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1016\/j.addr.2005.07.004","article-title":"The use of mucoadhesive polymers in vaginal delivery","volume":"57","author":"Valenta","year":"2005","journal-title":"Adv Drug Deliv Rev"},{"key":"2021050323561840400_bib27","first-page":"296","article-title":"In vivo comparative evaluation of the pomegranate (Punica granatum) peel extract as an alternative agent to nystatin against oral candidiasis","volume":"43","author":"Bassiri-Jahromi","year":"2018","journal-title":"Iran J Med Sci"},{"key":"2021050323561840400_bib28","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S1473-3099(17)30316-X","article-title":"The global problem of antifungal resistance: prevalence, mechanisms, and management","volume":"17","author":"Perlin","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"2021050323561840400_bib29","first-page":"1","article-title":"Azole antifungal resistance in Candida albicans and emerging non-albicans Candida species","volume":"7","author":"Whaley","year":"2016","journal-title":"Front Microbiol"},{"key":"2021050323561840400_bib30","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.indcrop.2018.07.038","article-title":"Mitracarpus frigidus: a promising antifungal in the treatment of vulvovaginal candidiasis","volume":"123","author":"Campos","year":"2018","journal-title":"Ind Crops Prod"},{"key":"2021050323561840400_bib31","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.cmi.2019.03.028","article-title":"Resistance of Candida to azoles and echinocandins worldwide","volume":"25","author":"Pristov","year":"2019","journal-title":"Clin Microbiol Infect"},{"key":"2021050323561840400_bib32","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.biopha.2018.12.076","article-title":"Are the statins promising antifungal agents against invasive candidiasis","volume":"111","author":"Lima","year":"2019","journal-title":"Biomed Pharmacother"},{"key":"2021050323561840400_bib33","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1574-6968.2006.00370.x","article-title":"Growth inhibition of Candida species and Aspergillus fumigatus by statins","volume":"262","author":"Macreadie","year":"2006","journal-title":"FEMS Microbiol Lett"},{"key":"2021050323561840400_bib34","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/j.1574-6968.2010.01972.x","article-title":"In vitro synergistic interactions of the effects of various statins and azoles against some clinically important fungi","volume":"307","author":"Nyilasi","year":"2010","journal-title":"FEMS Microbiol Lett"},{"key":"2021050323561840400_bib35","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/j.1574-6968.2008.01160.x","article-title":"Animal models of mucosal Candida infection","volume":"283","author":"Naglik","year":"2008","journal-title":"FEMS Microbiol Lett"},{"key":"2021050323561840400_bib36","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/CVM-1-3-161","article-title":"Are statins anti-inflammatory","volume":"1","author":"Blake","year":"2000","journal-title":"Trials"},{"key":"2021050323561840400_bib37","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1093\/mmy\/myt032","article-title":"Comparative adherence of Candida albicans and Candida dubliniensis to human buccal epithelial cells and extracellular matrix proteins","volume":"52","author":"Jordan","year":"2014","journal-title":"Med Mycol"},{"key":"2021050323561840400_bib38","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.jconrel.2004.11.034","article-title":"The vagina as a route for systemic drug delivery","volume":"103","author":"Hussain","year":"2005","journal-title":"J Control Release"},{"key":"2021050323561840400_bib39","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.archoralbio.2003.12.002","article-title":"Comparative permeability of various chemical markers through human vaginal and buccal mucosa as well as porcine buccal and mouth floor mucosa","volume":"49","author":"Van Eyk","year":"2004","journal-title":"Arch Oral Biol"},{"key":"2021050323561840400_bib40","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ijpharm.2005.09.002","article-title":"Porcine vaginal mucosa as an in vitro permeability model for human vaginal mucosa","volume":"305","author":"Van Eyk","year":"2005","journal-title":"Int J Pharm"},{"key":"2021050323561840400_bib41","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1007\/s11095-009-9831-4","article-title":"In silico prediction of drug permeability across buccal mucosa","volume":"26","author":"Kokate","year":"2009","journal-title":"Pharm Res"},{"key":"2021050323561840400_bib42","doi-asserted-by":"crossref","first-page":"550","DOI":"10.3109\/10717544.2014.928760","article-title":"Advanced topical drug delivery system for the management of vaginal candidiasis","volume":"23","author":"Johal","year":"2016","journal-title":"Drug Deliv"},{"key":"2021050323561840400_bib43","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1002\/bkcs.11962","article-title":"Viscosity effects of hydrophilic polymers on transport of collagen hydrolysate across reconstructed human buccal tissue","volume":"41","author":"Koo","year":"2020","journal-title":"Bull Korean Chem Soc"},{"key":"2021050323561840400_bib44","first-page":"126","article-title":"Problems and pitfalls in cardiac drug therapy","volume":"2","author":"Stone","year":"2001","journal-title":"Rev Cardiovasc Med"},{"key":"2021050323561840400_bib45","first-page":"e2020","article-title":"The concomitant use of atorvastatin and amlodipine leading to rhabdomyolysis","volume":"10","author":"Khan","year":"2018","journal-title":"Cureus"},{"key":"2021050323561840400_bib46","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1007\/s40262-020-00876-0","article-title":"Influence of drug-drug interactions on the pharmacokinetics of atorvastatin and its major active metabolite ortho-OH-Atorvastatin in aging people living with HIV","volume":"59","author":"Courlet","year":"2020","journal-title":"Clin Pharmacokinet"},{"key":"2021050323561840400_bib47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15761\/JTS.1000181","article-title":"An updated review of interactions of statins with antibacterial and antifungal agents","volume":"3","author":"Eljaaly","year":"2017","journal-title":"J Transl Sci"}],"container-title":["Medical Mycology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/mmy\/article-pdf\/59\/5\/476\/37168720\/myaa071.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/mmy\/article-pdf\/59\/5\/476\/37168720\/myaa071.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T10:19:43Z","timestamp":1667643583000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mmy\/article\/59\/5\/476\/5895500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,21]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,8,21]]},"published-print":{"date-parts":[[2021,5,4]]}},"URL":"https:\/\/doi.org\/10.1093\/mmy\/myaa071","relation":{},"ISSN":["1369-3786","1460-2709"],"issn-type":[{"value":"1369-3786","type":"print"},{"value":"1460-2709","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,5]]},"published":{"date-parts":[[2020,8,21]]}}}