{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T21:19:43Z","timestamp":1788470383027,"version":"build-2803163510"},"reference-count":54,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003758","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa e ao Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico do Maranh\u00e3o","doi-asserted-by":"publisher","award":["BM-02332\/19; INFRA-02012\/21; BATI-05406\/21"],"award-info":[{"award-number":["BM-02332\/19; INFRA-02012\/21; BATI-05406\/21"]}],"id":[{"id":"10.13039\/501100003758","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centro Universit\u00e1rio do Maranh\u00e3o","award":["00"],"award-info":[{"award-number":["00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Candidiasis is the most common fungal infection among immunocompromised patients. Its treatment includes the use of antifungals, which poses limitations such as toxicity and fungal resistance. Plant-derived extracts, such as Punica granatum, have been reported to have antimicrobial activity, but their antifungal effects are still unknown. We aimed to evaluate the antifungal and antiviral potential of the ethyl acetate fraction of P. granatum (PgEA) and its isolated compound galloyl-hexahydroxydiphenoyl-glucose (G-HHDP-G) against Candida spp. In silico analyses predicted the biological activity of G-HHDP-G. The minimum inhibitory concentrations (MIC) of PgEA and G-HHDP-G, and their effects on biofilm formation, preformed biofilms, and phospholipase production were determined. In silico analysis showed that G-HHDP-G has antifungal and hepatoprotective effects. An in vitro assay confirmed the antifungal effects of PgEA and G-HHDP-G, with MIC in the ranges of 31.25\u2013250 \u03bcg\/mL and 31.25 \u2265 500 \u03bcg\/mL, respectively. G-HHDP-G and PgEA synergistically worked with fluconazole against planktonic cells. The substances showed antibiofilm action, alone or in combination with fluconazole, and interfered with phospholipase production. The antifungal and antibiofilm actions of PgEA and G-HHDP-G, alone or in combination with fluconazole, in addition to their effects on reducing Candida phospholipase production, identify them as promising candidates for therapeutics.<\/jats:p>","DOI":"10.3390\/antibiotics11020265","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T08:14:46Z","timestamp":1645431286000},"page":"265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Ethyl Acetate Fraction of Punica granatum and Its Galloyl-HHDP-Glucose Compound, Alone or in Combination with Fluconazole, Have Antifungal and Antivirulence Properties against Candida spp."],"prefix":"10.3390","volume":"11","author":[{"given":"Aline Michelle Silva","family":"Mendon\u00e7a","sequence":"first","affiliation":[{"name":"Graduate Program in Microbial Biology, CEUMA University, UniCEUMA, S\u00e3o Lu\u00eds 65055-310, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3082-1101","authenticated-orcid":false,"given":"Cristina de Andrade","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Biology Laboratory, Maranh\u00e3o Federal Institute, IFMA, S\u00e3o Lu\u00eds 65030-005, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9043-490X","authenticated-orcid":false,"given":"Roberval Nascimento","family":"Moraes-Neto","sequence":"additional","affiliation":[{"name":"Graduate Program in Health Sciences, Federal University of Maranh\u00e3o, UFMA, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Souza","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Graduate Program in Microbial Biology, CEUMA University, UniCEUMA, S\u00e3o Lu\u00eds 65055-310, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7209-7986","authenticated-orcid":false,"given":"Renata","family":"Mondego-Oliveira","sequence":"additional","affiliation":[{"name":"Maur\u00edcio de Nassau Faculty, UNINASSAU, S\u00e3o Lu\u00eds 65040-840, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7149-6985","authenticated-orcid":false,"given":"Camila Evangelista Carnib","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Graduate Program in Health Sciences, Federal University of Maranh\u00e3o, UFMA, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4206-0904","authenticated-orcid":false,"given":"Lu\u00eds Cl\u00e1udio Nascimento","family":"da Silva","sequence":"additional","affiliation":[{"name":"Graduate Program in Microbial Biology, CEUMA University, UniCEUMA, S\u00e3o Lu\u00eds 65055-310, MA, Brazil"},{"name":"Graduate Program in Odontology, CEUMA University, UniCEUMA, S\u00e3o Lu\u00eds 65075-120, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidio Gon\u00e7alves","family":"Lima-Neto","sequence":"additional","affiliation":[{"name":"Graduate Program in Microbial Biology, CEUMA University, UniCEUMA, S\u00e3o Lu\u00eds 65055-310, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7073-8308","authenticated-orcid":false,"given":"Rafael Cardoso","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Graduate Program in Health Sciences, Federal University of Maranh\u00e3o, UFMA, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2506-169X","authenticated-orcid":false,"given":"Eduardo Martins","family":"de Sousa","sequence":"additional","affiliation":[{"name":"Graduate Program in Microbial Biology, CEUMA University, UniCEUMA, S\u00e3o Lu\u00eds 65055-310, MA, Brazil"},{"name":"Graduate Program in Health Sciences, Federal University of Maranh\u00e3o, UFMA, S\u00e3o Lu\u00eds 65080-805, MA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.17765\/1983-1870.2015v8n1p7-17","article-title":"Esp\u00e9cies Se Candida spp. Em Isolados Cl\u00ednicos e Suscetibilidade a Antif\u00fangicos de Uso Hospitalar","volume":"8","author":"Althaus","year":"2015","journal-title":"Sa\u00fade e Pesqui."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1007\/s12257-018-0477-0","article-title":"Invasive Fungal Infections and Their Epidemiology: Measures in the Clinical Scenario","volume":"24","author":"Bajpai","year":"2019","journal-title":"Biotechnol. 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