{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:25:24Z","timestamp":1791433524380,"version":"4.3.3"},"reference-count":61,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Flavonoids are a class of phenolic compounds commonly found in fruits, vegetables, grains, flowers, tea, and wine. They differ in their chemical structures and characteristics. Such compounds show various biological functions and have antioxidant, antimicrobial, anti-inflammatory, and antiapoptotic properties. The aim of this study was to evaluate the\n            <jats:italic>in vitro<\/jats:italic>\n            interactions of flavonoids with fluconazole against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida tropicalis<\/jats:named-content>\n            strains resistant to fluconazole, investigating the mechanism of synergism. Three combinations formed by the flavonoids (+)-catechin hydrated, hydrated quercetin, and (\u2212)-epigallocatechin gallate at a fixed concentration with fluconazole were tested. Flavonoids alone had no antifungal activity within the concentration range tested, but when they were used as a cotreatment with fluconazole, there was significant synergistic activity. From this result, we set out to evaluate the possible mechanisms of cell death involved in this synergism. Isolated flavonoids did not induce morphological changes or changes in membrane integrity in the strains tested, but when they were used as a cotreatment with fluconazole, these changes were quite significant. When evaluating mitochondrial damage and the production of reactive oxygen species (ROS) only in the cotreatment, changes were observed. Flavonoids combined with fluconazole were shown to cause a significant increase in the rate of damage and the frequency of DNA damage in the tested strains. The cotreatment also induced an increase in the externalization of phosphatidylserine, an important marker of early apoptosis. It is concluded that flavonoids, when combined with fluconazole, show activity against strains of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. tropicalis<\/jats:named-content>\n            resistant to fluconazole, promoting apoptosis by exposure of phosphatidylserine in the plasma membrane and morphological changes, mitochondrial depolarization, intracellular accumulation of ROS, condensation, and DNA fragmentation.\n          <\/jats:p>","DOI":"10.1128\/aac.00651-13","type":"journal-article","created":{"date-parts":[[2013,12,24]],"date-time":"2013-12-24T04:23:33Z","timestamp":1387859013000},"page":"1468-1478","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":107,"title":["Synergistic Effect of the Flavonoid Catechin, Quercetin, or Epigallocatechin Gallate with Fluconazole Induces Apoptosis in Candida tropicalis Resistant to Fluconazole"],"prefix":"10.1128","volume":"58","author":[{"given":"Cec\u00edlia Rocha","family":"da Silva","sequence":"first","affiliation":[{"name":"Department of Clinical and Toxicological Analysis, School of Pharmacy, Laboratory of Bioprospection and Experiments in Yeast (LABEL), Federal University of Ceara, Fortaleza, CE, Brazil"},{"name":"Department of Pathology and Legal Medicine, School of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Batista","family":"de Andrade Neto","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis, School of Pharmacy, Laboratory of Bioprospection and Experiments in Yeast (LABEL), Federal University of Ceara, Fortaleza, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosana","family":"de Sousa Campos","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis, School of Pharmacy, Laboratory of Bioprospection and Experiments in Yeast (LABEL), Federal University of Ceara, Fortaleza, CE, Brazil"},{"name":"Department of Pathology and Legal Medicine, School of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narjara Silvestre","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis, School of Pharmacy, Laboratory of Bioprospection and Experiments in Yeast (LABEL), Federal University of Ceara, Fortaleza, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Let\u00edcia Serpa","family":"Sampaio","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis, School of Pharmacy, Laboratory of Bioprospection and Experiments in Yeast (LABEL), Federal University of Ceara, Fortaleza, CE, 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