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This study aimed to evaluate the chemical composition, antifungal activity, reduction of fungal virulence, and the preliminary toxicity of the fixed oil from the inner mesocarp of <jats:italic>C. coriaceum<\/jats:italic> tested against three <jats:italic>Candida<\/jats:italic> yeasts. The oil was characterized by gas chromatography (GC\u2010MS and GC\u2010FID). Antifungal activity was assessed using the serial microdilution method. Additionally, the potential of the oil as an enhancer of fluconazole action was tested at sub\u2010inhibitory concentrations (MIC\/8). The mechanism of action of <jats:italic>C. coriaceum<\/jats:italic> fixed oil was determined by evaluating the inhibition of morphological transition in <jats:italic>Candida<\/jats:italic> spp. The chemical composition of the fixed oil of <jats:italic>C. coriaceum<\/jats:italic> comprised both unsaturated and saturated fatty acids. Oleic (61\u2009%) and palmitic (33\u2009%) acids were the major constituents. Regarding its anti\u2010<jats:italic>Candida<\/jats:italic> activity, the oil inhibited the growth of <jats:italic>C. albicans<\/jats:italic> (IC<jats:sub>50<\/jats:sub>: 371\u2005\u03bcg\/mL) and <jats:italic>C. tropicalis<\/jats:italic> (IC<jats:sub>50<\/jats:sub>: 830\u2005\u03bcg\/mL). Furthermore, the oil reversed the antifungal resistance of <jats:italic>C. albicans<\/jats:italic> and <jats:italic>C. tropicalis<\/jats:italic>, restoring the susceptibility to fluconazole and reducing their IC<jats:sub>50<\/jats:sub> from 12.33\u2005\u03bcg\/mL and 362\u2005\u03bcg\/mL to 0.22\u2005\u03bcg\/mL and 13.93\u2005\u03bcg\/mL, respectively. The fixed oil of <jats:italic>C. coriaceum<\/jats:italic> completely inhibited the morphological transition of <jats:italic>C. albicans<\/jats:italic> and <jats:italic>C. tropicalis<\/jats:italic> at a concentration of 512\u2005\u03bcg\/mL, but exhibited limited low antifungal potential against <jats:italic>C. krusei<\/jats:italic>. The observed antifungal activity may be attributed to the overproduction of reactive oxygen species. Additionally, the oil showed no toxic effect on the <jats:italic>Drosophila melanogaster in\u2005vivo<\/jats:italic> model. The fixed oil from the inner mesocarp of <jats:italic>C. coriaceum<\/jats:italic> emerge as a strong candidate for the development of new pharmaceutical formulations to treat infections caused by <jats:italic>Candida<\/jats:italic> spp.<\/jats:p>","DOI":"10.1002\/cbdv.202301960","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T03:34:54Z","timestamp":1704857694000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Exploring the Fluconazole\u2010Resistance Modifying Activity and Potential Mechanism of Action of Fixed Oil from <i>Caryocar coriaceum<\/i> Wittm. (Caryocaraceae) against <i>Candida<\/i> Species"],"prefix":"10.1002","volume":"21","author":[{"given":"Jos\u00e9 Weverton","family":"Almeida\u2010Bezerra","sequence":"first","affiliation":[{"name":"Department of Botany Federal University of Pernambuco\u2013UFPE, s\/n  Rua Professor Moraes Rego Recife Pernambuco 50.670-901 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Pereira da Cruz","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Regional University of Cariri\u2013URCA  1161, Rua Cel. Ant\u00f4nio Luiz Crato Cear\u00e1 63.105-000 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviane","family":"Bezerra da Silva","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Regional University of Cariri\u2013URCA  1161, Rua Cel. 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