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In this context, we evaluated the anti\u2010<jats:italic>Candida<\/jats:italic> potential and the cytotoxic profile of eugenol derivatives. Anti\u2010<jats:italic>Candida<\/jats:italic> activity was evaluated on <jats:italic>C. albicans<\/jats:italic> and <jats:italic>C. parapsilosis<\/jats:italic> strains by minimum inhibitory concentration (MIC), scanning electron microscopy (SEM), and molecular docking calculations at the site of the enzyme lanosterol\u201014\u2010\u03b1\u2010demethylase active site, responsible for ergosterol formation. The cytotoxic profile was evaluated in HepG2 cells, in the presence and absence of the metabolizing system (S9 system). The results indicated compounds <jats:bold>1b<\/jats:bold> and <jats:bold>1d<\/jats:bold> as the most active ones. The compounds have anti\u2010<jats:italic>Candida<\/jats:italic> activity against both strains with MIC ranging from 50 to 100\u2009\u03bcg\u2009ml<jats:sup>\u22121<\/jats:sup>. SEM analyses of <jats:bold>1b<\/jats:bold> and <jats:bold>1d<\/jats:bold> indicated changes in the envelope architecture of both <jats:italic>C. albicans<\/jats:italic> and <jats:italic>C. parapsilosis<\/jats:italic> like the ones of eugenol and fluconazole, respectively. Docking results of the evaluated compounds indicated a similar binding pattern of fluconazole and posaconazole at the lanosterol\u201014\u2010\u03b1\u2010demethylase binding site. In the presence of the S9 system, compound <jats:bold>1b<\/jats:bold> showed the same cytotoxicity profile as fluconazole (1.08 times) and compound <jats:bold>1d<\/jats:bold> had 1.23 times increase in cytotoxicity. Eugenol and other evaluated compounds showed a significant increase in cytotoxicity. Our results suggest compound <jats:bold>1b<\/jats:bold> as a promising starting point candidate to be used in the design of new anti\u2010<jats:italic>Candida<\/jats:italic> agent prototypes.<\/jats:p>","DOI":"10.1111\/cbdd.14131","type":"journal-article","created":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T16:06:51Z","timestamp":1660838811000},"page":"350-363","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<scp>Anti\u2010<\/scp><i>Candida<\/i>, docking studies, and in vitro metabolism\u2010mediated cytotoxicity evaluation of Eugenol derivatives"],"prefix":"10.1111","volume":"101","author":[{"given":"Jessyca Aparecida Paes","family":"Dutra","sequence":"first","affiliation":[{"name":"Graduate Program of Pharmaceutical Sciences, Health Sciences Center Federal University of Esp\u00edrito Santo  Bonfim Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Canal","family":"Maximino","sequence":"additional","affiliation":[{"name":"Graduate Program of Pharmaceutical Sciences, Health Sciences Center Federal University of Esp\u00edrito Santo  Bonfim Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita\u00a0de\u00a0C\u00e1ssia\u00a0Ribeiro","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Graduate Program of Pharmaceutical Sciences, Health Sciences Center Federal University of Esp\u00edrito Santo  Bonfim Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Alves Bezerra","family":"Morais","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Physics, Exact, Natural and Health Sciences Center Federal University of Esp\u00edrito Santo  Guararema Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William\u00a0Cezar","family":"de Lima Silva","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Exact Sciences Center Federal University of Esp\u00edrito Santo  Goiabeiras Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Pereira","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Graduate Program of Pharmaceutical Sciences, Health Sciences Center Federal University of Esp\u00edrito Santo  Bonfim Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro Cunha","family":"Neto","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Exact Sciences Center Federal University of Esp\u00edrito Santo  Goiabeiras Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valdemar Lacerda","family":"J\u00fanior","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Exact Sciences Center Federal University of Esp\u00edrito Santo  Goiabeiras Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warley","family":"de Souza Borges","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Exact Sciences Center Federal University of Esp\u00edrito Santo  Goiabeiras Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo Rezende","family":"Kitagawa","sequence":"additional","affiliation":[{"name":"Graduate Program of Pharmaceutical Sciences, Health Sciences Center Federal University of Esp\u00edrito Santo  Bonfim Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12504"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01223-07"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)51495-2"},{"issue":"11","key":"e_1_2_8_5_1","first-page":"B4698","article-title":"Candida and Candidaemia, susceptibility and epidemiology","volume":"60","author":"Arendrup M. 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