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These compounds proved to be promising antifungal compounds towards <jats:italic>Saccharomyces cerevisiae<\/jats:italic> and <jats:italic>Candida albicans<\/jats:italic>, especially in synergy with fluconazole. Simulations of docking to the cytochrome P450 14\u03b1-demethylase (azoles\u2019 primary molecular target) proved that the new <jats:bold>Ke<\/jats:bold> derivatives are capable of inhibiting this enzyme by binding to the active site. Cytotoxicity towards hACSs (human adipose-derived stromal cells) of the individual compounds was studied and the IC<jats:sub>50<\/jats:sub> values were higher than the MIC<jats:sub>50<\/jats:sub> for <jats:italic>C<\/jats:italic>. <jats:italic>albicans<\/jats:italic> and <jats:italic>S<\/jats:italic>. <jats:italic>cerevisiae<\/jats:italic>. <jats:bold>KeP<\/jats:bold> and <jats:bold>KeOP<\/jats:bold> increased the level of the p21 gene transcript but did not change the level of p53 gene transcript, a major regulator of apoptosis, and decreased the mitochondrial membrane potential. Taken together, the results advocate that the new ketoconazole derivatives have a similar mechanism of action and block the lanosterol 14\u03b1-demethylase and thus inhibit the production of ergosterol in <jats:italic>C<\/jats:italic>. <jats:italic>albicans<\/jats:italic> membranes.<\/jats:p>","DOI":"10.1038\/s41598-019-52525-7","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T11:05:29Z","timestamp":1573124729000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["New diphenylphosphane derivatives of ketoconazole are promising antifungal agents"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9748-7083","authenticated-orcid":false,"given":"Rodrigo F. 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