New diphenylphosphane derivatives of ketoconazole are promising antifungal agents.

ABSTRACT: Four new derivatives of ketoconazole (Ke) were synthesized: diphenylphosphane (KeP), and phosphane chalcogenides: oxide (KeOP), sulphide (KeSP) and selenide (KeSeP). These compounds proved to be promising antifungal compounds towards Saccharomyces cerevisiae and Candida albicans, especially in synergy with fluconazole. Simulations of docking to the cytochrome P450 14α-demethylase (azoles' primary molecular target) proved that the new Ke 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 IC₅₀ values were higher than the MIC₅₀ for C. albicans and S. cerevisiae. KeP and KeOP increased the level of the p21 gene transcript but did n

SUBMITTER: de Almeida RFM 

PROVIDER: S-EPMC6838151 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature