Synthesis, biological evaluation and structure–activity correlation study of a series of imidazol-based compounds as Candida albicans inhibitors

• New 2-(1H-imidazol-1-yl)-1-phenylethanols were synthesized and evaluated as antifungal.
• The most active compounds possess an antifungal activity comparable or higher than Fluconazole.
• The most active compounds were synthesized and tested as pure enantiomers.
• A ligand-based computational study was carried out to rationalize the experimental data.
• Active compounds possess a low cytotoxicity on the human lung adenocarcinoma epithelial cells (A549).

A new series of 2-(1H-imidazol-1-yl)-1-phenylethanol derivatives was synthesized. The antifungal activity was evaluated in vitro against different fungal species. The biological results show that the most active compounds possess an antifungal activity comparable or higher than Fluconazole against Candida albicans, non-albicans Candida species, Cryptococcus neoformans and dermathophytes. Because of their racemic nature, the most active compounds 5f and 6c were tested as pure enantiomers. For 6c the (R)-enantiomer resulted more active than the (S)-one, otherwise for 5f the (S)-enantiomer resulted the most active. To rationalize the experimental data, a ligand-based computational study was carried out; the results of the modelling study show that (S)-5f and (R)-6c perfectly align to the ligand-based model, showing the same relative configuration. Preliminary studies on the human lung adenocarcinoma epithelial cells (A549) have shown that 6c, 5e and 5f possess a low cytotoxicity.

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