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

Francesca Moraca, Daniela De Vita, Fabiana Pandolfi, Roberto Di Santo, Roberta Costi, Roberto Cirilli, Felicia Diodata D'Auria, Simona Panella, Anna Teresa Palamara, Giovanna Simonetti, Maurizio Botta, Luigi Scipione

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)665-673
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Volume83
DOIs
Publication statusPublished - Aug 18 2014

Keywords

  • Antifungal
  • Azole derivatives
  • Enantioselective synthesis
  • Ligand-based drug design

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology
  • Medicine(all)

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