title: Synthesis, biological evaluation and structure-activity correlation study of a series of imidazol-based compounds as Candida albicans inhibitors.
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.
authors.affiliation: Department of "Biotecnologie, Chimica e Farmacia", "Università degli Studi di Siena", Via A. Moro 2, 53100 Siena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Moraca
authors.affiliation: Department of "Chimica e Tecnologie del Farmaco", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: De Vita
authors.affiliation: Department of "Chimica e Tecnologie del Farmaco", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Pandolfi
authors.affiliation: Department of "Chimica e Tecnologie del Farmaco", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy; "Istituto Pasteur-Fondazione Cenci Bolognetti", Department of "Chimica e Tecnologie del Farmaco", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Santo
authors.affiliation: Department of "Chimica e Tecnologie del Farmaco", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy; "Istituto Pasteur-Fondazione Cenci Bolognetti", Department of "Chimica e Tecnologie del Farmaco", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Costi
authors.affiliation: "Dipartimento del Farmaco", Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cirilli
authors.affiliation: Department of "Sanità Pubblica e Malattie Infettive", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy.
authors.forename: Felicia Diodata
authors.initials: FD
authors.lastname: D'Auria
authors.affiliation: Department of "Sanità Pubblica e Malattie Infettive", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Panella
authors.affiliation: Department of "Sanità Pubblica e Malattie Infettive", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy.
authors.forename: Anna Teresa
authors.initials: AT
authors.lastname: Palamara
authors.affiliation: Department of "Sanità Pubblica e Malattie Infettive", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Simonetti
authors.affiliation: Department of "Biotecnologie, Chimica e Farmacia", "Università degli Studi di Siena", Via A. Moro 2, 53100 Siena, Italy. Electronic address: maurizio.botta@unisi.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
authors.affiliation: Department of "Chimica e Tecnologie del Farmaco", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy. Electronic address: Luigi.scipione@uniroma1.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Scipione
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002176:Candida albicans / Q000187:drug effects* / Q000201:enzymology; D002460:Cell Line; D060326:Chemistry Techniques, Synthetic; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D008958:Models, Molecular; D011487:Protein Conformation; D058886:Sterol 14-Demethylase / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D007093:Imidazoles; C029899:imidazole; D058886:Sterol 14-Demethylase
keywords: Antifungal; Azole derivatives; Enantioselective synthesis; Ligand-based drug design