2. Academic Validation
  3. 1-[(3-Aryloxy-3-aryl)propyl]-1H-imidazoles, new imidazoles with potent activity against Candida albicans and dermatophytes. Synthesis, structure-activity relationship, and molecular modeling studies

1-[(3-Aryloxy-3-aryl)propyl]-1H-imidazoles, new imidazoles with potent activity against Candida albicans and dermatophytes. Synthesis, structure-activity relationship, and molecular modeling studies

  • J Med Chem. 2008 Jul 10;51(13):3841-55. doi: 10.1021/jm800009r.
Giuseppe La Regina 1,  Felicia Diodata D'Auria,  Andrea Tafi,  Francesco Piscitelli,  Stefania Olla,  Fabiana Caporuscio,  Lucia Nencioni,  Roberto Cirilli,  Francesco La Torre,  Nadja Rodrigues De Melo,  Steven L Kelly,  David C Lamb,  Marino Artico,  Maurizio Botta,  Anna Teresa Palamara,  Romano Silvestri
Affiliations

Affiliation

  • 1 Dipartimento di Studi Farmaceutici, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
PMID: 18529046 DOI: 10.1021/jm800009r
Abstract

New 1-[(3-aryloxy-3-aryl)propyl]-1 H-imidazoles were synthesized and evaluated against Candida albicans and dermatophytes in order to develop structure-activity relationships (SARs). Against C. albicans the new imidazoles showed minimal inhibitory concentrations (MICs) comparable to those of ketoconazole, miconazole, and econazole, and were more potent than fluconazole. Several derivatives ( 10, 12, 14, 18- 20, 24, 28, 29, 30, and 34) turned out to be potent inhibitors of C. albicans strains resistant to fluconazole, with MIC values less than 10 microg/mL. Against dermatophytes strains, compounds 20, 25, and 33 (MIC <or= 5 microg/mL) were equipotent to ketoconazole, econazole, and miconazole. SARs of imidazoles 10- 44 were rationalized with reasonable accuracy by a previously developed quantitative pharmacophore for Antifungal agents.

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