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

Giuseppe La Regina, 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

Research output: Contribution to journalArticlepeer-review

Abstract

New 1-[(3-aryloxy-3-aryl)propyl]-1H-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 μg/mL. Against dermatophytes strains, compounds 20, 25, and 33 (MIC ≤ 5 μg/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.

Original languageEnglish
Pages (from-to)3841-3855
Number of pages15
JournalJournal of Medicinal Chemistry
Volume51
Issue number13
DOIs
Publication statusPublished - Jul 10 2008

ASJC Scopus subject areas

  • Organic Chemistry

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