1-[(3-Aryloxy-3-aryl)propyl]-1H-imidazoles, New Imidazoles with Potent Activity againstCandida albicansand Dermatophytes. Synthesis, Structure−Activity Relationship, and Molecular Modeling Studies
| Autor: | Giuseppe La Regina, Anna Teresa Palamara, Lucia Nencioni, Steven L. Kelly, Nadja Rodrigues de Melo, Maurizio Botta, Romano Silvestri, Marino Artico, Francesco La Torre, Fabiana Caporuscio, Stefania Olla, Roberto Cirilli, D'Auria Fd, David C. Lamb, Francesco Piscitelli, Andrea Tafi |
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| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Antifungal Agents Econazole Cell Survival Stereochemistry medicine.disease_cause Chemical synthesis Structure-Activity Relationship Cell Line Tumor Candida albicans Drug Discovery medicine Humans Computer Simulation Molecular Structure biology Chemistry Arthrodermataceae Imidazoles Stereoisomerism biology.organism_classification Corpus albicans Dermatophyte Molecular Medicine Ketoconazole Miconazole Fluconazole medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 51:3841-3855 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm800009r |
| Popis: | 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 (MICor= 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. |
| Databáze: | OpenAIRE |
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