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 microg/mL. Against dermatophytes strains, compounds 20, 25, and 33 (MIC e 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.
1-[(3-Aryloxy-3-aryl)propyl]-2H-imidazoles, new imidazoles with potent activity against Candida albicans and dermatophytes. Synthesis, structure-activity relationship, and molecular modeling studies / LA REGINA, Giuseppe; D'Auria, Felicia Diodata; Tafi, A; Piscitelli, Francesco; Olla, S; Caporuscio, F; Nencioni, Lucia; Cirilli, R; La Torre, R; De Melo N., R; Kelly S., L; Lamb D., C; Artico, Marino; Botta, M; Palamara, ANNA TERESA; Silvestri, Romano. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 51:(2008), pp. 3841-3855. [10.1021/jm800009r]
1-[(3-Aryloxy-3-aryl)propyl]-2H-imidazoles, new imidazoles with potent activity against Candida albicans and dermatophytes. Synthesis, structure-activity relationship, and molecular modeling studies
LA REGINA, GIUSEPPE;D'AURIA, Felicia Diodata;PISCITELLI, FRANCESCO;NENCIONI, Lucia;ARTICO, Marino;PALAMARA, ANNA TERESA;SILVESTRI, Romano
2008
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 microg/mL. Against dermatophytes strains, compounds 20, 25, and 33 (MIC e 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
