TY - JOUR
T1 - 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
AU - La Regina, Giuseppe
AU - D'Auria, Felicia Diodata
AU - Tafi, Andrea
AU - Piscitelli, Francesco
AU - Olla, Stefania
AU - Caporuscio, Fabiana
AU - Nencioni, Lucia
AU - Cirilli, Roberto
AU - La Torre, Francesco
AU - De Melo, Nadja Rodrigues
AU - Kelly, Steven L.
AU - Lamb, David C.
AU - Artico, Marino
AU - Botta, Maurizio
AU - Palamara, Anna Teresa
AU - Silvestri, Romano
PY - 2008/7/10
Y1 - 2008/7/10
N2 - 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.
AB - 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.
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U2 - 10.1021/jm800009r
DO - 10.1021/jm800009r
M3 - Article
C2 - 18529046
AN - SCOPUS:46849105237
VL - 51
SP - 3841
EP - 3855
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 13
ER -