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

G. LA REGINA
F. D'AURIA
F. PISCITELLI
S. OLLA
F. CAPORUSCIO
L. NENCIONI
R. CIRILLI
F. LA TORRE
N. RODRIGUES DE MELO
S. KELLY
D. LAMB
M. ARTICO
A. PALAMARA
R. SILVESTRI
TAFI, ANDREA
BOTTA, MAURIZIO

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Publication date

January 2008

DOI

10.1021/jm800009r

Publisher

American Chemical Society (ACS)

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...