Imidazole analogues of fluoxetine, a novel class of anti-Candida agents.
Imidazole analogues of fluoxetine have been obtained by replacing the methylamino terminus of aminopropane chain with the imidazole ring. The newly designed imidazoles showed potent anti-Candida activity, superior to those of miconazole and other antifungal agents of clinical interest. 1-(4-Chlorophenyl)-1-(2,4-dichlorophenoxy)-3-(1H-imidazol-1-yl)propane (16), the most active among test imidazoles, was about 2-fold more active and as much less cytotoxic than miconazole. High increase of activity was observed with methyl, nitro, fluorine, and chlorine (Cl > F > CH(3) > NO(2) > CF(3)).
Silvestri
Romano
R
Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Università degli Studi di Roma La Sapienza, P.le A. Moro 5, I-00185 Roma, Italy. romano.silvestri@uniroma1.it
Artico
Marino
M
La Regina
Giuseppe
G
Di Pasquali
Alessandra
A
De Martino
Gabriella
G
D'Auria
Felicia Diodata
FD
Nencioni
Lucia
L
Palamara
Anna Teresa
AT
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005473:Fluoxetine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D007093:Imidazoles; D005473:Fluoxetine