Imidazole Analogues of Fluoxetine, a Novel Class of Anti-Candida Agents

• Published in: Journal of medicinal chemistry Vol. 47; no. 16; pp. 3924 - 3926
• Main Authors: Silvestri, Romano, Artico, Marino, La Regina, Giuseppe, Di Pasquali, Alessandra, De Martino, Gabriella, D'Auria, Felicia Diodata, Nencioni, Lucia, Palamara, Anna Teresa
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 29.07.2004; Amer Chemical Soc
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Biological and medical sciences; Candida albicans - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Chemistry, Medicinal; Fluoxetine - analogs & derivatives; Fluoxetine - chemical synthesis; Fluoxetine - pharmacology; Humans; Imidazoles - chemical synthesis; Imidazoles - pharmacology; Life Sciences & Biomedicine; Medical sciences; Microbial Sensitivity Tests; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Structure-Activity Relationship; ANTIFUNGAL AGENTS; ANTIBACTERIAL; Candida albicans; Five membered ring; Ether; Nitrogen heterocycle; Benzene derivatives; In vitro; Fungi; Antifungal agent; Structure activity relation; Chlorine Organic compounds; Fungi Imperfecti; Chemical synthesis; Thallophyta
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm049856v

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 > CH3 > NO2 > CF3).