Synthesis of New Linear Guanidines and Macrocyclic Amidinourea Derivatives Endowed with High Antifungal Activity against Candida spp. and Aspergillus spp

• Published in: Journal of medicinal chemistry 2009-12, Vol.52 (23), p.7376-7379
• Main Authors: Manetti, Fabrizio, Castagnolo, Daniele, Raffi, Francesco, Zizzari, Alessandra T, Rajamäki, Suvi, D’Arezzo, Silvia, Visca, Paolo, Cona, Alessandra, Fracasso, Maria Enrica, Doria, Denise, Posteraro, Brunella, Sanguinetti, Maurizio, Fadda, Giovanni, Botta, Maurizio
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Aspergillus - drug effects; Biological and medical sciences; Candida - drug effects; Drug Design; Guanidine - analogs & derivatives; Guanidine - chemical synthesis; Guanidine - chemistry; Guanidine - pharmacology; Humans; Macrocyclic Compounds - chemical synthesis; Macrocyclic Compounds - chemistry; Macrocyclic Compounds - pharmacology; Medical sciences; Microbial Sensitivity Tests; Pharmacology. Drug treatments; Urea - analogs & derivatives; Urea - chemical synthesis; Urea - chemistry; Urea - pharmacology
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm900760k

New linear and cyclic guanidines were synthesized and tested in vitro for their antifungal activity toward clinically relevant strains of Candida species, in comparison to fluconazole. Macrocyclic compounds showed a minimum inhibitory concentration in the micromolar range and a biological activity profile in some cases better than that of fluconazole. One macrocyclic derivative was also tested against Aspergillus species and showed high antifungal activity comparable to that of amphotericin B and itraconazole.