Studies on the antifungal properties of N-thiolated β-lactams

• Published in: Bioorganic & medicinal chemistry Vol. 16; no. 16; pp. 7832 - 7837
• Main Authors: O’Driscoll, Marci, Greenhalgh, Kerriann, Young, Ashley, Turos, Edward, Dickey, Sonja, Lim, Daniel V.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.08.2008; Elsevier Science
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal activity; Antifungal agents; Antifungal Agents - pharmacology; Bacillus anthracis; beta-Lactams - pharmacology; Biological and medical sciences; Candida; Candida - drug effects; Candida albicans; Fungistatic activity; Immunodiffusion; Medical sciences; Microbial Sensitivity Tests; Microscopy, Electron, Transmission; N-Thiolated β-lactams; Pharmacology. Drug treatments; Staphylococcus aureus; Structure-Activity Relationship; Sulfhydryl Compounds - pharmacology; Trypan Blue - chemistry; Candida albicans; Antifungal activity; N-Thiolated β-lactams; Fungistatic activity; Four membered ring; Sulfur Organic compounds; Nitrogen heterocycle; Pesticides; Benzene derivatives; Lactam; In vitro; Fungicide; Fungi; Antifungal agent; Structure activity relation; Chlorine Organic compounds; Fungi Imperfecti
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2008.06.035

Investigations into the antifungal properties of N-thiolated β-lactams are described. N-Thiolated β-lactams had previously been shown to have antibacterial activity against a narrow selection of pathogenic bacteria including Staphylococcus aureus and Bacillus anthracis, as well as apoptotic-inducing activity in a variety of human cancer cell lines. We now have found that these lactams also possess antifungal activity against Candida and other fungi by exerting powerful cytostatic effects that disrupt the structural integrity of cytoplasmic membranes. The mode of action and structure–activity trends of these lactams as antifungals parallel that previously seen in our antibacterial studies.