Synthesis, antifungal and haemolytic activity of a series of bis(pyridinium)alkanes

• Published in: Bioorganic & medicinal chemistry Vol. 15; no. 10; pp. 3422 - 3429
• Main Authors: Ng, Clarissa K.L., Singhal, Vatsala, Widmer, Fred, Wright, Lesley C., Sorrell, Tania C., Jolliffe, Katrina A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.05.2007; Elsevier Science
• Subjects: Alkanes - chemical synthesis; Alkanes - pharmacology; Amphotericin B - pharmacology; Anti-Infective Agents, Local - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal activity; Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - pharmacology; Biological and medical sciences; Bispyridinium; Candida albicans - drug effects; Cryptococcus neoformans - drug effects; Dequalinium - pharmacology; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; Fungal phospholipase B1; Fungi - drug effects; Fungi - enzymology; Haemolytic activity; Hemolytic Agents - chemical synthesis; Hemolytic Agents - pharmacology; Humans; In Vitro Techniques; Indicators and Reagents; Magnetic Resonance Spectroscopy; Medical sciences; Microbial Sensitivity Tests; Mycoses - microbiology; Pharmacology. Drug treatments; Phospholipases - antagonists & inhibitors; Pyridines - pharmacology; Pyridinium Compounds - chemical synthesis; Pyridinium Compounds - pharmacology; Structure-Activity Relationship; Antifungal activity; Bispyridinium; Fungal phospholipase B1; Haemolytic activity; Candida albicans; Organic cation; Cryptococcus neoformans; Toxicity; Cytotoxicity; Esterases; Fungi; Antifungal agent; Pyridinium compounds; Structure activity relation; Fungi Imperfecti; Chemical synthesis; Thallophyta; Human; Hemolysis; Enzyme; Aliphatic compound; Iminium compounds; Red blood cell; Enzyme inhibitor; In vitro; Phospholipase; Octenidine; Fungal phospholipase Bl; Hydrolases; Organic dication
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2007.03.018

A series of bis(pyridinium)alkanes have been prepared and their antifungal activity, haemolytic activity and ability to inhibit fungal phospholipase B1 have been investigated, together with those of the commercially available antiseptics octenidine and dequalinium. Removal of the amino substituents from the pyridinium rings resulted in a significant decrease in antifungal activity. However, shortening or removing the alkyl chains attached to the amino groups had little effect on antifungal activity and significantly reduced haemolytic activity. Only octenidine was a strong inhibitor of fungal phospholipase B1.