Synthesis, antifungal, haemolytic and cytotoxic activities of a series of bis(alkylpyridinium)alkanes

• Published in: Bioorganic & medicinal chemistry Vol. 17; no. 17; pp. 6329 - 6339
• Main Authors: Obando, Daniel, Pantarat, Namfon, Handke, Rosemary, Koda, Yasuko, Widmer, Fred, Djordjevic, Julianne T., Ellis, David H., Sorrell, Tania C., Jolliffe, Katrina A.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.09.2009; Elsevier
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal activity; Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - toxicity; Biological and medical sciences; Bispyridinium; Candida albicans; Candida albicans - drug effects; Cryptococcus neoformans; Cryptococcus neoformans - drug effects; Fungal phospholipase B; Haemolytic activity; Hemolysis; Lysophospholipase - antagonists & inhibitors; Lysophospholipase - metabolism; Medical sciences; Microbial Sensitivity Tests; Pharmacology. Drug treatments; Phospholipase A2 Inhibitors; Phospholipases A2 - metabolism; Pyridinium Compounds - chemical synthesis; Pyridinium Compounds - chemistry; Pyridinium Compounds - toxicity; Swine; Antifungal activity; Bispyridinium; Fungal phospholipase B; Haemolytic activity; Candida albicans; Hemolysis; Organic cation; Cryptococcus neoformans; Enzyme; Toxicity; Red blood cell; Cytotoxicity; Esterases; In vitro; Biological activity; Carboxylic ester hydrolases; Fungi; Antifungal agent; Pyridinium compounds; Lysophospholipase; Hydrolases; Fungi Imperfecti; Chemical synthesis; Organic dication
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2009.07.037

A series of bis(alkylpyridinium)alkanes have been synthesised and their antifungal activity has been evaluated. A series of bis(alkylpyridinium)alkanes with a twelve carbon spacer between the positive charges was synthesised and their antifungal activity has been investigated. Compounds with 2-pentyl, 4-pentyl, 4-hexyl, 4-octyl, 4-propylbenzene, 3,4-dipentyl, 4-(5′-nonyl) and 3-methyl,4-pentyl head groups were the most potent antifungal agents with MICs in the range of 1.4–2.7 μM against reference strains of both Cryptococcus neoformans and Candida albicans.