Synthesis and Evaluation of a Series of Bis(pentylpyridinium) Compounds as Antifungal Agents
Daniel Obando, Yasuko Koda, Namfon Pantarat, Sophie Lev, Xiaoming Zuo, Johanes Bijosono Oei, Fred Widmer, Julianne Djordjevic, Tania Sorrell, Katrina Jolliffe
However, inclusion of an ortho‐substituted benzene ring in the centre of the alkyl spacer resulted in decreased cytotoxicity and hemolytic activity, while maintaining antifungal potency. Replacement of the alkyl and aromatic‐containing spacers by more hydrophilic ethylene glycol groups resulted in a loss of antifungal activity. Some of the compounds inhibited fungal PLB1 activity, but the low correlation of this inhibition with antifungal potency indicates PLB1 inhibition is unlikely to be the predominant mode of antifungal action of this class of compounds, with preliminary studies suggesting they may act via disruption of fungal mitochondrial function.
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