Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/114311
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Type: Journal article
Title: Synthesis and evaluation of a series of bis(pentylpyridinium) compounds as antifungal agents
Author: Obando, D.
Koda, Y.
Pantarat, N.
Lev, S.
Zuo, X.
Bijosono Oei, J.
Widmer, F.
Djordjevic, J.
Sorrell, T.
Jolliffe, K.
Citation: ChemMedChem, 2018; 13(14):1421-1436
Publisher: Wiley
Issue Date: 2018
ISSN: 1860-7179
1860-7187
Statement of
Responsibility: 
Daniel Obando, Yasuko Koda, Namfon Pantarat, Sophie Lev, Xiaoming Zuo, Johanes Bijosono Oei, Fred Widmer, Julianne T. Djordjevic, Tania C. Sorrell and Katrina A. Jolliffe
Abstract: A series of bis(4-pentylpyridinium) compounds with a variety of spacers between the pyridinium headgroups was synthesised and their antifungal activity has been investigated. Lengthening the alkyl spacer between the pentylpyridinium headgroups from twelve to sixteen methylene units resulted in increased antifungal activity against C. neoformans and C. albicans, but also resulted in increased hemolytic activity and cytotoxicity against mammalian cells. However, inclusion of an ortho-substituted benzene ring in the centre of the alkyl spacer resulted in reduced 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.
Keywords: Antifungal agents; bispyridinium compounds; haemolytic activity; medicinal chemistry; structure-activity relationships
Rights: © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
RMID: 0030088800
DOI: 10.1002/cmdc.201800331
Grant ID: http://purl.org/au-research/grants/nhmrc/402413
Appears in Collections:Medicine publications

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