Synthesis and evaluation of cationic norbornanes as peptidomimetic antibacterial agents

Date

2015

Authors

Hickey, S.M.
Ashton, T.D.
Khosa, S.K.
Robson, R.N.
White, J.M.
Li, J.
Nation, R.L.
Yu, H.Y.
Elliott, A.G.
Butler, M.S.

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Journal article

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Organic and Biomolecular Chemistry, 2015; 13(22):6225-6241

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Abstract

A series of structurally amphiphilic biscationic norbornanes have been synthesised as rigidified, low molecular weight peptidomimetics of cationic antimicrobial peptides. A variety of charged hydrophilic functionalities were attached to the norbornane scaffold including aminium, guanidinium, imidazolium and pyridinium moieties. Additionally, a range of hydrophobic groups of differing sizes were incorporated through an acetal linkage. The compounds were evaluated for antibacterial activity against both Gram-negative and Gram-positive bacteria. Activity was observed across the series; the most potent of which exhibited an MIC's ≤ 1 μg mL(-1) against Streptococcus pneumoniae, Enterococcus faecalis and several strains of Staphylococcus aureus, including multi-resistant methicillin resistant (mMRSA), glycopeptide-intermediate (GISA) and vancomycin-intermediate (VISA) S. aureus.

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Data source: Supplementary information, http://pubs.rsc.org.access.library.unisa.edu.au/en/Content/ArticleLanding/2015/OB/C5OB00621J#!divAbstract

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Copyright 2015 Royal Society of Chemistry

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