Issue 22, 2015

Synthesis and evaluation of cationic norbornanes as peptidomimetic antibacterial agents

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.

Graphical abstract: Synthesis and evaluation of cationic norbornanes as peptidomimetic antibacterial agents

Supplementary files

Article information

Article type
Paper
Submitted
30 Mar 2015
Accepted
27 Apr 2015
First published
27 Apr 2015

Org. Biomol. Chem., 2015,13, 6225-6241

Author version available

Synthesis and evaluation of cationic norbornanes as peptidomimetic antibacterial agents

S. M. Hickey, T. D. Ashton, S. K. Khosa, R. N. Robson, J. M. White, J. Li, R. L. Nation, H. Y. Yu, A. G. Elliott, M. S. Butler, J. X. Huang, M. A. Cooper and F. M. Pfeffer, Org. Biomol. Chem., 2015, 13, 6225 DOI: 10.1039/C5OB00621J

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