Synthesis and evaluation of cationic norbornanes as peptidomimetic antibacterial agents

Shane M Hickey, Trent Damon Ashton, Simren K Khosa, Ryan N Robson, Jonathan White, Jian Li, Roger Leigh Nation, Heidi Yu, Alysha G Elliott, Mark S Butler, Johnny X Huang, Matthew A Cooper, Frederick Matthew Pfeffer

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

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 ?g 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.
Original languageEnglish
Pages (from-to)6225 - 6241
Number of pages17
JournalOrganic & Biomolecular Chemistry
Volume13
Issue number22
DOIs
Publication statusPublished - 2015

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