title: 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.
authors.affiliation: Research Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria 3216, Australia.
authors.forename: Shane M
authors.initials: SM
authors.lastname: Hickey
authors.forename: Trent D
authors.initials: TD
authors.lastname: Ashton
authors.forename: Simren K
authors.initials: SK
authors.lastname: Khosa
authors.forename: Ryan N
authors.initials: RN
authors.lastname: Robson
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: White
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Roger L
authors.initials: RL
authors.lastname: Nation
authors.forename: Heidi Y
authors.initials: HY
authors.lastname: Yu
authors.forename: Alysha G
authors.initials: AG
authors.lastname: Elliott
authors.forename: Mark S
authors.initials: MS
authors.lastname: Butler
authors.forename: Johnny X
authors.initials: JX
authors.lastname: Huang
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cooper
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Pfeffer
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002412:Cations / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D009636:Norbornanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D057786:Peptidomimetics; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D002412:Cations; D009636:Norbornanes; D057786:Peptidomimetics