title: Biofilm-eradicating properties of quaternary ammonium amphiphiles: simple mimics of antimicrobial peptides.
abstract: Bacterial biofilms are difficult to eradicate because of reduced antibiotic sensitivity and altered metabolic processes; thus, the development of new approaches to biofilm eradication is urgently needed. Antimicrobial peptides (AMPs) and quaternary ammonium cations (QACs) are distinct, yet well-known, classes of antibacterial compounds. By mapping the general regions of charge and hydrophobicity of QACs onto AMP structures, we designed a small library of QACs to serve as simple AMP mimics. In order to explore the role that cationic charge plays in biofilm eradication, structures were varied with respect to cationic character, distribution of charge, and alkyl side chain. The reported compounds possess minimum biofilm eradication concentrations (MBEC) as low as 25 μM against Gram-positive biofilms, making them the most active anti-biofilm structures reported to date. These potent AMP mimics were synthesized in 1-2 steps and hint at the minimal structural requirements for biofilm destruction.
authors.affiliation: Department of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA 19122 (USA).
authors.forename: Megan C
authors.initials: MC
authors.lastname: Jennings
authors.forename: Laura E
authors.initials: LE
authors.lastname: Ator
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Paniak
authors.forename: Kevin P C
authors.initials: KP
authors.lastname: Minbiole
authors.forename: William M
authors.initials: WM
authors.lastname: Wuest
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D000644:Quaternary Ammonium Compounds; D013501:Surface-Active Agents
keywords: amphiphile; antibacterial; antimicrobial peptide; biofilm; biological activity