title: TMEDA-derived biscationic amphiphiles: An economical preparation of potent antibacterial agents.
abstract: Bis-alkylated derivatives of N,N,N',N'-tetramethylethylenediamine (TMEDA) represent a well-known class of versatile biscationic amphiphiles, owing to their low cost and ease of preparation. Asymmetric TMEDA derivatives, however, have been studied significantly less, particularly in regards to their antimicrobial properties. We have thus prepared a series of 36 mono- and bis-alkylated TMEDA derivatives to evaluate their inhibition of bacterial growth. This series of compounds showed low micromolar activity against a panel of four bacteria. Optimal inhibition was observed when the biscationic amphiphiles possessed modest asymmetry and were composed of between 20 and 24 total carbon atoms in the side chains. These amphiphiles were prepared in a simple two-step procedure, utilizing inexpensive materials and atom-economical reactions, making them practical for further development.
authors.affiliation: Department of Chemistry, Villanova University, Villanova, PA 19085, United States.
authors.forename: Jacob W
authors.initials: JW
authors.lastname: Black
authors.affiliation: Department of Chemistry, Temple University, Philadelphia, PA 19122, United States.
authors.forename: Megan C
authors.initials: MC
authors.lastname: Jennings
authors.affiliation: Department of Chemistry, Temple University, Philadelphia, PA 19122, United States.
authors.forename: Julianne
authors.initials: J
authors.lastname: Azarewicz
authors.affiliation: Department of Chemistry, Villanova University, Villanova, PA 19085, United States.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Paniak
authors.affiliation: Department of Chemistry, Villanova University, Villanova, PA 19085, United States.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Grenier
authors.affiliation: Department of Chemistry, Temple University, Philadelphia, PA 19122, United States.
authors.forename: William M
authors.initials: WM
authors.lastname: Wuest
authors.affiliation: Department of Chemistry, Villanova University, Villanova, PA 19085, United States. Electronic address: kevin.minbiole@villanova.edu.
authors.forename: Kevin P C
authors.initials: KP
authors.lastname: Minbiole
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; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000254:growth & development; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development; D005029:Ethylenediamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D002412:Cations; D005029:Ethylenediamines; D013501:Surface-Active Agents; C005798:N,N,N',N'-tetramethylethylenediamine
keywords: Amphiphile; Antibacterial; Antiseptic; Asymmetric; TMEDA