title: The antimicrobial activity of mono-, bis-, tris-, and tetracationic amphiphiles derived from simple polyamine platforms.
abstract: A series of 34 amphiphilic compounds varying in both number of quaternary ammonium groups and length of alkyl chains has been assembled. The synthetic preparations for these structures are simple and generally high-yielding, proceeding in 1-2 steps without the need for chromatography. Antibacterial MIC data for these compounds were determined, and over half boast single digit MIC values against a series of gram-positive and gram-negative bacteria. MIC variation mostly hinged on the length of the alkyl chain, where a dodecyl group led to optimal activity; surprisingly, the number of cations and/or basic nitrogens was less important in dictating bioactivity. Additional structural variation was prepared in a trisamine series dubbed 12,3,X,3,12, providing a series of potent amphiphiles functionalized with varied allyl, alkyl, and benzyl groups. Tetraamines were also investigated, culminating in a two-step preparation of a tetracationic structure that showed only modestly improved bioactivity versus amphiphiles with two or three cations.
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, Temple University, Philadelphia, PA 19122, United States.
authors.forename: Megan C
authors.initials: MC
authors.lastname: Jennings
authors.affiliation: Department of Chemistry, Villanova University, Villanova, PA 19085, United States.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Shanahan
authors.affiliation: Department of Chemistry, Villanova University, Villanova, PA 19085, United States.
authors.forename: Maureen D
authors.initials: MD
authors.lastname: Joyce
authors.affiliation: Department of Chemistry, Villanova University, Villanova, PA 19085, United States.
authors.forename: Celina N
authors.initials: CN
authors.lastname: Santiago
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.
authors.forename: Kevin P C
authors.initials: KPC
authors.lastname: Minbiole
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002412:Cations / Q000737:chemistry; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011073:Polyamines / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D002412:Cations; D011073:Polyamines; D000644:Quaternary Ammonium Compounds
keywords: Amphiphile; Antibacterial; Biscationic; Tetracationic; Triscationic