title: The Development of Next-Generation Pyridinium-Based multiQAC Antiseptics.
abstract: A series of 18 bis- and tris-pyridinium amphiphiles were prepared and tested for both antimicrobial activity and lytic capability, in comparison with the commercially available pyridinium antiseptic cetylpyridinium chloride (CPC). Assessments were made against Gram-positive and Gram-negative bacteria, including two methicillin-resistant Staphylococcus aureus (MRSA) strains. While 2Pyr-11,11 was identified as one of the most potent antimicrobial quaternary ammonium compounds (QACs) reported to date, boasting nanomolar inhibition against five of six bacteria tested, no significant improvement in bioactivity of tris-pyridinium amphiphiles over their bis-pyridinium counterparts was observed. However, the multicationic QACs (multiQACs) presented herein did display significant advantages over the monocationic CPC; while similar red blood cell lysis was observed, superior activity against both Gram-negative bacteria and resistant S. aureus strains led to the discovery of four pyridinium-based multiQACs with advantageous therapeutic indices.
authors.affiliation: Department of Chemistry, Villanova University, 800 E. Lancaster Avenue, Villanova, PA, 19085, USA.
authors.forename: Saleh E
authors.initials: SE
authors.lastname: Al-Khalifa
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.affiliation: Department of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA, 19122, USA.
authors.forename: William M
authors.identifier: 0000-0002-5198-7744
authors.initials: WM
authors.lastname: Wuest
authors.affiliation: Department of Chemistry, Villanova University, 800 E. Lancaster Avenue, Villanova, PA, 19085, USA.
authors.forename: Kevin P C
authors.identifier: 0000-0003-4263-9833
authors.initials: KP
authors.lastname: Minbiole
mesh_terms: D000891:Anti-Infective Agents, Local / Q000737:chemistry* / Q000494:pharmacology; D002412:Cations / Q000737:chemistry; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011726:Pyridinium Compounds / Q000737:chemistry* / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000891:Anti-Infective Agents, Local; D002412:Cations; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds
keywords: antiseptics; methicillin-resistant staphylococcus aureus (MRSA); quaternary ammonium compounds