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The Development of Next‐Generation Pyridinium‐Based multiQAC Antiseptics
Author(s) -
AlKhalifa Saleh E.,
Jennings Megan C.,
Wuest William M.,
Minbiole Kevin P. C.
Publication year - 2017
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201600546
Subject(s) - pyridinium , cetylpyridinium chloride , antimicrobial , antiseptic , staphylococcus aureus , bacteria , pyridinium compounds , chemistry , microbiology and biotechnology , biochemistry , biology , organic chemistry , pulmonary surfactant , genetics
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.