Chimeric Amphiphilic Disinfectants: Quaternary Ammonium/Quaternary Phosphonium Hybrid Structures

Chimeric Amphiphilic Disinfectants: Quaternary Ammonium/Quaternary Phosphonium Hybrid Structures

Cationic biocides play a crucial role in the disinfection of domestic and healthcare surfaces. Due to the rise of bacterial resistance towards common cationic disinfectants like quaternary ammonium compounds (QACs), the development of novel actives is necessary for effective infection prevention and...

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Bibliographic Details
Published in:ChemMedChem Vol. 19; no. 11; pp. e202300718 - n/a
Main Authors: Leatherbury, Moneya S., Thierer, Laura M., Sanchez, Christian A., Vargas‐Cuebas, Germán G., Petersen, Ashley A., Amoo, Lauren E., Bezold, Elise L., Washington, Keshyne C., Mistrot, M. Brody, Zdilla, Michael J., Wuest, William M., Minbiole, Kevin P. C.
Format: Journal Article
Language:English
Published: Germany Wiley Subscription Services, Inc 03-06-2024
Subjects:
Ammonium
Ammonium compounds
Amphiphiles
Antibacterial activity
Antiinfectives and antibacterials
Antimicrobial activity
Antiseptics
Biocides
Biological activity
Cationic Biocide
Cations
Chimera
Disinfectants
Disinfection & disinfectants
Drug resistance
Hybrid structures
Lysis
Opportunist infection
QPC
Quaternary ammonium compounds
Quaternary ammonium salts
Quaternary Phosphonium Compounds
Strains (organisms)
Disinfectants
Cationic Biocide
QPC
Amphiphiles
Chimera
Quaternary Phosphonium Compounds
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Summary:Cationic biocides play a crucial role in the disinfection of domestic and healthcare surfaces. Due to the rise of bacterial resistance towards common cationic disinfectants like quaternary ammonium compounds (QACs), the development of novel actives is necessary for effective infection prevention and control. Toward this end, a series of 15 chimeric biscationic amphiphilic compounds, bearing both ammonium and phosphonium residues, were prepared to probe the structure and efficacy of mixed cationic ammonium‐phosphonium structures. Compounds were obtained in two steps and good yields, with straightforward and chromatography‐free purifications. Antibacterial activity evaluation of these compounds against a panel of seven bacterial strains, including two MRSA strains as well as opportunistic pathogen A. baumannii, were encouraging, as low micromolar inhibitory activity was observed for multiple structures. Alkyl chain length on the ammonium group was, as expected, a major determinant of bioactivity. In addition, high therapeutic indexes (up to 125‐fold) for triphenyl phosphonium‐bearing amphiphiles were observed when comparing antimicrobial activity to mammalian cell lysis activity. The Minbiole/Wuest collaboration has prepared a series of chimeric quaternary phosphonium/ammonium compounds as novel amphiphilic disinfectant leads. These compounds, examined with x‐ray crystallography and charge density analysis, proved to be potent antimicrobials with favorable therapeutic indices.
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ISSN:1860-7179
1860-7187
1860-7187
DOI:10.1002/cmdc.202300718