Molecular design of antimicrobial conjugated oligoelectrolytes with enhanced selectivity toward bacterial cells.

Journal: Chemical science
Published Date:

Abstract

A series of cationic conjugated oligoelectrolytes (COEs) was designed to understand how variations in molecular dimensions impact the relative activity against bacteria and mammalian cells. These COEs kept a consistent distyrylbenzene framework but differed in the length of linker between the core and the cationic site and the length of substitute on the quaternary ammonium functioned group. Their antimicrobial efficacy, mammalian cell cytotoxicity, hemolytic activity, and cell association were determined. We find that hydrophobicity is a factor that controls the degree of COE association to cells, but efficacy and cytotoxicity depend on more subtle structural features. was found to be the optimal structure with a minimum inhibitory concentration (MIC) of 4 μg mL against K12, low cytotoxicity against HepG2 cells and negligible hemolysis of red blood cells, even at 1024 μg mL. A time-kill kinetics study of against K12 demonstrates bactericidal activity. These findings provide the first systematic investigation of how COEs may be modulated to achieve low mammalian cell cytotoxicity with the long-range perspective of finding candidates suitable for developing a broad-spectrum antimicrobial agent.

Authors

  • Jakkarin Limwongyut
    Center for Polymers and Organic Solids, Department of Chemistry and Biochemistry, University of California Santa Barbara CA 93106 USA bazan@chem.ucsb.edu.
  • Chenyao Nie
    Departments of Chemistry and Chemical Engineering, National University of Singapore 117543 Singapore niechenyao@nus.edu.sg.
  • Alex S Moreland
    Center for Polymers and Organic Solids, Department of Chemistry and Biochemistry, University of California Santa Barbara CA 93106 USA bazan@chem.ucsb.edu.
  • Guillermo C Bazan
    Center for Polymers and Organic Solids, Department of Chemistry and Biochemistry, University of California Santa Barbara CA 93106 USA bazan@chem.ucsb.edu.

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