Open AccessAmide Moieties Modulate the Antimicrobial Activities of Conjugated Oligoelectrolytes against Gram‐negative Bacteria
Author(s) -
Limwongyut Jakkarin,
Moreland Alex S.,
Nie Chenyao,
Read de Alaniz Javier,
Bazan Guillermo C.
Publication year - 2022
Publication title -
chemistryopen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.644
H-Index - 29
ISSN - 2191-1363
DOI - 10.1002/open.202100260
Subject(s) - antimicrobial , chemistry , conjugated system , cytotoxicity , escherichia coli , gram negative bacteria , bacteria , combinatorial chemistry , cationic polymerization , amide , biochemistry , in vitro , organic chemistry , biology , genetics , gene , polymer
Cationic conjugated oligoelectrolytes (COEs) are a class of compounds that can be tailored to achieve relevant in vitro antimicrobial properties with relatively low cytotoxicity against mammalian cells. Three distyrylbenzene‐based COEs were designed containing amide functional groups on the side chains. Their properties were compared to two representative COEs with only quaternary ammonium groups. The optimal compound, COE2−3C−C3‐Apropyl , has an antimicrobial efficacy against Escherichia coli with an MIC=2 μg mL −1 , even in the presence of human serum albumin low cytotoxicity (IC 50 =740 μg mL −1 ) and minimal hemolytic activity. Moreover, we find that amide groups increase interactions between COEs and a bacterial lipid mimic based on calcein leakage assay and allow COEs to readily permeabilize the cytoplasmic membrane of E. coli . These findings suggest that hydrogen bond forming moieties can be further applied in the molecular design of antimicrobial COEs to further improve their selectivity towards bacteria.