Amide Moieties Modulate the Antimicrobial Activities of Conjugated Oligoelectrolytes against Gram-negative Bacteria

Abstract

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 (IC50=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.

ICB Affiliated Authors

Authors
Jakkarin Limwongyut, Dr. Alex S. Moreland, Dr. Chenyao Nie, Prof. Javier Read de Alaniz, Prof. Guillermo C. Bazan
Date
Type
Peer-Reviewed Article
Journal
Chemistry Open
Volume
11
Number
2
Pages
e202100260