Open AccessSynthesis and Biological Activity of Highly Cationic Dendrimer Antibiotics
Author(s) -
Harrison W. VanKoten,
Wendy M. Dlakic,
Robert Engel,
Mary J. Cloninger
Publication year - 2016
Publication title -
molecular pharmaceutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.13
H-Index - 127
eISSN - 1543-8392
pISSN - 1543-8384
DOI - 10.1021/acs.molpharmaceut.6b00628
Subject(s) - dendrimer , antimicrobial , cationic polymerization , antibacterial activity , chemistry , bacteria , gram negative bacteria , microbiology and biotechnology , pathogenic bacteria , antibiotics , antibiotic resistance , amidoamine , combinatorial chemistry , escherichia coli , biology , biochemistry , organic chemistry , gene , genetics
The development of pathogenic bacteria resistant to current treatments is a major issue facing the world today. Here, the synthesis and biological activity of fourth generation poly(amidoamine) dendrimers decorated with 1-hexadecyl-azoniabicylo[2.2.2]octane (C 16 -DABCO), a quaternary ammonium compound known to have antibacterial activity, are described. This highly cationic dendrimer antibiotic was tested against several Gram positive and Gram negative strains of pathogenic bacteria and exhibited activity against both. Higher activity toward the Gram positive strains that were tested was observed. After the antimicrobial activity was assessed, E. coli and B. cereus were subjected to a resistance selection study. This study demonstrated that a multivalent approach to antimicrobial design significantly reduces the likelihood of developing bacterial resistance. Highly cationic dendrimers were also used as pretreatment of a membrane to prevent biofilm formation.