Synthesis and Biological Activity of Highly Cationic Dendrimer Antibiotics.
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 (C16-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.
Department of Chemistry and Biochemistry, Montana State University , 103 Chemistry and Biochemistry Building, Bozeman, Montana 59717, United States.
Harrison W
HW
VanKoten
Department of Chemistry and Biochemistry, Montana State University , 103 Chemistry and Biochemistry Building, Bozeman, Montana 59717, United States.
Wendy M
WM
Dlakic
Department of Chemistry and Biochemistry, Queens College, City University of New York , 65-30 Kissena Boulevard, Queens, New York 11367, United States.
Robert
R
Engel
Department of Chemistry and Biochemistry, Montana State University , 103 Chemistry and Biochemistry Building, Bozeman, Montana 59717, United States.
Mary J
MJ
Cloninger
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D050091:Dendrimers / Q000737:chemistry*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D050091:Dendrimers; D000644:Quaternary Ammonium Compounds
antibiotic; cationic; dendrimers; multivalency; quaternary ammonium compound
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