2015
DOI: 10.1021/acs.jmedchem.5b00443
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Membrane Active Small Molecules Show Selective Broad Spectrum Antibacterial Activity with No Detectable Resistance and Eradicate Biofilms

Abstract: Treating bacterial biofilms with conventional antibiotics is limited due to ineffectiveness of the drugs and higher propensity to develop bacterial resistance. Development of new classes of antibacterial therapeutics with alternative mechanisms of action has become imperative. Herein, we report the design, synthesis, and biological evaluations of novel membrane-active small molecules featuring two positive charges, four nonpeptidic amide groups, and variable hydrophobic/hydrophilic (amphiphilic) character. The… Show more

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Cited by 85 publications
(85 citation statements)
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“…Antimicrobial peptides and mimics thereof (i.e., quaternary ammonium cationic compounds) eradicate biofilm cells through membrane lysis; however, identifying potent membrane-lysing agents that target bacterial membranes over mammalian membranes has proven challenging 33, 48, 49 . Our Wohl-Aue derived HPs demonstrated little, if any, hemolytic activity against RBCs at 200 µM (≤1 to ≤7% hemolysis, Table 3).…”
Section: Resultsmentioning
confidence: 99%
“…Antimicrobial peptides and mimics thereof (i.e., quaternary ammonium cationic compounds) eradicate biofilm cells through membrane lysis; however, identifying potent membrane-lysing agents that target bacterial membranes over mammalian membranes has proven challenging 33, 48, 49 . Our Wohl-Aue derived HPs demonstrated little, if any, hemolytic activity against RBCs at 200 µM (≤1 to ≤7% hemolysis, Table 3).…”
Section: Resultsmentioning
confidence: 99%
“…Although there has been much interest in identifying non‐growth altering biofilm inhibitors and dispersal agents over the past two decades,7 few classes of biofilm‐eradicating agents are known. Biofilm‐eradicating agents typically operate through the disruption of bacterial membranes (for example, antimicrobial peptides,8, 9 quaternary ammonium cations/QACs) 10. Although these compounds are indeed valuable, new biofilm‐eradicating agents with complementary modes of action are of great importance and have multiple therapeutic applications to address persistent bacterial infections.…”
Section: Methodsmentioning
confidence: 99%
“…Antimicrobial peptides (AMPs) [18][19][20] and mimics 21 are the most well-known biofilm-eradicating agents. AMPs are naturally occurring peptides used in host immune or general defence responses to bacterial infection and operate through the destruction of bacterial membranes causing cell lysis and death.…”
mentioning
confidence: 99%