Membrane Active Phenylalanine
Conjugated Lipophilic
Norspermidine Derivatives with Selective Antibacterial Activity
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Abstract
Natural and synthetic membrane active
antibacterial agents offer
hope as potential solutions to the problem of bacterial resistance
as the membrane-active nature imparts low propensity for the development
of resistance. In this report norspermidine based antibacterial molecules
were developed that displayed excellent antibacterial activity against
various wild-type bacteria (Gram-positive and Gram-negative) and drug-resistant
bacteria (methicillin-resistant <i>Staphylococcus aureus</i>, vancomycin-resistant <i>Enterococcus faecium</i>, and
β-lactam-resistant <i>Klebsiella pneumoniae</i>).
In a novel structure–activity relationship study it has been
shown how incorporation of an aromatic amino acid drastically improves
selective antibacterial activity. Additionally, the effect of stereochemistry
on activity, toxicity, and plasma stability has also been studied.
These rapidly bactericidal, membrane active antibacterial compounds
do not trigger development of resistance in bacteria and hence bear
immense potential as therapeutic agents to tackle multidrug resistant
bacterial infections