Norbornane-based cationic antimicrobial peptidomimetics targeting the bacterial membrane.

Abstract The design, synthesis and evaluation of a small series of potent amphiphilic norbornane antibacterial agents has been performed (compound 10 MIC = 0.25 μg/mL against MRSA). Molecular modelling indicates rapid aggregation of this class of antibacterial agent prior to membrane association and insertion. Two fluorescent analogues (compound 29 with 4-amino-naphthalimide and 34 with 4-nitrobenz-2-oxa-1,3-diazole fluorophores) with good activity (MIC = 0.5 μg/mL against MRSA) were also constructed and confocal microscopy studies indicate that the primary site of interaction for this family of compounds is the bacterial membrane. Graphical abstract Image 1 Highlights • Antibacterial norbornane based amphiphiles with MIC as low as 0.25 μg/mL. • Fluorescent microscopy of fluorophore-tagged analogues shows membrane localisation. • Molecular modelling indicates rapid aggregation prior to membrane insertion. [ABSTRACT FROM AUTHOR]