2. Academic Validation
  3. Norbornane-based cationic antimicrobial peptidomimetics targeting the bacterial membrane

Norbornane-based cationic antimicrobial peptidomimetics targeting the bacterial membrane

  • Eur J Med Chem. 2018 Dec 5:160:9-22. doi: 10.1016/j.ejmech.2018.09.072.
Shane M Hickey 1,  Trent D Ashton 2,  Gareth Boer 3,  Christie A Bader 4,  Michael Thomas 5,  Alysha G Elliott 6,  Carsten Schmuck 7,  Heidi Y Yu 8,  Jian Li 8,  Roger L Nation 8,  Matthew A Cooper 6,  Sally E Plush 4,  Douglas A Brooks 4,  Frederick M Pfeffer 9
Affiliations

Affiliations

  • 1 Cancer Research Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5000, Australia. Electronic address: shane.hickey@unisa.edu.au.
  • 2 The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, 3010, Australia.
  • 3 Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria, 3216, Australia.
  • 4 Cancer Research Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5000, Australia.
  • 5 Research School of Chemistry, The Australian National University, Acton, ACT, 2601, Australia.
  • 6 Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, 4072, Australia.
  • 7 Institute for Organic Chemistry, University of Duisburg-Essen, 45117, Essen, Germany.
  • 8 Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Science, Royal Parade, Parkville, Victoria, 3052, Australia.
  • 9 Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria, 3216, Australia. Electronic address: fred.pfeffer@deakin.edu.au.
PMID: 30316060 DOI: 10.1016/j.ejmech.2018.09.072
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.

Keywords

Amphiphilic; Antibacterial; Antimicrobial; Fluorescence; Naphthalimide; Norbornane and microscopy.

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