Norbornane-based cationic antimicrobial peptidomimetics targeting the bacterial membrane

Shane M. Hickey, Trent D. Ashton, Gareth Boer, Christie A. Bader, Michael Thomas, Alysha G. Elliott, Carsten Schmuck, Heidi Y. Yu, Jian Li, Roger L. Nation, Matthew A. Cooper, Sally E. Plush, Douglas A. Brooks, Frederick M. Pfeffer

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)9-22
Number of pages14
JournalEuropean Journal of Medicinal Chemistry
Volume160
DOIs
Publication statusPublished - 5 Dec 2018

Keywords

  • Amphiphilic
  • Antibacterial
  • Antimicrobial
  • Fluorescence
  • Naphthalimide
  • Norbornane and microscopy

Cite this

Hickey, S. M., Ashton, T. D., Boer, G., Bader, C. A., Thomas, M., Elliott, A. G., Schmuck, C., Yu, H. Y., Li, J., Nation, R. L., Cooper, M. A., Plush, S. E., Brooks, D. A., & Pfeffer, F. M. (2018). Norbornane-based cationic antimicrobial peptidomimetics targeting the bacterial membrane. European Journal of Medicinal Chemistry, 160, 9-22. https://doi.org/10.1016/j.ejmech.2018.09.072