Tuning the Anthranilamide Peptidomimetic Design to Selectively Target Planktonic Bacteria and Biofilm

Rajesh Kuppusamy; Muhammad Yasir; Tsz Tin Yu; Florida Voli; Orazio Vittorio; Michael J Miller; Peter Lewis; David StC Black; Mark Willcox; Naresh Kumar

doi:10.3390/antibiotics12030585

Tuning the Anthranilamide Peptidomimetic Design to Selectively Target Planktonic Bacteria and Biofilm

Antibiotics (Basel). 2023 Mar 15;12(3):585. doi: 10.3390/antibiotics12030585.

Authors

Rajesh Kuppusamy^{1

2}, Muhammad Yasir², Tsz Tin Yu¹, Florida Voli³, Orazio Vittorio^{3

4

5}, Michael J Miller⁶, Peter Lewis⁷, David StC Black¹, Mark Willcox², Naresh Kumar¹

Affiliations

¹ School of Chemistry, The University of New South Wales (UNSW), Sydney, NSW 2052, Australia.
² School of Optometry and Vision Science, The University of New South Wales (UNSW), Sydney, NSW 2052, Australia.
³ Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW 2052, Australia.
⁴ School of Clinical Medicine, University of New South Wales, Sydney, NSW 2052, Australia.
⁵ ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of New South Wales, Sydney, NSW 2052, Australia.
⁶ School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Newcastle, NSW 2308, Australia.
⁷ Hunter Biological Solutions Pty Ltd., Newcastle, NSW 2310, Australia.

Abstract

There is a pressing need to develop new antimicrobials to help combat the increase in antibiotic resistance that is occurring worldwide. In the current research, short amphiphilic antibacterial and antibiofilm agents were produced by tuning the hydrophobic and cationic groups of anthranilamide peptidomimetics. The attachment of a lysine cationic group at the tail position increased activity against E. coli by >16-fold (from >125 μM to 15.6 μM) and greatly reduced cytotoxicity against mammalian cells (from ≤20 μM to ≥150 μM). These compounds showed significant disruption of preformed biofilms of S. aureus at micromolar concentrations.

Keywords: anthranilamide; biofilm; peptidomimetics.

Grants and funding

This work was supported by a DP from the Australian Research Council Discovery project DP180100845 and a National Health and Medical Research Ideas grant (APP1183597).