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
Affiliations
Rajesh Kuppusamy
School of Chemistry, The University of New South Wales (UNSW), Sydney, NSW 2052, Australia
Muhammad Yasir
School of Optometry and Vision Science, The University of New South Wales (UNSW), Sydney, NSW 2052, Australia
Tsz Tin Yu
School of Chemistry, The University of New South Wales (UNSW), Sydney, NSW 2052, Australia
Florida Voli
Children’s Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW 2052, Australia
Orazio Vittorio
Children’s Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW 2052, Australia
Michael J. Miller
School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Newcastle, NSW 2308, Australia
Peter Lewis
Hunter Biological Solutions Pty Ltd., Newcastle, NSW 2310, Australia
David StC Black
School of Chemistry, The University of New South Wales (UNSW), Sydney, NSW 2052, Australia
Mark Willcox
School of Optometry and Vision Science, The University of New South Wales (UNSW), Sydney, NSW 2052, Australia
Naresh Kumar
School of Chemistry, The University of New South Wales (UNSW), Sydney, NSW 2052, Australia
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.
