Design and synthesis of short amphiphilic cationic peptidomimetics based on biphenyl backbone as antibacterial agents

Kuppusamy, R; Yasir, M; Berry, T; Cranfield, CG; Nizalapur, S; Yee, E; Kimyon, O; Taunk, A; Ho, KKK; Cornell, B; Manefield, M; Willcox, M; Black, DSC; Kumar, N

Design and synthesis of short amphiphilic cationic peptidomimetics based on biphenyl backbone as antibacterial agents

Kuppusamy, R Yasir, M Berry, T

Cranfield, CG

Nizalapur, S Yee, E Kimyon, O Taunk, A Ho, KKK Cornell, B

Manefield, M Willcox, M Black, DSC Kumar, N

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Publication Type:: Journal Article
Citation:: European Journal of Medicinal Chemistry, 2018, 143 pp. 1702 - 1722
Issue Date:: 2018-01-01

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Field	Value	Language
dc.contributor.author	Kuppusamy, R	en_US
dc.contributor.author	Yasir, M	en_US
dc.contributor.author	Berry, T https://orcid.org/0000-0002-2882-0313	en_US
dc.contributor.author	Cranfield, CG https://orcid.org/0000-0003-3608-5440	en_US
dc.contributor.author	Nizalapur, S	en_US
dc.contributor.author	Yee, E	en_US
dc.contributor.author	Kimyon, O	en_US
dc.contributor.author	Taunk, A	en_US
dc.contributor.author	Ho, KKK	en_US
dc.contributor.author	Cornell, B https://orcid.org/0000-0003-4166-3241	en_US
dc.contributor.author	Manefield, M	en_US
dc.contributor.author	Willcox, M	en_US
dc.contributor.author	Black, DSC	en_US
dc.contributor.author	Kumar, N	en_US
dc.date.available	2020-05-25T19:07:39Z
dc.date.issued	2018-01-01	en_US
dc.identifier.citation	European Journal of Medicinal Chemistry, 2018, 143 pp. 1702 - 1722	en_US
dc.identifier.issn	0223-5234	en_US
dc.identifier.uri	http://hdl.handle.net/10453/120721
dc.description.abstract	© 2017 Elsevier Masson SAS Antimicrobial peptides (AMPs) and their synthetic mimics have received recent interest as new alternatives to traditional antibiotics in attempts to overcome the rise of antibiotic resistance in many microbes. AMPs are part of the natural defenses of most living organisms and they also have a unique mechanism of action against bacteria. Herein, a new series of short amphiphilic cationic peptidomimetics were synthesized by incorporating the 3′-amino-[1,1′-biphenyl]-3-carboxylic acid backbone to mimic the essential properties of natural AMPs. By altering hydrophobicity and charge, we identified the most potent analogue 25g that was active against both Gram-positive Staphylococcus aureus (MIC = 15.6 μM) and Gram-negative Escherichia coli (MIC = 7.8 μM) bacteria. Cytoplasmic permeability assay results revealed that 25g acts primarily by depolarization of lipids in cytoplasmic membranes. The active compounds were also investigated for their cytotoxicity to human cells, lysis of lipid bilayers using tethered bilayer lipid membranes (tBLMs) and their activity against established biofilms of S. aureus and E. coli.	en_US
dc.relation	http://purl.org/au-research/grants/arc/DP160101664
dc.relation.ispartof	European Journal of Medicinal Chemistry	en_US
dc.relation.isbasedon	10.1016/j.ejmech.2017.10.066	en_US
dc.subject.classification	Medicinal & Biomolecular Chemistry	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Biofilms	en_US
dc.subject.mesh	Escherichia coli	en_US
dc.subject.mesh	Staphylococcus aureus	en_US
dc.subject.mesh	Cations	en_US
dc.subject.mesh	Biphenyl Compounds	en_US
dc.subject.mesh	Anti-Bacterial Agents	en_US
dc.subject.mesh	Surface-Active Agents	en_US
dc.subject.mesh	Microbial Sensitivity Tests	en_US
dc.subject.mesh	Cell Survival	en_US
dc.subject.mesh	Molecular Structure	en_US
dc.subject.mesh	Structure-Activity Relationship	en_US
dc.subject.mesh	Dose-Response Relationship, Drug	en_US
dc.subject.mesh	Drug Design	en_US
dc.subject.mesh	Peptidomimetics	en_US
dc.title	Design and synthesis of short amphiphilic cationic peptidomimetics based on biphenyl backbone as antibacterial agents	en_US
dc.type	Journal Article
utslib.citation.volume	143	en_US
utslib.for	0304 Medicinal and Biomolecular Chemistry	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
utslib.for	0305 Organic Chemistry	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Students
utslib.copyright.status	open_access
pubs.publication-status	Published	en_US
pubs.volume	143	en_US

Abstract:

© 2017 Elsevier Masson SAS Antimicrobial peptides (AMPs) and their synthetic mimics have received recent interest as new alternatives to traditional antibiotics in attempts to overcome the rise of antibiotic resistance in many microbes. AMPs are part of the natural defenses of most living organisms and they also have a unique mechanism of action against bacteria. Herein, a new series of short amphiphilic cationic peptidomimetics were synthesized by incorporating the 3′-amino-[1,1′-biphenyl]-3-carboxylic acid backbone to mimic the essential properties of natural AMPs. By altering hydrophobicity and charge, we identified the most potent analogue 25g that was active against both Gram-positive Staphylococcus aureus (MIC = 15.6 μM) and Gram-negative Escherichia coli (MIC = 7.8 μM) bacteria. Cytoplasmic permeability assay results revealed that 25g acts primarily by depolarization of lipids in cytoplasmic membranes. The active compounds were also investigated for their cytotoxicity to human cells, lysis of lipid bilayers using tethered bilayer lipid membranes (tBLMs) and their activity against established biofilms of S. aureus and E. coli.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/120721