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Positional isomers of biphenyl antimicrobial peptidomimetic amphiphiles

Tague, A.J., Putsathit, P., Riley, T.V., Keller, P.A. and Pyne, S.G. (2021) Positional isomers of biphenyl antimicrobial peptidomimetic amphiphiles. ACS Medicinal Chemistry Letters, 12 (3). pp. 413-419.

Link to Published Version: https://doi.org/10.1021/acsmedchemlett.0c00611
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Abstract

Small-molecule antimicrobial peptidomimetic amphiphiles represent a promising class of novel antimicrobials with the potential for widespread therapeutic application. To investigate the role of spatial positioning for key hydrophobic and hydrophilic groups on the antimicrobial efficacy and selectivity, positional isomers of the lead biphenyl antimicrobial peptidomimetic compound 1 were synthesized and subjected to microbial growth inhibition and mammalian toxicity assays. Positional isomer 4 exhibited 4–8× increased efficacy against the pathogenic Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli (MIC = 2 μg/mL), while isomers 2, 3, and 7 exhibited a 4× increase in activity against Acinetobacter baumannii (MIC = 4 μg/mL). Changes in molecular shape had a significant impact on Gram-negative antibacterial efficacy and the resultant spectrum of activity, whereas all structural isomers exhibited significant efficacy (MIC = 0.25–8 μg/mL) against Gram-positive bacterial pathogens (e.g., methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecalis).

Item Type: Journal Article
Murdoch Affiliation(s): Medical, Molecular and Forensic Sciences
Publisher: American Chemical Society
Copyright: © 2021 American Chemical Society
URI: http://researchrepository.murdoch.edu.au/id/eprint/59840
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