Positional isomers of biphenyl antimicrobial peptidomimetic amphiphiles
Document Type
Journal Article
Publication Title
ACS Medicinal Chemistry Letters
Publisher
American Chemical Society
School
School of Medical and Health Sciences
RAS ID
32814
Funders
Australian National Health and Medical Research Council
Grant Number
NHMRC Number : 1124032
Grant Link
http://purl.org/au-research/grants/nhmrc/1124032
Abstract
© 2021American Chemical Society. 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).
DOI
10.1021/acsmedchemlett.0c00611
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Comments
Tague, A. J., Putsathit, P., Riley, T. V., Keller, P. A., & Pyne, S. G. (2021). Positional isomers of biphenyl antimicrobial peptidomimetic amphiphiles. ACS Medicinal Chemistry Letters, 12(3), 413-419. https://doi.org/10.1021/acsmedchemlett.0c00611