Popoola, Precious I. A. ORCID: https://orcid.org/0000-0002-3961-3782, Allam, Thomas L. ORCID: https://orcid.org/0009-0009-9897-333X, Lilley, Rebecca J., Manwani, Chandni ORCID: https://orcid.org/0000-0002-5068-2527, Keers, Olivia B., Tan, Junyang, Yang, Kylie ORCID: https://orcid.org/0000-0002-4455-3681, Long, Yifan, Clark, Ewan R. ORCID: https://orcid.org/0000-0001-7287-2631, White, Lisa J., Hilton, Kira L. F., Rankin, Jennifer, Baker, Jennifer ORCID: https://orcid.org/0009-0008-1290-7845, Bennett, Charlotte, Wilson, Hollie B., Morton, Evelyn R., Keskküla, Alvaro, Martin, Bethany, O'Connor, Christopher ORCID: https://orcid.org/0009-0005-6429-4620, Sutton, J. Mark, Hind, Charlotte K., Garrett, Michelle D., Haynes, Cally J. E. ORCID: https://orcid.org/0000-0003-4262-8560 and Hiscock, Jennifer R. ORCID: https://orcid.org/0000-0002-1406-8802 (2026) Amino acid appended supramolecular self-associating amphiphiles demonstrate dual activity against both MRSA and ovarian cancer. Chemical Science. ISSN 2041-6520 (Print), 2041-6539 (Online) (doi:10.1039/D5SC03376D)

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Abstract

Differences in the lipid composition of prokaryotic and eukaryotic cell membranes are well understood and can be exploited to produce novel antimicrobials. However, what is less well recognised is that alteration in the phospholipid composition of the cell membrane is also one of the first phenotypic changes when a cell becomes cancerous. In addition, changes in phospholipid cell membrane composition are a known cause of drug resistance in both microbial disease and cancer. Here we present a novel, next generation series of chiral, amino acid appended supramolecular self-associating amphiphiles that suggest membrane active technologies can be used to produce novel drugs which simultaneously fight against two of the greatest global health threats facing us today, antimicrobial resistant infections and cancer diseases. We demonstrate the antimicrobial and anticancer efficacy of this membrane active amphiphile technology against susceptible and resistant Staphylococcus aureus and ovarian cancer cells. We propose a mode of action through a combination of vesicle, NMR spectroscopy and patch clamp experiments, and provide evidence that supports the potential for this class of compound to be developed as pharmaceutical agents against these diseases through in vitro drug metabolism and pharmacokinetics experiments alongside in vivo Galleria mellonella toxicity experiments.

Item Type:	Article
Uncontrolled Keywords:	supramolecular, antimicrobial
Subjects:	Q Science > QR Microbiology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI)
Last Modified:	31 Mar 2026 15:28
URI:	https://gala.gre.ac.uk/id/eprint/52707

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