Amino acid appended supramolecular self-associating amphiphiles demonstrate dual activity against both MRSA and ovarian cancer

Sep 22, 2026

Uploaded by Aurelia

A novel series of chiral amino-acid appended supramolecular self-associating amphiphiles is presented as a membrane-active technology aimed at antimicrobial resistant infections and cancer. The work demonstrates antimicrobial and anticancer activity against susceptible and resistant Staphylococcus aureus and ovarian cancer cells. A proposed mechanism integrates vesicle formation with NMR spectroscopy and patch clamp experiments, supported by in vitro metabolism/pharmacokinetics and in vivo Galleria mellonella toxicity results.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

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Introduction

Antimicrobial resistance and cancer as global threats

Need for new antimicrobials and drug development pipeline

Cancer burden and ovarian cancer mortality drivers

Drug repurposing and off-target antimicrobial activity

Chemical Science EDGE ARTICLE Cite this: DOI: 10 .1039/d5sc03376d All publication charges for this article have been paid for by the Royal Society of Chemistry Received 9th May 2025 Accepted 20th January 2026 DOI: 10.1039/d5sc03376d[rsc.li/chemical-science](rsc.li/chemical-science) Amino acid appended supramolecular selfassociating amphiphiles demonstrate dual activity against both MRSA and ovarian cancer Precious I. A. Popoola, a Thomas L. Allam, b Rebecca J. Lilley,a Chandni Manwani, a Olivia B. Keers,a Junyang Tan,c Kylie Yang, c Yifan Long,c Ewan R. Clark,d Lisa J. White,a Kira L. F. Hilton,a Jennifer Rankin,e Jennifer Baker, e Charlotte Bennett,e Hollie B. Wilson,e Evelyn R. Morton,c Alvaro Keskküla,c Bethany Martin,f Christopher O'Connor, f J. Mark Sutton,f Charlotte K. Hind,*f Michelle D. Garrett,*a Cally J. E. Haynes *c and Jennifer R. Hiscock *a 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. Introduction The rise of antimicrobial resistant (AMR) bacterial infections and cancer are two of the greatest health threats facing humanity today. A report generated in 2014 attributed 8.8 million deaths to cancer in that year alone, while simultaneously predicting that by the year 2050, ten million people per year will die from the primary eﬀects of AMR.1 The present impact of AMR was con􀀁rmed by a recent study, which reported 4.95 million and 1.27 million deaths from the indirect and direct eﬀects ofAMR respectively during 2019 .2 This means that over this time period, AMR was directly responsible for the same a University of Kent, Canterbury, CT2 7NH, [UK. E-mail: J.R.Hiscock@Kent.ac.uk](UK. E-mail: J.R.Hiscock@Kent.ac.uk); M.D. [Garrett@kent.ac.uk](Garrett@kent.ac.uk) bSchool of Chemistry, University of Southampton, High􀀁eld, Southampton, SO17 1BJ, UK cChemistry Department, UCL, 20 Gordon Street, London WC1H 0AJ, UK. E-mail: cally. [haynes@ucl.ac.uk](haynes@ucl.ac.uk) dSchool of Science, University of Greenwich, Chatham Maritime, Kent, ME4 4TB, UK eCancer Research Horizons, Babraham Research Campus, Cambridge, CB22 3AT, UK fResearch and Evaluation, Porton Down, UKHSA, Salisbury SP4 0JG, UK. E-mail: [Charlotte.Hind@UKHSA.gov.uk](Charlotte.Hind@UKHSA.gov.uk) number, if not more deaths than those directly attributed to either HIV/AIDs or malaria.2 This rise in AMR has traditionally been attributed to the misuse of antimicrobial agents, including antibiotics, across multiple sectors.3–6 In addition, although we do not yet truly understand the impacts of the COVID-19 pandemic on increased rate of AMR infections, there was a high level of AMR bacterial co-infections con􀀁rmed within pa

FAQs

What does the study propose as the main therapeutic concept for MRSA and ovarian cancer?

It proposes membrane-active technologies based on chiral amino-acid appended supramolecular self-associating amphiphiles to simultaneously target antimicrobial-resistant infections and cancer diseases.

Which organisms and cell types were tested to show dual activity?

The amphiphile technology was tested against susceptible and resistant Staphylococcus aureus for antimicrobial activity, and against ovarian cancer cells for anticancer activity.

How is the proposed mode of action investigated?

The mode of action is proposed through combined vesicle-related evidence with NMR spectroscopy and patch clamp experiments.

What experimental evidence supports the potential for pharmaceutical development?

Evidence includes in vitro drug metabolism and pharmacokinetics experiments, alongside in vivo Galleria mellonella toxicity experiments.

Sep 22, 2026

Uploaded by Aurelia