Porter, Jack, Noble, Amanda R., Signoret, Nathalie orcid.org/0000-0003-4977-4149 et al. (2 more authors) (2024) Exploring a Gemcitabine-Glucose Hybrid as a Glycoconjugate Prodrug. ACS Omega. pp. 31703-31713. ISSN 2470-1343
Abstract
Nucleoside analogues are established treatments for cancer and viral infection. Gemcitabine is a commonly employed nucleoside analogue displaying anticancer properties against a range of tumor types but is rapidly inactivated in vivo. Efforts to bolster its pharmaceutical profile include investigating prodrug forms. Herein, we explore the synthesis of a novel glucose-gemcitabine glycoconjugate, targeting uptake via glucose transport. We select a redox-reactive disulfide linker for conjugation of gemcitabine (through N4-cytosine) with glucose. Evaluation of this glycoconjugate reveals increased toxicity against androgen insensitive PC3 prostate cancer cells compared to LNCaP (which have lower levels of glucose transporter GLUT1). These preliminary results suggest that glycoconjugation of nucleosides may be an effective approach to targeting cells which display increased uptake and metabolism of glucose.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | Publisher Copyright: © 2024 The Authors. Published by American Chemical Society. |
Dates: |
|
Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) The University of York > Faculty of Sciences (York) > Hull York Medical School (York) |
Depositing User: | Pure (York) |
Date Deposited: | 02 Aug 2024 08:20 |
Last Modified: | 05 Dec 2024 00:28 |
Published Version: | https://doi.org/10.1021/acsomega.4c02417 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1021/acsomega.4c02417 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:215655 |
Download
Filename: porter-et-al-2024-exploring-a-gemcitabine-glucose-hybrid-as-a-glycoconjugate-prodrug.pdf
Description: Exploring a Gemcitabine-Glucose Hybrid as a GlycoconjugateProdrug
Licence: CC-BY 2.5