Exploring a Gemcitabine-Glucose Hybrid as a Glycoconjugate Prodrug

Jack Porter; Amanda R. Noble; Nathalie Signoret; Martin A. Fascione; Gavin J. Miller

doi:10.1021/acsomega.4c02417

Exploring a Gemcitabine-Glucose Hybrid as a Glycoconjugate Prodrug

Jack Porter, Amanda R. Noble, Nathalie Signoret, Martin A. Fascione, Gavin J. Miller^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	31703-31713
Number of pages	11
Journal	ACS Omega
Volume	9
Issue number	29
DOIs	https://doi.org/10.1021/acsomega.4c02417
Publication status	Published - 9 Jul 2024

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© 2024 The Authors. Published by American Chemical Society.

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Exploring a Gemcitabine-Glucose Hybrid as a GlycoconjugateProdrug
© 2024 The Authors.
Final published version, 2.22 MBLicence: CC BY

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Exploring a Gemcitabine-Glucose Hybrid as a Glycoconjugate Prodrug

Abstract

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