Cited by 122Carbohydrate Chemistry and SynthesisNanoparticle-Based Drug DeliverySynthesis and biological activity

Targeting the Delivery of Glycan-Based Paclitaxel Prodrugs to Cancer Cells via Glucose Transporters

Lin, Yih-Shyan, Tungpradit, Rudeewan, Sinchaikul, Supachok, An, Feng-Ming, Liu, Der-Zen, Phutrakul, Suree, Chen, Shui-Tein·2008·Journal of Medicinal Chemistry

Abstract

This report describes the synthesis of four novel paclitaxel based prodrugs with glycan conjugation (1-4). Glycans were conjugated using an ester or ether bond as the linker between 2'-paclitaxel and the 2'-glucose or glucuronic acid moiety. These prodrugs showed good water solubility and selective cytotoxicity against cancer cell lines, but showed reduced toxicity toward normal cell lines and cancer cell lines with low expression levels of GLUTs. The ester conjugated prodrug 1 showed the most cytotoxicity among the prodrugs examined and could be transported into cells via GLUTs. Fluorescent and confocal microscopy demonstrated that targeted cells exhibited morphological changes in tubulin and chromosomal alterations that were similar to those observed with paclitaxel treatment. Therefore, these glycan-based prodrugs may be good drug candidates for cancer therapy, and the glycan conjugation approach is an alternative method to enhance the targeted delivery of other drugs to cancer cells that overexpress GLUTs.

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Crossref · 10.1021/jm8006257

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43 of 43 references verified0 citation errors · 0 not checkable

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  • Glucose conjugates of several cancer chemotherapeutics, including paclitaxel and doxorubicin, experienced a higher therapeutic efficacy in vivo.

    “Glucose conjugates of several cancer chemotherapeutics, including paclitaxel and doxorubicin [159,160,161], experienced a higher therapeutic efficacy in vivo.”

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Authors
Lin, Y.-S., Tungpradit, R., Sinchaikul, S., An, F.-M., Liu, D.-Z., Phutrakul, S., & Chen, S.-T.
Affiliations
National Taiwan University (TW)
Corresponding author
Chen, Shui-Tein
Venue
Journal of Medicinal Chemistry
Published
2008-11-16
Volume
51
Issue
23
Pages
7428-7441
ISSN
  • 0022-2623 (ISSN-L)
  • 1520-4804
OpenAlex
W2095581830
Cited by
120
References
43
Citations by year
2026: 5 · 2025: 6 · 2024: 13 · 2023: 6 · 2022: 8 · 2021: 4 · 2020: 8 · 2019: 8 · 2018: 4 · 2017: 8 · 2016: 11 · 2015: 6 · 2014: 5 · 2013: 8 · 2012: 6
FWCI
2.32
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Medicinal Chemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Chemistry › Organic Chemistry › Carbohydrate Chemistry and Synthesis
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
Keywords
paclitaxel prodrug, glucose transporters, glucuronic acid, cytotoxicity, tubulin, anticancer drug delivery
MeSH terms
Animals, Cell Line, Cricetulus, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Cricetinae, Humans, Polysaccharides, Prodrugs, Stereoisomerism, Drug Design, Molecular Structure, CHO Cells, Drug Delivery Systems, Paclitaxel, Cell Proliferation, Glucose Transport Proteins, Facilitative

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