Targeting the delivery of glycan-based paclitaxel prodrugs to cancer cells via glucose transporters

Yih Shyan Lin, Rudeewan Tungpradit, Supachok Sinchaikul, Feng Ming An, Der Zen Liu, Suree Phutrakul, Shui Tein Chen

Research output: Contribution to journalArticle

65 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)7428-7441
Number of pages14
JournalJournal of Medicinal Chemistry
Volume51
Issue number23
DOIs
Publication statusPublished - Dec 11 2008

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Facilitative Glucose Transport Proteins
Prodrugs
Paclitaxel
Polysaccharides
Neoplasms
Cell Line
Esters
Glucuronic Acid
Tubulin
Confocal Microscopy
Pharmaceutical Preparations
Ether
Solubility
Glucose
Water

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

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.

In: Journal of Medicinal Chemistry, Vol. 51, No. 23, 11.12.2008, p. 7428-7441.

Research output: Contribution to journalArticle

Lin, YS, Tungpradit, R, Sinchaikul, S, An, FM, Liu, DZ, Phutrakul, S & Chen, ST 2008, 'Targeting the delivery of glycan-based paclitaxel prodrugs to cancer cells via glucose transporters', Journal of Medicinal Chemistry, vol. 51, no. 23, pp. 7428-7441. https://doi.org/10.1021/jm8006257
Lin, Yih Shyan ; Tungpradit, Rudeewan ; Sinchaikul, Supachok ; An, Feng Ming ; Liu, Der Zen ; Phutrakul, Suree ; Chen, Shui Tein. / Targeting the delivery of glycan-based paclitaxel prodrugs to cancer cells via glucose transporters. In: Journal of Medicinal Chemistry. 2008 ; Vol. 51, No. 23. pp. 7428-7441.
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