Targeting the delivery of glycan-based paclitaxel prodrugs to cancer cells via glucose transporters
Resource
Journal of Medicinal Chemistry, 51(23), 7428-7441
Journal
Journal of Medicinal Chemistry
Pages
7428-7441
Date Issued
2008
Date
2008
Author(s)
Lin, Yih-Shyan
Tungpradit, Rudeewan
Sinchaikul, Supachok
An, Feng-Ming
Liu, Der-Zen
Phutrakul, Suree
Chen, Shui-Tein
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. ? 2008 American Chemical Society.
SDGs
Other Subjects
glucose transporter; glucuronic acid; glycan derivative; paclitaxel derivative; prodrug; tubulin; animal cell; article; cancer cell culture; cell structure; chromosome; conjugation; controlled study; drug cytotoxicity; drug selectivity; drug solubility; drug synthesis; drug targeting; drug transport; human; human cell; nonhuman; reaction analysis; Animals; Cell Line; Cell Proliferation; CHO Cells; Cricetinae; Cricetulus; Dose-Response Relationship, Drug; Drug Delivery Systems; Drug Design; Drug Evaluation, Preclinical; Glucose Transport Proteins, Facilitative; Humans; Molecular Structure; Paclitaxel; Polysaccharides; Prodrugs; Stereoisomerism
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