5-Fluorocytosine–Sugar Conjugates for Glucose Transporter-Mediated Tumor Targeting: Synthesis, Cytotoxicity, and Cellular Uptake Mechanism

Two novel sugar-conjugated 5-fluorocytosine (5-FC) antineoplastic compounds were designed and synthesized to improve the selective drug uptake by targeting the tumor-specific glucose transporter (GLUT). The antitumor activity of these compounds was evaluated in four different human cancer cell lines...

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Bibliographic Details
Published inTransactions of Tianjin University Vol. 25; no. 6; pp. 611 - 617
Main Authors Wang, Yu, Cheng, Xiaofei, Zhao, Hongxia, Gao, Qingzhi
Format Journal Article
LanguageEnglish
Published Tianjin Tianjin University 01.12.2019
Springer Nature B.V
Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China
Subjects
Anticancer properties
Biotechnology
Conjugates
Cytotoxicity
Engineering
Glucose
Humanities and Social Sciences
Inhibitors
Lung cancer
Mechanical Engineering
multidisciplinary
Prostate
Research Article
Science
Toxicity
Transport
5-Fluorocytosine glycoconjugate
Glucose transporter overexpressed
Tumor targeting
Warburg effect
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Summary:Two novel sugar-conjugated 5-fluorocytosine (5-FC) antineoplastic compounds were designed and synthesized to improve the selective drug uptake by targeting the tumor-specific glucose transporter (GLUT). The antitumor activity of these compounds was evaluated in four different human cancer cell lines: A549 (human lung cancer cell line), HT29 (human colorectal cancer cell line), H460 (human lung cancer cell line), and PC3 (human prostate cancer cell line). The sugar conjugates exhibited cytotoxicity similar to or higher than 5-FC and 1-hexylcarbamoyl-5-FC in A549, HT29, H460, and PC3. Furthermore, GLUT-mediated transport of the glycoconjugate was investigated with GLUT inhibitor-mediated cytotoxicity analysis in a GLUT-overexpressing HT29 cell line. The cell-killing potency of 5-FC glycoconjugate was found to depend significantly on the GLUT inhibitor, and the cellular uptake of molecules was regulated by GLUT-mediated transport. All the results demonstrate the potential advantages of glycoconjugation for Warburg effect-targeted drug design.
ISSN:1006-4982
1995-8196
DOI:10.1007/s12209-019-00213-y