Methyl 6‐Amino‐6‐deoxy‐d‐pyranoside‐Conjugated Platinum(II) Complexes for Glucose Transporter (GLUT)‐Mediated Tumor Targeting: Synthesis, Cytotoxicity, and Cellular Uptake Mechanism. (2nd May 2016)

• Record Type: Journal Article
• Authors: Li, Taoli; Gao, Xiangqian; Yang, Liu; Shi, Yunli; Gao, Qingzhi
• Is Part Of: ChemMedChem. Volume 11:Number 10(2016)
• Page Start: 1069
• Page End: 1077
• Publication Date: 2016-05-02
• Subjects: aminodeoxypyranosides -- glucose transporter (GLUT) -- glycoconjugates -- platinum(II) complexes -- Warburg effect; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201600079
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: Methyl 6‐aminodeoxy‐d ‐pyranoside‐derived platinum(II) glycoconjugates were designed and synthesized based on the clinical drug oxaliplatin for glucose transporter (GLUT)‐mediated tumor targeting. In addition to a substantial improvement in water solubility, the conjugates exhibited cytotoxicity similar to or higher than that of oxaliplatin in six different human cancer cell lines. GLUT‐mediated transport of the complexes was investigated with a cell‐based fluorescence competition assay and GLUT‐inhibitor‐mediated cytotoxicity analysis in a GLUT‐overexpressing human colorectal adenocarcinoma (HT29) cell line. The antitumor effect of the aminodeoxypyranoside‐conjugated platinum(II) complexes was found to depend significantly on the GLUT inhibitor, and the cellular uptake of the molecules was regulated by GLUT‐mediated transport. The results from this study demonstrate the potential advantages of aminodeoxypyranosides as sugar motifs for glycoconjugation for Warburg‐effect‐targeted drug design. These fundamental results also support the potential of aminodeoxypyranoside‐conjugated platinum(II) complexes as lead compounds for further preclinical evaluation. Abstract : Sweet‐talking tumors : This study focused on the design, synthesis, and mechanistic studies of aminodeoxypyranoside‐conjugated platinum(II) complexes targeting the Warburg effect, the phenomenon by which tumor tissues metabolize significantly more glucose than normal tissues. The results demonstrate the potential advantages of aminodeoxypyranosides as sugar motifs for glucose transporter (GLUT)‐mediated drug uptake for targeted therapy.