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Design, Synthesis of Novel Platinum(II) Glycoconjugates, and Evaluation of Their Antitumor Effects
- Source :
- Chemical biologydrug design. 87(6)
- Publication Year :
- 2015
-
Abstract
- A new series of sugar-conjugated (trans-R, R-cyclohexane-1, 2-diamine)-2-halo-malonato-platinum(II) complexes were designed and synthesized to target tumor-specific glucose transporters (GLUTs). The water solubility of the sugar-conjugated platinum (II) complexes was greatly improved by average of 570-fold, 33-fold, and 94-fold, respectively, compared to cisplatin (1.0 mg/mL), carboplatin (17.1 mg/mL), and the newest generation of clinical drug oxaliplatin (6.0 mg/mL). Despite the high water solubility, the platinum(II) glycoconjugates exhibited a notable increase in cytotoxicity by a margin of 1.5- to 6.0-fold in six different human cancer cell lines with respect to oxaliplatin. The potential GLUT1 transportability of the complexes was investigated through a molecular docking study and was confirmed with GLUT1 inhibitor-mediated cytotoxicity dependency evaluation. The results showed that the sugar-conjugated platinum(II) complexes can be recognized by the glucose recognition binding site of GLUT1 and their cell killing effect depends highly on the GLUT1 inhibitor, quercetin. The research presenting a prospective concept for targeted therapy anticancer drug design, and with the analysis of the synthesis, water solubility, antitumor activity, and the transportability of the platinum(II) glycoconjugates, this study provides fundamental data supporting the inherent potential of these designed conjugates as lead compounds for GLUT-mediated tumor targeting.
- Subjects :
- 0301 basic medicine
Organoplatinum Compounds
Glycoconjugate
chemistry.chemical_element
Antineoplastic Agents
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cell Line, Tumor
Drug Discovery
medicine
Humans
Cytotoxicity
Platinum
Pharmacology
Cisplatin
chemistry.chemical_classification
Organic Chemistry
Glucose transporter
Carboplatin
Oxaliplatin
030104 developmental biology
Cell killing
chemistry
030220 oncology & carcinogenesis
Molecular Medicine
Drug Screening Assays, Antitumor
Glycoconjugates
medicine.drug
Subjects
Details
- ISSN :
- 17470285
- Volume :
- 87
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Chemical biologydrug design
- Accession number :
- edsair.doi.dedup.....1b0993aaddf72458a53e524573a8ce77