2-Deoxyglucose conjugated platinum (II) complexes for targeted therapy: design, synthesis, and antitumor activity

Area of Science:

• Oncology
• Drug Delivery
• Medicinal Chemistry

Background:

• Malignant neoplasms exhibit increased glycolysis (Warburg effect) compared to normal cells.
• Targeting glucose transporter 1 (GLUT1) is a strategy for cancer therapy.
• 2-deoxyglucose (2-DG) is a glucose analog that can be utilized by cancer cells.

Purpose of the Study:

• To design and synthesize novel 2-deoxyglucose (2-DG) conjugated platinum (II) complexes.
• To evaluate the potential of these complexes for GLUT1-mediated anticancer drug delivery.
• To assess the in vitro cytotoxicity of the synthesized compounds against human cancer cell lines.

Main Methods:

• Molecular docking analysis using the GLUT1 protein crystal structure to predict GLUT1 transportability.
• Molecular dynamics simulation to identify the GLUT1 binding site for 2-DG.
• Synthesis of 2-DG conjugated platinum (II) complexes.
• In vitro cytotoxicity assays using seven human cancer cell lines.

Main Results:

• The 2-DG conjugated platinum (II) complexes were recognized by the GLUT1 binding site, indicating potential GLUT1 transportability.
• The synthesized complexes exhibited improved in vitro cytotoxicity against cancer cell lines overexpressing GLUT1 compared to Oxaliplatin.
• A positive correlation was observed between GLUT1 expression levels and the antitumor effects of the complexes.

Conclusions:

• The 2-DG conjugated platinum (II) complexes are effective GLUT1 transportable substrates.
• These complexes demonstrate enhanced anticancer activity, offering a promising therapeutic strategy for GLUT1-overexpressing cancers.
• The findings support the development of these complexes as lead compounds for pharmaceutical research and development.