Hydrazonate-Based Copper(II) Metallodrugs: Insights into Solution Behavior, G-Quadruplex DNA Interaction, and
Monalisa Mohanty1, Sudhir Lima1, Pratikshya Das Pattanayak1
1Department of Chemistry, National Institute of Technology, Rourkela, 769008, Odisha, India.
Chemistry, an Asian Journal
|March 13, 2025
Summary
New copper complexes show strong binding to G-quadruplex DNA (G4-DNA), a potential cancer target. These complexes exhibit significant cytotoxicity against cancer cells, indicating G4-DNA is key to their anticancer activity.
Area of Science:
- Coordination Chemistry
- Biophysical Chemistry
- Cancer Therapeutics
Background:
- G-quadruplex DNA (G4-DNA) structures in telomeres and oncogenes are promising cancer targets.
- Copper complexes are explored for their potential in cancer treatment due to their diverse biological activities.
Purpose of the Study:
- To synthesize and characterize novel copper(II) complexes.
- To investigate the solution behavior and DNA binding interactions of these complexes.
- To evaluate their anticancer potential and mechanism of action.
Main Methods:
- Synthesis and single-crystal X-ray diffraction of copper complexes.
- Solution behavior analysis using HRMS and ESR.
- Spectroscopic studies and molecular docking for DNA interaction.
- DNA nuclease activity and cytotoxicity assays (Annexin V/PI staining).
Main Results:
- Three copper complexes, including mononuclear and dinuclear structures, were successfully synthesized and characterized.
- Complexes maintained integrity in solution but showed ligand exchange.
- Higher affinity for G4-DNA over duplex DNA was observed, with complex 3 being the strongest binder.
- Significant cytotoxicity against HeLa and MCF-7 cancer cell lines was demonstrated, inducing apoptosis.
Conclusions:
- The synthesized copper complexes exhibit selective binding to G4-DNA.
- The observed anticancer activity is strongly correlated with G4-DNA interaction.
- These complexes represent potential therapeutic agents for cancer treatment targeting G4-DNA.
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