Structural features and oxidative stress towards plasmid DNA of apramycin copper complex

Area of Science:

• Coordination chemistry
• Biophysical chemistry
• Molecular biology

Background:

• Aminoglycoside antibiotics like apramycin are crucial in medicine.
• Copper ions are involved in various biological processes and can interact with biomolecules.
• Understanding metal-antibiotic interactions can reveal new therapeutic strategies.

Purpose of the Study:

• To investigate the interaction between apramycin and copper(II) ions.
• To characterize the structure and DNA-damaging activity of the copper(II)-apramycin complex.
• To explore the mechanism of DNA damage induced by the complex.

Main Methods:

• Potentiometric titrations
• Electron Paramagnetic Resonance (EPR), UV-Vis, and Circular Dichroism (CD) spectroscopy
• Nuclear Magnetic Resonance (NMR) spectroscopy, including IR-COSY
• Plasmid DNA electrophoresis

Main Results:

• Apramycin binds copper(II) at pH 6.5 with a 2:1 stoichiometry, utilizing hydroxyl and amino groups of ring III.
• The Cu(II)-apramycin complex exhibits enhanced DNA strand breakage activity compared to free Cu(II).
• DNA damage yield is higher with ascorbic acid than with hydrogen peroxide in the presence of the complex.

Conclusions:

• The Cu(II)-apramycin complex is structurally defined and possesses potent DNA-cleaving capabilities.
• The complex represents a promising agent for DNA-targeting applications.
• The interaction mechanism suggests potential for novel therapeutic development.