Copper(ii) mixed-ligand polypyridyl complexes with doxycycline - structures and biological evaluation

Area of Science:

• Coordination Chemistry
• Medicinal Chemistry
• Biochemistry

Background:

• Doxycycline is a known Matrix Metalloproteinase (MMP) inhibitor.
• Copper(II) complexes are explored for therapeutic applications.
• Developing novel compounds against drug-resistant pathogens and cancer is crucial.

Purpose of the Study:

• Synthesize and characterize novel mixed-ligand copper(II) complexes with doxycycline.
• Evaluate their DNA cleavage, MMP-2 inhibition, anticancer, and antimalarial activities.
• Determine the structure-activity relationship of these complexes.

Main Methods:

• Synthesis of copper(II) complexes using doxycycline and nitrogen-based ligands (bpy, phen, dpq, dppz).
• Characterization via X-ray crystallography, spectroscopy, and elemental analysis.
• In vitro assays for plasmid DNA cleavage, MMP-2 inhibition, cytotoxicity against MCF-7 and HeLa cell lines, and antimalarial activity against Plasmodium falciparum strains.

Main Results:

• Successful synthesis and structural elucidation of four copper(II) complexes.
• Complexes 2-4 showed significant plasmid DNA cleavage via an oxidative mechanism.
• All complexes inhibited MMP-2, with complex 3 being the most potent.
• Complex 3 exhibited the highest anticancer activity against MCF-7 and HeLa cells (IC50 = 0.46 ± 0.05 μM).
• Complex 3 demonstrated superior antimalarial activity against chloroquine-resistant Plasmodium falciparum Dd2 compared to artesunate.

Conclusions:

• The synthesized copper(II) complexes possess diverse biological activities.
• Complex 3 shows promising potential as an anticancer and antimalarial agent.
• Further investigation into the mechanism of action and in vivo efficacy is warranted.