Dinuclear silver and gold bisNHC complexes as drug candidates for cancer therapy

Area of Science:

• Inorganic Chemistry
• Medicinal Chemistry
• Cancer Biology

Background:

• Metal-N-heterocyclic carbene (NHC) complexes are explored for therapeutic potential.
• Silver(I) and gold(I) complexes offer unique electronic properties for drug development.

Purpose of the Study:

• To synthesize and characterize novel dinuclear silver(I) and gold(I) complexes with bidentate N-heterocyclic carbene ligands.
• To evaluate the anticancer activity of these complexes against human ovarian cancer cells.
• To elucidate the mechanism of action for the most active complex.

Main Methods:

• Synthesis and characterization of four dinuclear silver(I) and gold(I) bisNHC complexes.
• In vitro anticancer activity screening using the A2780 human ovarian cancer cell line.
• Mechanistic studies involving reactive oxygen species (ROS) production and thioredoxin reductase (TrxR) inhibition assays.

Main Results:

• Complex 4 exhibited strong and selective anticancer activity against A2780 cells.
• Complex 4 was found to enhance oxidative stress by stimulating ROS production.
• The complex inhibited the activity of thioredoxin reductase, a key antioxidant enzyme.

Conclusions:

• Dinuclear metal-NHC complexes can be designed to possess significant anticancer properties.
• Ligand and electronic property tuning is crucial for modulating reactivity and selectivity.
• Complex 4 represents a promising lead compound for novel anticancer drug development.