Cyclometallated Au(iii) dithiocarbamate complexes: synthesis, anticancer evaluation and mechanistic studies

Area of Science:

• Organometallic Chemistry
• Medicinal Chemistry
• Cancer Research

Background:

• Cyclometallated gold(III) complexes are explored for therapeutic potential.
• Dithiocarbamate ligands can modulate the properties of metal complexes.

Purpose of the Study:

• Synthesize and characterize novel cationic mixed cyclometallated gold(III) dithiocarbamate complexes.
• Evaluate their in vitro cytotoxic properties against various cancer and healthy cell lines.
• Investigate their mechanism of action, including interactions with biological molecules.

Main Methods:

• Synthesis and crystal structure determination of gold(III) complexes.
• In vitro cytotoxicity assays using human cancer and healthy cell lines.
• Glutathione and N-acetyl cysteine stability studies.
• Intracellular uptake measurements.
• DNA interaction studies.
• Thioredoxin reductase inhibition assays.
• Reactive oxygen species generation assessment.

Main Results:

• Cationic mixed cyclometallated gold(III) dithiocarbamate complexes were synthesized in good yields.
• The crystal structure of one complex, [(C^N)AuS2CNEt2]PF6, was determined.
• Complexes exhibited cytotoxicity against cancer cell lines and were susceptible to glutathione reduction.
• Mechanism of action involves intracellular uptake, DNA interaction, and thioredoxin reductase inhibition, but not reactive oxygen species formation.

Conclusions:

• The synthesized gold(III) complexes possess promising cytotoxic properties.
• Their mechanism of action is multifaceted, involving interactions with key cellular components.
• Further research into these complexes may lead to novel anticancer agents.