Broad Spectrum Functional Activity of Structurally Related Monoanionic Au(III) Bis(Dithiolene) Complexes

Area of Science:

• Medicinal Chemistry
• Inorganic Chemistry
• Pharmacology

Background:

• Gold complexes are explored for therapeutic applications.
• Dithiolene and diselenolene ligands offer diverse coordination chemistry.
• Structure-activity relationships are crucial for drug development.

Purpose of the Study:

• To synthesize and evaluate the biological properties of novel gold (III) bis(dithiolene/diselenolene) complexes.
• To investigate their potential as anticancer, antimicrobial, and anti-HIV agents.
• To explore their in vivo toxicity and mechanism of action.

Main Methods:

• Synthesis of sixteen structurally related gold (III) complexes.
• In vitro evaluation of anticancer activity against ovarian cancer cell lines (A2780, OVCAR8).
• In vitro assessment of antimicrobial and antiplasmodial activities.
• In vivo toxicity studies in zebrafish embryos.
• Mechanistic studies involving thioredoxin reductase and human serum albumin interactions.

Main Results:

• Most complexes exhibited significant anticancer activity, with IC50 values as low as 0.1 μM against A2780 cells.
• Complexes with Ph4P+ counter-ions were generally more active and less toxic in vivo than Et4N+ analogues.
• Exceptional antiplasmodial activity was observed for several Ph4P+ complexes against Plasmodium berghei liver stages.
• Antibacterial/fungal activities were highest for Et4N+ complexes.
• Mechanistic studies suggest thioredoxin reductase as a potential target.

Conclusions:

• The evaluated gold (III) complexes display promising anticancer, antiplasmodial, and antimicrobial properties.
• Structural modifications, particularly the counter-ion, significantly influence biological activity and toxicity.
• These complexes warrant further investigation as potential drug candidates for various diseases.