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Published on: May 28, 2014
Gold(iii) bis(dithiolene) complexes: from molecular conductors to prospective anticancer, antimicrobial and
Diana Fontinha1, Sílvia A Sousa2, Tânia S Morais3
1Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal.
Abstract:
The anticancer, antimicrobial and antiplasmodial activities of six gold(iii) bis(dithiolene) complexes were studied. Complexes 1-6 showed relevant anticancer properties against A2780/A2780cisR ovarian cancer cells (IC50 values of 0.08-2 μM), also being able to overcome cisplatin resistance in A2780cisR cells. Complex 1 also exhibited significant antimicrobial activity against Staphylococcus aureus (minimum inhibitory concentration (MIC) values of 12.1 ± 3.9 μg mL-1) and both Candida glabrata and Candida albicans (MICs of 9.7 ± 2.7 and 19.9 ± 2.4 μg mL-1, respectively). In addition, all complexes displayed antiplasmodial activity against the Plasmodium berghei parasite liver stages, even exhibiting better results than the ones obtained using primaquine, an anti-malarial drug. Mechanistic studies support the idea that thioredoxin reductase, but not DNA, is a possible target of these complexes. Complex 1 is stable under biological conditions, which would be important if this compound is ever to be considered as a drug. Overall, the results obtained evidenced the promising biological activity of complex 1, which might have potential as a novel anticancer, antimicrobial and antiplasmodial agent to be used as an alternative to current therapeutics.
Insights
Six gold(III) bis(dithiolene) complexes demonstrate potent anticancer, antimicrobial, and antiplasmodial activities. Complex 1 shows particular promise as a potential therapeutic agent against drug-resistant cancers and infectious diseases.
Area of Science:
- Inorganic Chemistry
- Medicinal Chemistry
- Pharmacology
Background:
- Gold(III) complexes are explored for therapeutic applications.
- Dithiolene ligands can modulate the properties of metal complexes.
- Drug resistance necessitates the development of novel therapeutic agents.
Purpose of the Study:
- To synthesize and evaluate the biological activities of six gold(III) bis(dithiolene) complexes.
- To investigate their potential as anticancer, antimicrobial, and antiplasmodial agents.
- To explore their mechanism of action and stability.
Main Methods:
- Synthesis of six gold(III) bis(dithiolene) complexes.
- In vitro evaluation of anticancer activity against ovarian cancer cell lines (A2780/A2780cisR).
- Antimicrobial susceptibility testing against Staphylococcus aureus and Candida species.
- Antiplasmodial assays against Plasmodium berghei.
- Mechanistic studies involving enzyme inhibition and stability tests.
Main Results:
- Complexes 1-6 exhibited significant anticancer activity (IC50: 0.08-2 μM) and overcame cisplatin resistance.
- Complex 1 showed potent antimicrobial activity against Staphylococcus aureus and Candida species (MICs: 9.7-19.9 μg mL-1).
- All complexes displayed antiplasmodial activity, with some outperforming primaquine.
- Mechanistic studies suggest thioredoxin reductase as a potential target, not DNA.
- Complex 1 demonstrated stability under biological conditions.
Conclusions:
- Gold(III) bis(dithiolene) complexes possess broad-spectrum biological activities.
- Complex 1 is a promising candidate for development as a novel anticancer, antimicrobial, and antiplasmodial therapeutic.
- These complexes offer potential alternatives to existing treatments, particularly in cases of drug resistance.
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