Gold(iii) bis(dithiolene) complexes: from molecular conductors to prospective anticancer, antimicrobial and antiplasmodial agents. Issue 6 (11th May 2020)

• Record Type: Journal Article
• Authors: Fontinha, Diana; Sousa, Sílvia A.; Morais, Tânia S.; Prudêncio, Miguel; Leitão, Jorge H.; Le Gal, Yann; Lorcy, Dominique; Silva, Rafaela A. L.; Velho, Mariana F. G.; Belo, Dulce; Almeida, M.; Guerreiro, Joana F.; Pinheiro, Teresa; Marques, Fernanda
• Is Part Of: Metallomics. Volume 12:Issue 6(2020)
• Page Start: 974
• Page End: 987
• Publication Date: 2020-05-11
• Subjects: Metals -- Physiological effect -- Periodicals; 572.51
• DOI: 10.1039/d0mt00064g
• Languages: English
• ISSNs: 1756-5901

Abstract

Abstract : Gold(iii ) bis(dithiolene) complexes were evaluated as therapeutic drugs. [Net4 ][Au(Et-thiazdt)2 ], 1, exhibits interesting anticancer, antibacterial, antifungal and antimicrobial properties. 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.