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Gold(iii) bis(dithiolene) complexes: from molecular conductors to prospective anticancer, antimicrobial and antiplasmodial agents

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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.

Graphical abstract: Gold(iii) bis(dithiolene) complexes: from molecular conductors to prospective anticancer, antimicrobial and antiplasmodial agents

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Supplementary files

Article information


Submitted
12 Mar 2020
Accepted
27 Apr 2020
First published
27 Apr 2020

Metallomics, 2020, Advance Article
Article type
Paper

Gold(III) bis(dithiolene) complexes: from molecular conductors to prospective anticancer, antimicrobial and antiplasmodial agents

D. Fontinha, S. A. Sousa, T. S. Morais, M. Prudêncio, J. H. Leitão, Y. Le Gal, D. Lorcy, R. A. L. Silva, M. F. G. Velho, D. Belo, M. Almeida, J. F. Guerreiro, T. Pinheiro and F. Marques, Metallomics, 2020, Advance Article , DOI: 10.1039/D0MT00064G

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