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

Diana Fontinha; Sílvia A. Sousa; Tânia S. Morais; Miguel Prudêncio; Jorge H. Leitão; Yann Le Gal; Dominique Lorcy; Rafaela A. L. Silva; Mariana F. G. Velho; Dulce Belo; M. Almeida; Joana F. Guerreiro; Teresa Pinheiro; Fernanda Marques

doi:10.1039/D0MT00064G

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

Diana Fontinha,^a Sílvia A. Sousa,^b Tânia S. Morais,

^c Miguel Prudêncio,

^a Jorge H. Leitão,

^b Yann Le Gal,^d Dominique Lorcy,

^d Rafaela A. L. Silva,^e Mariana F. G. Velho,^ef Dulce Belo,^e M. Almeida,

^e Joana F. Guerreiro,

^e Teresa Pinheiro^g and Fernanda Marques

*^e

Author affiliations

* Corresponding authors

^a Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal

^b iBB-Institute for Bioengineering and Biosciences, Departmento de Bioengenharia, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal

^c Centro de Química Estrutural, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal

^d Univ Rennes, CNRS, ISCR (Institut des Sciences Chimiques de Rennes) – UMR 6226, F-35000 Rennes, France

^e Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10 (km 139,7), 2695-066 Bobadela LRS, Portugal
E-mail: fmarujo@ctn.tecnico.ulisboa.pt

^f Instituto de Telecomunicações, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1, Lisboa, Portugal

^g iBB-Institute for Bioengineering and Biosciences, Departamento de Engenharia e Ciências Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 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.

Metallomics

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

Abstract

Supplementary files

Article information

Download Citation

Search articles by author

Spotlight

Advertisements