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

Metallomics. 2020 Jun 24;12(6):974-987. doi: 10.1039/d0mt00064g.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Female
  • Gold / chemistry*
  • Humans
  • Microbial Sensitivity Tests
  • Ovarian Neoplasms / metabolism
  • Plasmodium berghei / drug effects
  • Prospective Studies
  • Spectrometry, Fluorescence
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / metabolism
  • Structure-Activity Relationship
  • Thioredoxin-Disulfide Reductase / metabolism

Substances

  • Anti-Bacterial Agents
  • Antimalarials
  • Antineoplastic Agents
  • Gold
  • Thioredoxin-Disulfide Reductase