In vitro studies of the activity of dithiocarbamate organoruthenium complexes against clinically relevant fungal pathogens

Molecules. 2014 Apr 24;19(4):5402-20. doi: 10.3390/molecules19045402.

Abstract

The in vitro antifungal activity of nine dirutheniumpentadithiocarbamate complexes C1-C9 was investigated and assessed for its activity against four different fungal species with clinical interest and related to invasive fungal infections (IFIs), such as Candida spp. [C. albicans (two clinical isolates), C. glabrata, C. krusei, C. parapsolisis, C. tropicalis, C.dubliniensis (six clinical isolates)], Paracoccidioides brasiliensis (seven clinical isolates), Cryptococcus neoformans and Sporothrix schenckii. All synthesized complexes C1-C9 and also the free ligands L1-L9 were submitted to in vitro tests against those fungi and the results are very promising, since some of the obtained MIC (minimal inhibitory concentration) values were very low (from 10-6 mol mL-1 to 10-8 mol mL-1) against all investigated clinically relevant fungal pathogens, except for C. glabrata, that the MIC values are close to the ones obtained for fluconazole, the standard antifungal agent tested. Preliminary structure-activity relations (SAR) might be suggested and a strong influence from steric and lipophilic parameters in the antifungal activity can be noticed. Cytotoxicity assays (IC50) showed that the complexes are not as toxic (IC50 values are much higher-30 to 200 fold-than MIC values). These ruthenium complexes are very promising lead compounds for novel antifungal drug development, especially in IFIs, one of most harmful emerging infection diseases (EIDs).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology*
  • Antifungal Agents / toxicity
  • Candida / drug effects*
  • Candida / physiology
  • Cell Line
  • Cell Survival / drug effects
  • Coordination Complexes / pharmacology*
  • Coordination Complexes / toxicity
  • Cricetinae
  • Cryptococcus neoformans / drug effects
  • Cryptococcus neoformans / physiology
  • Humans
  • Inhibitory Concentration 50
  • Microbial Sensitivity Tests
  • Ruthenium / chemistry
  • Sporothrix / drug effects
  • Sporothrix / physiology
  • Thiocarbamates / chemistry

Substances

  • Antifungal Agents
  • Coordination Complexes
  • Thiocarbamates
  • Ruthenium