Gold(I) and Gold(III) N-Heterocyclic Carbene Complexes as Antibacterial Agents and Inhibitors of Bacterial Thioredoxin Reductase

ChemMedChem. 2021 Nov 19;16(22):3402-3409. doi: 10.1002/cmdc.202100381. Epub 2021 Aug 3.

Abstract

A series of (NHC)Au(I)Cl monocarbene complexes and their gold(III) analogues (NHC)Au(III)Cl3 were prepared and investigated as antibacterial agents and inhibitors of bacterial TrxR. The complexes showed stronger antibacterial effects against the Gram-positive MRSA and E. faecium strains than against several Gram-negative bacteria. All complexes were efficient inhibitors of bacterial thioredoxin reductase, indicating that inhibition of this enzyme might be involved in their mechanism of action. The efficacy of gold(I) and gold(III) analogues was comparable in most of the assays. The cytotoxicity of the gold NHC compounds against cancer and human cells was overall weaker than the activity against the Gram-positive bacteria, suggesting that their optimization as antibacterials warrants further investigation.

Keywords: N-heterocyclic carbene; antibacterial; gold; thioredoxin reductase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Gold / chemistry
  • Gold / pharmacology*
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / enzymology
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacteria / enzymology
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology*
  • Humans
  • Methane / analogs & derivatives*
  • Methane / chemistry
  • Methane / pharmacology
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Structure-Activity Relationship
  • Thioredoxin-Disulfide Reductase / antagonists & inhibitors*
  • Thioredoxin-Disulfide Reductase / metabolism

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Heterocyclic Compounds
  • carbene
  • Gold
  • Thioredoxin-Disulfide Reductase
  • Methane

Grants and funding