An Organogold Compound as Potential Antimicrobial Agent against Drug-Resistant Bacteria: Initial Mechanistic Insights

ChemMedChem. 2021 Oct 6;16(19):3060-3070. doi: 10.1002/cmdc.202100342. Epub 2021 Jul 23.

Abstract

The rise of antimicrobial resistance has necessitated novel strategies to efficiently combat pathogenic bacteria. Metal-based compounds have been proven as a possible alternative to classical organic drugs. Here, we have assessed the antibacterial activity of seven gold complexes of different families. One compound, a cyclometalated Au(III) C^N complex, showed activity against Gram-positive bacteria, including multi-drug resistant clinical strains. The mechanism of action of this compound was studied in Bacillus subtilis. Overall, the studies point towards a complex mode of antibacterial action, which does not include induction of oxidative stress or cell membrane damage. A number of genes related to metal transport and homeostasis were upregulated upon short treatment of the cells with gold compound. Toxicity tests conducted on precision-cut mouse tissue slices ex vivo revealed that the organogold compound is poorly toxic to mouse liver and kidney tissues, and may thus, be treated as an antibacterial drug candidate.

Keywords: Antibiotics; drug resistant bacteria; gold compounds; mode of action.; organometallic drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Gram-Positive Bacteria / drug effects*
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Organogold Compounds / chemical synthesis
  • Organogold Compounds / chemistry
  • Organogold Compounds / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Organogold Compounds

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