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Pyrazolyl-Pyridine Ruthenium Complexes: A New Metallic Line of Defense Against Acinetobacter baumannii.

M Cassiem Joseph1,2, Sheldon Sookai1, Monika Nowakowska1

  • 1School of Chemistry, University of the Witwatersrand, Johannesburg, South Africa.

Chembiochem : a European Journal of Chemical Biology
|May 10, 2026
PubMed
Summary
This summary is machine-generated.

Novel ruthenium (Ru(II)) complexes show potent antibacterial activity against drug-resistant Acinetobacter baumannii. These metalloantibiotics offer a promising new strategy to combat antimicrobial resistance (AMR).

Keywords:
AMRESKAPEinorganic medicinal chemistrymetallodrugsmetals in medicine

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Area of Science:

  • Coordination Chemistry
  • Medicinal Chemistry
  • Microbiology

Background:

  • Antimicrobial resistance (AMR) necessitates novel antibiotics with unique mechanisms of action.
  • Transition-metal complexes offer diverse chemical properties for drug development.
  • ESKAPE pathogens are a critical threat due to multidrug resistance.

Purpose of the Study:

  • To synthesize and evaluate Ru(II) pyrazolyl-pyridine half-sandwich complexes for antibacterial and antifungal activity.
  • To explore new metalloantibiotic frameworks beyond existing pyridyl-triazolyl systems.
  • To investigate the mechanism of action of potent Ru(II) complexes against resistant bacteria.

Main Methods:

  • Synthesis and structural characterization (X-ray diffraction) of Ru(II) complexes.
  • Antimicrobial screening using the CO-ADD platform.
  • Cytotoxicity, hemolysis, DNA-binding assays, and in silico modeling.

Main Results:

  • Ru(II) complexes C1-C3 demonstrated selective efficacy against Acinetobacter baumannii.
  • Potent compounds exhibited favorable therapeutic windows with low cytotoxicity and hemolysis.
  • Mechanism studies indicated DNA interaction via intercalation and groove binding.

Conclusions:

  • Ru(II) pyrazolyl-pyridine complexes represent a promising class of next-generation metalloantibiotics.
  • Coordination chemistry provides a valuable approach to developing novel antimicrobial agents.
  • These findings contribute to addressing the urgent global challenge of AMR.