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Oligonuclear polypyridylruthenium(II) complexes: selectivity between bacteria and eukaryotic cells.

Anil K Gorle¹, Xin Li¹, Sebastian Primrose²

¹School of Physical, Environmental and Mathematical Sciences, University of New South Wales, Australian Defence Force Academy, Canberra, ACT 2600, Australia.

The Journal of Antimicrobial Chemotherapy

|March 7, 2016

Summary

Ruthenium complexes show potent bactericidal activity against Gram-positive and Gram-negative bacteria. These novel antimicrobial agents demonstrate potential for development, with favorable toxicity profiles and achievable in vivo concentrations.

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The Synthesis, Characterization and Reactivity of a Series of Ruthenium N-triphosPh Complexes

The Synthesis, Characterization and Reactivity of a Series of Ruthenium N-triphosPh Complexes

Published on: April 10, 2015

Area of Science:

Inorganic Chemistry
Antimicrobial Research
Toxicology

Background:

The rise of antibiotic resistance necessitates the development of novel antimicrobial agents.
Ruthenium complexes are being explored for their therapeutic potential due to their unique coordination chemistry and biological activities.

Purpose of the Study:

To evaluate the in vitro antimicrobial activity and cytotoxicity of di-, tri-, and tetra-nuclear ruthenium complexes.
To compare the efficacy of these complexes against Gram-positive and Gram-negative bacteria.
To assess the potential of the least toxic complex for in vivo applications by comparing its minimum inhibitory concentration (MIC) with achievable serum concentrations.

Main Methods:

Minimum Inhibitory Concentration (MIC) assays and time-kill curve experiments were used to determine antimicrobial activity.
Alamar blue cytotoxicity assay was employed to assess toxicity against eukaryotic cells.
Preliminary pharmacokinetic studies in mice were conducted to determine serum concentrations over time.

Main Results:

The ruthenium complexes (Rubb12, Rubb12-tri, Rubb12-tetra) exhibited high activity against Gram-positive bacteria (MICs 1-2 mg/L) and variable activity against Gram-negative bacteria.
Time-kill experiments confirmed bactericidal activity within 3-8 hours.
Complexes showed significantly lower toxicity to liver and kidney cells compared to bacterial cells (approx. 50x for Gram-positive, 25x for Gram-negative).
Pharmacokinetic studies indicated that serum concentrations exceeding MIC values are achievable for Rubb12 at a dose of 32 mg/kg.

Conclusions:

Ruthenium complexes, particularly Rubb12, show promise as novel antimicrobial agents.
Further structural modification of dinuclear ruthenium complexes could enhance selectivity towards bacteria over eukaryotic cells.