Dinuclear ruthenium(ii) antimicrobial agents that selectively target polysomes in vivo

Publication Type:
Journal Article
Citation:
Chemical Science, 2014, 5 (2), pp. 685 - 693
Issue Date:
2014-02-01
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Wide-field fluorescence microscopy at high magnification was used to study the intracellular binding site of Rubb16in Escherichia coli. Upon incubation of E. coli cells at the minimum inhibitory concentration, Rubb16localised at ribosomes with no significant DNA binding observed. Furthermore, Rubb16condensed the ribosomes when they existed as polysomes. It is postulated that the condensation of polysomes would halt protein production, and thereby inhibit bacterial growth. The results of this study indicate that the family of inert dinuclear ruthenium complexes Rubbnselectively target RNA over DNA in vivo. Selective RNA targeting could be advantageous for the development of therapeutic agents, and because of differences in ribosome structure between bacteria and eukaryotic cells, the Rubbncomplexes could be selectively toxic to bacteria. In support of this hypothesis, the toxicity of Rubb16was found to be significantly less to liver and kidney cell lines than against a range of bacteria. © 2014 The Royal Society of Chemistry.
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