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

作者：Li Fangfei; Harry Elizabeth J; Bottomley Amy L; Edstein Michael D; Birrell Geoffrey W; Woodward Clifford E; Keene F Richard^*; Collins J Grant

来源：Chemical Science, 2014, 5(2): 685-693.

DOI：10.1039/c3sc52166d

Wide-field fluorescence microscopy at high magnification was used to study the intracellular binding site of Rubb(16) in Escherichia coli. Upon incubation of E. coli cells at the minimum inhibitory concentration, Rubb(16) localised at ribosomes with no significant DNA binding observed. Furthermore, Rubb(16) condensed 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 Rubb(n) selectively 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 Rubb(n) complexes could be selectively toxic to bacteria. In support of this hypothesis, the toxicity of Rubb(16) was found to be significantly less to liver and kidney cell lines than against a range of bacteria.

• 出版日期2014