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An N-Acetyl Cysteine Ruthenium Tricarbonyl Conjugate Enables Simultaneous Release of CO and Ablation of Reactive Oxygen Species.


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Authors

Seixas, João D 
Chaves-Ferreira, Miguel 
Montes-Grajales, Diana 
Gonçalves, Ana M 
Marques, Ana R 

Abstract

We have designed and synthesised a [Ru(CO)3 Cl2 (NAC)] pro-drug that features an N-acetyl cysteine (NAC) ligand. This NAC carbon monoxide releasing molecule (CORM) conjugate is able to simultaneously release biologically active CO and to ablate the concurrent formation of reactive oxygen species (ROS). Complexes of the general formulae Ru(CO)3 (L)3 , including [Ru(CO)3 Cl(glycinate)] (CORM-3), have been shown to produce ROS through a water-gas shift reaction, which contributes significantly, for example, to their antibacterial activity. In contrast, NAC-CORM conjugates do not produce ROS or possess antibacterial activity. In addition, we demonstrate the synergistic effect of CO and NAC both for the inhibition of nitric oxide (formation) and in the expression of tumour-necrosis factor (TNF)-α. This work highlights the advantages of combining a CO-releasing scaffold with the anti-oxidant and anti-inflammatory drug NAC in a unique pro-drug.

Description

Keywords

N-acetyl cysteine, anti-oxidants, carbon monoxide, prodrugs, reactive oxygen species, ruthenium

Journal Title

Chemistry

Conference Name

Journal ISSN

0947-6539
1521-3765

Volume Title

21

Publisher

Wiley
Sponsorship
Engineering and Physical Sciences Research Council (EP/M003647/1)
We thank the EU (Marie Curie CIG to G.J.L.B.), FCT Portugal (FCT Investigator to G.J.L.B.; SFRH/BPD/95253/2013 to J.D.S.) and the EPSRC for funding. The NMR spectrometers are part of The National NMR Facility, supported by Fundação para a Ciência e a Tecnologia (RECI/BBB-BQB/0230/2012). G.J.L.B. is a Royal Society University Research Fellow.