title: An N-Acetyl Cysteine Ruthenium Tricarbonyl Conjugate Enables Simultaneous Release of CO and Ablation of Reactive Oxygen Species.
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 ](2+) , 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.
authors: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa (Portugal) www.gbernardes-lab.com.|Instituto de Tecnologia Química e Biológica-António Xavier, Universidade Nova de Lisboa, Av da República, 2780-157 Oeiras (Portugal).|Alfama Ltd., Instituto de Biologia Experimental e Tecnológica, IBET, Av. da República, EAN, 2780-157 Oeiras (Portugal).
authors: João D
authors: JD
authors: Seixas
authors: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa (Portugal) www.gbernardes-lab.com.
authors: Miguel
authors: M
authors: Chaves-Ferreira
authors: Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW Cambridge (UK).|School of Pharmaceutical Sciences, University of Cartagena, Campus of Zaragocilla, Cartagena, Bolivar 130015 (Colombia).
authors: Diana
authors: D
authors: Montes-Grajales
authors: Alfama Ltd., Instituto de Biologia Experimental e Tecnológica, IBET, Av. da República, EAN, 2780-157 Oeiras (Portugal).
authors: Ana M
authors: AM
authors: Gonçalves
authors: Alfama Ltd., Instituto de Biologia Experimental e Tecnológica, IBET, Av. da República, EAN, 2780-157 Oeiras (Portugal).
authors: Ana R
authors: AR
authors: Marques
authors: Instituto de Tecnologia Química e Biológica-António Xavier, Universidade Nova de Lisboa, Av da República, 2780-157 Oeiras (Portugal).
authors: Lígia M
authors: LM
authors: Saraiva
authors: School of Pharmaceutical Sciences, University of Cartagena, Campus of Zaragocilla, Cartagena, Bolivar 130015 (Colombia).
authors: Jesus
authors: J
authors: Olivero-Verbel
authors: Instituto de Tecnologia Química e Biológica-António Xavier, Universidade Nova de Lisboa, Av da República, 2780-157 Oeiras (Portugal).|Alfama Ltd., Instituto de Biologia Experimental e Tecnológica, IBET, Av. da República, EAN, 2780-157 Oeiras (Portugal).
authors: Carlos C
authors: CC
authors: Romão
authors: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa (Portugal) www.gbernardes-lab.com. gbernardes@medicina.ulisboa.pt, gb453@cam.ac.uk.|Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW Cambridge (UK). gbernardes@medicina.ulisboa.pt, gb453@cam.ac.uk.
authors: Gonçalo J L
authors: GJ
authors: Bernardes
keywords: N-acetyl cysteine; anti-oxidants; carbon monoxide; prodrugs; reactive oxygen species; ruthenium