TY - JOUR
T1 - An N-Acetyl Cysteine Ruthenium Tricarbonyl Conjugate Enables Simultaneous Release of CO and Ablation of Reactive Oxygen Species
AU - Seixas, João D.
AU - Chaves-Ferreira, Miguel
AU - Montes-Grajales, Diana
AU - Gonçalves, Ana M.
AU - Marques, Ana R.
AU - Saraiva, Lígia M.
AU - Olivero-Verbel, Jesus
AU - Romao, Carlos Jose
AU - Bernardes, Gonçalo J L
PY - 2015/10/1
Y1 - 2015/10/1
N2 - We have designed and synthesised a [Ru(CO)3Cl2(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)3Cl(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.
AB - We have designed and synthesised a [Ru(CO)3Cl2(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)3Cl(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.
KW - anti-oxidants
KW - carbon monoxide
KW - N-acetyl cysteine
KW - prodrugs
KW - reactive oxygen species
KW - ruthenium
UR - http://www.scopus.com/inward/record.url?scp=84943449535&partnerID=8YFLogxK
U2 - 10.1002/chem.201502474
DO - 10.1002/chem.201502474
M3 - Article
AN - SCOPUS:84943449535
SN - 0947-6539
VL - 21
SP - 14708
EP - 14712
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 42
ER -