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

Chemistry : a European Journal
João D SeixasGonçalo J L Bernardes

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.

References

Jul 5, 2003·Circulation Research·James E ClarkRoberto Motterlini
Jan 6, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Yiru GuoRoberto Bolli
Apr 4, 2007·Dalton Transactions : an International Journal of Inorganic Chemistry·Tony R JohnsonRoberto Motterlini
Nov 21, 2007·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Muntaser D MusamehRoberto Motterlini
Nov 8, 2008·Expert Opinion on Biological Therapy·Seetal DoddMichael Berk
Sep 3, 2010·Nature Reviews. Drug Discovery·Roberto Motterlini, Leo E Otterbein
Jan 6, 2011·Journal of the American Chemical Society·Teresa Santos-SilvaMaria J Romão
Feb 26, 2011·Angewandte Chemie·Steffen RomanskiHans-Günther Schmalz
Jun 8, 2011·The Journal of Biological Chemistry·Ana Filipa N TavaresLígia M Saraiva
Jul 7, 2011·Current Medicinal Chemistry·T Santos-SilvaM J Romão
Sep 2, 2011·Dalton Transactions : an International Journal of Inorganic Chemistry·Fabio ZobiAnna Yu Bogdanova
Dec 14, 2011·Antimicrobial Agents and Chemotherapy·Ana C PenaAna Pamplona
Jan 10, 2012·Journal of the American Chemical Society·Júlio S RebouçasBrian R James
Feb 22, 2012·Chemical Society Reviews·Carlos C RomãoGonçalo J L Bernardes
Sep 14, 2012·Journal of the American Chemical Society·Brian W MichelChristopher J Chang
Jan 24, 2014·Angewandte Chemie·Rakesh K PathakShanta Dhar
Jan 28, 2014·European Journal of Medicinal Chemistry·Pengpeng WangQian Zheng
Apr 30, 2014·Chemical Communications : Chem Comm·Qinqin ChengYangzhong Liu
Jul 30, 2014·Angewandte Chemie·Sandra García-Gallego, Gonçalo J L Bernardes
Nov 28, 2014·Dalton Transactions : an International Journal of Inorganic Chemistry·João D SeixasCarlos C Romão
Dec 6, 2014·Angewandte Chemie·Miguel Chaves-FerreiraGonçalo J L Bernardes
Feb 11, 2015·Chemical Communications : Chem Comm·Inês S AlbuquerqueGonçalo J L Bernardes

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Citations

May 9, 2018·Experimental Lung Research·David LinAnthony M Szema
Dec 11, 2019·Medicinal Research Reviews·Xiaoxiao YangBinghe Wang
Mar 2, 2021·Acta Pharmaceutica Sinica. B·Dominik BakalarzMarcin Magierowski
Jun 3, 2021·Antioxidants·Sofia S MendesLígia M Saraiva
Jul 3, 2021·Pharmaceutics·Alexandra-Cristina Munteanu, Valentina Uivarosi

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Methods Mentioned

BETA
Confocal microscopy
enzyme-linked immunosorbent assay
ELISA

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