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| 1 | S-Nitroso-N-acetyl-L-cysteine ethyl ester(SNACET) and N-acetyl-L-cysteine ethyl ester(NACET)–Cysteine-based drug candidates with unique pharmacological profiles for oral use as NO, H_2S and GSH suppliers and as antioxidants: Results and overview显示文摘S-Nitrosothiols or thionitrites with the general formula RSNO are formally composed of the nitrosyl cation(NOt) and a thiolate(RSà), the base of the corresponding acids RSH. The smallest S-nitrosothiol is HSNO and derives from hydrogen sulfide(HSH, H_2S). The most common physiological S-nitrosothiols are derived from the amino acid L-cysteine(Cys SH). Thus, the simplest S-nitrosothiol is S-nitroso-L-cysteine(Cys SNO). Cys SNO is a spontaneous potent donor of nitric oxide(NO) which activates soluble guanylyl cyclase to form cyclic guanosine monophosphate(c GMP). This activation is associated with multiple biological actions that include relaxation of smooth muscle cells and inhibition of platelet aggregation.Like NO, Cys SNO is a short-lived species and occurs physiologically at concentrations around 1 n M in human blood. Cys SNO can be formed from Cys SH and higher oxides of NO including nitrous acid(HONO)and its anhydride(N_2O_3). The most characteristic feature of RSNO is the S-transnitrosation reaction by which the NOtgroup is reversibly transferred to another thiolate. By this way numerous RSNO can be formed such as the low-molecular-mass S-nitroso-N-acetyl-L-cysteine(SNAC) and S-nitroso-glutathione(GSNO), and the high-molecular-mass S-nitrosol-L-cysteine hemoglobin(Hb Cys SNO) present in erythrocytes and S-nitrosol-L-cysteine albumin(Alb Cys SNO) present in plasma at concentrations of the order of 200 n M. All above mentioned RSNO exert NO-related biological activity, but they must be administered intravenously. This important drawback can be overcome by lipophilic charge-free RSNO.Thus, we prepared the ethyl ester of SNAC, the S-nitroso-N-acetyl-L-cysteine ethyl ester(SNACET), from synthetic N-acetyl-L-cysteine ethyl ester(NACET). Both NACET and SNACET have improved pharmacological features over N-acetyl-L-cysteine(NAC) and S-nitroso-N-acetyl-L-cysteine(SNAC), respectively,including higher oral bioavailability. SNACET exerts NO-related activities which can be utilized in the urogenital tract and in the cardiovascular system. NACET, with high oral bioavailability, is a strong antioxidant and abundant precursor of GSH, unlike its free acid N-acetyl-L-cysteine(NAC). Here, we review the chemical and pharmacological properties of SNACET and NACET as well as their analytical chemistry.We also report new results from the ingestion of S-[^(15) N]nitroso-N-acetyl-L-cysteine ethyl ester(S^(15) NACET) demonstrating the favorable pharmacological profile of SNACET. | Dimitrios Tsikas Kathrin S.Schwedhelm Andrzej Surdacki Daniela Giustarini Ranieri Rossi Lea Kukoc-Modun George Kedia Stefan ückert | 2018 | Journal of Pharmaceutical Analysis2018，8，1： | 3 |
| 2 | S-Adenosyl-L-methionine towards hepatitis C virus expression: Need to consider S-Adenosyl-L-methionine's chemistry, physiology and pharmacokinetics显示文摘S-Adenosyl-L-methionine(SAM) is a cofactor serving as a methyl donor in numerous enzymatic reactions. It has been reported that SAM has the potential to modify antioxidant-enzymes, glutathione-biosynthesis and methionine adenosyltransferases-1/2 in hepatitis C virus-expressing cells at millimolar concentrations. The efficacy of SAM at micromolar concentrations and the underlying mechanisms remain to be demonstrated. | Dimitrios Tsikas Erik Hanff Alexander Bollenbach | 2017 | World Journal of Gastroenterology2017，23，40： | 2 |
| 3 | Electrosprayionization mass spectrometry of low-molecular-mass S-nitroso compounds and their thiols显示文摘 | Tsikas D Raida M Sandmann J | 2000 | J Chromatogr BBiomed Sci Appl2000，742，1： | 1 |
| 4 | Asymmetric dimeth- ylarginine(ADMA)-A modulator of nociception in opiate tol- erance and addiction显示文摘 | Kielstein A Tsikas D Galloway GP | 2007 | Nitric Oxide2007，17，2： | 1 |
| 5 | Signal transducer and activator of transcription 3 - mediated regulation of miR - 199a - 5p links cardiomyocyte and endothelial cell function in the heart : A key role for ubiquitin - conjugating enzymes 显示文摘 | Haghikia A Missol- Kolka E Tsikas D | 2011 | EurHeart J2011，32，10： | 1 |
| 6 | Suppression of endothelial progenitor cells in human coronary artery disease by the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine显示文摘 | Thum T Tsikas D Stein S | 2005 | J Am Coll Cardiol2005，46，： | 1 |
| 7 | Early renal ischemia-reperfusion injury in humans is dominated by IL-6 release from the allograft显示文摘 | de Vries DK Lindeman JH Tsikas D | | 0，，07： | 1 |
| 8 | Endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine in pregnant women who subsequently develop pre - eclampsic 显示文摘 | Savvidou MD Hingorani AD Tsikas D | 2003 | Lancte2003，361，9368： | 1 |
| 9 | Suppression of endothelial progenitor cells in human coronary artery disease by the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine显示文摘 | Thum T Tsikas D Stein S | 2005 | J Am Coil Cardiol2005，46，9： | 1 |
| 10 | Oxidative stress and human diseases:Origin,link,measurement,mechanisms,and biomarkers显示文摘 | Giustarini D Dalle-Donne I Tsikas D | 2009 | Crit Rev Clin Lab Sci2009，46，56： | 1 |
| 11 | High performance liquid chromatography ultraviolet assay for human erythrocytic catalase activity by measuring glutathione as o - phthalaldehyde derivative显示文摘 | Anke Bfihmer Jens Jordan Dimitrios Tsikas | 2011 | Anal Biochem2011，410，2： | 1 |
| 12 | Simultaneous derivatization and quantification of the nitric oxide metabolites nitrite and nitrate in biological fluids by gas chromatography/mass spectrometry显示文摘 | TSIKAS D | 2000 | Anal Chem2000，72，2： | 1 |
| 13 | Analysis of nitrite and nitrate in biological fluids by assays based on the Griess reaction: Appraisal of the Griess reaction in the L-arginine/nitric oxide area of research显示文摘 | Tsikas D | 2007 | Journal of Chromatography B-Analytical Technolgies in the Biomedical and life Science2007，851，12： | 1 |
| 14 | Simultaneous UPLC-MS/MS quantification of the endocanna- binoids 2-arachidonoyl glycerol (2AG), 1-arachidonoyl glycerol (lAG), and anandamide in human plasma: minimization of matrix-effects, 2AG/1AG isomerization and degradation by toluene solvent extraction显示文摘 | TSIKAS D TRETTIN A ZOERNER | 2011 | J Chromatogr B2011，879，17： | 1 |
| 15 | Suppression of endothelial progenitor cells in human coronary artery disease by the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine 显示文摘 | Thum T Tsikas D Stein S | 2005 | J Am Coll Cardiol2005，46，9： | 1 |
| 16 | Pitfalls with nitric oxide synthase activity assays and their avoidance by gas chromatography- mass spectrometry显示文摘 | TSIKAS D | 2015 | Kidney Int2015，87，4： | 1 |
| 17 | No effects of atorvastatin on nitric oxide, prostacyclin, thromboxane and oxidative stress in type 2 diabetes mellitus patients of the DALI study显示文摘 | TSIKAS D PHAM V V SUCHY M T | 2015 | Pharmacol Res2015，94，1： | 1 |
| 18 | Endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine in pregnant women who subsequently develop pre-eclampsia显示文摘 | Savvidou MD Hingorani AD Tsikas D | 2003 | Lancet2003，361，9368： | 1 |
| 19 | Pathogenic Cycle Between the Endogenous Nitric Oxide Synthase Inhibitor Asymmetrical Dimethylarginine and the Leukocyte-Derived Hemoprotein Myeloperoxidase显示文摘 | Eike-Christin von Leitner Anna Klinke Dorothee Atzler Jessica L. Slocum Natalie Lund Jan T. Kielstein Renke Maas Robin Schmidt-Haupt Michaela Pekarova Olaf Hellwinkel Dimitrios Tsikas Louis G. D?Alecy Denise Lau Stephan Willems Lukas Kubala Heimo Ehmke Th | 2011 | Circulation2011，，24： | 1 |
| 20 | Urinary 8-iso-Prostaglandin F2α as a Risk Marker in Patients With Coronary Heart Disease: A Matched Case-Control Study显示文摘 | Edzard Schwedhelm Asja Bartling Henrike Lenzen Dimitrios Tsikas Renke Maas Jens Brümmer Frank-Mathias Gutzki Jürgen Berger Jürgen C. Fr?lich Rainer H. B?ger | 2004 | Circulation: Journal of the American Heart Association2004，，7： | 1 |
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