5545-17-5Relevant academic research and scientific papers
On N-acetylcysteine. Part I. Experimental and theoretical approaches of the N-acetylcysteine/H2O2 complexation
Arroub,Berges,Abedinzadeh,Langlet,Gardes-Albert
, p. 2094 - 2101 (1994)
The complexation of N-acetylcysteine (RSH) with hydrogen peroxide has been studied experimentally and theoretically. Experimentally we have measured the evolution of RSH, H2O2, and RSSR (N-acetylcystine) as a function of time. Surprisingly, H2O2 decays by a biphasic process, which is not the case for RSH and RSSR. In the first stage of the kinetics, H2O2 disappears without oxidizing the thiol function of RSH. By analogy with glutathione (GSH), the formation of a complex between RSH and H2O2 has been proposed. The thermodynamic equilibrium constant of complex formation has been determined. Theoretical calculations were performed within the SIBFA method to pinpoint the sites of complexation in isolated and hydrated states. A mixed 'discrete-continuum' model was used to evaluate the solvent effect. The two stable complexes found in isolated state have different behaviour under the influence of the solvent. Comparison with complexed GSH is discussed.
A kinetic analysis of oxidation of the antioxidant N-acetyl-l-cysteine (NAC) by Pt(IV) complexes
You, Daofeng,Ren, Yanli,Huo, Shuying,Dong, Jingran,Ren, Shuguang,Shi, Tiesheng
, p. 295 - 304 (2016)
N-acetyl-l-cysteine (NAC) is an antioxidant and a supplement and has been demonstrated to have protective effects for a variety of toxic effects of heavy metals. Although previous works have shown that NAC can ameliorate the severe toxic effects of cisplatin, there is a lack of understanding of the interactions between NAC and Pt(IV)-based prodrugs. In this work, the oxidation of NAC by a cisplatin prodrug (cis-[Pt(NH3)2Cl4]), by a prototype of Pt(IV) anticancer drug ormaplatin ([Pt(dach)Cl4]) and by a model compound (trans-[PtCl2(CN)4]2-) was characterized in detail. NAC was oxidized to NAC-disulfide as identified by mass spectrometric analysis. Time-resolved spectral and stopped-flow kinetic measurements were carried out over a wide pH range, demonstrating that the oxidation followed overall second-order kinetics. The observed second-order rate constants k′ versus pH profiles were established. A reaction mechanism was deduced, involving three parallel rate-determining steps; conceivable transition states were also proposed for these steps. Rate constants of the rate-determining steps, obtained from the simulations of rate equation to the k′-pH profiles, were largely correlated with the electron density on the sulfur atom in NAC. The Pt(IV) prodrugs can execute oxidative stress in the biological systems of the human body by direct oxidation of relevant molecules, similar to HOCl/OCl- and chloroamines. Instead, the oxidative stress involved in the severe toxic effects of cisplatin is produced via a different mode. NAC could be a chemoprotecting agent also for the Pt(IV) anticancer drugs if recent drug delivery technologies are used.
Entropy-Controlled Cu(II)-Catalyzed Oxidation of N-Acetyl-L-Cysteine by Methylene Blue in Acidic Medium
Sharma, Ranjana,Pal, Mahender,Mishra
, p. 1093 - 1109 (2017)
Kinetics of the oxidation of N-acetyl-L-cysteine (NAC) by methylene blue (MB) catalyzed by Cu(II) have been investigated in presence of HCl. The reaction follows a first order kinetics in MB while the concentration order in NAC is zero. Hydrogen ions retard the rate of reaction. The reaction involves the participation of nanoparticles as revealed by SEM, XRD and FTIR techniques and a gel-like Cu-NAC network acts like the effective catalyst. The reaction conforms to Eley-Rideal mechanism at lower [NAC] while at higher [NAC], the kinetics are explained by extended Eley-Rideal mechanism. The reaction is regulated by the size and morphology of the nanoparticles and is controlled by the entropy of activation.
Electrochemical Evidence in Mechanism of Toxicity of Mefenamic Acid Overdose in the Presence of Glutathione and N-Acetyl-L-Cysteine
Amani, Ameneh,Amooshahi, Parvaneh,Khazalpour, Sadegh
, (2020)
In this study, the electrochemical oxidation of mefenamic acid was investigated in the presence of glutathione and N-acetyl-L-cysteine. The results revealed that the mefenamic acid was involved in a catalytic reaction with glutathione and N-acetyl-L-cysteine. This investigation presents some electrochemical evidence for the mechanism of action of these compounds in mefenamic acid poisoning.
Enhanced Cellular Polysulfides Negatively Regulate TLR4 Signaling and Mitigate Lethal Endotoxin Shock
Zhang, Tianli,Ono, Katsuhiko,Tsutsuki, Hiroyasu,Ihara, Hideshi,Islam, Waliul,Akaike, Takaaki,Sawa, Tomohiro
, p. 686 - 4,698 (2019)
Cysteine persulfide and cysteine polysulfides are cysteine derivatives having sulfane sulfur atoms bound to cysteine thiol. Accumulating evidence has suggested that cysteine persulfides/polysulfides are abundant in prokaryotes and eukaryotes and play important roles in diverse biological processes such as antioxidant host defense and redox-dependent signal transduction. Here, we show that enhancement of cellular polysulfides by using polysulfide donors developed in this study resulted in marked inhibition of lipopolysaccharide (LPS)-initiated macrophage activation. Polysulfide donor treatment strongly suppressed LPS-induced pro-inflammatory responses in macrophages by inhibiting Toll-like receptor 4 (TLR4) signaling. Other TLR signaling stimulants—including zymosan A-TLR2 and poly(I:C)-TLR3—were also significantly suppressed by polysulfur donor treatment. Administration of polysulfide donors protected mice from lethal endotoxin shock. These data indicate that cellular polysulfides negatively regulate TLR4-mediated pro-inflammatory signaling and hence constitute a potential target for inflammatory disorders. Zhang et al. developed potent persulfide donors consisting of sulfane sulfur atoms stabilized by N-acetyl-L-cysteine (NAC polysulfides) via disulfide bonds at both sides. Strong anti-inflammatory activity of NAC polysulfides was demonstrated in cultured macrophage models and a mouse endotoxin shock model.
Insights into the reactivity of gold-dithiocarbamato anticancer agents toward model biomolecules by using multinuclear NMR spectroscopy
Boscutti, Giulia,Marchio, Luciano,Ronconi, Luca,Fregona, Dolores
, p. 13428 - 13436 (2013)
Some gold(III)-dithiocarbamato derivatives of either single amino acids or oligopeptides have shown promise as potential anticancer agents, but their capability to interact with biologically relevant macromolecules is still poorly understood. We investigated the affinity of the representative complex [Au IIIBr2(dtc-Sar-OCH3)] (dtc: dithiocarbamate; Sar: sarcosine (N-methylglycine)) with selected model molecules for histidine-, methionine-, and cysteine-rich proteins (that is, 1-methylimidazole, dimethylsulfide, and N-acetyl-L-cysteine, respectively). In particular, detailed mono- and multinuclear NMR studies, in combination with multiple 13C/15N enrichments, allowed interactions to be followed over time and indicated somewhat unexpected reaction pathways. Whereas dimethylsulfide proved to be unreactive, a sudden multistep redox reaction occurred in the presence of the other potential sulfur donor, N-acetyl-L-cysteine (confirmed if glutathione was used instead). On the other hand, 1-methylimidazole underwent an unprecedented acid-base reaction with the gold(III) complex, rather than the expected coordination to the metal center by replacing, for instance, a bromide. Our results are discussed herein and compared with the data available in the literature on related complexes; our findings confirm that the peculiar reactivity of gold(III)-dithiocarbamato complexes can lead to novel reaction pathways and, therefore, to new cytotoxic mechanisms in cancer cells. To react or not to react? Model nitrogen- and sulfur-donor compounds can be treated with a representative gold(III)- dithiocarbamato anticancer agent to evaluate potential reactivity of such anticancer agents toward biomolecules (see figure). Detailed NMR studies show that the interaction with physiologically relevant species can lead to unexpected reaction pathways that may contribute to the novel mechanisms of cytotoxicity observed for this class of complexes. Copyright
On N-acetylcysteine. Part II. Oxidation of N-acetylcysteine by hydrogen peroxide: Kinetic study of the overall process
Abedinzadeh,Arroub,Gardes-Albert
, p. 2102 - 2107 (1994)
The oxidation kinetics of N-acetylcysteine (RSH) by hydrogen peroxide has been studied at neutral pH at different concentration ratios from 0.2 to 20 (4 x 10-4 mol L-1 ≤ [RSH]0 ≤ 2 x 10- mol L-1, 10-4 mol L-1 ≤ [H2O2]0 ≤ 10-2 mol L-1). In all the cases studied, N-acetyleystine (RSSR) is the only oxidized product formed. Our kinetic data have focused on the importance of the concentration ratio to reach the stoichiometric oxidation of N-acetylcysteine by hydrogen peroxide. Indeed non-stoichiometric oxidation of RSH occurs at relatively low concentration ratios (R 2.5. Moreover, it has been shown that in the first minutes of the reaction there is the formation of a complex between RSH and H2O2, the stoichiometry of the complex being RSH concentration-dependent for a given R (R > 2.5). Reaction mechanisms have been quantitatively established and the k values of each step determined.
Efficient Amino-Sulfhydryl Stapling on Peptides and Proteins Using Bifunctional NHS-Activated Acrylamides
Silva, Maria J. S. A.,Faustino, Hélio,Coelho, Jaime A. S.,Pinto, Maria V.,Fernandes, Adelaide,Compa?ón, Ismael,Corzana, Francisco,Gasser, Gilles,Gois, Pedro M. P.
supporting information, p. 10850 - 10857 (2021/04/15)
Widely used reagents in the peptide functionalization toolbox, Michael acceptors and N-hydroxysuccinimide (NHS) activated esters, are combined in NHS-activated acrylamides for efficient chemoselective amino-sulfhydryl stapling on native peptides and proteins. NHS-activated acrylamides allow for a fast functionalization of N-terminal cysteines (k2=1.54±0.18×103 M?1 s?1) under dilute aqueous conditions, enabling selectivity over other nucleophilic amino acids. Additionally, the versatility of these new bioconjugation handles was demonstrated in the cross-linking of in-chain or C-terminal cysteines with nearby lysine residues. NHS-activated acrylamides are compatible with the use of other cysteine selective reagents, allowing for orthogonal dual-modifications. This strategy was successfully applied to the late-stage functionalization of peptides and proteins with a PEG unit, fluorescent probe, and cytotoxic agent. The level of molecular control offered by NHS-activated acrylamides is expected to promote amino-sulfhydryl stapling technology as a powerful strategy to design functional bioconjugates.
PROCESS OF MAKING N,N'-DIACETYL-L-CYSTINE
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Page/Page column 16-17, (2021/11/06)
An effective process of making Ν,Ν'-diacetyl-L-Cystine ( NDAC ), which process is fast, green, does not require labor-intensive isolation or purification of the product, by yielding products in desired ratio, and has improved yield and purity. The process comprising the steps of Forming a reaction mixture, starting with a cystine derivative di-tert- butyl-L-cystine as the dihydrochloride form; Acetylating said di-tert-butyl-L-cystine to obtain Ν,Ν'-diacetyl-di-tert- butyl-L-cystine; followed by Removing said tert- butyl groups from said Ν,Ν'-diacetyl-di-tert-butyl- L-cystine to obtain Ν,Ν'-diacetyl-L-cystine product; and Isolating said Ν,Ν'-diacetyl-L-Cystine product from said reaction mixture; wherein said acetylating agent is acetic anhydride.
Bacterial flavoprotein monooxygenase YxeK salvages toxic S-(2-succino)-adducts via oxygenolytic C–S bond cleavage
Ellis, Holly R.,Kammerer, Bernd,Lagies, Simon,Matthews, Arne,Sch?nfelder, Julia,Schleicher, Erik,Stull, Frederick,Teufel, Robin
, (2021/10/06)
Thiol-containing nucleophiles such as cysteine react spontaneously with the citric acid cycle intermediate fumarate to form S-(2-succino)-adducts. In Bacillus subtilis, a salvaging pathway encoded by the yxe operon has recently been identified for the detoxification and exploitation of these compounds as sulfur sources. This route involves acetylation of S-(2-succino)cysteine to N-acetyl-2-succinocysteine, which is presumably converted to oxaloacetate and N-acetylcysteine, before a final deacetylation step affords cysteine. The critical oxidative cleavage of the C–S bond of N-acetyl-S-(2-succino)cysteine was proposed to depend on the predicted flavoprotein monooxygenase YxeK. Here, we characterize YxeK and verify its role in S-(2-succino)-adduct detoxification and sulfur metabolism. Detailed biochemical and mechanistic investigation of YxeK including 18O-isotope-labeling experiments, homology modeling, substrate specificity tests, site-directed mutagenesis, and (pre-)steady-state kinetics provides insight into the enzyme’s mechanism of action, which may involve a noncanonical flavin-N5-peroxide species for C–S bond oxygenolysis.
