121-24-4Relevant articles and documents
Pro-oxidant activity of apocynin radical
Castor, Lidyane Regina Gomes,Locatelli, kátia Andreza,Ximenes, Valdecir Farias
, p. 1636 - 1643 (2010)
Apocynin has been widely used as an NADPH oxidase inhibitor in many experimental models. However, concern regarding the efficacy, selectivity, and oxidative side effects of the inhibitor is increasing. In this study, our aim was to characterize the pro-oxidant properties of apocynin and the structurally-related compounds vanillin and vanillic acid. Glutathione (GSH), cysteine, ovalbumin, and the coenzyme NADPH were chosen as potential target biomolecules that could be affected by transient free radicals from apocynin, vanillin and vanillic acid. Additionally, trolox and rifampicin were used as models of hydroquinone moieties, which are particularly susceptible to oxidation. Transient radicals were generated by horseradish peroxidase/hydrogen peroxide-mediated oxidation. In the presence of apocynin, oxidation of GSH was increased seven-fold, and the product of this reaction was identified as GSSG. Similar results were obtained for oxidation of cysteine and ovalbumin. Oxidation of the coenzyme NADPH increased more than 100-fold in the presence of apocynin. Apocynin also caused rapid oxidation of trolox and rifampicin to their quinone derivatives. In conclusion, the pro-oxidant activity of apocynin is related to its previous oxidation leading to transient free radicals. This characteristic may underlie some of the recent findings regarding beneficial or deleterious effects of the phytochemical.
Turning pyridoxine into a catalytic chain-breaking and hydroperoxide- decomposing antioxidant
Singh, Vijay P.,Poon, Jia-Fei,Engman, Lars
, p. 1478 - 1487 (2013)
Vitamin B6 is involved in a variety of enzymatic transformations. Some recent findings also indicate an antioxidant role of the vitamin in biological systems. We set out to turn pyridoxine (1a) into a catalytic chain-breaking and hydroperoxide-decomposing antioxidant by replacing the 2-methyl substituent with an alkyltelluro group. Target molecules 12 and derivatives 14, 17, 18, and 20 thereof were accessed by subjecting suitably substituted 2-halopyridin-3-ols to aromatic substitution using sodium alkanetellurolates as nucleophiles and then LAH-reduction of ester groups. The novel pyridoxine compounds were found to inhibit azo-initiated peroxidation of linoleic acid an order of magnitude more efficiently than α-tocopherol in a water/chlorobenzene two-phase system containing N-acetylcysteine as a reducing agent in the aqueous phase. The most lipid-soluble pyridoxine derivative 20c was regenerable and could inhibit peroxidation for substantially longer time (>410 min) than α-tocopherol (87 min). The chalcogen-containing pyridoxines could also mimic the action of the glutathione peroxidase enzymes. Thus, compound 20a catalyzed reduction of hydrogen peroxide three times more efficiently than Ebselen in the presence of glutathione as a stoichiometric reducing agent.
Reversible reactions of thiols and thiyl radicals with nitrone spin traps
Potapenko, Dmitrii I.,Bagryanskaya, Elena G.,Tsentalovich, Yuri P.,Reznikov, Vladimir A.,Clanton, Thomas L.,Khramtsov, Valery V.
, p. 9315 - 9324 (2004)
The reactions of the reversible addition of thiols and thiyl radicals to the nitrone spin traps DMPO (5,5dimethyl-1-pyrroline N-oxide) and DEPMPO (5-diethoxyphosphoryl-5-methyl-l-pyrroline N-oxide) are described. Addition of the thiols to the double C=N b
REGENERATION OF VITAMIN E FROM α-CHROMANOXYL RADICAL BY GLUTATHIONE AND VITAMIN C
Niki, Etsuo,Tsuchiya, Jyunichi,Tanimura, Ritsuko,Kamiya, Yoshio
, p. 789 - 792 (1982)
α-Chromanoxyl radical formed by the interaction of α-tocopherol (vitamin E) with alkoxyl radical or DPPH was found by electron spin resonance spectroscopy to react with glutathione and vitamin C to regenerate α-tocopherol.
Chlorambucil conjugates of dinuclear p-cymene ruthenium trithiolato complexes: synthesis, characterization and cytotoxicity study in vitro and in vivo
Stíbal, David,Therrien, Bruno,Süss-Fink, Georg,Nowak-Sliwinska, Patrycja,Dyson, Paul J.,?ermáková, Eva,?ezá?ová, Martina,Tom?ík, Pavel
, p. 443 - 452 (2016)
Abstract: Four diruthenium trithiolato chlorambucil conjugates have been prepared via Steglich esterification from chlorambucil and the corresponding trithiolato precursors. All conjugates are highly cytotoxic towards human ovarian A2780 and A2780cisR cancer cell lines with IC50 values in the nanomolar range. The conjugates exhibit selectivity towards A2780 cells as compared to non-cancerous HEK293 cells, while being only slightly selective for RF24 and A2780cisR cells. In vivo, the conjugate [10]BF4 suppressed the growth of a solid Ehrlich tumor in immunocompetent NMRI mice but did not prolong their overall survival. The reactivity of the chlorambucil conjugates with glutathione, a potential target of the dinuclear ruthenium motive, and with the 2-deoxyguanosine 5′-monophosphate (dGMP—a model target of chlorambucil) was studied by mass spectrometry and NMR spectroscopy. The conjugates did not show catalytic activity for the oxidation of glutathione nor binding to nucleotides, indicating that glutathione oxidation and DNA alkylation are not key mechanisms of action. Graphical abstract: Four highly cytotoxic diruthenium trithiolato chlorambucil conjugates have been prepared. All conjugates exhibit selectivity towards A2780 cells as compared to HEK293 cells, while being only slightly active in RF24 and A2780cisR cells. In vivo, the best candidate suppressed the growth of a solid Ehrlich tumor in immunocompetent NMRI mice but did not prolong their overall survival.[Figure not available: see fulltext.]
The interaction of silver(II) complexes with biological macromolecules and antioxidants
Trotter, Katherine D.,Owojaiye, Olawale,Meredith, Stuart P.,Keating, Pat E.,Spicer, Mark D.,Reglinski, John,Spickett, Corinne M.
, p. 627 - 640 (2019)
Silver is widely used for its antimicrobial properties, but microbial resistance to heavy metals is increasing. Silver(II) compounds are more oxidizing and therefore have the potential to overcome resistance via extensive attack on cellular components, but have traditionally been hard to stabilize for biological applications. Here, the high oxidation state cation was stabilised using pyridinecarboxylate ligands, of which the 2,6-dicarboxypyridine Ag(II) complex (Ag2,6P) was found to have the best tractability. This complex was found to be more stable in phosphate buffer than DMSO, allowing studies of its interaction with water soluble antioxidants and biological macromolecules, with the aim of demonstrating its potential to oxidize them, as well as determining the reaction products. Spectrophotometric analysis showed that Ag2,6P was rapidly reduced by the antioxidants glutathione, ascorbic acid and vitamin E; the unsaturated lipids arachidonic and linoleic acids, model carbohydrate β-cyclodextrin, and protein cytochrome c also reacted readily. Analysis of the reaction with glutathione by NMR and electrospray mass spectrometry confirmed that the glutathione was oxidized to the disulfide form. Mass spectrometry also clearly showed the addition of multiple oxygen atoms to the unsaturated fatty acids, suggesting a radical mechanism, and cross-linking of linoleic acid was observed. The seven hydroxyl groups of β-cyclodextrin were found to be completely oxidized to the corresponding carboxylates. Treatment of cytochrome c with Ag2,6P led to protein aggregation and fragmentation, and dose-dependent oxidative damage was demonstrated by oxyblotting. Thus Ag2,6P was found to be highly oxidizing to a wide variety of polar and nonpolar biological molecules.
Oxidation/Reduction Potential of Glutathione
Millis, Kevin K.,Weaver, Kim H.,Rabenstein, Dallas L.
, p. 4144 - 4146 (1993)
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Covalent inhibition of histone deacetylase 8 by 3,4-dihydro-2H-pyrimido[1,2-c][1,3]benzothiazin-6-imine
Muth, Marius,J?nsch, Niklas,Kopranovic, Aleksandra,Kr?mer, Andreas,W?ssner, Nathalie,Jung, Manfred,Kirschh?fer, Frank,Brenner-Wei?, Gerald,Meyer-Almes, Franz-Josef
, p. 577 - 585 (2019)
Background: HDAC8 is an established target for T-cell lymphoma and childhood neuroblastoma. Benzothiazine-imines are promising HDAC8 inhibitors with unknown binding mechanism lacking a usual zinc binding group. Methods: In this study high-resolution and quantitative HPLC-coupled ESI-MS/MS techniques are combined with crystal structure determination and a variety of biochemical and computational methods to elucidate the reaction mechanism between benzothiazine-imine 1 and HDAC8. Results: 1) 1 is a covalent inhibitor of HDAC8; 2) inhibition is reversible in the presence of reducing agents; 3) C153 in the active site and C102 are involved in the inhibition mechanism; 4) 1 modifies various cysteines in HDAC8 forming either thiocyanates or mixed disulfides with 3; 5) 1 and 5 dock in close proximity to C153 within the active site. This is supposed to accelerate covalent inactivation particularly in HDAC8 and suggested as major determinant for the observed nanomolar potency and selectivity of 1. Conclusions: 1 and its analogs are interesting model compounds but unsuitable for therapeutic treatment due to their high unselective reactivity towards thiol groups. However, the postulated preceding non-covalent binding mode of 1 opens a door to optimized next generation compounds that combine potent and selective non-covalent recognition with low reactivity towards C153 at the active site of HDAC8. General significance: 1 represents a completely new class of inhibitors for HDAC8. Initial non-covalent interaction at the bottom of the active site is suggested to be the key for its selectivity. Further optimization of non-covalent interaction and thiol-reactivity provides opportunities to develop therapeutic useful covalent HDAC8 inhibitors.
Kinetics and equilibria of the thiol/disulfide exchange reactions of somatostatin with glutathione
Rabenstein, Dallas L.,Weaver, Kim H.
, p. 7391 - 7397 (1996)
Rate and equilibrium constants are reported for the thiol/disulfide exchange reactions of the peptide hormone somatostatin with glutathione (GSH). GSH reacts with the disulfide bond of somatostatin to form somatostatin-glutathione mixed disulfides (Cys3-SH, Cys14-SSG and Cys3-SSG, Cys14-SH), each of which can react with another molecule of GSH to give the reduced dithiol form of somatostatin and GSSG. The mixed disulfides also can undergo intramolecular thiol/disulfide exchange reactions to re-form the disulfide bond of somatostatin or to interconvert to the other mixed disulfide. Analysis of the forward and reverse rate constants indicates that, at physiological concentrations of GSH, the intramolecular thiol/disulfide exchange reactions that re-form the disulfide bond of somatostatin are much faster than reaction of the mixed disulfides with another molecule of GSH, even though the intramolecular reaction involves closure of a 38-membered ring. Thus, even though the disulfide bond of somatostatin is readily cleaved by thiol/disulfide exchange, it is rapidly reformed by intramolecular thiol/disulfide exchange reactions of the somatostatin-glutathione mixed disulfides. By comparison with rate constants reported for analogous reactions of model peptides measured under random coil conditions, it is concluded that disulfide bond formation by intramolecular thiol/disulfide exchange in the somatostatin-glutathione mixed disulfides is not completely random, but rather it is directed to some extent by conformational properties of the mixed disulfides that place the thiol and mixed disulfide groups in close proximity. A reduction potential of -0.221 V was calculated for the disulfide bond of somatostatin from the thiol/disulfide exchange equilibrium constant.
Metabolic inactivation of five glycidyl ethers in lung and liver of humans, rats and mice in vitro
Boogaard,De Kloe,Bierau,Kuiken,Borkulo,VanSittert
, p. 485 - 502 (2000)
1. Some glycidyl ethers (GE) have been shown to be direct mutagens in short-term in vitro tests and consequently GE are considered to be potentially mutagenic in vivo. However, GE may be metabolically inactivated in the body by two different enzymatic routes: conjugation of the epoxide moiety with the endogenous tripeptide glutathione (GSH) catalysed by glutathione S-transferase (GST) or hydrolysis of the epoxide moiety catalysed by epoxide hydrolase (EH). 2. The metabolic inactivation of five different GE, the diglycidyl ethers of bisphenol A (BADGE), 4,4'-dihydroxy-3,3',5,5'-tetramethylbiphenyl (Epikote YX4000) and 1,6-hexanediol (HDDGE) and the GE of 1-dodecanol (C12GE) and o-cresol (o-CGE), has been studied in subcellular fractions of human, C3H mouse and F344 rat liver and lung. 3. All GE were chemically very stable and resistant to aqueous hydrolysis, but were rapidly hydrolysed by EH in cytosolic and microsomal fractions of liver and lung. The aromatic GE were very good substrates for EH. In general, microsomal EH is more efficient than cytosolic EH in hydrolysis of GE, and human microsomes are more efficient than rodent microsomes. 4. The more water-soluble GE, o-CGE and HDDGE, were good substrates for GST whereas the more lipophilic GE, YX4000 and C12GE, were poor substrates for GST. In general, rodents are more efficient in GSH conjugation of GE than humans. 5. In general, the epoxide groups of YX4000 are the most and those of HDDGE the least efficiently inactivated of the five GE under study. For the other three GE no general trend was observed: the relative efficiency of inactivation varied with organ and species. 6. The large variation in metabolism observed with five representative GE indicate that GE have variable individual properties and should not be considered as a single, homogenous class of compounds.
Biomimetic catalytic oxidative coupling of thiols using thiolate-bridged dinuclear metal complexes containing iron in water under mild conditions
Zhang, Yahui,Yang, Dawei,Li, Ying,Zhao, Xiangyu,Wang, Baomin,Qu, Jingping
, p. 6492 - 6502 (2019)
A green and efficient approach to disulfides via oxidative coupling of thiols was developed by adopting a biomimetic thiolate-bridged iron-ruthenium complex as the catalyst. Using environmentally friendly oxygen as the oxidant, a wide range of thiols including biologically important molecules can be smoothly converted into corresponding disulfides in water. Notably, two potential intermediate species were successfully isolated and unambiguously characterized, which is essential to reveal the detailed mechanism of this transformation. This catalytic system represents a rare and desired heteronuclear bimetallic scaffold for understanding the biological process of S-S bond formation from the viewpoint of bioinspired catalysis.
Vicinal disulfide constrained cyclic peptidomimetics: A turn mimetic scaffold targeting the norepinephrine transporter
Brust, Andreas,Wang, Ching-I. A.,Daly, Norelle L.,Kennerly, Joe,Sadeghi, Mahsa,Christie, Macdonald J.,Lewis, Richard J.,Mobli, Mehdi,Alewood, Paul F.
, p. 12020 - 12023 (2013)
Loopy peptides: Peptide turn mimetics of a clinically relevant norepinephrine reuptake inhibitor were developed employing a high-throughput synthesis approach to generate peptide thioesters, with subsequent cyclization through native chemical ligation. The vicinal disulfide constrained cyclic peptidomimetics (see scheme) show high structural and functional similarity to the parent peptide, though with superior metabolic stability. Copyright
Efficient oxidation of cysteine and glutathione catalyzed by a dinuclear areneruthenium trithiolato anticancer complex
Giannini, Federico,Suess-Fink, Georg,Furrer, Julien
, p. 10552 - 10554 (2011)
The highly cytotoxic diruthenium complex [(p-MeC6H 4Pri)2Ru2(SC6H 4-p-Me)3]+ (1), water-soluble as the chloride salt, is shown to efficiently catalyze oxidation of the thiols cysteine and glutathione to give the corresponding disulfides, which may explain its high in vitro anticancer activity.
Thermodynamics of the oxidation-reduction reaction {2 glutathione red(aq) + NADPox(aq) = glutathioneox(aq) + NADPred(aq)}
Tewari, Yadu B.,Goldberg, Robert N.
, p. 1361 - 1381 (2003)
Microcalorimetry, spectrophotometry and high performance liquid chromatography were used to conduct a thermodynamic investigation of the glutathione reductase catalyzed reaction. The reaction involves the breaking of a disulfide bond and is useful in the repair of enzymes. The results of the equilibrium and calorimetric measurements were analyzed in terms of a chemical equilibrium model that accounts for the multiplicity of ionic states of the reactants and products.
Derivatization of chlorin e6 with maleimide enhances its photodynamic efficacy in HepG2 cells
Guo, Xiuhan,Wang, Shisheng,Zhang, Fan,Li, Guangzhe,Li, Yueqing,Zhao, Weijie
, p. 1093 - 1098 (2020)
Three derivatives of chlorin e6 (1-3) were synthesized by introduction of maleimide, cysteine and glutathione at C-13 carboxyl of the chlorin scaffold. The evaluation of their PDT effects showed that compound 1, the derivative with a maleimide group, exhibited more potent photocytotoxicity against HepG2 cells (IC50 3.2 μM) than 2 (IC50 6.7 μM) and 3 (IC50 10.2 μM), although the cellular uptake of 1 was slightly lower than that of 2 and 3. The high PDT effect of 1 was found to be in agreement with the high level of intracellular singlet oxygen. Further investigation of the mechanism revealed that 1 can significantly lower the GSH level in HepG2 cells due to the addiction reaction of maleimide and GSH, thus resulting in the reduction of ROS scavenging and the enhancement of cellular oxidative stress. This approach to improve PDT effects of photosensitizers by means of interfering with the cellular redox system and enhancing cellular oxidative stress offers a new strategy for development of photosensitizers in cancer therapy.
Glutathione-dependent generation of reactive oxygen species by the peroxidase-catalyzed redox cycling of flavonoids
Galati, Giuseppe,Chan, Tom,Wu, Bin,O'Brien, Peter J.
, p. 521 - 525 (1999)
Catalytic concentrations of apigenin (a flavone containing a phenol B ring) and naringin or naringenin (flavanones containing a phenol B ring) caused extensive GSH oxidation at a physiological pH in the presence of peroxidase. Only catalytic H2O2 concentrations were required, indicating a redox cycling mechanism that generated H2O2 was involved. Extensive oxygen uptake ensued, the extent of which was proportional to the extent of GSH oxidation to GSSG and was markedly increased by superoxide dismutase. These results suggest that prooxidant phenoxyl radicals formed by these flavonoids co-oxidized GSH to form thiyl radicals which activated oxygen. GSH also prevented the peroxidase-catalyzed oxidative destruction of these flavonoids which suggests that phenoxyl radicals initiated the oxidative destruction. This is the first time that a group of flavonoids have been identified as prooxidants independent of autoxidation reactions catalyzed by the transition metal ions Fe3+, Fe2+, Mn2+, and Cu2+.
A New Quantification Method Using Electrochemical Mass Spectrometry
Xu, Chang,Zheng, Qiuling,Zhao, Pengyi,Paterson, Joseph,Chen, Hao
, p. 685 - 693 (2019)
Mass spectrometry-based quantification method has advanced rapidly. In general, the methods for accurate quantification rely on the use of authentic target compounds or isotope-labeled compounds as standards, which might be not available or difficult to synthesize. To tackle this grand challenge, this paper presents a novel approach, based on electrochemistry (EC) combined with mass spectrometry (MS). In this approach, a target compound is allowed to undergo electrochemical oxidation and then subject to MS analysis. The oxidation current recorded from electrochemistry (EC) measurement provides information about the amount of the oxidized analyte, based on the Faraday’s Law. On the other hand, the oxidation reaction yield can be determined from the analyte MS signal changes upon electrolysis. Therefore, the total amount of analyte can be determined. In combination with liquid chromatography (LC), the method can be applicable to mixture analysis. The striking strength of such a method for quantitation is that neither standard compound nor calibration curve is required. Various analyte molecules such as dopamine, norepinephrine, and rutin as well as peptide glutathione in low quantity were successfully quantified using our method with the quantification error ranging from ? 2.6 to +?4.6%. Analyte in a complicated matrix (e.g., uric acid in urine) was also accurately measured. [Figure not available: see fulltext.].
Glutathione reacts with glyoxal at the N-terminal
Nomi, Yuri,Aizawa, Haruko,Kurata, Tadao,Shindo, Kazutoshi,Van Nguyen, Chuyen
, p. 2408 - 2411 (2009)
The elevation of such dicarbonyl compounds as glyoxal and the depletion of GSH occur simultaneously in diabetic patients. Enabling a nonenzymatic glycation reaction with GSH and glyoxal is therefore proposed. However, the reaction mechanism for GSH and glyoxal has not been precisely defined. We isolated in this study the major products obtained by the reaction of GSH and glyoxal under physiological conditions, and clarified the chemical structure of these compounds by MS and NMR analyses for the first time. We identified the major product after 24 h as N-[3-(2, 5-dioxomorpholin-3-yl)- propanoyl] cysteinylglycine, and the one after 30 min as N-glycoloyl-γ- glutamylcysteinylglycine (the intermediate of the former compound). Our results suggest that GSH reacted with glyoxal at the α-NH2 group of the glutamate residue, but not at the SH group of the cysteine residue.
Oxidation of Thioglycolic Acid and Glutathione by (trans-Cyclohexane-1,2-diamine-N,N,N',N'-tetraacetato)manganate(III) in Aqueous Media
Gangopadhyay, Sumana,Ali, Mahammad,Dutta, Amitava,Banerjee, Pradyot
, p. 841 - 846 (1994)
The kinetics of the electron-transfer reactions of the manganese(III) complex of trans-cyclohexane-1,2-diamine-N,N,N',N'-tetraacetate (cdta(4-)) with two thiols thioglycolic acid and glutathione has been investigated at 30 deg C in aqueous media in the range pH 2.0-10.33 with varying reductant concentrations at constant ionic strength, I = 0.20 mol dm-3 (NaClO4).The reactions are first order both in complex and reductants and follow the general rate law, -d/dt = kobs = k.Both the reactions have been assumed to proceed via an inner-sphere mechanism with support for this coming from the observation of a rapid initial increase in absorption followed by a slower decay.This indicates the formation of an inner-sphere associated species which decomposes unimolecularly leading to the transfer of the electron from the thiol to the oxidant.Additional support for this mechanism comes from a comparison of the water-exchange rate of (1-) with the higher limit of the electron-transfer rates.The pH-rate profiles are bell-shaped curves and were successfully modelled by fitting the experimental data to a computer-fitted program thereby evaluating the reactivity of all the reacting species of the reductants.
Electrochemical evidences in oxidation of acetaminophen in the presence of glutathione and N-acetylcysteine
Shayani-Jam, Hasan,Nematollahi, Davood
, p. 409 - 411 (2010)
Electrochemical oxidation of acetaminophen has been studied in the presence of glutathione and acetylcysteine. Our results indicate that N-acetyl-p-benzoquinone-imine (NAPQI) participates in a catalytic reaction with glutathione and N-acetylcysteine. Also, the observed homogeneous rate constants of the reaction of NAPQI with glutathione and acetylcysteine were estimated.
Interaction of Glutathione with Hydrogen Peroxide: A Kinetic Model
Zinatullina,Kasaikina,Kuz’min,Khrameeva
, p. 266 - 272 (2019)
Abstract: The kinetics of the interaction of glutathione (GSH) with hydrogen peroxide (H2O2) was studied. It was shown that the rate of GSH consumption nonlinearly depended on reactant concentrations and the process was accompanied by the appearance of radicals with a relatively low rate, which was a fraction of a percent of the rate of GSH consumption. Based on the experimental results and literature data on the reactions of GSH with H2O2 and thiyl radicals, a kinetic model of the complex interaction of GSH and H2O2 in an aqueous solution at 37°C was proposed. The model includes 15 quasi-elementary reactions with corresponding rate constants, including the formation of the intermediate complex GSH–H2O2 and its subsequent reactions with the formation of final products. Computer simulation based on the model developed satisfactorily described the reaction kinetics in a wide range of reactant concentrations.
Thiol-disulfide exchanges modulate aldo-keto reductase family 1 member B10 activity and sensitivity to inhibitors
Shen, Yi,Zhong, Linlin,Markwell, Stephen,Cao
, p. 530 - 537 (2010)
The reversible thiol/disulfide exchange is an important regulatory mechanism of protein enzymatic activity. Many protein enzymes are susceptible to S-thiolation induced by reactive oxygen species (ROS); and the glutathione (GSH) and free amino acid cysteine (Cys) are critical cellular thiol anti-oxidants, protecting proteins from irreversible oxidative damage. In this study, we found that aldo-keto reductase family 1 member B10 (AKR1B10) contains 4 Cys residues, i.e., Cys45, Cys187, Cys200, and Cys299. Exposing AKR1B10 to ROS mixtures resulted in significant decrease of its free sulfhydryl groups, up to 40-50% in the presence of physiological thiol cysteine at 0.5 or 1.0 mM; and accordingly, AKR1B10 enzymatic activity was reversibly decreased, in parallel with the oxidation of the sulfhydryl groups. ROS-induced thiolation also affected the sensitivity of AKR1B10 to inhibitors EBPC, epalrestat, and statil. Together our results showed for the first time that AKR1B10's enzymatic activity and inhibitor sensitivity are modulated by thiol/disulfide exchanges.
Interaction profile of diphenyl diselenide with pharmacologically significant thiols
Hassan, Waseem,Teixeira Rocha, Joao Batista
, p. 12287 - 12296 (2012)
Diphenyl diselenide has shown interesting biological activities in various free-radical-induced damage models and can be considered as a potential candidate drug against oxidative stress. Apart from its anti-oxidant activity, this compound can oxidize various thiols. However there are no detailed studies in the literature about the thiol oxidase-like activity of this compound against biologically significant mono and di-thiols with respect to various pH conditions. Keeping in mind the scarcity of data in this area of organochalcogen chemistry, we report for the first time the kinetics of thiol oxidation by diphenyl diselenide, which was carried out in a commonly used phosphate buffer, not only at physiological pH, but also at a number of acidic values. The relative reactivities of the different thiols with diphenyl diselenide were independent of the pKa of the thiol group, such that at pH 7.4, cysteine and dithiothreitol were the most reactive, while 2,3-dimercapto-1-propanesulfonic acid and glutathione were weakly reactive and extremely low reactivity was observed with dimercaptosuccinic acid. Rate of oxidation was dependent on the pH of the incubation medium. The results obtained will help us in the design of rational strategies for the safe pharmacological use of diphenyl diselenide.
Reaction mechanisms of allicin and allyl-mixed disulfides with proteins and small thiol molecules
Miron, Talia,Listowsky, Irving,Wilchek, Meir
, p. 1912 - 1918 (2010)
Allylsulfides from garlic are chemopreventive agents. Entering cells they are expected to initially interact with glutathione. Accordingly, reaction mechanisms of the product, S-allylthio-glutathione, with model proteins and thiols were analyzed in cell f
Novel conversion of thiols into disulfides, via S-nitrosothiol intermediates using trichloronitromethane
Demir, Ayhan S.,Igdir, A. Cigdem,Mahasneh, Ali S.
, p. 12399 - 12404 (1999)
An efficient oxidative coupling of thiols to give disulfides via thionitrite (S-nitrosothiol) intermediate is described using trichloronitromethane as efficient reagent in organic solvents and water. Cysteine and glutathione are converted into the corresponding disulfides in water in high yields.
Interaction between Glutathione and Resveratrol in the Presence of Hydrogen Peroxide: A Kinetic Model
Zinatullina,Kasaikina,Khrameeva,Indeykina,Kononikhin
, p. 255 - 263 (2021/04/26)
Abstract: The kinetics of interaction between glutathione (GSH) and unsaturated phenol resveratrol (RVT) in deionized water in the presence of hydrogen peroxide (H2O2) is studied. At a physiological concentration (0.1–10 mM), GSH containing two carboxyl groups forms acidic solutions (pH of 3–4); the GSH molecules are associated into dimers. Under these conditions, GSH is quite slowly oxidized by atmospheric oxygen, and the reaction between GSH and H2O2 is accompanied by the formation of radicals. The thiyl radical initiation rate (Wi) is a few fractions of a percent of the GSH consumption rate; however, it is sufficient to initiate a thiol–ene chain reaction between GSH and RVT. Using the experimental data on the kinetics and the product composition and the published data on reactions of GSH with H2O2 and thiyl radicals, a kinetic model of the complex interaction between GSH and RVT in the presence of H2O2 in an aqueous medium at 37°C is proposed. The model includes 19 quasi-elementary reactions with respective rate constants, in particular, the formation of intermediate GSH–H2O2 and GSH–GSH complexes, the formation of radicals, and their subsequent transformations into final products in reactions with RVT and GSH. A computer simulation based on the developed model adequately describes the features of the process kinetics in a wide reactant concentration range.
Reduction of an asymmetric Pt(IV) prodrug fac-[Pt(dach)Cl3(OC(=O)CH3)] by biological thiol compounds: kinetic and mechanistic characterizations
Huo, Shuying,Ma, Dongying,Song, Changying,Sun, Jingjing,Wang, Yafang
, p. 623 - 631 (2021/11/22)
An asymmetric Pt(IV) prodrug fac-[Pt (dach)Cl3(OC(=O)CH3)] (dach = 1,2-diaminocyclohexane) was synthesized, and the reduction of the Pt(IV) prodrug by three biological thiols glutathione (GSH), cysteine (Cys) and homocysteine (Hcy) was investigated by a stopped-flow spectrometer. All the reductions were followed by an overall second-order reaction with first-order in both [Pt(IV)] and [thiol]. The reduction of the Pt(IV) prodrug occurred through a chloride bridge (Pt-Cl-S) mediated two electron transfer process. Therefore, the coordinated chloride possesses a better bridging effect than the oxygen atom from the coordinated –CH3COO? of the Pt(IV) prodrug. A reactivity trend of k′Cys > k′GSH > k′Hcy is found, illustrating that the reactivity is followed by the trend of Cys > GSH > Hcy in pH 7.4 buffer. Graphical abstract: Transition state is formed between the axially coordinated chloride of the platinum(IV) complex and the sulfur atom from the thiol/thiolate group of Cys/Hcy/GSH.[Figure not available: see fulltext.].
