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.
Diallyl Trisulfide Is a Fast H2S Donor, but Diallyl Disulfide Is a Slow One: The Reaction Pathways and Intermediates of Glutathione with Polysulfides
Liang, Dong,Wu, Haixia,Wong, Ming Wah,Huang, Dejian
, p. 4196 - 4199 (2015)
Diallyl trisulfide (DATS) reacts rapidly with glutathione (GSH) to release H2S through thiol-disulfide exchange followed by allyl perthiol reduction by GSH. Yet diallyl disulfide (DADS) only releases a minute amount of H2S via a sluggish reaction with GSH through an α-carbon nucleophilic substitution pathway. The results clarify the misunderstanding of DADS as a rapid H2S donor, which is attributed to its DATS impurity.
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.
Protein S-thiolation by glutathionylspermidine (Gsp): The role of Escherichia coli Gsp synthetase/amidase in redox regulation
Chiang, Bing-Yu,Chen, Tzu-Chieh,Pai, Chien-Hua,Chou, Chi-Chi,Chen, Hsuan-He,Ko, Tzu-Ping,Hsu, Wen-Hung,Chang, Chun-Yang,Wu, Whei-Fen,Wang, Andrew H.-J.,Lin, Chun-Hung
, p. 25345 - 25353 (2010)
Certain bacteria synthesize glutathionylspermidine (Gsp), from GSH and spermidine. Escherichia coli Gsp synthetase/amidase (GspSA) catalyzes both the synthesis and hydrolysis of Gsp. Prior to the work reported herein, the physiological role(s) of Gsp or how the two opposing GspSA activities are regulated had not been elucidated. We report that Gsp-modified proteins from E. coli contain mixed disulfides of Gsp and protein thiols, representing a new type of post-translational modification formerly undocumented. The level of these proteins is increased by oxidative stress. We attribute the accumulation of such proteins to the selective inactivation of GspSA amidase activity. X-ray crystallography and a chemical modification study indicated that the catalytic cysteine thiol of the GspSA amidase domain is transiently inactivated byH 2O2 oxidation to sulfenic acid, which is stabilized by a very short hydrogen bond with a water molecule. We propose a set of reactions that explains how the levels of Gsp and Gsp S-thiolated proteins are modulated in response to oxidative stress. The hypersensitivities of GspSA and GspSA/glutaredoxin null mutants toH2O2 support the idea that GspSA and glutaredoxin act synergistically to regulate the redox environment of E. coli.
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
Catalytic properties of oligonuclear cobalt acetate complexes in oxidation of glutathione with hydrogen peroxide
Ruzanov,Fisher,Eremin,Antonov,Fedorova,Stepanova,Belyaev,Simanova
, p. 904 - 905 (2008)
Catalytic activity of oligonuclear cobalt(III) and cobalt(II, III) oxoacetate complexes in homogeneous oxidation of glutathione with hydrogen peroxide was studied.
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.
Kinetic study of the antioxidant activity of pyrroloquinolinequinol (PQQH2, a reduced form of pyrroloquinolinequinone) in micellar solution
Ouchi, Aya,Nakano, Masahiko,Nagaoka, Shin-Ichi,Mukai, Kazuo
, p. 450 - 456 (2009)
Kinetic study of the aroxyl radical-scavenging action of pyrroloquinolinequinol [PQQH2, a reduced form of pyrroloquinolinequinone (PQQ)] and water-soluble antioxidants (vitamin C, cysteine, glutathione, and uric acid) has been performed. The se
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.]
Redox-regulated methionine oxidation of Arabidopsis thaliana glutathione transferase Phi9 induces H-site flexibility
Tossounian, Maria-Armineh,Wahni, Khadija,Van Molle, Inge,Vertommen, Didier,Astolfi Rosado, Leonardo,Messens, Joris
, (2018)
Glutathione transferase enzymes help plants to cope with biotic and abiotic stress. They mainly catalyze the conjugation of glutathione (GSH) onto xenobiotics, and some act as glutathione peroxidase. With X-ray crystallography, kinetics, and thermodynamics, we studied the impact of oxidation on Arabidopsis thaliana glutathione transferase Phi 9 (GSTF9). GSTF9 has no cysteine in its sequence, and it adopts a universal GST structural fold characterized by a typical conserved GSH-binding site (G-site) and a hydrophobic co-substrate-binding site (H-site). At elevated H2O2 concentrations, methionine sulfur oxidation decreases its transferase activity. This oxidation increases the flexibility of the H-site loop, which is reflected in lower activities for hydrophobic substrates. Determination of the transition state thermodynamic parameters shows that upon oxidation an increased enthalpic penalty is counterbalanced by a more favorable entropic contribution. All in all, to guarantee functionality under oxidative stress conditions, GSTF9 employs a thermodynamic and structural compensatory mechanism and becomes substrate of methionine sulfoxide reductases, making it a redox-regulated enzyme.
