scholarly journals Redox properties and prooxidant cytotoxicity of a neuroleptic agent 6,7-dinitrodihydroquinoxaline-2,3-dione (DNQX).

2013 ◽  
Vol 60 (2) ◽  
Author(s):  
Jonas Šarlauskas ◽  
Aušra Nemeikaitė-Čėnienė ◽  
Lina Misevičienė ◽  
Kastis Krikštopaitis ◽  
Žilvinas Anusevičius ◽  
...  
Keyword(s):  
Electrochemical Reduction ◽  
Bovine Leukemia Virus ◽  
Reduction Potential ◽  
Leukemia Virus ◽  
Redox Properties ◽  
Single Electron ◽  
Reduction Peak ◽  
Neuroleptic Agent ◽  
Electron Reduction ◽  
Dt Diaphorase

In order to characterize the possible mechanism(s) of cytotoxicity of a neuroleptic agent 6,7-dinitrodihydroquinoxaline-2,3-dione (DNQX) we examined the redox properties of DNQX, and its mononitro- (NQX) and denitro- (QX) derivatives. The irreversible electrochemical reduction of the nitro groups of DNQX was characterized by the reduction peak potentials (Ep,7) of -0.43 V and -0.72 V vs. Ag/AgCl at pH 7.0, whereas NQX was reduced at Ep,7 = -0.67 V. The reactivities of DNQX and NQX towards the single-electron transferring enzymes NADPH:cytochrome P-450 reductase and NADPH:adrenodoxin reductase/adrenodoxin complex were similar to those of model nitrobenzenes with the single-electron reduction potential (E¹₇) values of -0.29 V - -0.42 V. DNQX and NQX also acted as substrates for two-electron transferring mammalian NAD(P)H:quinone oxidoreductase (DT-diaphorase). The cytotoxicity of DNQX in bovine leukemia virus-transformed lamb kidney fibroblasts (line FLK) was prevented by antioxidants and an inhibitor of NQO1, dicoumarol, and was enhanced by the prooxidant alkylating agent 1,3-bis(2-chloromethyl)-1-nitrosourea. A comparison with model nitrobenzene compounds shows that the cytotoxicity of DNQX and NQX reasonably agrees with the ease of their electrochemical reduction, and/or their reactivities towards the used enzymatic single-electron reducing systems. Thus, our data imply that the cytotoxicity of DNQX in FLK cells is exerted mainly through oxidative stress.

scholarly journals The toxicity of aromatic nitrocompounds to bovine leukemia virus-transformed fibroblasts: the role of single-electron reduction

1995 ◽  
Vol 1268 (2) ◽  
pp. 159-164 ◽  
Author(s):  
Narimantas Čènas ◽  
Ausra Nemeikaitè ◽  
Egle Dičkancaitè ◽  
Zilvinas Anusevičius ◽  
Henrikas Nivinskas ◽  
...  
Keyword(s):  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Single Electron ◽  
Aromatic Nitrocompounds ◽  
Transformed Fibroblasts ◽  
Electron Reduction

scholarly journals Reduction of nitroaromatic compounds by NAD(P)H:quinone oxidoreductase (NQO1): the role of electron-accepting potency and structural parameters in the substrate specificity.

2006 ◽  
Vol 53 (3) ◽  
pp. 569-576 ◽  
Author(s):  
Lina Miseviciene ◽  
Zilvinas Anusevicius ◽  
Jonas Sarlauskas ◽  
Narimantas Cenas
Keyword(s):  
Active Center ◽  
Reduction Potential ◽  
Structural Parameters ◽  
Nitroaromatic Compounds ◽  
Electronic Coupling ◽  
Quinone Binding ◽  
Lower Reactivity ◽  
Electron Reduction ◽  
Dt Diaphorase

We aimed to elucidate the role of electronic and structural parameters of nitroaromatic compounds in their two-electron reduction by NAD(P)H:quinone oxidoreductase (NQO1, DT-diaphorase, EC 1.6.99.2). The multiparameter regression analysis shows that the reactivity of nitroaromatic compounds (n=38) increases with an increase in their single-electron reduction potential and the torsion angle between nitrogroup(s) and the aromatic ring. The binding efficiency of nitroaromatics in the active center of NQO1 exerted a less evident role in their reactivity. The reduction of nitroaromatics is characterized by more positive entropies of activation than the reduction of quinones. This points to a less efficient electronic coupling of nitroaromatics with the reduced isoalloxazine ring of FAD, and may explain their lower reactivity as compared to quinones. Another important but poorly understood factor enhancing the reactivity of nitroaromatics is their ability to bind at the dicumarol/quinone binding site in the active center of NQO1.

scholarly journals Experimental and Theoretical Evidence for Nitrogen–Fluorine Halogen Bonding in Silver-Initiated Radical Fluorinations

2019 ◽  
Author(s):  
Ryan Baxter ◽  
Alyssa Hua ◽  
Sarah Baker ◽  
Samantha Bidwell ◽  
Hrant Hratchian
Keyword(s):  
Reduction Potential ◽  
Halogen Bonding ◽  
Electronic Structure Calculations ◽  
Electrochemical Analysis ◽  
Single Electron ◽  
Halogen Bonds ◽  
Ambient Conditions ◽  
Electron Reduction ◽  
Theoretical Evidence ◽  
Structure Calculations

<div>We report experimental and computational evidence for nitrogen–fluorine halogen bonding in Ag(I)-initiated radical C–H fluorinations. Simple pyridines form [N–F–N]+ halogen bonds with Selectfluor to facilitate single-electron reduction by catalytic Ag(I). Pyridine electronics affect the extent of halogen bonding, leading to notable differences in selectivity between mono- and bis-fluorinated products. Electronic structure calculations show that halogen bonding to various pyridines alters the single-electron reduction potential of Selectfluor, which is consistent with experimental electrochemical analysis. Multinuclear correlation NMR also provides spectroscopic evidence for pyridine halogen bonding to Selectfluor under ambient conditions.</div>

scholarly journals Role of single-electron reduction potential in inhibition of reverse transcriptase by streptonigrin and sakyomicin A.

1987 ◽  
Vol 40 (5) ◽  
pp. 702-705 ◽  
Author(s):  
YOSHIO INOUYE ◽  
KEIKO OOGOSE ◽  
YUKINORI TAKE ◽  
TAE KUBO ◽  
SHOSHIRO NAKAMURA
Keyword(s):  
Reverse Transcriptase ◽  
Reduction Potential ◽  
Single Electron ◽  
Electron Reduction

Redox Properties of Novel Antioxidant 5,8-Dihydroxycoumarin: Implications for its Prooxidant Cytotoxicity

2005 ◽  
Vol 60 (11-12) ◽  
pp. 849-854 ◽  
Author(s):  
Aušra Nemeikaitė-Čėnienė ◽  
Audronė Marozienė ◽  
Audrius Pukalskas ◽  
Petras Rimantas Venskutonis ◽  
Narimantas Čėnasb
Keyword(s):  
Reduced Glutathione ◽  
Leukemia Virus ◽  
Redox Properties ◽  
Cytotoxic Action ◽  
Hydrogen Electrode ◽  
Midpoint Potential ◽  
Normal Hydrogen ◽  
Hierochloe Odorata ◽  
Dt Diaphorase ◽  
Cytochrome P 450

The aim of this work was to characterize the redox properties of the new antioxidant 5,8- dihydroxycoumarin (5,8-DHC), isolated from sweet grass (Hierochloë odorata L.), and to determine its impact on its cytotoxic action. Reversible electrochemical oxidation of 5,8- DHC at pH 7.0 was characterized by the midpoint potential (Ep/2) of 0.23 V vs. the normal hydrogen electrode. 5,8-DHC was slowly autoxidized at pH 7.0, and it was active as a substrate for peroxidase (POD, EC 1.11.1.7) and tyrosinase (TYR, EC 1.14.18.1). Oxidation of 5,8-DHC by POD/H2O2 yielded the product(s) which reacted with reduced glutathione and supported the oxidation of NADPH by ferredoxin:NADP+ reductase (FNR, EC 1.18.1.2) and NAD(P)H:quinone oxidoreductase (NQO1, DT-diaphorase, EC 1.6.99.2). The concentration of 5,8-DHC for 50% survival of bovine leukemia virus-transformed lamb kidney fibroblasts (line FLK) during a 24-h incubation was (60 ± 5.5) μm. Cytotoxicity of 5,8-DHC was decreased by desferrioxamine, catalase, the antioxidant N,N’-diphenyl-p-phenylene diamine, and potentiated by 1,3-bis-(2-chloroethyl)-1-nitrosourea and dicumarol, an inhibitor of NQO1. This shows that 5,8-DHC possesses the oxidative stress-type cytotoxicity, evidently due to the action of quinodal oxidation product(s). The protective effect of isoniazide, an inhibitor of cytochrome P-450 2E1, points to hydroxylation of 5,8-DHC as additional toxification route, whereas the potentiating effect of 3,5-dinitrocatechol, an inhibitor of catechol-omethyltransferase (COMT, EC 2.1.1.6), points to the o-methylation of hydroxylation products as the detoxification route.

scholarly journals Experimental and Theoretical Evidence for Nitrogen–Fluorine Halogen Bonding in Silver-Initiated Radical Fluorinations

2019 ◽  
Author(s):  
Ryan Baxter ◽  
Alyssa Hua ◽  
Sarah Baker ◽  
Samantha Bidwell ◽  
Hrant Hratchian
Keyword(s):  
Reduction Potential ◽  
Halogen Bonding ◽  
Electronic Structure Calculations ◽  
Electrochemical Analysis ◽  
Single Electron ◽  
Halogen Bonds ◽  
Ambient Conditions ◽  
Electron Reduction ◽  
Theoretical Evidence ◽  
Structure Calculations

<div>We report experimental and computational evidence for nitrogen–fluorine halogen bonding in Ag(I)-initiated radical C–H fluorinations. Simple pyridines form [N–F–N]+ halogen bonds with Selectfluor to facilitate single-electron reduction by catalytic Ag(I). Pyridine electronics affect the extent of halogen bonding, leading to notable differences in selectivity between mono- and bis-fluorinated products. Electronic structure calculations show that halogen bonding to various pyridines alters the single-electron reduction potential of Selectfluor, which is consistent with experimental electrochemical analysis. Multinuclear correlation NMR also provides spectroscopic evidence for pyridine halogen bonding to Selectfluor under ambient conditions.</div>

scholarly journals Electrochemical Study of the Redox Properties of Levulinic Acid in Organic and Aqueous-Organic Solutions

2021 ◽  
Vol 14 (3) ◽  
pp. 388-395
Author(s):  
Galina V. Burmakina ◽  
Keyword(s):  
Dimethyl Sulfoxide ◽  
Levulinic Acid ◽  
Reduction Potential ◽  
Redox Properties ◽  
Electrochemical Methods ◽  
Electrochemical Study ◽  
Electron Reduction ◽  
Organic Solutions

The redox properties of levulinic acid (LA) were studied by electrochemical methods in acetonitrile, a mixture of acetonitrile with water, ethanol, acetone, and dimethyl sulfoxide. It was shown that the irreversible two-electron reduction of LA under the studied conditions leads to the formation of γ-valerolactone. This reduction potential depends on the solvent and shifted anodically by following order: dimethyl sulfoxide

Cytotoxicity of Nitroaromatic Explosives and their Biodegradation Products in Mice Splenocytes: Implications for their Immunotoxicity

2008 ◽  
Vol 63 (7-8) ◽  
pp. 519-525 ◽  
Author(s):  
Valė Miliukiene ◽  
Narimantas Čėnas
Keyword(s):  
Oxidative Stress ◽  
Reduction Potential ◽  
Environmental Pollutants ◽  
Protective Effects ◽  
Nitroaromatic Explosives ◽  
Important Group ◽  
Mammalian Cell Lines ◽  
Structure Activity ◽  
Electron Reduction ◽  
Dt Diaphorase

Nitroaromatic explosives like 2,4,6-trinitrotoluene (TNT) and 2,4,6-trinitrophenyl-Nmethyl- nitramine (tetryl) comprise an important group of toxic environmental pollutants, whose toxicity is mainly attributed to the flavoenzyme electrontransferase-catalyzed redox cycling of their free radicals (oxidative stress) and DT-diaphorase [NAD(P)H:quinone oxidoreductase, NQO1, EC 1. 6.99.2]-catalyzed formation of alkylating nitroso and/or hydroxylamine metabolites. Because of the incomprehensive data on the immunotoxic effects of nitroaromatic explosives, we have studied the structure-cytotoxicity relationships in the action of tetryl, TNT as well as its amino and hydroxylamino metabolites, and related nitroaromatic compounds towards mouse splenocyte cells. The protective effects of desferrioxamine and the antioxidant N,N′-diphenyl-p-phenylene diamine against the cytotoxicity of TNT and other nitroaromatics showed that the oxidative stress-type cytotoxicity mechanism takes place. In addition, the cytotoxicity of nitroaromatics is also partly prevented by an inhibitor of NQO1, dicumarol. The cytotoxicity of the amino metabolites of TNT is also partly prevented by α- naphthoflavone and isoniazide, which points to the involvement of cytochromes P-450 in their activation. In general the cytotoxicity of nitroaromatics in splenocytes increases with an increase in their single-electron reduction potential, Eζ . This points to the prevailing mechanism of the oxidative stress-type cytotoxicity. The obtained structure-activity relationship and the studies of other mammalian cell lines showed that the immunotoxic potential of nitroaromatic explosives may decrease in the order tetryl ≥TNT ≥ hydroxylamino metabolites of TNT > amino and diamino metabolites of TNT.

scholarly journals QSARs in prooxidant mammalian cell cytotoxicity of nitroaromatic compounds: the roles of compound lipophilicity and cytochrome P-450- and DT-diaphorase-catalyzed reactions

Chemija ◽  
2020 ◽  
Vol 31 (3) ◽  
Author(s):  
Aušra Nemeikaitė-Čėnienė ◽  
Jonas Šarlauskas ◽  
Violeta Jonušienė ◽  
Lina Misevičienė ◽  
Audronė Marozienė ◽  
...  
Keyword(s):  
Mammalian Cell ◽  
Water Distribution ◽  
Reduction Rate ◽  
Human Colon ◽  
Nitroaromatic Compounds ◽  
Single Electron ◽  
Cell Cytotoxicity ◽  
Electron Reduction ◽  
Adrenodoxin Reductase ◽  
Dt Diaphorase

Frequently, the aerobic mammalian cell cytotoxicity of nitroaromatic compounds (ArNO2) increases with their single-electron reduction potential (E17), thus reflecting the relationship between their enzymatic single-electron reduction rate and E17. This shows that the main factor of ArNO2 cytotoxicity is redox cycling and oxidative stress. In this work, we found that the reactivity of a series of nitrobenzenes, nitrofurans and nitrothiophenes towards single-electron transferring NADPH:cytochrome P-450 reductase and adrenodoxin reductase/adrenodoxin increases with their E17. However, their cytotoxicity in mouse hepatoma MH22a and human colon carcinoma HCT-116 cells exhibited a poorly expressed dependence on E17. The correlations were significantly improved after the introduction of compound octanol/water distribution coefficient at pH 7.0 (log D) as a second variable. This shows that the lipophilicity of ArNO2 enhances their cytotoxicity. The inhibitors of cytochromes P-450, α-naphthoflavone, isoniazid and miconazole, and an inhibitor of DT-diaphorase, dicoumarol, in most cases decreased the cytotoxicity of several randomly chosen compounds. This shows that the observed cytotoxicity vs E17 relationships in fact reflect the superposition of several cytotoxicity mechanisms.

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