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Enzymatic redox reactions of the explosive 4,6-dinitrobenzofuroxan (DNBF): implications for its toxic action.

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Nemeikaitė-Čėnienė A., Šarlauskas J., Misevièienė L., Anusevièius Ž., Marozienė A., Čėnas N.

vol. 51

issue 4

1081-1086

With an aim to understand the toxicity mechanisms of the explosive 4,6-dinitro- benzofuroxan (DNBF), we studied its single-electron reduction by NADPH:cytochrome P450 reductase and ferredoxin:NADP+ reductase, and two- electron reduction by DT-diaphorase and Enterobacter cloacae nitroreductase. The enzymatic reactivities of DNBF and another explosive 2,4,6-trinitrotoluene (TNT) were similar, except for the much lower reactivity of DNBF towards nitroreductase. DNBF was less cytotoxic in FLK cells than TNT. However, their action shared the same mechanisms, oxidative stress and activation by DT-diaphorase. The lower cytotoxicity of DNBF may be explained by the negative electrostatic charge of its adduct with water which may impede cellular membrane penetration, and by the formation of its less reactive adducts with intracellular reduced glutathione.

Two-electron reduction of nitroaromatic compounds by Enterobacter cloacae NAD(P)H nitroreductase: Description of quantitative structure-activity relationships.

100%

Nivinskas H., Koder R. L., Anusevièius Ž., Šarlauskas J., Miller A.-F., Čenas N.

2000

vol. 47

issue 4

941-949

Enterobacter cloacae NAD(P)H:nitroreductase catalyzes the reduction of a series of nitroaromatic compounds with steady-state bimolecular rate constants (kcat/Km) ranging from 104 M-1s-1 to 107 M-1s-1 , and oxidizing 2 moles NADH per mole mononitrocompound. Oxidation of excess NADH by polynitrobenzenes including explosives 2,4,6-trinitrotoluene (TNT) and 2,4,6-trinitrophenyl-N-methylnitramine (tetryl), has been observed as a slower secondary process, accompanied by O2 consumption. This type of 'redox cycling' was not related to reactions of nitroaromatic anion-radicals, but was caused by the autoxidation of relatively stable reaction products. The logs kcat/Km of all the compounds examined exhibited parabolic dependence on their enthalpies of single-electron- or two-electron (hydride) reduction, obtained by quantum mechanical calculations. This type of quantitative structure-activity relationships shows that the reactivity of nitroaromatics towards E. cloacae nitroreductase depends mainly on their hydride accepting properties, but not on their particular structure, and does not exclude the possibility of multistep hydride transfer.

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2 Acta Biochimica Polonica

1 2004

1 2000

2 Anusevièius Ž.

2 Šarlauskas J.

1 Koder R. L.

1 Marozienė A.

1 Miller A.-F.

1 Misevièienė L.

1 Nemeikaitė-Čėnienė A.

1 Nivinskas H.

1 Čenas N.

1 Čėnas N.

Search results

Enzymatic redox reactions of the explosive 4,6-dinitrobenzofuroxan (DNBF): implications for its toxic action.

Two-electron reduction of nitroaromatic compounds by Enterobacter cloacae NAD(P)H nitroreductase: Description of quantitative structure-activity relationships.