4- Nitroquinoline-N-oxide

Among the aromatics, it was found that 4-nitroquinoline N-oxide [56-57-5] is a powerful carcinogen producing malignant tumors when painted on the skin of mice (80). It was further estabUshed that the 2-methyl, 2-ethyl, and 6-chloro derivatives of 4-nitro quinoline oxide are also carcinogens (81). 

Carbamate esters of zinc, zineb, and ziram are carcinogenic and teratogenic in animals, but this is attributed to the action of the carbamate esters and not to zinc (Elinder 1986). Results of studies with small mammals showed zinc to be cocarcinogenic with 4-nitroquinoline-N-oxide on oral cancer, and with N-ethyl-N-nitrosourea on brain cancer (Leonard and Gerber 1989). 

An important example is the reduction of nitroquinoline N-oxide. This proceeds via the hydroxylamine, which is an extremely carcinogenic metabolite, probably the ultimate carcinogen (Fig. 4.40). 

The nitro group of 4-nitropyridine-N-oxide (1) was hydrogenated preferentially over palladium in neutral medium -2 but in acid the N-oxide was also reduced (Eqn. 19.1).2 Hydrogenation of 1 or 4-nitroquinoline-N-oxide over Raney nickel at elevated temperatures and pressures resulted in the reduction of both the nitro group and the N-oxide.3.4 Hydrogenation of 2-nitropyridine-N-oxide gave only 2-aminopyridine.5... 

Ascorbate Potentiated Cytotoxicity of Nitroaromatic Compounds. Extensive research aimed at finding chemicals or chemical systems that will sensitize hypoxic cells, which are ordinarily very resistant to radiation or chemicals, is being conducted in the field of radiobiology. Of particular interest are the investigations (58-6J) of the catalytic effect of certain carcinogens upon the oxidation of ascorbate. 4-Nitroquinoline N-oxide (4-NQO), which is one of many compounds (52,62,63) that mediate the ascorbate-oxygen reaction, is used as an example. 

Servos, J., Haase, E., and Brendel, M. (1993) Gene SNQ2 of Saccharomyces cerevisiae, which confers resistance to 4-nitroquinoline-N-oxide and other chemicals, encodes a 169 kDa protein homologous to ATP-dependent permeases. Molecular General Genetics, 236, 214-218. 

Cui, Z., Shiraki, T., Hirata, D., and Miyakawa, T. (1998) Yeast gene YRRl, which is required for resistance to 4-nitroquinoline N-oxide, mediates transcriptional activation of the multidrug resistance transporter gene SNQ2. Molecular Microbiology, 29. 1307-1315. 

Quinones such as the anti-cancer drug adriamycin can undergo one-electron reduction catalysed by NADPH cytochrome P-450 reductase. The semiquinone product may be oxidized back to the quinone with the concomitant production of superoxide anion radical, giving rise to redox cycling and potential cytotoxicity (see Chapter 6). An important example is the reduction of nitroquinoline N-oxide. This proceeds via the hydroxylamine, which is an extremely carcinogenic metabolite, probably the ultimate carcinogen (figure 4,391. 

These compounds include 3-methyl-4-nitroquinoline-N-oxide, azoxy-benzene, diphenylnitrosamine, 1-naphthylamine and methyl orange... 

Johanssen, S.L. et al.. Snuff induced carcinogenesis effect of snuff in rats initiated with 4-nitroquinoline-N-oxide, Cancer Res., 49, 303, 1989. 

Poot, M. et al., Werner syndrome diploid fibroblasts are sensitive to 4-nitroquinoline-N-oxide and 8-methoxypsoralen implications for the disease phenotype, FASEB J., 7, 757,2002. 

Two stage mouse pulmonary carcinogenesis initiated with 4-nitroquinoline-N-oxide and promoted with glycerol Oral administration of astilbin, (+)-taxifolin or the extract showed potent inhibitory activities. 

Nitroquinoline, 435 8-Nitroquinoline, 435 4-Nitroquinoline N-oxide, 437 Nitrosamine, 156, 203-220, 398 A -Nitrosoanatabine, 204 -Nitrosobis(2-oxopropyl)amine, 204 -Nitrosodibenzylamine, 214 Nitrosodiethanolamine, 204 N-Nitroso group, 414 N-Nitroso-2- hydioxymorpholine, 216 N-Nitrosomorpholine, 205, 214, 216 N -Nitrosonomicotine, 204, 205, 214, 217-220 N -Nitrosonomicotine 1-N-oxide, 217 Nitrosophenol, 38... 

Detection according to (geno)toxicity has been reported recently. Such system is based on the collection over microtiter plates of 1 min eluate fractions. After evaporation and redissolution in suitable solvents, the (geno)toxicity of each individual fraction is determined before and after enzyme activation, by means of the umu test. (Geno)toxicity is measured against 4-nitroquinoline-N-oxide and 2-aminoanthracene standards, exhibiting detection limits of the order of 0.1 pgl ... 

Trifluoromethylquinoline-N-oxide under similar conditions gave 4-cyano-3-trifluoromethylquinoline in 48% yield [91], while 4-nitroquinoline-N-oxide gave (31) on reaction with potassium cyanide and ethyl cyanoacetate [92]. 

In fig 2 is displayed the first derivative of the sampled voltammograms derived from single and double potential step chronoamperometric measurements for the reduction of 4-nitroquinoline-N- oxide on a T1 upd platinum electrode. The reduction of heterocyclic nitro compounds follows an E.C.E. mechanism. 

However in the case of 4-nitroquinoline -N- oxide the chemical step is fast relative to the rate of mass transport in the time scales of our experiment and the electrochemical reaction is controlled by diffusion. The product of the first reduction step of p-nitroquinoline -N- oxide undergoes very rapidly a chemical change to form R-NO which is further reduced to form R-NHOH. Single step chronovoltammetry gives no direct evidence for the existence of this reaction. 

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