Disease relevance of Nitrofuran

• Another nitrofuran, 4,6-dimethyl-2-(5-nitro-2-furyl)-pyrimidine, provided the following types of neoplasms in 30 female rats at risk: squamous cell carcinomas of the forestomach (30), sarcomas of the intestine (21), adenocarcinomas of the kidney (2) [1].
• Further, increased toxicity did not necessarily lead to increased chemopotentiation, nor was potentiation directly related to the metabolism/binding of the nitrofuran [2].
• A naturally occurring cardiomyopathy (round heart disease) which is potentiated by inbreeding and a cardiomyopathy produced by furazolidone, a nitrofuran derivative, were studied for an associated alpha1-antitrypsin deficiency in two flocks of turkeys (one inbred for round heart disease and a commercial flock) [3].
• POR exhibited no MTZ reductase activity either in extracts of H. pylori or following overexpression in E. coli; RdxA exhibited no nitrofuran reductase activity, and FrxA exhibited no MTZ reductase activity [4].
• In the search for new therapeutic tools against American Trypanosomiasis palladium complexes with bioactive nitrofuran-containing thiosemicarbazones as ligands were obtained [5].

High impact information on Nitrofuran

• A close correlation was found between the carcinogenicities and destructive activities of nitrofuran derivatives on the sebaceous glands [6].
• Under aerobic conditions, trypanothione reductase is not inactivated by these redox-cycling substrates, whereas under anaerobic conditions the nitrofuran compounds cause irreversible inactivation of the enzyme [7].
• Enhancement of toxicity from N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea in V79 spheroids by a nitrofuran [2].
• These results provide direct evidence of a nitrofuran reductase activity associated with the mitochondrial outer membrane that is far more important than that of respiratory chain enzymes [8].
• A similar stimulatory effect of ferredoxin on metronidazole reduction, but not on nitrofuran reduction, is observed in incubations containing purified NADPH:ferredoxin oxidoreductase from S. oleracea [9].

Chemical compound and disease context of Nitrofuran

• Recombinant His-tagged RdxA, FrxA, and POR, overexpressed in nitroreductase-deficient Escherichia coli, each rapidly reduced NTZ, whereas only FrxA and to a lesser extent POR reduced nitrofuran substrates (furazolidone, nitrofurantoin, and nitrofurazone) [4].
• Nifurzide, a nitrofuran antiinfectious agent: interaction with Escherichia coli cells [10].
• The mutagenic activity of nitrofuran derivatives and of niridazole is easily demonstrated by spot tests using E. coli WP2 and its uvrA derivative but not by spot tests using the S. typhimurium strains developed by Ames [11].
• Earlier work showed that Escherichia coli contains at least two enzymes which reduce nitrofurazone and other nitrofuran derivatives [12].
• Action of some nitrofuran derivatives on glucose metabolism, ATP levels, and macromolecule synthesis in Escherichia coli [13].

Biological context of Nitrofuran

• Investigation of 5-nitrofuran derivatives: synthesis, antibacterial activity, and quantitative structure-activity relationships [14].
• The sensitivity, accuracy, and convenience of the method make it suitable for clinical monitoring and pharmacokinetic/bioavailability studies with 5-nitrofuran derivatives [15].
• Nitrofuran inhibition of microsomal lipid peroxidation [16].
• Transferable nitrofuran resistance conferred by R-plasmids in clinical isolates of Escherichia coli [17].
• In addition, the expression of the nprB gene seems to be constitutive, whereas nprA gene expression is inducible by a wide range of nitroaromatic and heterocyclic compounds, including several dinitroaromatics, nitrofuran derivatives, CB1954, 2-aminofluorene, benzo[a]pyrene, salicylic acid, and paraquat [18].

Anatomical context of Nitrofuran

• Certain 2-aminothiazole-substituted 5-nitrofuran carcinogens specifically and potently induce tumors of the urinary tract [19].
• In view of the relatively low oxygen tension in the renal inner medulla and bladder mucosa, these results suggest that medullary and transitional epithelial nitro-reductases may be involved in the pathogenesis of 5-nitrofuran toxicity [20].
• Reduction of nitrofuran derivatives by xanthine oxidase and microsomes. Isolation and identification of reduction products [21].
• The activation step may involve reduction of the nitrofuran to an amino group probably by the enzyme reductase I. Most cultured cell systems, such as bacteria, yeast, Neurospora, mammalian cells and human lymphocytes, can probably bring about this reduction [22].
• 5-Nitrofuran derivatives of fatty acid hydrazides induce differentiation in human myeloid leukaemic cell lines [23].

Associations of Nitrofuran with other chemical compounds

• Nitrofurantoin is a synthetic nitrofuran commonly used for the treatment and prophylaxis of urinary tract infections [24].
• Inhibitory action of a 5-nitrofuran (SQ 18506) against nucleic acid synthesis in Trypanosoma cruzi [25].
• The nitrite-releasing activity of the major enzyme purified from rhesus monkey liver was also tested on fifty-two nitro compounds including nineteen nitrofuran derivatives [26].
• The assayed nitrofuran compounds did not inhibit LADH lipoamide reductase activity, at variance with their action on glutathione reductase (Grinblat et al., Biochem Pharmacol 38: 767-772, 1989) [27].
• A recA strain (which was very sensitive to the lethal effects of AF2 and nitrofurazone) lacked the ability to repair daughter-strand gaps caused by nitrofuran-induced lesions [28].

Gene context of Nitrofuran

• The mutational specificity of the 5-nitrofuran derivative furazolidone was determined in the lacI gene of Escherichia coli [29].
• Oxygen-insensitive nitroreductases: analysis of the roles of nfsA and nfsB in development of resistance to 5-nitrofuran derivatives in Escherichia coli [30].
• Mutagenic properties of a nitrofuran, 7-methoxy-2-nitronaphtho[2, 1-b]furan (R7000), in lacI transgenic mice [31].
• LADH catalyzed nitrofuran reduction to products more reduced than the nitroanion, which were not reoxidized by oxygen [27].
• The nitrofuran reductase activity of Escherichia coli K12 strains was separated into two components by passage through Sepharose 4B-200 [32].

Analytical, diagnostic and therapeutic context of Nitrofuran

• Simultaneous separation of nitrofuran antibiotics and their metabolites by using micellar electrokinetic capillary chromatography [33].
• These compounds are active against nitrofuran- and nitroimidazole-resistant T.cruzi strains and maintain their activity even if the hosts are immunosuppressed and are thus logical candidates for clinical trials with Chagas disease patients [34].
• Simultaneous determination of nitrofuran derivatives in various animal substrates by high-performance liquid chromatography [35].
• Mutagenic activities of simple nitrofuran derivatives. I. Comparison of related compounds in the phage inductest, chloroplast-bleaching and bacterial-repair and mutagenicity tests [36].
• ESR spin trapping studies of free radicals generated from nitrofuran derivative analogues of nifurtimox by electrochemical and Trypanosoma cruzi reduction [37].

References