The reduction of Furacin by cell-free extracts of Furacin-resistant and parent-susceptible strains of Escherichia coli

Asnis, Robert E.

doi:10.1016/0003-9861(57)90551-9

Cited by 83 publications

(31 citation statements)

References 10 publications

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“…The mutagenic and antimicrobial activity of these compounds is mediated by short-lived intermediates formed during their reduction by nitroreductases (31,32). Two types of nitroreductases have been identified in Escherichia coli (6,10,32). Oxygen-insensitive nitroreductases are flavoproteins that mediate the transfer of two electrons from NAD(P)H to the nitro moiety of nitrosubstituted compounds (10); biologically active intermediates produced through this pathway include nitroso and hydroxylamine derivatives that are further reduced to yield biologically inactive products (32).…”

mentioning

confidence: 99%

Regulation of thenfsAGene inEscherichia coliby SoxS

2002

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In Escherichia coli, the response to oxidative stress due to elevated levels of superoxide is mediated, in part, by the soxRS regulon. One member of the soxRS regulon, nfsA, encodes the major oxygen-insensitive nitroreductase in Escherichia coli which catalyzes the reduction of nitroaromatic and nitroheterocyclic compounds by NADPH. In this study we investigate the regulation of nfsA in response to the superoxide generating compound paraquat. The transcription start site (TSS) of nfsA was located upstream of the ybjC gene, a small open reading frame of unknown function located directly upstream of nfsA, suggesting that these two genes form an operon. The activity of the promoter associated with this TSS was confirmed with lacZ fusions and was shown to be inducible by paraquat. Footprinting and band shift analysis showed that purified His-tagged SoxS protein binds to a 20-base sequence 10 bases upstream of the ؊35 promoter sequence in the forward orientation, suggesting that the ybjC-nfsA promoter is a class I SoxS-dependent promoter.

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confidence: 99%

Regulation of thenfsAGene inEscherichia coliby SoxS

2002

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“…Although they undoubtedly have immense therapeutic value as broad spectrum antimicrobial agents (20), with resistance to nitrofurans being an infrequent occurrence, nitrofurans are now regarded as being sufficiently mutagenic to preclude their use in human treatment for infections or in the treatment of animals in the human food supply (21). The generally accepted mechanism of action of nitrofurans as antibiotics is that they are reduced by bacterial nitroreductases to highly reactive metabolites that then covalently react with and poison essential components of the bacterial cellular machinery (22,23). We therefore wished to determine if the nitrofurans identified as inhibitors of estrogen signaling did so specifically; three nitrofurans (i.e., EMBL-153448, furaltadone, and nitrofurantoin) had relatively poor or no inhibition of estrogen signaling ( Table 1) and also did not inhibit human topoisomerase I or II activity at 100 Amol/L (data not shown), indicating that the nitrofuran group alone is insufficient to inhibit topoisomerase activity.…”

Section: Discussionmentioning

confidence: 99%

Thanatop: A Novel 5-Nitrofuran that Is a Highly Active, Cell-Permeable Inhibitor of Topoisomerase II

Polycarpou‐Schwarz

Müller²,

Denger³

et al. 2007

Cancer Research

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A series of nitrofuran-based compounds were identified as inhibitors of estrogen signaling in a cell-based, high-throughput screen of a diverse library of small molecules. These highly related compounds were subsequently found to inhibit topoisomerase II in vitro at concentrations similar to that required for the inhibition of estrogen signaling in cells. The most potent nitrofuran discovered is f10-fold more active than etoposide phosphate, a topoisomerase II inhibitor in clinical use. The nitrofurans also inhibit topoisomerase I activity, with f20-fold less activity. Moreover, the nitrofurans, in contrast to etoposide, induce a profound cell cycle arrest in the G 0 -G 1 phase of the cell cycle, do not induce doublestranded DNA breaks, are not substrates for multidrug resistance protein-1 export from the cell, and are amenable to synthetic development. In addition, the nitrofurans synergize with etoposide phosphate in cell killing. Clonogenic assays done on a panel of human tumors maintained ex vivo in nude mice show that the most active compound identified in the screen is selective against tumors compared with normal hematopoietic stem cells. However, this compound had only moderate activity in a mouse xenograft model. This novel class of topoisomerase II inhibitor may provide additional chemotherapeutic strategies for the development of cytotoxic agents with proven clinical utility. [Cancer Res 2007;67(9):4451-8]

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“…In bacteria it is known that nitrofuran derivatives such as nitrofurantoin are activated by flavoproteins (Asnis et al, 1957) and that mutants resistant to the toxic effects of these compounds have lost nitroreductase activity (reductase 1) (McCalla et al, 1978). Similar reductive processes have been proposed to account for their toxicity towards mammalian cells (Olive & McCalla, 1975).…”

Section: Discussionmentioning

confidence: 99%

Flurbiprofen, a non-steroid anti-inflammatory agent, protects cells against hypoxic cell radiosensitizers in vitro

Millar¹,

Jinks²,

Powles³

1981

Br J Cancer

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Summary.-Overnight exposure of Chinese hamster cells (V79-753B) to 5 x 10-5M flurbiprofen (2-(2-fluoro-4-biphenyl)propionic acid) in vitro reduced the cytotoxic effects of misonidazole, 1-methyl -4-nitro -5 -phenoxysulphonylimidazole (NSC 38087) and nitrofurantoin, both in air and in hypoxia at 37°C. Flurbiprofen did not alter the cells' uptake of 14C-misonidazole, nor did it affect the radiosensitivity of aerobic or anaerobic cells, or the degree of hypoxic-cell radiosensitization produced by the sensitizers. When flurbiprofen-treated cells were exposed to melphalan there was no protection against cytotoxicity. These data suggest that flurbiprofen may inhibit the catabolism of radiosensitizers to toxic products and indicate the need to examine whether it will protect against misonidazole-induced toxicity in vivo.

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The reduction of Furacin by cell-free extracts of Furacin-resistant and parent-susceptible strains of Escherichia coli

Cited by 83 publications

References 10 publications

Regulation of thenfsAGene inEscherichia coliby SoxS

Regulation of thenfsAGene inEscherichia coliby SoxS

Thanatop: A Novel 5-Nitrofuran that Is a Highly Active, Cell-Permeable Inhibitor of Topoisomerase II

Flurbiprofen, a non-steroid anti-inflammatory agent, protects cells against hypoxic cell radiosensitizers in vitro

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