Reversible interaction of a reactive intermediate derived from furazolidone with glutathione and protein

Vroomen, L.H.M.; Berghmans, M.C.J.; Groten, J.P.; Koeman, J.H.; Bladeren, P.J. van

doi:10.1016/s0041-008x(88)80007-3

Cited by 47 publications

(16 citation statements)

References 17 publications

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“…The veterinary antbiotic furazolidone 5 is converted to a reactive acrylonitrile metabolite by swine liver microsomes and this electrophilic metabolite can undergo reversible Michael addition reactions with thiols (Scheme 3) [39]. This metabolite also forms covalent adducts when incubated with microsomal proteins.…”

Section: The Reversibility Of the Michael Additionmentioning

confidence: 99%

Reversible Michael Additions: Covalent Inhibitors and Prodrugs

Johansson¹

2012

Mini Reviews in Medicinal Chemistry

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Covalent inhibition is an efficient molecular mechanism for inhibiting enzymes or modulating the function of proteins and is found in the action of many drugs and biologically active natural products. However, it is has been less appreciated that the formation of covalent bonds can be reversible or irreversible. This review focuses on biologically active compounds that are Michael acceptors and how the reversible nature of the Michael addition reaction influences biological activity and how this can be exploited in designing prodrugs.

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Section: The Reversibility Of the Michael Additionmentioning

confidence: 99%

Reversible Michael Additions: Covalent Inhibitors and Prodrugs

Johansson¹

2012

Mini Reviews in Medicinal Chemistry

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“…Moreover, the reduction of the nitro group of the nitrofuran ring, during the metabolic pathway of FUZ, eventually results in the formation of active metabolites capable of binding to tissue macromolecules, such as DNA and proteins (Vroomen et al, 1987(Vroomen et al, , 1988De Angelis et al, 1999;Laurentius et al, 2002). These protein-bound metabolites can also bind with thiols like glutathione (GSH) and thus reducing its level in the cell (Vroomen et al, 1988(Vroomen et al, , 1990. The modest fall in total glutathione levels would render the cell more susceptible to oxidantinduced genotoxicity which is associated with DNA instability (Weitberg et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

Potential role of cysteine and methionine in the protection against hormonal imbalance and mutagenicity induced by furazolidone in female rats

2008

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“…For mutagenic activation of furylfuramide (cis form), cis-trans isomerization (25)(26)(27) and reduction of the nitro group of 5-nitrofuran (28,29) are important in the metabolic pathway. The cis-trans isomerization is based on the formation of nitro anion radicals.…”

Section: Discussionmentioning

confidence: 99%

Suppression of Chemical Mutagens-Induced SOS Response by Phenolic Acids from Black Rice Bran Using Salmonella typhimurium TA1535/pSK1002 umu Test

Miyazawa

Oshima²,

Tokura

et al. 2003

J. Oleo Sci.

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In the evaluation of the carcinogenicity or mutagenicity caused by environmental chemicals, it is quite important to determine factors present in our environment that may affect these activities. With the development of techniques for detecting possible environmental carcinogens and mutagens (1), it has been shown that ordinary diets contain many kinds of mutagens and antimutagens. Abstract: A methanol extract from black rice bran showed a suppressive effect of the SOS-inducing activity on the mutagen 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide) in the Salmonella typhimurium TA1535/pSK1002 umu test. The methanol extract was reextracted with hexane, chloroform, ethylacetate, butanol and water. The ethylacetate fraction showed a suppressive effect. Suppressive compounds in an acidic fraction of the ethylacetate fraction were isolated by silica gel column chromatography and identified as vanillic acid (1) and protocatechuic acid (2) by GC, GC/MS, IR and 1 H and 13 C NMR spectroscopy. Compounds 1 and 2 suppressed the furylfuramide-induced SOS response in the umu test. Compounds 1 and 2 suppressed 37.7 and 44.5% of the SOS-inducing activity on furylfuramide at a concentration of 1.20 mmol/mL. These compounds were assayed with other mutagens, 4-nitroquinolin 1-oxide (4NQO) and N-methyl-N -nitro-N-nitrosoguanidine (MNNG), which do not require liver metabolizing enzymes. In addition, compounds 1 and 2 were assayed with aflatoxin B 1 (AfB 1 ) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which require liver metabolizing enzymes. These compounds showed suppressive effects of the SOS-inducing activity against furylfuramide, 4NQO, MNNG, AfB 1 and Trp-P-1. To research the structure-activity relationship, veratric acid (3) as a similar compound of 1 and methyl esters of 1,2 and 3 (1Me, 2Me and 3Me) were also assayed with all chemical mutagens. Compounds 1Me, 2Me and 3Me exhibited stronger suppressive effects of the SOS-inducing activity against all chemical mutagens than 1,2 and 3.

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Reversible interaction of a reactive intermediate derived from furazolidone with glutathione and protein

Cited by 47 publications

References 17 publications

Reversible Michael Additions: Covalent Inhibitors and Prodrugs

Reversible Michael Additions: Covalent Inhibitors and Prodrugs

Potential role of cysteine and methionine in the protection against hormonal imbalance and mutagenicity induced by furazolidone in female rats

Suppression of Chemical Mutagens-Induced SOS Response by Phenolic Acids from Black Rice Bran Using Salmonella typhimurium TA1535/pSK1002 umu Test

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