Isolation and structural characterization of acrylamide-pyridoxamine adducts.


:Pyridoxamine (PM) is an effective inhibitor of the formation of the carcinogen acrylamide (AA) from its precursors in low-moisture model systems. Although AA is widely assumed to act by scavenging carbonyl compounds, no alternative pathways have to date been explored. In this work, we found AA to directly react with PM in a low-moisture acrylamide-pyridoxamine model system heated at 140 °C for up to 40 min. The reaction products gave four major chromatographic peaks that were assigned to acrylamide-pyridoxamine adducts. Two of the adducts (AA-PM-1 and AA-PM-3) were selected for isolation and structural characterization with various spectroscopic (UV, fluorescence, IR, and NMR) and mass spectrometric techniques (MS, MS/MS). As shown by the proposed reaction scheme, PM can directly react with AA via Michael addition. The reaction involves a nucleophilic attack of the PM amine group on AA (an α,β-unsaturated carbonyl compound) to give adduct AA-PM-3, which was identified as 3-(((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)methyl)amino)propanamide. However, AA-PM-3 further reacts with any additional AA present in the medium to give adduct AA-PM-1 identified as 3,3'-(((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)methyl)azanediyl)dipropanamide. The time courses of these adduct formation reactions were studied in cookies supplemented with PM, where AA-PM-3 was found to be the predominant structure.


Chem Res Toxicol


Arribas-Lorenzo G,Pintado-Sierra M,Morales FJ




Has Abstract


2011-03-21 00:00:00












  • The major metabolite of equilin, 4-hydroxyequilin, autoxidizes to an o-quinone which isomerizes to the potent cytotoxin 4-hydroxyequilenin-o-quinone.

    abstract::The risk factors for women developing breast and endometrial cancers are all associated with a lifetime of estrogen exposure. Estrogen replacement therapy in particular has been correlated with a slight increased cancer risk. Previously, we showed that equilenin, a minor component of Premarin (Wyeth-Ayerst), was metab...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Zhang F,Chen Y,Pisha E,Shen L,Xiong Y,van Breemen RB,Bolton JL

    更新日期:1999-02-01 00:00:00

  • Maillard reaction products modulating the growth of human tumor cells in vitro.

    abstract::We investigated the effect of a series of Maillard reaction products formed from carbohydrates under household heating conditions on the growth of human tumor cells in vitro. 4-Hydroxy-5-methyl-3-(2H)-furanone (1) was found to potently enhance the proliferation of human tumor cells. In contrast, the Maillard-type chro...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Marko D,Habermeyer M,Kemény M,Weyand U,Niederberger E,Frank O,Hofmann T

    更新日期:2003-01-01 00:00:00

  • Methemoglobin Formation and Characterization of Hemoglobin Adducts of Carcinogenic Aromatic Amines and Heterocyclic Aromatic Amines.

    abstract::Arylamines (AAs) and heterocyclic aromatic amines (HAAs) are structurally related carcinogens formed during the combustion of tobacco or cooking of meat. They undergo cytochrome P450 mediated N-hydroxylation to form metabolites which bind to DNA and lead to mutations. The N-hydroxylated metabolites of many AAs also ca...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Pathak KV,Chiu TL,Amin EA,Turesky RJ

    更新日期:2016-03-21 00:00:00

  • DNA Polymerases η and ζ Combine to Bypass O(2)-[4-(3-Pyridyl)-4-oxobutyl]thymine, a DNA Adduct Formed from Tobacco Carcinogens.

    abstract::4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are important human carcinogens in tobacco products. They are metabolized to produce a variety 4-(3-pyridyl)-4-oxobutyl (POB) DNA adducts including O(2)-[4-(3-pyridyl)-4-oxobut-1-yl]thymidine (O(2)-POB-dT), the most abundant POB adduc...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Gowda AS,Spratt TE

    更新日期:2016-03-21 00:00:00

  • Detection of weak estrogenic flavonoids using a recombinant yeast strain and a modified MCF7 cell proliferation assay.

    abstract::A newly developed recombinant yeast strain, in which the human estrogen receptor has been stably integrated into the genome of the yeast, was used to gain information on the estrogenic activity of a large series of dietary flavonoids. Among 23 flavonoids investigated, 8 were found to markedly stimulate the transcripti...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Breinholt V,Larsen JC

    更新日期:1998-06-01 00:00:00

  • Patterns of resistance to exonuclease digestion of oligonucleotides containing polycyclic aromatic hydrocarbon diol epoxide adducts at N6 of deoxyadenosine.

    abstract::The effect of adduct stereochemistry on the susceptibility to hydrolysis by snake venom (VPD) and bovine spleen (SPD) phosphodiesterases was investigated with short deoxyoligonucleotides containing defined adducts derived from alkylation of the exocyclic 6-amino group of dA by polycyclic aromatic hydrocarbon diol epox...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Ilankumaran P,Pannell LK,Gebreselassie P,Pilcher AS,Yagi H,Sayer JM,Jerina DM

    更新日期:2001-09-01 00:00:00

  • Mechanism of the N-hydroxylation of primary and secondary amines by cytochrome P450.

    abstract::Cytochrome P450 enzymes (CYPs) metabolize alkyl- and arylamines, generating several different products. For the primary and secondary amines, some of these reactions result in hydroxylated amines, which may be toxic. Thus, when designing new drugs containing amine groups, it is important to be able to predict if a giv...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Seger ST,Rydberg P,Olsen L

    更新日期:2015-04-20 00:00:00

  • Covalent Modification of CDK2 by 4-Hydroxynonenal as a Mechanism of Inhibition of Cell Cycle Progression.

    abstract::Oxidative stress is a contributing factor in a number of chronic diseases, including cancer, atherosclerosis, and neurodegenerative diseases. Lipid peroxidation that occurs during periods of oxidative stress results in the formation of lipid electrophiles, which can modify a multitude of proteins in the cell. 4-Hydrox...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Camarillo JM,Rose KL,Galligan JJ,Xu S,Marnett LJ

    更新日期:2016-03-21 00:00:00

  • Dominant contribution of P450 3A4 to the hepatic carcinogenic activation of aflatoxin B1.

    abstract::The hepatic carcinogen aflatoxin B1 (AFB1) is metabolized in the liver by at least four different P450s, all of which exhibit large interindividual differences in the expression levels. These differences could affect the individual risk of hepatocellular carcinoma (HCC). We investigated the metabolism of AFB1 in a pan...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Kamdem LK,Meineke I,Gödtel-Armbrust U,Brockmöller J,Wojnowski L

    更新日期:2006-04-01 00:00:00

  • Profiling the reactive metabolites of xenobiotics using metabolomic technologies.

    abstract::A predominant pathway of xenobiotic-induced toxicity is initiated by bioactivation. Characterizing reactive intermediates will provide information on the structure of reactive species, thereby defining a potential bioactivation mechanism. Because most reactive metabolites are not stable, it is difficult to detect them...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Li F,Lu J,Ma X

    更新日期:2011-05-16 00:00:00

  • In vitro model of mammary estrogen metabolism: structural and kinetic differences between catechol estrogens 2- and 4-hydroxyestradiol.

    abstract::Estrogens and their oxidative metabolites, the catechol estrogens, have been implicated in the development of breast cancer; yet, relatively little is known about estrogen metabolism in the breast. To determine how the parent hormone, 17 beta-estradiol (E(2)), is metabolized, we used recombinant, purified phase I enzy...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Dawling S,Hachey DL,Roodi N,Parl FF

    更新日期:2004-09-01 00:00:00

  • Identification and characterization of thiosemicarbazones with antifungal and antitumor effects: cellular iron chelation mediating cytotoxic activity.

    abstract::Thiosemicarbazones derived from acetylpyrazines were prepared by condensing an acetylpyrazine or a ring-substituted acetylpyrazine with thiosemicarbazide. Using the same procedure, N, N-dimethylthiosemicarbazones were synthesized from acetylpyrazines and N, N-dimethylthiosemicarbazide. A total of 20 compounds (16 nove...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Opletalová V,Kalinowski DS,Vejsová M,Kunes J,Pour M,Jampílek J,Buchta V,Richardson DR

    更新日期:2008-09-01 00:00:00

  • Inhibition of topoisomerase I function by nitidine and fagaronine.

    abstract::The benzophenanthridine alkaloids nitidine and fagaronine were characterized as inhibitors of topoisomerase I function. In common with the antitumor agent camptothecin, both nitidine and fagaronine stabilized the covalent binary complex formed between calf thymus topoisomerase I and DNA. The effects of these compounds...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Wang LK,Johnson RK,Hecht SM

    更新日期:1993-11-01 00:00:00

  • Genotoxicity-related chemistry of human metabolites of benzo[ghi]perylene (B[ghi]P) investigated using electro-optical arrays and DNA/microsome biocolloid reactors with LC-MS/MS.

    abstract::There is limited and sometimes contradictory information about the genotoxicity of the polycyclic aromatic hydrocarbon benzo[ghi]perylene (B[ghi]P). Using recently developed metabolic toxicity screening arrays and a biocolloid reactor-LC-MS/MS approach, both featuring films of DNA and human metabolic enzymes, we demon...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Pan S,Li D,Zhao L,Schenkman JB,Rusling JF

    更新日期:2013-08-19 00:00:00

  • Identification and characterization of deoxyguanosine adducts of methyl vinyl ketone and ethyl vinyl ketone. Genotoxicity of the ketones in the SOS Chromotest.

    abstract::The reaction of the alpha, beta-unsaturated ketones methyl vinyl ketone (MVK) and ethyl vinyl ketone (EVK) with nucleosides and 5'-mononucleotides was studied. The genotoxic activity of MVK and EVK in the SOS Chromotest was investigated. Three different types of adducts with deoxyguanosine were found and their structu...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Eder E,Hoffman C,Deininger C

    更新日期:1991-01-01 00:00:00

  • Differential metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in mice humanized for CYP1A1 and CYP1A2.

    abstract::The procarcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine formed during the cooking of foods. Metabolism of PhIP by CYP1A2 differs substantially between humans and rodents, with more N2-hydroxylation (activation) and less 4'-hydroxylation (detoxication) in humans....

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Cheung C,Ma X,Krausz KW,Kimura S,Feigenbaum L,Dalton TP,Nebert DW,Idle JR,Gonzalez FJ

    更新日期:2005-09-01 00:00:00

  • Determination of in vitro- and in vivo-formed DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline by capillary liquid chromatography/microelectrospray mass spectrometry.

    abstract::Capillary liquid chromatography/microelectrospray mass spectrometry has been applied to the detection of deoxyribonucleoside adducts of the food-derived mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) from in vitro and in vivo sources. Constant neutral loss (CNL) and selective reaction monitoring (SRM) techniques...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Gangl ET,Turesky RJ,Vouros P

    更新日期:1999-10-01 00:00:00

  • Nanomaterials and Innate Immunity: A Perspective of the Current Status in Nanosafety.

    abstract::Human exposure to engineered nanomaterials (ENMs) is inevitable due to the plethora of applications for which they are being manufactured and integrated within. ENMs demonstrate plentiful advantages in terms of industrial approaches as well as from a consumer perspective. However, despite such positives, doubts remain...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Cronin JG,Jones N,Thornton CA,Jenkins GJS,Doak SH,Clift MJD

    更新日期:2020-05-18 00:00:00

  • Ethical guidelines to publication of chemical research. American Chemical Society.

    abstract::The guidelines embodied in this document were revised by the editors of the Publication Division of the American Chemical Society in January 1994 and endorsed by the Society Committee on Publications. ...

    journal_title:Chemical research in toxicology

    pub_type: 指南,杂志文章



    更新日期:1994-07-01 00:00:00

  • Modeling liver-related adverse effects of drugs using knearest neighbor quantitative structure-activity relationship method.

    abstract::Adverse effects of drugs (AEDs) continue to be a major cause of drug withdrawals in both development and postmarketing. While liver-related AEDs are a major concern for drug safety, there are few in silico models for predicting human liver toxicity for drug candidates. We have applied the quantitative structure-activi...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Rodgers AD,Zhu H,Fourches D,Rusyn I,Tropsha A

    更新日期:2010-04-19 00:00:00

  • Cytochrome P450 3A4-mediated bioactivation of raloxifene: irreversible enzyme inhibition and thiol adduct formation.

    abstract::Raloxifene is a selective estrogen receptor modulator which is effective in the treatment of osteoporosis in postmenopausal women. We report herein that cytochrome P450 (P450)3A4 is inhibited by raloxifene in human liver microsomal incubations. The nature of the inhibition was irreversible and was NADPH- and preincuba...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Chen Q,Ngui JS,Doss GA,Wang RW,Cai X,DiNinno FP,Blizzard TA,Hammond ML,Stearns RA,Evans DC,Baillie TA,Tang W

    更新日期:2002-07-01 00:00:00

  • Role of human glutathione S-transferases in the inactivation of reactive metabolites of clozapine.

    abstract::The conjugation of reactive drug metabolites to GSH is considered an important detoxification mechanism that can be spontaneous and/or mediated by glutathione S-transferases (GSTs). In case GSTs play an important role in GSH conjugation, genetically determined deficiencies in GSTs may be a risk factor for adverse drug...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Dragovic S,Boerma JS,van Bergen L,Vermeulen NP,Commandeur JN

    更新日期:2010-09-20 00:00:00

  • Glutamate dehydrogenase covalently binds to a reactive metabolite of acetaminophen.

    abstract::The mechanism of the hepatotoxicity of the analgesic acetaminophen is believed to be mediated by covalent binding to protein; however, critical targets which effect the toxicity are unknown. It has been shown that mitochondrial respiration in vivo is inhibited in mice as early as 1 h following a hepatotoxic dose of ac...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Halmes NC,Hinson JA,Martin BM,Pumford NR

    更新日期:1996-03-01 00:00:00

  • Reactive sulfur species: kinetics and mechanism of the hydrolysis of cysteine thiosulfinate ester.

    abstract::The kinetics and mechanisms of the hydrolysis of cysteine thiosulfinate ester (CyS(O)SCy ( x- ), x = 0-2) have been investigated by stopped-flow spectrophotometry between pH 6 and pH 14. The rate-limiting reaction of hydroxide is observed for pH < 13. More complicated kinetics are observed above pH 13, where the hydro...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Nagy P,Ashby MT

    更新日期:2007-09-01 00:00:00

  • Mechanism of cytochrome P450-catalyzed aromatic hydroxylation of estrogens.

    abstract::The mechanism of aromatic hydroxylation of estrogens by cytochrome P450 enzymes has been examined by comparing the oxidation of estrone with that of substrates carrying additional aromaticity such as equilenin and the structural analog 2-naphthol. Hamster liver microsomes preferentially catalyzed the conversion of est...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Sarabia SF,Zhu BT,Kurosawa T,Tohma M,Liehr JG

    更新日期:1997-07-01 00:00:00

  • Benomyl, aldehyde dehydrogenase, DOPAL, and the catecholaldehyde hypothesis for the pathogenesis of Parkinson's disease.

    abstract::The dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is detoxified mainly by aldehyde dehydrogenase (ALDH). We find that the fungicide benomyl potently and rapidly inhibits ALDH and builds up DOPAL in vivo in mouse striatum and in vitro in PC12 cells and human cultured fibroblasts and glial cells. The in vi...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Casida JE,Ford B,Jinsmaa Y,Sullivan P,Cooney A,Goldstein DS

    更新日期:2014-08-18 00:00:00

  • Information-Derived Mechanistic Hypotheses for Structural Cardiotoxicity.

    abstract::Adverse events resulting from drug therapy can be a cause of drug withdrawal, reduced and or restricted clinical use, as well as a major economic burden for society. To increase the safety of new drugs, there is a need to better understand the mechanisms causing the adverse events. One way to derive new mechanistic hy...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Svensson F,Zoufir A,Mahmoud S,Afzal AM,Smit I,Giblin KA,Clements PJ,Mettetal JT,Pointon A,Harvey JS,Greene N,Williams RV,Bender A

    更新日期:2018-11-19 00:00:00

  • Potentialities and pitfalls accompanying chemico-pharmacological strategies against endogenous electrophiles and carbonyl stress.

    abstract::The use of powerful analytical technologies to detect endogenous carbonyls formed as byproducts of oxidative cell injury has revealed that these species contribute to many human diseases. As electrophiles, they are attacked by reactive centers in cell macromolecules to form adducts, the levels of which serve as useful...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Burcham PC

    更新日期:2008-04-01 00:00:00

  • Formation and structure of cross-linking and monomeric pyrrole autoxidation products in 2,5-hexanedione-treated amino acids, peptides, and protein.

    abstract::2,5-Hexanedione (2,5-HD) is the neurotoxic gamma-diketone metabolite of the industrial solvent n-hexane. Substantial evidence indicates that 2,5-HD reacts with neurofilament protein lysine epsilon-amines to yield 2,5-dimethylpyrrole adducts and that this reaction is critical to the mechanism of toxicity. Alkylpyrroles...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Zhu M,Spink DC,Yan B,Bank S,DeCaprio AP

    更新日期:1994-07-01 00:00:00

  • Analysis of 3'-phosphoglycolaldehyde residues in oxidized DNA by gas chromatography/negative chemical ionization/mass spectrometry.

    abstract::Deoxyribose oxidation in DNA represents a biologically important facet of oxidative DNA damage that gives rise to protein-DNA cross-links and base adducts. Toward the goal of quantifying deoxyribose oxidation chemistry in cells, we report a method for the quantification of 3'-phosphoglycolaldehyde (PGA) residues, whic...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章


    authors: Collins C,Awada MM,Zhou X,Dedon PC

    更新日期:2003-12-01 00:00:00