Reduction of the indoloquinone anticancer drug EO9 by purified DT-diaphorase: a detailed kinetic study and analysis of metabolites.


:DT-diaphorase has been implicated in the activation and mechanism of cytotoxicity of the investigational indoloquinone anticancer drug EO9. Here, we have used a highly purified DT-diaphorase isolated from rat Walker tumour cells to provide unambiguous evidence for the ability of this enzyme to catalyze reduction of EO9 and to provide a more detailed characterization of the reaction. Under the conditions used hypoxia had no effect on the initial rate of this reduction but did effect the nature and stability of metabolites formed. Electron spin resonance (ESR) spectrometry studies showed that DT-diaphorase reduced EO9 to a highly oxygen-sensitive metabolite that is probably the hydroquinone. In the presence of air, this metabolite is auto-oxidized to generate both drug- and oxygen-based radicals. Comproportionation:disproportionation reactions may also be involved in the generation of these radical species. The identification of these metabolites may contribute to the understanding of the molecular mechanism of DNA damage and cytotoxicity exerted by EO9.


Biochem Pharmacol


Biochemical pharmacology


Bailey SM,Lewis AD,Knox RJ,Patterson LH,Fisher GR,Workman P




Has Abstract


1998-09-01 00:00:00














  • Concordance between enzyme activity and genotype of glutathione S-transferase theta (GSTT1).

    abstract::Blood samples from 140 healthy German volunteers were used to further characterize the genetic polymorphism of the human theta class glutathione S-transferase 1 (GSTT1). For measurements of GSTT1 activity, hemolysates were incubated in vitro with different concentrations of dichloromethane. The resulting enzymatically...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Bruhn C,Brockmöller J,Kerb R,Roots I,Borchert HH

    更新日期:1998-11-01 00:00:00

  • Tetradecanoyl phorbol-13-acetate counteracts the responsiveness of cultured thyroid cells to thyrotropin.

    abstract::We have studied the effects of TPA on the metabolism of porcine thyroid cells cultured for 1-4 days in the absence (control cells) and in the presence of 0.1 mU/ml TSH (TSH cells). The phospholipid turnover, evaluated after a 2 hr incorporation of 32P-phosphate into phospholipids, is markedly modified by the presence ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Haye B,Aublin JL,Champion S,Lambert B,Jacquemin C

    更新日期:1985-11-01 00:00:00

  • Pre-clinical and translational pharmacology of a human interleukin-22 IgG fusion protein for potential treatment of infectious or inflammatory diseases.

    abstract::Interleukin (IL)-22 plays protective roles in infections and in inflammatory diseases that have been linked to its meditation of innate immunity via multiple mechanisms. IL-22 binds specifically to its heterodimeric receptor, which is expressed on a variety of epithelial tissues. UTTR1147A is a recombinant fusion prot...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Stefanich EG,Rae J,Sukumaran S,Lutman J,Lekkerkerker A,Ouyang W,Wang X,Lee D,Danilenko DM,Diehl L,Loyet KM,Herman A

    更新日期:2018-06-01 00:00:00

  • Allosteric regulation of arylamine N-acetyltransferase 1 by adenosine triphosphate.

    abstract::In the present study, a screen of adenosine analogs as potential modulators of arylamine-N-acetyltransferase 1 activity identified ATP as an inhibitor within its range of physiological concentrations. Kinetically, ATP was a non-competitive inhibitor with respect to the acetyl acceptor but a competitive inhibitor with ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Minchin RF,Rosengren KJ,Burow R,Butcher NJ

    更新日期:2018-12-01 00:00:00

  • Kynurenic acid inhibits glutamatergic transmission to CA1 pyramidal neurons via α7 nAChR-dependent and -independent mechanisms.

    abstract::Glutamatergic hypofunction and elevated levels of kynurenic acid (KYNA) in the brain are common features of patients with schizophrenia. In vivo studies indicate that in the hippocampus KYNA decreases glutamate levels, presumably via inhibition of α7 nicotinic receptors (nAChRs). Here we tested the hypothesis that bas...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Banerjee J,Alkondon M,Albuquerque EX

    更新日期:2012-10-15 00:00:00

  • "Supersulfated" heparin fragments, a new type of low-molecular weight heparin. Physico-chemical and pharmacological properties.

    abstract::A new type of low-molecular-weight heparin (ss-LMW-H) was prepared (by controlled depolymerization and concurrent sulfation of heparin with a mixture of sulfuric and chlorosulfonic acid), to test the influence of extra-sulfate groups on biological properties of heparin fragments. The fragments had an average molecular...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Naggi A,Torri G,Casu B,Pangrazzi J,Abbadini M,Zametta M,Donati MB,Lansen J,Maffrand JP

    更新日期:1987-06-15 00:00:00

  • Evaluation of estrogen receptor, antiestrogen binding sites and calmodulin for antiestrogen resistance of two clones derived from the MCF-7 breast cancer cell line.

    abstract::Estrogen receptor (ER), antiestrogen binding sites (AEBS) and calmodulin (CaM) are potential targets of antiestrogen (AE) action. To analyse further which of these targets are primarily involved in the antiproliferative activity of these drugs against human breast cancers, two cell clones, namely the RTx6 and LY-2 var...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Borras M,Jin L,Bouhoute A,Legros N,Leclercq G

    更新日期:1994-11-29 00:00:00

  • Effects of iron deprivation on the pathology and stress protein expression in murine X-linked muscular dystrophy.

    abstract::Duchenne muscular dystrophy (DMD) is caused by dystrophin deficiency, which results in muscle necrosis and the upregulation of heat shock/stress proteins (HSP). We hypothesized that reactive oxygen species, and in particular hydroxyl radicals (.OH), participate in muscle necrosis and HSP expression. It was assumed tha...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Bornman L,Rossouw H,Gericke GS,Polla BS

    更新日期:1998-09-15 00:00:00

  • Effects of the peroxisome proliferator mono(2-ethylhexyl)phthalate in primary hepatocyte cultures derived from rat, guinea pig, rabbit and monkey. Relationship between interspecies differences in biotransformation and peroxisome proliferating potencies.

    abstract::Primary hepatocyte cultures derived from rat, rabbit, guinea pig and monkey have been treated in vitro with metabolites of di(2-ethylhexyl)phthalate, i.e. mono(2-ethylhexyl)phthalate (MEHP), mono(5-carboxy-2-ethylpentyl)phthalate (metabolite V) and mono(2-ethyl-5-oxohexyl)phthalate (metabolite VI). In rat hepatocyte c...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Dirven HA,van den Broek PH,Peeters MC,Peters JG,Mennes WC,Blaauboer BJ,Noordhoek J,Jongeneelen FJ

    更新日期:1993-06-22 00:00:00

  • Dimebolin is a 5-HT6 antagonist with acute cognition enhancing activities.

    abstract::Dimebolin (Dimebon), is a non-selective antihistamine approved in Russia for the treatment of allergy. Recently, this drug has been shown to be neuroprotective in cellular models of Alzheimer's disease and Huntington's disease, and to preserve cognitive function when chronically administered to AF64A lesioned rats. In...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Schaffhauser H,Mathiasen JR,Dicamillo A,Huffman MJ,Lu LD,McKenna BA,Qian J,Marino MJ

    更新日期:2009-10-15 00:00:00

  • Upregulation of PKR pathway mediates glucolipotoxicity induced diabetic cardiomyopathy in vivo in wistar rats and in vitro in cultured cardiomyocytes.

    abstract:AIMS:Protein Kinase R (PKR) plays a key role in inflammation and insulin resistance. Cytokines, high fat diet, infection and various stress signals can activate PKR. However, the functional significance of PKR in diabetic cardiomyopathy (DCM) is not explored so far. Thus the aim of the present study was to investigate ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Mangali S,Bhat A,Jadhav K,Kalra J,Sriram D,Vamsi Krishna Venuganti V,Dhar A

    更新日期:2020-07-01 00:00:00

  • Flow linear dichroism supports an accordion model for the salt-induced condensation of chromatin.

    abstract::The salt-induced condensation of chromatin has been studied with flow-linear dichroism technique using an intercalative dye (methylene blue) to selectively monitor the linker orientation. At low ionic strength both linkers and chromatosomes (with their flat faces) are oriented preferentially parallel to the chromatin ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kubista M,Nielsen PE,Nordén B

    更新日期:1988-05-01 00:00:00

  • Identification of psychedelic new psychoactive substances (NPS) showing biased agonism at the 5-HT2AR through simultaneous use of β-arrestin 2 and miniGαq bioassays.

    abstract::Psychedelic new psychoactive substances (NPS), compounds exerting their main pharmacological effects through the activation of the serotonin 2A receptor (5-HT2AR), continuously comprise a substantial portion of the reported NPS. However, these substances and their exact mechanism of action, differentiating them from n...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Pottie E,Dedecker P,Stove CP

    更新日期:2020-12-01 00:00:00

  • Determination of the magnitude and enantioselectivity of ligand binding to rat and rabbit serum albumins using immobilized-protein high performance liquid chromatography stationary phases.

    abstract::Rat, rabbit and human serum albumins were immobilized on an HPLC stationary phase, and the resulting phases were tested for their abilities to determine the extent and enantioselectivity of ligand binding to the respective albumins. A series of achiral and chiral compounds were chromatographed on the phases including ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Massolini G,Aubry AF,McGann A,Wainer IW

    更新日期:1993-10-05 00:00:00

  • Potentiation of the biochemical effects of beta-phenylethylhydrazine by deuterium substitution.

    abstract::The concentrations of dopamine (DA), m-tyramine (mTA), p-tyramine (pTA) and serotonin (5-HT) in the striata of rats 18 hr after the administration of three different doses (5, 50, or 100 mg/kg) of beta-phenylethylhydrazine (phenelzine, PEH) were measured. These concentrations were compared to those following the admin...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Dyck LE,Durden DA,Yu PH,Davis BA,Boulton AA

    更新日期:1983-05-01 00:00:00

  • Molsidomine inhibits the chemoattractant-induced respiratory burst in human neutrophils via a no-independent mechanism.

    abstract::3-Morpholino-sydnonimine (SIN-1) is a NO-releasing compound which mimics the effects of cGMP through activation of soluble guanylyl cyclase. Its prodrug, molsidomine (SIN-10), does not release NO but does modulate various cell functions. These findings prompted us to study the effects of SIN-10 and SIN-1 on the respir...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Ervens J,Seifert R

    更新日期:1992-08-18 00:00:00

  • History of ectonucleotidases and their role in purinergic signaling.

    abstract::Ectonucleotidases are key for purinergic signaling. They control the duration of activity of purinergic receptor agonists. At the same time, they produce hydrolysis products as additional ligands of purinergic receptors. Due to the considerable diversity of enzymes, purinergic receptor ligands and purinergic receptors...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Zimmermann H

    更新日期:2020-11-06 00:00:00

  • Concomitant downregulation of proliferation/survival pathways dependent on FGF-R3, JAK2 and BCMA in human multiple myeloma cells by multi-kinase targeting.

    abstract::The identification of proliferation/survival pathways constitutively activated by genetic alterations in multiple myeloma (MM), or sustained by the bone marrow (BM) microenvironment, provides novel opportunities for the development of targeted therapies. The deregulated function of protein tyrosine kinases plays a cri...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Cassinelli G,Ronchetti D,Laccabue D,Mattioli M,Cuccuru G,Favini E,Nicolini V,Greco A,Neri A,Zunino F,Lanzi C

    更新日期:2009-11-01 00:00:00

  • Prodrug research: futile or fertile?

    abstract::The objective of this Commentary is to help clarify and illustrate what prodrugs are, what they are not, which benefits they can offer, and what their limits are. To this end, a number of criteria of classification and evaluation are presented. This is followed by a discussion of the pharmaceutical, pharmacokinetic an...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Testa B

    更新日期:2004-12-01 00:00:00

  • cis-Diamminedichloroplatinum(II) (DDP)-induced crosslinking and crosslink removal in L1210 cells in vitro after theophylline co-treatment.

    abstract::The present study investigated the mechanism by which theophylline decreases cis-diamminedichloroplatinum(II) (DDP)-induced DNA crosslinking in L1210 cells. Alkaline elution of DNA from L1210 cells treated with DDP in the presence and absence of 1 mM theophylline showed that theophylline decreased interstrand crosslin...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Ducore JM

    更新日期:1986-02-15 00:00:00

  • Contribution of non-ADH pathways to ethanol oxidation in hepatocytes from fed and hyperthyroid rats. Effect of fructose and xylitol.

    abstract::The metabolism of (1R)[1-3H]ethanol, [2-3H]lactate or [2-3H]xylitol was studied in hepatocytes from fed or T3-treated rats in the presence or absence of fructose or xylitol. The yields of tritium in ethanol, lactate, water, glycerol and glucose were determined. A simple model, describing the metabolic fate of tritium ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Vind C,Grunnet N

    更新日期:1985-03-01 00:00:00

  • Alcohol-induced ketonemia is associated with lowering of blood glucose, downregulation of gluconeogenic genes, and depletion of hepatic glycogen in type 2 diabetic db/db mice.

    abstract::Alcoholic ketoacidosis and diabetic ketoacidosis are life-threatening complications that share the characteristic features of high anion gap metabolic acidosis. Ketoacidosis is attributed in part to the massive release of ketone bodies (e.g., β-hydroxybutyrate; βOHB) from the liver into the systemic circulation. To da...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Srinivasan MP,Shawky NM,Kaphalia BS,Thangaraju M,Segar L

    更新日期:2019-02-01 00:00:00

  • Prostaglandin D2 induces the production of human beta-defensin-3 in human keratinocytes.

    abstract::The antimicrobial peptide human beta-defensin-3 (hBD-3) is produced by epidermal keratinocytes and protects the skin from infections. This peptide induces the release of a lipid mediator, prostaglandin D(2) from dermal mast cells. Prostaglandin D(2) binds to cell-surface G protein-coupled receptors, D prostanoid recep...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kanda N,Ishikawa T,Watanabe S

    更新日期:2010-04-01 00:00:00

  • Antioxidant activity of adrenergic agents derived from catechol.

    abstract::The ability of adrenergic catechol derivatives, including dobutamine, dopamine, and isoproterenol, to inhibit lipid peroxidation was examined. All the catechol derivatives we tested strongly inhibited lipid peroxidation. Dobutamine was a more powerful inhibitor of iron-catalyzed lipid peroxidation than the other agent...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Miura T,Muraoka S,Ogiso T

    更新日期:1998-06-15 00:00:00

  • Cellular uptake, cytotoxicity, and transport kinetics of anthracyclines in human sensitive and multidrug-resistant K562 cells.

    abstract::Multidrug resistance in tumor cells is often associated with the presence of an approximately 170 kDa plasma membrane glycoprotein (Pgp) that acts as a drug-efflux pump and decreases intracellular antitumor drug concentration. We measured the uptake of seven anthracyclines (daunorubicin, doxorubicin, 4'-epi-doxorubici...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Praet M,Stryckmans P,Ruysschaert JM

    更新日期:1996-05-17 00:00:00

  • Evidence in vivo for elevation of intracellular free Ca2+ in the liver after diquat, acetaminophen, and CCl4.

    abstract::Several hepatotoxic agents with varied chemical mechanisms of toxicity (acetaminophen, diquat, and CCl4) depress membrane calcium pumps and/or enhance the permeability of membranes to calcium. To probe the relevance of these findings to maintenance of calcium homeostasis after toxins in vivo, we measured the activity ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Tsokos-Kuhn JO

    更新日期:1989-09-15 00:00:00

  • Inhibition of indoleamine 2,3-dioxygenase activity in IFN-gamma stimulated astroglioma cells decreases intracellular NAD levels.

    abstract::Astroglia provide essential metabolic and neurotropic support to cells within the CNS and participate in the cellular immune response with microglia/macrophages following activation by the pro-inflammatory cytokine IFN-gamma. Activation of glial cells results in local oxidative stress and induction of a number of prot...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Grant R,Kapoor V

    更新日期:2003-09-15 00:00:00

  • Increased glutathione peroxidase activity in human blood mononuclear cells upon in vitro incubation with n-3 fatty acids.

    abstract::Fish oil-enriched diets have been shown to increase the n-3 polyunsaturated fatty acid (PUFA) content of cell membranes, in vivo, and to simultaneously enhance the glutathione peroxidase (glutathione: H2O2 oxidoreductase, EC (GSH-Px) activity of platelets and erythrocytes both in animals and humans. The pres...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Joulain C,Prigent AF,Némoz G,Lagarde M

    更新日期:1994-04-20 00:00:00

  • The influence of picolines on glutathione transferase activity and subunit composition in human liver derived Hep G2 cells.

    abstract::Hep G2 cells, an established cell line derived from a human hepatoma, have retained a number of hepatocytic phase I and II reactions. The influence of picolines (2-, 3- and 4-methylpyridine), related compounds and some classical enzyme inducers on specific glutathione transferase (GST) activity and its subunit composi...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Dierickx PJ

    更新日期:1994-11-16 00:00:00

  • Induction of UDP-glucuronyl transferase mRNA in embryonic chick livers by phenobarbital.

    abstract::Administration of phenobarbital to chick embryos increased hepatic microsomal UDP-glucuroyltransferase activity some 25-fold. The large phenobarbital-induced increase of UDP-glucuronyltransferase activity was correlated to an equivalent increase of immunochemically measurable UDP-glucuronyltransferase protein. Poly(A+...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Jackson MR,Kennedy SM,Lown G,Burchell B

    更新日期:1986-04-01 00:00:00