Structure-activity relationship of pyrimidine base analogs as ligands of orotate phosphoribosyltransferase.


:Eighty pyrimidine base analogs were evaluated as inhibitors of mouse liver orotate phosphoribosyltransferase (OPRTase, EC Based on these findings and an extensive literature review, a structure-activity relationship has been formulated for the binding of pyrimidine base analogs to OPRTase. This study provides a basis for the rational design of new inhibitors of this enzyme, and several such compounds are proposed. Additionally, 4,6-dihydroxypyrimidine has been found to be a potent OPRTase inhibitor. Eleven OPRTase inhibitors were also evaluated as inhibitors of orotidine 5'-monophosphate decarboxylase (ODCase, EC 5-Azauracil, 5-azaorotate, and barbituric acid inhibited ODCase significantly only after preincubation with PRPP and MgCl2 in the presence of cytosol.


Biochem Pharmacol


Biochemical pharmacology


Niedzwicki JG,Iltzsch MH,el Kouni MH,Cha S




Has Abstract


1984-08-01 00:00:00














  • (2,6-Dimethylphenylsulphonyl)nitromethane: a new structural type of aldose reductase inhibitor which follows biphasic kinetics and uses an allosteric binding site.

    abstract::Many of the complications of diabetes seem to be due to aldose reductase (aldehyde reductase 2, ALR2) catalysing the increased conversion of glucose to sorbitol. Therapy with aldose reductase inhibitors (ARIs) could, therefore, decrease the development of diabetic complications. (2,6-Dimethylphenylsulphonyl)nitrometha...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Ward WH,Cook PN,Mirrlees DJ,Brittain DR,Preston J,Carey F,Tuffin DP,Howe R

    更新日期:1991-11-06 00:00:00

  • Relative contribution of rat cytochrome P450 isoforms to the metabolism of caffeine: the pathway and concentration dependence.

    abstract::The aim of the present study was to estimate the relative contribution of rat P450 isoforms to the metabolism of caffeine and to assess the usefulness of caffeine as a marker substance for estimating the activity of P450 in rat liver and its potential for pharmacokinetic interactions in pharmacological experiments. Th...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kot M,Daniel WA

    更新日期:2008-04-01 00:00:00

  • Interleukin-1beta converting enzyme (caspase-1) in intestinal inflammation.

    abstract::An imbalance of T helper cell type 1 (Th1) versus type 2 (Th2) polarization in favor of Th1 cell subsets appears to be a key pathogenic mechanism in chronic inflammatory bowel disease (IBD), in particular in Crohn's disease. The interferon gamma-inducing factor interleukin (IL)-18 acts in strong synergism with the Th1...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Siegmund B

    更新日期:2002-07-01 00:00:00

  • Suppression of receptor-mediated Ca2+ mobilization and functional leukocyte responses by hyperforin.

    abstract::We have recently identified hyperforin, a lipophilic constituent of the herb Hypericum perforatum (St. John's wort), as a dual inhibitor of the proinflammatory enzymes cyclooxygenase-1 and 5-lipoxygenase. The aim of the present study was to further elucidate antiinflammatory properties and respective targets of hyperf...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Feisst C,Werz O

    更新日期:2004-04-15 00:00:00

  • Isoprenaline induction of cAMP-phosphodiesterase in guinea-pig macrophages occurs in the presence, but not in the absence, of the phosphodiesterase type IV inhibitor rolipram.

    abstract::The long-term effects of incubating freshly isolated, elicited guinea-pig peritoneal macrophages with the beta-adrenoceptor agonist isoprenaline and the selective inhibitor of phosphodiesterase (PDE) IV rolipram, on adenosine-3',5'-cyclic phosphate (cAMP)-specific PDE IV activity have been investigated. The level of c...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kochetkova M,Burns FM,Souness JE

    更新日期:1995-12-22 00:00:00

  • Increased concentrations of methylated 6-mercaptopurine metabolites and 6-thioguanine nucleotides in human leukemic cells in vitro by methotrexate.

    abstract::The effect of methotrexate (MTX) on 6-mercaptopurine (6-MP) metabolism was studied in four human leukemic cell lines in vitro. CCRF-CEM, WI-L2, TBJ, and HL-60 all expressed thiopurine methyltransferase (TPMT) activity. The cells were grown in horse serum-supplemented RPMI 1640 medium to which was added 4 microM of 6-M...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Giverhaug T,Loennechen T,Aarbakke J

    更新日期:1998-05-15 00:00:00

  • The effect of ifosfamide and its metabolites on intracellular glutathione levels in vitro and in vivo.

    abstract::The effect of ifosfamide and its metabolites on intracellular levels of glutathione in P388 cells in vitro has been studied. It is demonstrated that glutathione depletion occurs only in the presence of 4-hydroperoxyifosfamide and chloroacetaldehyde. In contrast isophosphoramide mustard had no effect on glutathione lev...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Lind MJ,McGown AT,Hadfield JA,Thatcher N,Crowther D,Fox BW

    更新日期:1989-06-01 00:00:00

  • Iron interactions and other biological reactions mediating the physiological and toxic actions of manganese.

    abstract::Chronic exposure to the divalent heavy metals, such as iron, lead, manganese (Mn), and chromium, has been linked to the development of severe, often irreversible neurological disorders and increased vulnerability to developing Parkinson's disease. Although the mechanisms by which these metals elicit or facilitate neur...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Roth JA,Garrick MD

    更新日期:2003-07-01 00:00:00

  • Clotrimazole inhibits and modulates heterologous association of the key glycolytic enzyme 6-phosphofructo-1-kinase.

    abstract::Clotrimazole is an antifungal azole derivative recently recognized as a calmodulin antagonist with promising anticancer effects. This property has been correlated with the ability of the drug to decrease the viability of tumor cells by inhibiting their glycolytic flux and consequently decreasing the intracellular conc...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Zancan P,Rosas AO,Marcondes MC,Marinho-Carvalho MM,Sola-Penna M

    更新日期:2007-05-15 00:00:00

  • Mechanism for Helicobacter pylori stimulation of interleukin-8 production in a gastric epithelial cell line (MKN 28): roles of mitogen-activated protein kinase and interleukin-1beta.

    abstract::Although it is known that the pathogenic mechanism of Helicobacter pylori involves the stimulated production of interleukin-8 (IL-8) as an inflammatory mediator, the details of the pathway remain unclear. The role of mitogen-activated protein kinase (MAPK) in IL-8 production by H. pylori has been examined in an in vit...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Yamada H,Aihara T,Okabe S

    更新日期:2001-06-15 00:00:00

  • Evidence that the loss of rat liver cytochrome P450 in vitro is not solely associated with the use of collagenase, the loss of cell-cell contacts and/or the absence of an extracellular matrix.

    abstract::Two methods avoiding the widespread technique of collagenase perfusion have been employed to study the regulation of total cytochrome P450 content in rat hepatocyte culture. One technique required the perfusion of the liver with the chelating agent EDTA to dissociate the parenchymal cells prior to culture. Over a peri...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Wright MC,Paine AJ

    更新日期:1992-01-22 00:00:00

  • Binding of [3H]quinuclidinyl benzilate to intestinal mucus. An artifact in identification of epithelial cell muscarinic receptors.

    abstract::The widely used muscarinic receptor ligand [3H]quinuclidinyl benzilate ([3H]QNB) was found to bind in a site-specific but artifactual manner to rat intestinal mucus, obscuring specific binding to muscarinic receptors on intestinal epithelial cells. Atropine inhibited [3H]QNB binding to mucus with an apparent IC50 of 2...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Rimele TJ,Gaginella TS

    更新日期:1982-02-15 00:00:00

  • Evidence that relaxation of hog biliary muscle is mediated by the interaction between the protein inhibitor of cyclic AMP dependent protein kinase and cholecystokinin C-terminal peptides.

    abstract::The interaction of various cholecystokinin (CCK) peptides with the protein inhibitor (PK-I) of cyclic AMP dependent protein kinase (A-PK) has been studied. The order of the affinities (ED50) for relaxation of hog biliary muscle by a series of C-terminal peptides of CCK correlated with the order of the potencies for A-...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kimura M,Kobayashi S,Kimura I

    更新日期:1983-03-01 00:00:00

  • Activation of 6-aminochrysene to genotoxic products by different forms of rat liver cytochrome P450 in an O-acetyltransferase-overexpressing Salmonella typhimurium strain (NM2009).

    abstract::Metabolic activation of a potent mutagen, 6-aminochrysene, to genotoxic products in a newly developed tester strain, Salmonella typhimurium NM2009, was studied in a rat liver microsomal monooxygenase system containing cytochrome P450 (P450). Since the tester strain was constructed by introducing an O-acetyltransferase...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Yamazaki H,Shimada T

    更新日期:1992-09-01 00:00:00

  • Relationship between 5-fluoro-2'-deoxyuridylate, 2'-deoxyuridylate, and thymidylate synthase activity subsequent to 5-fluorouracil administration, in xenografts of human colon adenocarcinomas.

    abstract::5-Fluorouracil (FUra) has been administered to mice bearing xenografts of human colon adenocarcinomas. In two tumor lines, HxGC3 and HxVRC5, intrinsically resistant to FUra, 2'-deoxyuridylate (dUMP) accumulated 13.4- and 23.9-fold above basal levels. In HxELC2 xenografts, which demonstrated some sensitivity to FUra, t...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Houghton JA,Weiss KD,Williams LG,Torrance PM,Houghton PJ

    更新日期:1986-04-15 00:00:00

  • On the role of thiol groups in the inhibition of liver microsomal Ca2+ sequestration by toxic agents.

    abstract::ATP-dependent Ca2+ sequestration by rat liver microsomes was assayed using three different methods, and characterized with regard to the effect of various inhibitors. When glucose and hexokinase were added in combination to deplete ATP in the incubation, Ca2+ uptake was followed by rapid release of Ca2+ from the micro...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Thor H,Hartzell P,Svensson SA,Orrenius S,Mirabelli F,Marinoni V,Bellomo G

    更新日期:1985-10-15 00:00:00

  • mRNA expression profiles for the response of human tumor cell lines to the antimalarial drugs artesunate, arteether, and artemether.

    abstract::The antimalarial artemisinin derivatives artesunate (ART), arteether (ARE), and artemether (ARM) reveal remarkable antineoplastic activity. In the present investigation, we identified mRNA expression profiles associated with the response of tumor cells to ART, ARE, and ARM. We performed correlation and hierarchical cl...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Efferth T,Olbrich A,Bauer R

    更新日期:2002-08-15 00:00:00

  • The solubilization of platelet membrane-bound acetylcholinesterase and aryl acylamidase by exogenous or endogenous phosphatidylinositol specific phospholipase C.

    abstract::Phosphatidylinositol specific phospholipase C from Staphylococcus aureus could solubilize acetylcholinesterase up to 55% from sheep platelets in the presence of ethylenediaminetetra acetic acid (EDTA). The endogenous phosphatidylinositol specific phospholipase C of platelets activated by deoxycholate (at 3-5 mM) could...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Majumdar R,Balasubramanian AS

    更新日期:1985-12-01 00:00:00

  • Why we should be vigilant: drug cytotoxicity observed with in vitro transporter inhibition studies.

    abstract::From routine in vitro drug-transporter inhibition assays, observed inhibition is typically assumed from direct interaction with the transporter. Other mechanisms that possibly reduce substrate uptake are not frequently fully examined. The objective of this study was to investigate the association of transporter inhibi...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Zheng X,Diao L,Ekins S,Polli JE

    更新日期:2010-10-01 00:00:00

  • Displacement of the bidentate malonate ligand from (d,l-trans-1,2-diaminocyclohexane)malonatoplatinum(II) by physiologically important compounds in vitro.

    abstract::Previous studies of platinum(II) compounds with bidentate leaving ligands have emphasized the contrast between the stability of the bidentate leaving ligand in vitro (T1/2 greater than 11 days in water) and the apparent reactivity of these bidentate platinum compounds in vivo. However, none of these studies actually m...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Mauldin SK,Plescia M,Richard FA,Wyrick SD,Voyksner RD,Chaney SG

    更新日期:1988-09-01 00:00:00

  • In vivo models of multiple myeloma (MM).

    abstract::The development of the plasma cell tumor (PCT) model was the first widely accepted in vivo model of multiple myeloma (MM). Potter and colleagues used this chemically induced PCT model to study the pathophysiology of malignant plasma cells and also used it to screen anti-MM agents. Two decades later the C57BL/KaLwRij m...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Sanchez E,Chen H,Berenson JR

    更新日期:2014-06-01 00:00:00

  • Glipentide and glucose metabolism in isolated rat hepatocytes.

    abstract::Glipentide, a second generation sulfonylurea, raised the cellular concentration of fructose 2,6-bisphosphate in isolated rat hepatocytes. Parallel to accumulating this regulatory metabolite, glipentide inhibited basal gluconeogenesis and increased the rate of L-lactate production, as well as the metabolic flux through...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: López-Alarcón L,Berbil-Bautista PR,Guijarro C,Felíu JE

    更新日期:1988-08-15 00:00:00

  • Deficient induction of sulfobromophthalein conjugating activity by phenobarbital in hamster liver.

    abstract::Administration of phenobarbital, a known inducer of glutathione S-transferase activity in rat liver, failed to stimulate sulfobromophthalein (BSP) conjugation by liver cytosol in hamsters. The latter displayed poor ability to conjugate this substrate, despite very high glutathione-conjugating activity with the broad-s...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Foliot A,Touchard D,Myara A,Trivin F,Chauffert M

    更新日期:1987-08-15 00:00:00

  • Differential signaling of human Mel1a and Mel1b melatonin receptors through the cyclic guanosine 3'-5'-monophosphate pathway.

    abstract::Cyclic guanosine 3'-5'-monophosphate (cGMP) has recently been shown to constitute a second messenger for Xenopus laevis melatonin Mel1c receptors. To verify whether cGMP levels are also modulated by mammalian melatonin receptors, we cloned the genes encoding the human Mel1a and Mel1b receptor subtypes and expressed th...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Petit L,Lacroix I,de Coppet P,Strosberg AD,Jockers R

    更新日期:1999-08-15 00:00:00

  • Metabolism of FK506, a potent immunosuppressive agent, by cytochrome P450 3A enzymes in rat, dog and human liver microsomes.

    abstract::The oxidative metabolism of FK506 by liver microsomes and purified cytochrome P450 (P450) enzymes from rats, dogs and humans was studied. The major metabolite formed by liver microsomes from all species was 13-demethylated FK506, named M-I. In adult rats, liver microsomal metabolic activity toward FK506 was higher in ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Shiraga T,Matsuda H,Nagase K,Iwasaki K,Noda K,Yamazaki H,Shimada T,Funae Y

    更新日期:1994-02-11 00:00:00

  • Pyroptotic and apoptotic cell death in iNOS and nNOS overexpressing K562 cells: A mechanistic insight.

    abstract::Previous studies from this lab and others have demonstrated that nitric oxide (NO) in a concentration dependent manner, modulated neutrophil and leukemic cell survival. Subsequent studies delineated importance of iNOS in neutrophil differentiation and leukemic cell death. On the contrary, role of nNOS in survival of t...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Sadaf S,Awasthi D,Singh AK,Nagarkoti S,Kumar S,Barthwal MK,Dikshit M

    更新日期:2020-06-01 00:00:00

  • Metabolism of protocatechuic acid influences fatty acid oxidation in rat heart: new anti-angina mechanism implication.

    abstract::Protocatechuic acid (PA), a structurally typical phenolic acid in danshen, shows anti-angina efficacy. But until now, besides scavenging of oxygen free radicals, the understanding of its anti-angina mechanism has been limited. In our study, based on a novel metabolic route of PA identified in rat heart and its influen...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Cao YG,Zhang L,Ma C,Chang BB,Chen YC,Tang YQ,Liu XD,Liu XQ

    更新日期:2009-03-15 00:00:00

  • alpha-fluoro-beta-alanine: effects on the antitumor activity and toxicity of 5-fluorouracil.

    abstract::We have shown previously that (R)-5-fluoro-5,6-dihydrouracil (FUraH(2)) attenuates the antitumor activity of 5-fluorouracil (FUra) in rats bearing advanced colorectal carcinoma. Presently, we found that alpha-fluoro-beta-alanine (FBAL), the predominant catabolite of FUra that is formed rapidly via FUraH(2), also decre...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Cao S,Baccanari DP,Rustum YM,Davis ST,Tansik RL,Porter DJ,Spector T

    更新日期:2000-04-15 00:00:00

  • Regulation of adenylate cyclase by cannabinoid drugs. Insights based on thermodynamic studies.

    abstract::The abilities of lipophilic cannabinoid drugs to regulate adenylate cyclase activity in neuroblastoma cell membranes were analyzed by thermodynamic studies. Arrhenius plots of hormone-stimulated adenylate cyclase activity exhibited a break point at 20 degrees. The break point was reduced to 14 degrees by benzyl alcoho...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Howlett AC,Scott DK,Wilken GH

    更新日期:1989-10-01 00:00:00

  • Glucosyl phosphotriesters of nucleosides: exchange mechanism of transmembrane transport and application to 5-fluoro-deoxyuridine.

    abstract::The structure and membrane interactions of lipophilic glucosyl phosphotriester derivatives of thymidine and 5-fluoro-deoxy thymidine are investigated by NMR spectroscopy. The self-association of these molecules, found in different solvents, presents a diastereoisomeric effect which is also observed in the transmembran...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Debouzy JC,Hervé M,Neumann JM,Gouyette C,Dupraz B,Huynh-Dinh T

    更新日期:1990-06-01 00:00:00