Glucuronic Acid Derivatives Research Articles

Isolation of lipid glucuronic acid and N-acetylglucosamine derivatives from a rat fibrosarcoma

Incubation of labeled UDP-GlcUA and UDP-GlcNAc with microsomes of a fibrosarcoma yielded labeled glycolipids resistant to hydrolysis with dilute alkali. These compounds have been tentatively identified as lipid-GlcNAc, lipid-GlcNAc-GlcUA and lipid-tetra and hexasaccharides containing both GlcUA and GlcNAc.

Stimulation of microsomal uridine diphosphate glucuronyltransferase by glucuronic acid derivatives.

The glucuronic acid adducts of 1-naphthol, 2-naphthol and 4-methylumbelliferone activate microsomal UDP-glucuronyltransferase (EC 2.4.1.17) when the enzyme is assayed with p-nitrophenol as aglycone. Phenyl glucuronide and oestriol 3beta-glucuronide also activate UDP-glucuronyltransferase. but to a lesser extent. Activation by glucuronides is not dependent on metal ions, but is blocked by prior treatment of microsomal fractions with p-chloromercuribenzoate. The kinetic mechanism of activation is concluded to be an increase in the affinity of the enzyme for UDP-glucuronic acid. Activation by 1-naphthyl glucuronide, at high concentrations of p-nitrophenol, is not affected by 1-naphthol. Apparently 1-naphthyl glucuronide activates the preparation by binding at a site that is separate from the site of glucuronidation of 1-naphthol. Further evidence for the existence of distinct effector sites for the glucuronides was provided by the finding that activation by glucuronides is inhibited competitively by aglycone glucosides. These glucosides do not inhibit the rate of glucuronidation of p-nitrophenol in the absence of glucuronide adducts, nor do they alter the rate of glucuronidation of 1-naphthol. When UDP-glucuronyltransferase is assayed with 1-naphthol as aglycone it is activated by p-nitrophenyl glucuronide, 4-methyl-umbelliferyl glucuronide and under appropriate conditions by its own glucuronide. These activations are similarly inhibited by aglycone glucosides. p-Nitrophenyl glucuronide also stimulates the rate of glucuronidation of o-aminophenol, o-aminobenzoate and bilirubin.

In vitro glucosylation of 1-naphthol by insects

Glucosylation in insects was investigated using tobacco hornworms ( Manduca sexta) as the primary test insect and 1-naphthol- 14C as the substrate. Of 6 common co-factors tested, only UDPG was utilized by the conjugating enzyme system. Neither the hornworm nor housefly enzymes could form the glucuronic acid derivative of 1-naphthol using UDPGA. Centrifugal fractionation of the hornworm homogenates showed that the glucosyltransferase activity was in the 105,000 g soluble fraction. In the housefly, the enzyme activity was associated with the 15,000 g pellet and to a lesser extent with the 105,000 g pellet. In vitro inhibition of the glucosyltransferase by sulphoxide, piperonyl butoxide, and other insecticide synergists was demonstrated.

Aryl-2-halogenoalkylamines—XXVI glucuronic, sulphuric and phosphoric esters of [formula omitted

It has been proposed that the high activity of NN- di-2- chloroethylaniline as an inhibitor of the growth of a mouse plasma cell tumour is mediated by the formation of the ethereal glucuronide of its p- hydroxy derivative. To test this hypothesis this conjugation and also the corresponding ethereal phosphate and sulphate have been synthesised and submitted to preliminary antineoplastic assays. The glucuronic acid derivative and its methyl ester exhibit high carcinostatic activity against the mouse plasma cell tumour (ADJ/PC6A). The ethereal phosphate also shows significant activity against this tumour but the sulphate is considerably less active. The significance of these results for the design of tissue specific anticancer agents is discussed.

Distribution of UDP-glucuronyl transferase among cell fractions of rat liver.

AbstractMicrosomal UDP‐glucuronyl transferases (uridine‐5′‐diphosphate‐glucuronate glucuronyl transferase, acceptor unspecific, EC 2.4.1.17) function in detoxification of a wide range of aglycons containing phenolic, alcoholic, carboxylic or amino acceptor groups through formation of water‐soluble glucuronic acid derivatives. To localize this activity within a specific cell component, purified rough‐surfaced endoplasmic reticulum and Golgi apparatus fractions from rat liver were compared with total homogenates. The UDP‐glucuronyl transferase specific activity of the Golgi apparatus fractions was less than or approximately equal to that of the total homogenate whereas this activity was concentrated 3–8 fold in the rough‐surfaced endoplasmic reticulum fraction depending upon substrate. We conclude that the rough‐surfaced endoplasmic reticulum is the major site of glucuronide formation within the microsome fraction of normal rat livers.

Nucleosides: Part LXII. Synthetic studies on nucleoside antibiotics. 2.syntheses of methyl 4-amino-4-deoxy-d-glucosiduronic acid derivatives related to the carbohydrate moiety of gougerotin

The first synthesis of 4-amino-4-deoxy- d-hexuronic acid has been achieved. Tritylation of methyl 4-azido-4-deoxy-α- d-glucopyranoside ( 1) gave the 6-trityl ether ( 2) which was converted into its 2,3-dibenzoate ( 3) and deritylated to methyl 4-azido-2,3-di- O-benzoyl-α- d-glucopyranoside ( 5). Oxidation of 5 afforded the glucuronic acid derivative 6 which upon esterification to 7, followed by reduction and benzoylation yielded methyl (methyl 4-benzamido-2,3-di- O-benzoyl-4-deoxy-α- d-glucopyranosid)uronate ( 8), the structure and conformation of which were firmly established by n.m.r. analysis. De-benzoylation of methyl (methyl 4-azido-2,3-di- O-benzoyl-4-deoxy-α- d-glucopyranosid)uronate ( 7) with sodium methylate to 9, followed by de-esterification and subsequent hydrogenation afforded crystalline methyl 4-amino-4-deoxy-α- d-glucopyranosiduronic acid ( 11), the structure of which was established by esterification and benzoylation to 8. N-Acetylation of 11 yielded methyl 4-acetamido-4-deoxy-α- d-glucopyranosiduronic acid ( 14) which was esterified and peracetylated to the methyl ester 16. Derivative 16 was also obtained by hydrogenation and peracetylation of 9. Epimerization at C-5 was not observed in the conversion of 7 → 11, which suggests that a total synthesis of the gougerotin-derived C-substance from the 4-amino-4-deoxy-hexuronic acid derivatives reported herein is feasible.

Sulphuric esters of polysaccharides as activators of a bradykinin-forming system in plasma.

PREVIOUS work1 has shown that intravenous injection of agar, a naturally occurring sulphuric ester of polygalactose, leads to an appreciable reduction in bradykininogen concentration as well as to a significant increase of p-tosylarginine methyl ester (TAMe) esterase activity in the plasma of the rat. Other results indicate that, besides agar, synthetic sulphuric esters of certain polysaccharides are potent activators of the bradykinin forming system in rat or human plasma in vitro. In the experiments demonstrating this activity, 0.2 per cent oxalated plasma was collected, avoiding contact with glass, and treated with 1 mg/ml. of 8-hydroxy quinoline (8HQ), an inhibitor of enzymes which destroy bradykinin2. Kinin formed was assayed on isolated, atropinized guinea-pig ileum which had been treated with antihistamine, using synthetic bradykinin as the standard. Powdered cellulose, glycogen from shellfish, inulin, soluble starch and agar were added to rat plasma, either as such, or after conversion to water soluble sulphuric esters by treatment with chlorosulphonic acid in pyridine3. The effects of carrageenin, a sulphuric ester of polygalactose, extracted from Irish moss, as well as of heparin, were also examined. When incubated at 37° C with rat plasma, all sulphuric ester polysaccharides caused stimulation of smooth muscle equivalent to, on average, 1.0 µg of bradykinin/ml. The active material formed had the characteristics of bradykinin; it was rapidly destroyed by plasma in the absence of 8HQ, as well as by chymotrypsin. Maximum activation was reached 1 min after the addition of 10−4 or 10−5 g of cellulose sulphate to 1 ml. of plasma (Fig. 1). Larger concentrations (10−3 g/ml.) of this activator were less effective during the early phase of the incubation, which suggests an inhibitory effect of excess sulphopolysaccharide on bradykinin production. Ten parts by weight of hexadimethrine bromide, previously shown to inhibit kinin formation4, inactivated one part of cellulose sulphate. None of the non-sulphated, native polysaccharides induced kinin formation; heparin, a sulphated derivative of polyglucosamine and glucuronic acid, previously shown5 to be an activator of certain kinin-forming agents, was much less active than the other sulphopolysaccharides examined. The amounts of bradykinin formed by optimal concentrations of cellulose sulphate in rat plasma were the same as those resulting from the exposure of plasma to powdered glass6. Either treatment led to a comparable depletion of plasma-kinin precursor, so that pre-incubation of plasma with glass in the absence of 8HQ, followed by incubation with cellulose sulphate and quinoline, did not result in kinin activity while, reciprocally, pre-incubation of plasma with cellulose sulphate in the absence of 8HQ, rendered it unresponsive to subsequent activation with glass in the presence of 8HQ.

Synthesis of amino sugar containing disaccharides. The synthesis of hyalobiuronic acid and chondrosine.

Hyalobiuronic acid, the unit disaccharide of hyaluronic acid, and chondrosine, that of chondroitin sulfuric acid A or C, were synthesized by condensing corresponding aminosugar derivatives with acetobromo derivative of glucuronic acid by the Koenigs-Knorr reaction.

Physiochemical studies on water contained in solid medicaments. IV. Character of hydrates of glucuronic acid deirivates

Physiochemical studies on water contained in solid medicaments. IV. Character of hydrates of glucuronic acid deirivates

Physicochemical studies on water contained in solid medicaments. 3. Character of hydrates of glucuronic acid derivatives

In the hydrated derivatives of glucuroic acid glucuronamide monohydrate, potassium glucuronate dihydrate, and sodium glucuronate isoniazone dihydrate, water of hydration present has different properties. These hydrates were submitted to the measurement of changes in weight, dielectric constant, and differential heat, activation energy of dehydration, and specific surface area by the BET method. The result of these measurements threw doubt on whether water of hydration in one mole of potassium glucuronate dihydrate and two moles on sodium glucuronate isoniazone dihydrate could be strictly called water of crystallization in its limited sense. Even if such water of hydration could be included in the scope of the water of crystallization, such water will be a problem in the manufacture of pharmaceutical preparations.

DISTRIBUTION AND EXCRETION OF [14C]‐NEOSTIGMINE IN THE RAT AND HEN

British Journal of Pharmacology and ChemotherapyVolume 25, Issue 1 p. 234-242 Free Access DISTRIBUTION AND EXCRETION OF [14C]-NEOSTIGMINE IN THE RAT AND HEN J. B. ROBERTS, J. B. ROBERTS Department of Pharmacology and General Therapeutics, University of LiverpoolSearch for more papers by this authorB. H. THOMAS, B. H. THOMAS Department of Pharmacology and General Therapeutics, University of LiverpoolSearch for more papers by this authorA. WILSON, A. WILSON Department of Pharmacology and General Therapeutics, University of LiverpoolSearch for more papers by this author J. B. ROBERTS, J. B. ROBERTS Department of Pharmacology and General Therapeutics, University of LiverpoolSearch for more papers by this authorB. H. THOMAS, B. H. THOMAS Department of Pharmacology and General Therapeutics, University of LiverpoolSearch for more papers by this authorA. WILSON, A. WILSON Department of Pharmacology and General Therapeutics, University of LiverpoolSearch for more papers by this author First published: August 1965 https://doi.org/10.1111/j.1476-5381.1965.tb01778.xCitations: 19AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat REFERENCES Beyer, K. H., Russo, H. F., Gass, S. R., Wilhoyte, K. M. & Pitt, A. A. (1950). Renal tubular elimination of N'-methylnicotinamide. Amer. J. Physiol., 160, 311– 320. Bollman, J. L. (1948). A cage which limits the activity of rats. J. Lab. clin. Med., 33, 1348. Brittain, R. T. & Spencer, P. S. J. (1963). An apparatus for the long-term collection of urine free from faecal and food contamination. J. Pharm. Pharmacol., 15, 483– 485. Goldstein, A., Krayer, O., Root, M. A., Acheson, G. H. & Doherty, M. E. (1949). Plasma neostigmine levels and Cholinesterase inhibition in dogs and myasthenic patients. J. Pharmacol, exp. Ther., 96, 56– 85. Kelly, R. G., Peets, E. A., Gordon, S. & Buyske, D. A. (1961). Determination of C14 and H3 in biological samples by Schöniger combustion and liquid scintillation techniques. Analyt. Biochem., 2, 267– 273. Kinard, F. E. (1957). Liquid scintillator for the analysis of tritium in water. Rev. Sci. Instrum., 28, 293– 294. Krayer, O., Goldstein, A. & Plachte, F. L. (1944). Studies on physostigmine and related substances. 1. Quantitative relation between dosage of physostigmine and inhibition of Cholinesterase activity in the blood serum of dogs. J. Pharmacol. exp. Ther., 80, 8– 30. Nowell, P. T., Scott, C. A. & Wilson, A. (1962a). Determination of neostigmine and pyridostigmine in the urine of patients with myasthenia gravis. Brit. J. Pharmacol., 18, 617– 624. Nowell, P. T., Scott, C. A. & Wilson, A. (1962b). Hydrolysis of neostigmine by plasma Cholinesterase. Brit. J. Pharmacol., 19, 498– 502. Peters, L., Fenton, K. J., Wolf, M. L. & Kandel, A. (1955). Inhibition of the renal tubular excretion of N'-methylnicotinamide (NMN) by small doses of a basic cyanine dye. J. Pharmacol. exp. Ther., 113, 148– 159. Rennick, B. R., Kandel, A. & Peters, L. (1956). Inhibition of the renal tubular excretion of tetraethylammonium and N'-methylnicotinamide by basic cyanine dyes. J. Pharmacol, exp. Ther., 118, 204– 219. Roberts, J. B., Thomas, B. H. & Wilson, A. (1963). Excretion of neostigmine labelled with carbon-14 in urine. Nature (Lond), 200, 1330. Scott, C. A. (1962). An Investigation of the Metabolism of Neostigmine. Ph.D. thesis at the University of Liverpool. Scott, C. A., Nowell, P. T. & Wilson, A. (1962). An investigation of the metabolism of neostigmine in patients with myasthenia gravis. J. Pharm. Pharmacol., 14, 31– 33T. Sperber, I. (1946). A new method for the study of renal tubular excretion in birds. Nature (Lond), 158, 131. Sperber, I. (1948). The excretion of some glucuronic acid derivatives and phenol sulphuric esters in the chicken. Ann. roy. agric. Coll. Sweden, 15, 317– 349. Sperber, I. (1949). Investigations on the circulatory system of the avian kidney. Zool. Bidrag. f. Uppsala, 27, 429– 448. Citing Literature Volume25, Issue1August 1965Pages 234-242 ReferencesRelatedInformation

グルクロン酸誘導体の赤外線吸収スペクトル (第1報)

グルクロン酸誘導体の赤外線吸収スペクトル (第1報)

A New Unsaturated Derivative of Glucuronic Acid

Cox, Hirst and Reynolds1 in investigating Szent-Györgyi's hexuronic acid, have suggested that, this acid may have the following structures: COOH.CO.CO.CH2.CHOH.CH2OH⇄ COOH.CO.C(OH)=CH.CHOH.CH2OH It will be noted that the second (enol) structure has a double bond. The acid reduces neutral silver nitrate, Fehling's solution, iodine and neutral permanganate2, and yields a trimethyl ether and a triacetyl derivative.