5-(m-Benzyloxybenzyl)barbituric acid acyclonucleoside, a uridine phosphorylase inhibitor, and 2′,3′,5′-tri-O-acetyluridine, a prodrug of uridine, as modulators of plasma uridine concentration: Implications for chemotherapy

Biochemical Pharmacology

Volumn 51, Issue 12, 1996, Pages 1601-1611

  Ashour, Osama M ^a   Naguib, Fardos N M ^a   El Kouni, Mahmond H ^a  

^a University of Alabama at Birmingham   (United States)

Author keywords

Chemotherapy; Inhibitor; Phosphorylase; Prodrug; Uridine

Indexed keywords

2',3',5' TRI O ACETYLURIDINE; 5 (3 BENZYLOXYBENZYL) BARBITURIC ACID ACYCLONUCLEOSIDE; PRODRUG; UNCLASSIFIED DRUG; URACIL; URIDINE; URIDINE PHOSPHORYLASE INHIBITOR;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; BIOAVAILABILITY; CONTROLLED STUDY; DOSE TIME EFFECT RELATION; DRUG BLOOD LEVEL; FEMALE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; INTRAPERITONEAL DRUG ADMINISTRATION; MOUSE; NONHUMAN; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL;

ANIMALS; BARBITURATES; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; FEMALE; MICE; MICE, INBRED STRAINS; PRODRUGS; TIME FACTORS; URIDINE;

EID: 0030000144     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/0006-2952(96)00102-5     Document Type: Article

References (81)

1. Klubes P, Cerna I and Meldon MA, Uridine rescue from the lethal toxicity of 5-fluorouracil in mice. Cancer Chemother Pharmacol 8: 17-21, 1982.
2. Martin DS, Stolfi RL, Sawyer RC, Spiegelman S and Young CW, High dose 5-fluorouracil with delayed uridine "rescue" in mice. Cancer Res 42: 3964-3970, 1982.
3. Klubes P and Cerna I, Use of undine rescue to enhance the antitumor selectivity of 5-fluorouracil. Cancer Res 43; 3182-3186, 1983.
4. Peters GJ, van Dijak J, Laurensse E, van Groeningen CJ, Lankelman J, Leyva A, Nadal JC and Pinedo HM, In vitro biochemical and in vivo biological studies of the uridine 'rescue' of 5-fluorouracil. Br J Cancer 57: 259-265, 1988.
5. Sommadossi J-P, Carlisle R, Schinazi RF and Zhou Z, Uridine reverses the toxicity of 3′-azido-3′-deoxythymidine in normal human granulocyte-macrophage progenitor cells in vitro without impairment of antiretroviral activity. Antimicrob Agents Chemother 32: 997-1001, 1988.
6. Sommadossi J-P, Zhu Z, Carlisle R, Xie MY, Weidner DA and el Kouni MH, Novel pharmacologic approaches for the treatment of AIDS and potential use of uridine phosphorylase inhibitors. In: Advances in Chemotherapy of AIDS (Eds. Diasio RB and Sommadossi J-P), pp 63-73. Pergamon Press, New York, 1990.
7. Keilbauch SA, Hobbs GA and Simpson MV, Anti-human immunodeficiency virus type 1 therapy and periphery neuropathy: Prevention of 2′,3′-dideoxycytidine toxicity in PC12 cells, a neuronal model by uridine and pyruvate. Mol Pharmacol 44: 702-706, 1993.
8. Tamura K, Woo J, Bakri MT and Thomson AW, Brequinar sodium inhibits interleukin-6-induced differentiation of a human B-cell line into IgM-secreting plasma cells. Immunology 79: 587-593, 1993.
9. Cherwinski HM, Byars N, Ballaron SJ, Nakano GM, Young JM and Ransom JT, Leflunomide interferes with pyrimidine nucleotide biosynthesis. Inflamm Res 44: 317-322, 1995.
10. Greene S, Watanabe K, Braatz-Trulson J and Lou L, Inhibition of dihydroorotate dehydrogenase by the immunosuppressive agent leflunomide. Biochem Pharmacol 50: 861-867, 1995.
11. Williamson RA, Yea CM, Robson PA, Curnock AP, Gadher S, Hambleton AB, Woodward K, Bruneau J-M, Hambleton P, Moss D, Thomson TA, Spinella-Jaegle S, Morand P, Courtin O, Sautés C, Westwood R, Hercend T, Kuo EA and Ruuth E, Dihydroorotate dehydrogenase is a high affinity binding protein for A77 1726 and mediator of a range of biological effects of the immunomodulatory compound. J Biol Chem 270: 22467-22472, 1995.
12. Myers CS, Napolitano M, Fisher H and Wagner GC, Uridine and stimulant-induced motor activity. Proc Soc Exp Biol Med 204: 49-53, 1993.
13. Myers CS, Fisher H and Wagner GC, Uridine potentiates haloperidol's disruption of conditioned avoidance responding. Brain Res 651: 194-198, 1994.
14. Geiger A and Yamasaki S, Cytidine and uridine requirement of the brain. J Neurochem 1: 93-100, 1956.
15. Bonavita V, Monaco P and Tripi E, Analisi degli effetti centrali di nucleotidi purinici e pirinmidinci e loro derivati III. Esperimenti farmacologici. Acta Neurol (Napoli) 19: 215-222, 1964.
16. Sanguined I and Zerbi D, L'impiego di alcuni nucleosidi non vasoattivi (citidina e uridina) nella terapia delle vasculopatie cerebrali. Minerva Med 56: 3352-3361, 1965.
17. Monticone GF, Bergamasco B and Congnazzo A, Sull'impiego terapeutico dei nucleosidi citidina ed uridina in alcune affezioni neurologiche. Minerva Med 57: 4348-4352, 1966.
18. Bonavita B and Zito M, Analisi dell'azione di nucleosidi pirimidinici sull'elettroencefallogramma umano attivato con megimide. Riv Neurol 38: 317-319, 1968.
19. Jann G and Delzanno GB, Azione della citidina ed uridina nel trattamento delle indromi neuropsichiche da encefalopatie di varia origine. Minerva Med 60: 2092-2108, 1969.
20. Sepe O, Efficacia dell'assoiazione citidina-uridina nelle affezioni vascolari dell'encefalo. Minerva Med 61: 5934-5941, 1970.
21. Roberts CA, Anticonvulsant effects of uridine: Comparative analysis of metrazol and penicillin induced foci. Brain Res 55: 291-308, 1973.
22. Roberts CA, Kreisman NR and Waltman M, Uridine anti-convulsant effects: Selective control of nucleoside incorporation in experimental epilepsy. Epilepsia 15: 479-500, 1974.
23. Dwivedi C and Harbison RD, Anticonvulsant activities of Δ-8 and Δ-9 tetrahydrocannabinol and uridine. Toxicol Appl Pharmacol 31: 452-458, 1975.
24. Guarneri P, Guarner R, Mocciaro C and Piccoli F, Interaction of uridine with GABA binding sites in cerebellar membranes of the rat. Neurochem Res 8: 1537-1545, 1983.
25. Guarneri P, Guarner R, Mocciaro C and Piccoli F, Interaction of uridine with GABA-mediated inhibitory transmission: Studies in vivo and in vitro. Epilepsia 26: 666-671, 1985.
26. Inoué S, Sleep-promoting substance (SPS) and physiological sleep regulation. Zoolog Sci 10: 557-576, 1993.
27. Kypson J and Hait G, Effects of uridine and inosine on glucose metabolism in skeletal muscle and activated lipolysis in adipose tissue. J Pharmacol Exp Ther 199: 565-574, 1976.
28. Kypson J and Hait G, Metabolic effects of inosine and uridine in rabbit hearts and rat skeletal muscles. Biochem Pharmacol 26: 1585-1591, 1977.
29. Elrick H, Hlad CJ Jr and Arai Y, Influence of certain nucleosides on glucose metabolism in man. Metabolism 11: 46-55, 1962.
30. Bushma MI, Parkhovchenko EI and Peschanskii VS, Effects of cytidine and uridine on the regeneration of the liver in rats poisoned with carbon tetrachloride. Bull Exp Biol Med 88: 722-723, 1980.
31. Songu E, Haugaard ES, Wildley G and Haugaard N, The relationship between uracil nucleotide concentrations and glycogen synthesis in hepatocytes from fed and fasted rats. Metabolism 30: 119-122, 1980.
32. Gallai V, Mazzotta G, Montesi S, Sarchielli P and Del Gatto F, Effects of uridine in the treatment of diabetic neuropathy: An electrophysiological study. Acta Neurol Scand 86: 3-7, 1992.
33. Buckley NM, Tsuboi KK and Zeic NJ, Effects of nucleosides on acute left ventricular failure in isolated dog heart. Circ Res 7: 847-857, 1959.
34. Kypson J, Hait G and Mathew R, Effects of uridine on the performance and the metabolism of oxygenated and hypoxic rabbit hearts. j Mol Cell Cardiol 10: 545-565, 1978.
35. Aussedat J, Verdetti J, Grably S and Rossi A, Nucleotides uridyliques et glycogene cardiaque: Effect de l'administration d'uridine et de ribose chez le rat. J Physiol (Paris) 78: 331-336, 1982.
36. Aussedat J, Effect of uridine supply on glycogen resynthesis after ischaemia in the isolated perfused rat heart. Cardiovasc Res 17: 145-151, 1983.
37. Aussedat J, Uridine incorporation in normal and ischaemic perfused rat heart. Mol Physiol 6: 247-256, 1984.
38. Meerson FZ and Dosmagabetova RS, The use of glucose and uridine to control contractility and extensibility disturbances in the nonischemized compartments of the heart in myocardial infarction. Kardiologiya 25: 91-94, 1985.
39. Kelly WN and Smith LH Jr, Hereditary orotic aciduria. In: The Metabolic Basis of Inherited Disease (Eds. Stanbury JB, Wyngaarden JB and Fredrickson DS), 4th Edn, pp. 1045-1071. McGraw-Hill, New York, 1978.
40. Monks A and Cysyk RL, Uridine regulation by the isolated rat liver: Perfusion with an artificial oxygen carrier. Am J Physiol 242: R465-R470, 1982.
41. Leyva A, van Groeningen CJ, Kraal I, Peters GJ, Lankelman J and Pinedo HM, Phase I and pharmacokinetic studies of high-dose uridine intended for rescue from 5-fluorouracil toxicity. Cancer Res 44: 5928-5933, 1984.
42. van Groeningen CJ, Leyva A, Kraal I, Peters GJ and Pinedo HM, Clinical and pharmacokinetic studies of prolonged administration of high-dose uridine intended for rescue from 5-FU toxicity. Cancer Treat Rep 70: 745-750, 1986.
43. Chan TCK, Markman M, Pfeifle CE, Taetle R, Abramson I and Howell SB, Uridine pharmacokinetics in cancer patients. Cancer Chemother Pharmacol 22: 83-86, 1988.
44. van Groeningen CJ, Peters GJ, Leyva A, Laurensse E and Pinedo HM, Reversal of 5-fluorouracil induced myelosuppression by prolonged administration of high-dose uridine. J Natl Cancer Inst 81: 157-162, 1989.
45. van Groeningen CJ, Peters FJ, Nadal JC, Leyva A, Laurensse E and Pinedo HM, Clinical and pharmacologic study of orally administered uridine. J Natl Cancer Inst 83: 437-441, 1991.
46. Peters GJ and van Groeningen CJ, Clinical relevance of biochemical modulation of 5-fluorouracil. Ann Oncol 2: 469-480, 1991.
47. van Groeningen CJ, Peters GJ and Pinedo HM, Modulation of fluorouracil toxicity with uridine. Semin Oncol 19: 148-154, 1992.
48. Sommadossi J-P, Cretton EM, Kidd LB, McClure HM, Anderson DC and el Kouni MH, Effects of 5-benzylacyclouridine, an inhibitor of uridine phosphorylase, on the pharmacokinetics of uridine in rhesus monkeys: Implications for chemotherapy. Cancer Chemother Pharmacol 37: 14-22, 1995.
49. Martin DS, Stolfi RL and Sawyer RC, Use of oral uridine as a substitute for patenteral uridine rescue of 5-fluorouracil therapy, with and without the uridine phosphorylase inhibitor 5-benzylacyclouridine. Cancer Chemother Pharmacol 24: 9-14, 1989.
50. Cradock JC, Vishnuvajjala BR, Chin TF, Hochstein HD and Ackerman TK, Undine-induced hyperthermia in the rabbit. J Pharm Pharmacol 38: 226-229, 1986.
51. Peters GJ, van Groeningen CJ, Laurensse E, Ley va A and Pinedo HM, Uridine-induced hypothermia in mice and rats in relation to plasma and tissue levels of uridine and its metabolites. Cancer Chemother Pharmacol 20: 101-108, 1987.
52. Falcone A, Darnowski JW, Puprecht RM, Chu SH, Burnett I and Calabresi P, Differential effect of benzylacyclouridine on the toxic and therapeutic effects of azidothymidine in mice. Blood 76: 2216-2221, 1990.
53. Heaf DJ and Davies JI, The effect of RNA supplementation of rat diets on the composition of body fluids. Br J Nutr 36: 381-402, 1976.
54. Karle JM, Anderson LW, Dietrick DD and Cysyk RL, Determination of serum and plasma uridine levels in mice, rats, and humans by high-pressure liquid chromatography. Anal Biochem 109: 41-46, 1980.
55. Moyer JD, Oliver JT and Handschumacher RE, Salvage of circulating pyrimidine nucleosides in the rat. Cancer Res 41: 3010-3017, 1981.
56. Keppler D and Holstege A, Pyrimidine nucleotide metabolism and its compartmemation. In: Metabolic Compartmentation (Ed. Seis H), pp. 147-203. Academic Press, London, 1982.
57. Holstege A, Manglitz D and Gerok W, Depletion of blood plasma cytidine due to increased hepatocellular salvage in D-galactosamine-treated rats. Eur J Biochem 141: 339-344, 1984.
58. Gasser T, Moyer JD and Handschumacher RE, Novel single pass exchange of circulating uridine in rat liver. Science 213: 777-778, 1981.
59. Dahnke H-G and Mosebach K-O, In-vivo-Untersuchungen zur Metabolisierung der Pyrimidinnucleoside. Hoppe-Seylers Z Physiol Chem 356: 1565-1574, 1975.
60. Holstege A, Pausch J and Gerok W, Effect of 5-diazouracil on the catabolism of circulating pyrimidines in rat liver and kidney. Cancer Res 46: 5576-5581, 1986.
61. Holstege A, Leser H-G, Pausch J and Gerok W, Uridine catabolism in Kupffer cells, endothelial cells, and hepatocytes. Eur J Biochem 149: 169-173, 1985.
62. Monks A, Ayers O and Cysyk RL, Effect of 5-benzylacyclo-uridine, a potent inhibitor of uridine phosphorylase, on the metabolism of circulating uridine by the isolated rat liver. Biochem Pharmacol 32: 2003-2009, 1983.
63. Holstege A, Gengenbacher H-M, Jehle L and Gerok W, Uridine catabolism by the isolated perfused rat liver. J Hepatol 14: 335-341, 1992.
64. Darnowski JW and Handschumacher RE, Tissue-specific enhancement of uridine utilization and 5-fluorouracil therapy in mice by benzylacyclouridine. Cancer Res 45: 5364-5368, 1985.
65. Sobrero A, Pizzorno G, Romanini A, Russello O, Rosso R, Civalleri D, Simoni G, Darnowski J and Handschumacher RE, Uridine levels in canine and human subjects. Proc Am Assoc Cancer Res 35: 319, 1987.
66. Ashour OM, Guarcello V, Khalifa MMA, Abdel-Raheem MH, Naguib FNM, Panzica RP and el Kouni MH, Elevation of plasma uridine by the uridine phosphorylase (UrdPase) inhibitor 5-(benzyloxybenzyl)barbituric acid acyclonucleoside (BBBA) in mice. Pharmacologist 53: 365, 1993.
67. Davis ST, Joyner SS, Chandrasurin P and Baccanari DP, Species-dependent differences in the biochemical effects and metabolism of 5-benzylacyclouridine. Biochem Pharmacol 45: 173-181, 1993.
68. Darnowski JW and Handschumachet RE, Enhancement of fluorouracil therapy by the manipulation of tissue uridine pools. Pharmacol Ther 41: 381-392, 1989.
69. Darnowski JW, Handschumacher RE, Wiegand RA, Goulete FA and Calabresi P, Tissue-specific expansion of uridine pools in mice. Effects of benzylacyclouridine, dipyridamole and exogenous uridine. Biochem Pharmacol 41: 2031-2036, 1991.
70. Von Borstel RW and Bamat MK, Acylated uridine and cytidine and uses thereof. PCT, Patent No. WO 89/03837, 1989.
71. Naguib FNM, Levesque DL, Wang E-C, Panzica RP and el Kouni MH, 5-Benzylbarbituric acid derivatives, potent and specific inhibitors of uridine phosphorylase. Biochem Pharmacol 46: 1273-1283, 1993.
72. Levesque DL, Wang E-C, Wei D-C, Tzeng C-C, Panzica RP, Naguib FNM and el Kouni MH, Synthesis of a new class of uridine phosphorylase inhibitors. J Heterocycl Chem 30: 1399-1404, 1993.
73. Ashour OM, Naguib FNM, Khalifa MMA, Abdel-Raheem MH and el Kouni MH, Inhibition constants of 5-(benzyloxybenzyl)barbituric acid acyclonucleoside (BBBA) for hepatic uridine phosphorylase (UrdPase) from different species. FASEB J 8: A95, 1994.
74. Ashour OM, Naguib FNM, Khalifa MMA, Abdel-Raheem MH, Panzica RP and el Kouni MH, Enhancement of 5-fluoro2′-deoxyuridine antitumor efficacy by the uridine phosphorylase inhibitor 5-(benzyloxybenzyl)barbituric acid acyclonucleoside. Cancer Res 55: 1092-1098, 1995.
75. el Kouni MH, Naguib FNM, Park KS, Cha S, Darnowski JW and Soong S-J, Circadian rhythm of hepatic uridine phosphorylase activity and plasma concentration of uridine in mice. Biochem Pharmacol 40: 2479-2485, 1990.
76. Naguib FNM, Soong S-J and el Kouni MH, Circadian rhythm of orotate phosphoribosyltransferase, pyrimidine, nucleoside phosphorylases and dihydrouracil dehydrogenase in mouse liver: Possible relevance to chemotherapy with 5-fluoropyrimidines. Biochem Pharmacol 45: 667-673, 1993.
77. Gomeni C and Gomeni R, IGPHARM Interactive Graphic Package for Pharmacokinetic Analysis. Comput Biomed Res 11: 345-361, 1978.
78. Marquardt DW, An algorithm for least squares estimation of nonlinear parameters. J Soc Ind Appl Math 11: 431-441, 1963.
79. Klubes P, Geffen DB and Cysyk RL, Comparison of the bioavailability of uridine in mice after either oral or parenteral administration. Cancer Chemother Pharmacol 17: 236-240, 1986.
80. Darnowski JW and Handschumacher RE, Benzylacyclouridine. Pharmacokinetics, metabolism and biochemical effects in mice. Biochem Pharmacol 37: 2613-2618, 1988.
81. Naguib FNM, el Kouni MH and Cha S, Enzymes of uracil catabolism in normal and neoplastic human tissues. Cancer Res 45: 5405-5412, 1985.