5-Phenylthioacyclouridine: A potent and specific inhibitor of uridine phosphorylase

Biochemical Pharmacology

Volumn 60, Issue 6, 2000, Pages 851-856

  El Kouni, Mahmoud H ^a   Goudgaon, Naganna M ^b,c,d   Rafeeq, Mohammad ^b   Al Safarjalani, Omar N ^a   Schinazi, Raymond F ^c,d   Naguib, Fardos N M ^a  

^a UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^b GULBARGA UNIVERSITY   (India)

^c ATLANTA VA MEDICAL CENTER   (United States)

^d EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

5 phenylthioacyclouridine; Chemotherapy; Inhibitor; Uridine phosphorylase

Indexed keywords

5 PHENYLTHIOACYCLOURIDINE; DIHYDROPYRIMIDINE DEHYDROGENASE; THIOURACIL DERIVATIVE; THYMIDINE; THYMIDINE KINASE; THYMIDINE PHOSPHORYLASE; THYMINE; UNCLASSIFIED DRUG; URACIL; URIDINE; URIDINE DERIVATIVE; URIDINE KINASE; URIDINE PHOSPHORYLASE;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANIMAL TISSUE; ARTICLE; CANCER INHIBITION; DRUG MECHANISM; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVE SITE; ENZYME CONFORMATION; ENZYME INACTIVATION; ENZYME SUBSTRATE; HUMAN; HUMAN TISSUE; LIVER; MOUSE; NONHUMAN; PRIORITY JOURNAL; PYRIMIDINE METABOLISM; STRUCTURE ACTIVITY RELATION;

ANIMALS; BINDING, COMPETITIVE; ENZYME INHIBITORS; FEMALE; HUMANS; KINETICS; LIVER; MICE; THIOURACIL; URIDINE PHOSPHORYLASE;

EID: 0034666741     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0006-2952(00)00410-X     Document Type: Article

References (52)

1. Niedzwicki J.G., el Kouni M.H., Chu S.H., Cha S. Pyrimidine acyclonucleosides, inhibitors of uridine phosphorylase. Biochem Pharmacol. 30:1981;2097-2101.
2. Woodman P.W., Sarrif A.M., Heidelberger C. Specificity of pyrimidine nucleoside phosphorylases and the phosphorolysis of 5-fluoro-2′-deoxyuridine. Cancer Res. 40:1980;507-511.
3. Ishitsuka H., Miwa M., Takemoto K., Fukuoka K., Itoga A., Maruyama H.B. Role of uridine phosphorylase for antitumor activity of 5′-deoxy-5-fluorouridine. Gann. 71:1980;112-123.
4. Veres Z., Szabolcs A., Szinai I., Dénes G., Jeney A. Enzymatic cleavage of 5-substituted-2′-deoxyuridines by pyrimidine nucleoside phosphorylases. Biochem Pharmacol. 35:1986;1057-1059.
5. Chu M.Y.W., Naguib F.N.M., Iltzsch M.H., el Kouni M.H., Chu S.H., Cha S., Calabresi P. Potentiation of 5-fluoro-2′-deoxyuridine antineoplastic activity by the uridine phosphorylase inhibitors benzylacyclouridine and benzyloxybenzylacyclouridine. Cancer Res. 44:1984;1852-1856.
6. el Kouni M.H., el Kouni M.M., Naguib F.N.M. Differences in activities and substrate specificity of human and murine pyrimidine nucleoside phosphorylases Implications for chemotherapy with 5-fluoropyrimidines . Cancer Res. 53:1993;3687-3693.
7. Ashour O.M., Naguib F.N.M., Khalifa M.M.A., Abdel-Raheem M.H., Panzica R.P., el Kouni M.H. Enhancement of 5-fluoro-2′-deoxyuridine antitumor efficacy by the uridine phosphorylase inhibitor 5-(benzyloxybenzyl)barbituric acid acyclonucleoside. Cancer Res. 55:1995;1092-1098.
8. el Kouni M.H., Naguib F.N.M., Park K.S., Cha S., Darnowski J.W., Soong S-j. Circadian rhythm of hepatic uridine phosphorylase activity and plasma concentration of uridine in mice. Biochem Pharmacol. 40:1990;2479-2485.
9. Naguib F.N.M., Soong S-j, el Kouni M.H. Circadian rhythm of orotate phosphoribosyltransferase, pyrimidine nucleoside phosphorylases and dihydrouracil dehydrogenase in mouse liver. Possible relevance to chemotherapy with 5-fluoropyrimidines. Biochem Pharmacol. 45:1993;667-673.
10. von Roemeling R., Hrushesky W. Determination of the therapeutic index of floxuridine by its circadian infusion pattern. J Natl Cancer Inst. 82:1990;386-393.
11. Martin D.S., Stolfi R.L., Sawyer R.C., Spiegeleman S., Young C.W. High-dose 5-fluorouracil with delayed uridine "rescue" in mice. Cancer Res. 42:1982;3964-3970.
12. Klubes P., Cerna I., Meldon M.A. Uridine rescue from lethal toxicity of 5-fluorouracil in mice. Cancer Chemother Pharmacol. 8:1982;17-21.
13. Klubes P., Cerna I. Use of uridine rescue to enhance antitumor selectivity of 5-fluorouracil. Cancer Res. 43:1983;3182-3186.
14. van Groeningen C.J., Peters G.J., Leyva A., Laurensse E., Pinedo H.M. Reversal of 5-fluorouracil-induced myelosuppression by prolonged administration of high-dose uridine. J Natl Cancer Inst. 81:1989;157-162.
15. Sommadossi J.P., Carlisle R., Schinazi R.F., 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. 32:1988;997-1001.
16. Sommadossi J.P., Zhu Z., Carlisle R., Xie M.Y., Weidner D.A., el Kouni M.H. Novel pharmacologic approaches for the treatment of AIDS and potential use of uridine phosphorylase inhibitors. Diasio R.B., Sommadossi J.P. Advances in Chemotherapy of AIDS. 1990;63-73 Pergamon Press, New York.
17. Monks A., Ayers O., Cysyk R.L. Effect of 5-benzylacyclouridine, a potent inhibitor of uridine phosphorylase, on the metabolism of circulating uridine by the isolated rat liver. Biochem Pharmacol. 32:1983;2003-2009.
18. Darnowski J.W., Handschumacher R.E. Tissue-specific enhancement of uridine utilization and 5-fluorouracil therapy in mice by benzylacyclouridine. Cancer Res. 45:1985;5364-5368.
19. Peters G.J., van Groeningen C.J., Laurensse E.J., Lankelma J., Leyva A., Pinedo H.M. Uridine-induced hypothermia in mice and rats in relation to plasma and tissue levels of uridine and its metabolites. Cancer Chemother Pharmacol. 20:1987;101-108.
20. Martin D.S., Stolfi R.L., Sawyer C. Use of oral uridine as a substitute for parenteral uridine rescue of 5-fluorouracil therapy, with and without the uridine phosphorylase inhibitor 5-benzylacyclouridine. Cancer Chemother Pharmacol. 24:1989;9-14.
21. Davis S.T., Joyner S.S., Chandrasurin P., Baccanari D.P. Species-dependent differences in the biochemical effects and metabolism of 5-benzylacyclouridine. Biochem Pharmacol. 45:1993;173-181.
22. Sommadossi J.-P., Cretton E.M., Kidd L.B., McClure H.M., Anderson D.C., el Kouni M.H. Effects of 5-benzylacyclouridine, an inhibitor of uridine phosphorylase, on the pharmacokinetics of uridine in rhesus monkeys Implications for chemotherapy . Cancer Chemother Pharmacol. 37:1995;14-22.
23. Ashour O.M., Naguib F.N.M., el Kouni M.H. 5-Benzyloxybenzylbarbituric acid acyclonucleoside, a uridine phosphorylase inhibitor, and 2′,3′,5′-triacetyluridine, a prodrug of uridine, as modulators of plasma uridine concentration. Implications for chemotherapy. Biochem Pharmacol. 51:1996;1601-1612.
24. Pizzorno G., Yee L., Burtness B.A., Marsh J.C., Darnowski J.W., Chu M.Y.W., Chu H.S., Chu E., Leffert J.J., Handschumacher R.E., Calabresi P. Phase I clinical and pharmacological studies of benzylacyclouridine, a uridine phosphorylase inhibitor. Clin Cancer Res. 4:1998;1165-1175.
25. Ashour O.M., Al Safarjalani O.N., Naguib F.N.M., Goudgaon N.M., Schinazi R.F., el Kouni M.H. Modulation of plasma uridine concentration by 5-(phenylselenenyl)acyclouridine, an inhibitor of uridine phosphorylase Relevance to chemotherapy . Cancer Chemother Pharmacol. 45:2000;351-361.
26. Niedzwicki J.G., Chu S.H., el Kouni M.H., Rowe E.C., Cha S. 5-Benzylacyclouridine and 5-benzyloxybenzylacyclouridine, potent inhibitors of uridine phosphorylase. Biochem Pharmacol. 31:1982;1857-1861.
27. Naguib F.N.M., el Kouni M.H., Chu S.H., Cha S. New analogues of benzylacyclouridines, specific and potent inhibitors of uridine phosphorylase from human and mouse livers. Biochem Pharmacol. 36:1987;2195-2201.
28. Naguib F.N.M., Levesque D.L., Wang E.-C., Panzica R.P., el Kouni M.H. 5-Benzylbarbituric acid derivatives, potent and specific inhibitors of uridine phosphorylase. Biochem Pharmacol. 46:1993;1273-1283.
29. Park K.S., el Kouni M.H., Krenitsky T.A., Chu S.H., Cha S. Inhibition of uridine phosphorylase from Escherichia coli by benzylacyclouridines. Biochem Pharmacol. 35:1986;3853-3855.
30. el Kouni M.H., Naguib F.N.M., Niedzwicki J.G., Iltzsch M.H., Cha S. Uridine phosphorylase from Schistosoma mansoni. J Biol Chem. 263:1988;6081-6086.
31. Goudgaon N.M., Naguib F.N.M., el Kouni M.H., Schinazi R.F. Phenylselenenyl- and phenylthio-substituted pyrimidines as inhibitors of dihydrouracil dehydrogenase and uridine phosphorylase. J Med Chem. 36:1993;4250-4254.
32. el Kouni M.H., Naguib F.N.M., Panzica R.P., Otter B.A., Chu S.H., Gosselin G., Chu C.K., Schinazi R.F., Shealy Y.F., Goudgaon N., Ozerov A.A., Ueda T., Iltzsch M.H. Effect of modifications in the pentose moiety and conformational changes on the binding of nucleoside ligands to uridine phosphorylase from Toxoplasma gondii. Biochem Pharmacol. 51:1996;1687-1700.
33. Chua B.H.L., Watson P., Kleinhans B., Morgan H.E. Effect of 5- benzyloxybenzylacyclouridine on the labeling of UTP and RNA in perfused rat heart. Fedn Proc. 44:1985;1773.
34. Ashour O.M., Naguib F.N.M., Panzica R.P., Al Safarjalani O.N., el Kouni M.H. Modulation of 5-fluorouracil host toxicity by 5-(benzyloxybenzyl)barbituric acid acyclonucleoside, a uridine phosphorylase inhibitor, and 2′,3′,5′-tri-o-acetyluridine, a prodrug of uridine. Biochem Pharmacol. 60:2000;427-431.
35. Chu S.-H., Wiemann M.C., Chu M.Y., Calabresi P. Modulation of FUdR toxicity by two benzylacyclouridine analogs. Proc Am Assoc Cancer Res. 28:1987;410.
36. Calabresi P., Falcone A., St. Clair MH, Wiemann MC, Chu SH and Darnowski JW, Benzylacyclouridine reverses azidothymidine-induced bone marrow suppression without impairment of anti-human immunodeficiency virus activity. Blood. 76:1990;2210-2215.
37. Goudgaon N.M., Lee N.M., el Kouni M.H. 5-Arylthioacyclouridines Potent inhibitors of uridine phosphorylase . Proc Am Assoc Cancer Res. 36:1995;1716.
38. Roth B., Bunnett J.F. 5-Arylthiopyrimidines. V Kinetics of the cyclization of 4-oxo derivatives to 10H- and 10-alkylpyrimido[5,4-b][1,4]benzothiazines (1,3-diazaphenothiazines) . J Am Chem Soc. 87:1965;340-349.
39. Rosowsky A., Kim S.H., Wick M. Synthesis and antitumor activity of an acyclonucleoside derivative of 5-fluorouracil. J Med Chem. 24:1981;1171-1181.
40. Wilkinson G.N. Statistical estimations in enzyme kinetics. Biochem J. 80:1961;324-332.
41. Cleland W.W. The statistical analysis of enzyme kinetic data. Adv Enzymol. 29:1967;1-32.
42. Dixon M., Webb E.C. Enzymes. 1979;Academic Press, New York.
43. Bradford M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 72:1976;248-254.
44. Gasser T., Moyer J.D., Handschumacher R.E. Novel single-pass exchange of circulating uridine in rat liver. Science. 213:1981;777-778.
45. Holstege A., Leser H.-G., Pausch J., Gerok W. Uridine catabolism in Kupffer cells, endothelial cells, and hepatocytes. Eur J Biochem. 149:1985;169-173.
46. Holstege A., Pausch J., Gerok W. Effect of 5-diazouracil on the catabolism of circulating pyrimidines in rat liver and kidney. Cancer Res. 46:1986;5576-5581.
47. Monks A., Cysyk R.L. Uridine regulation by the isolated rat liver Perfusion with an artificial oxygen carrier . Am J Physiol. 242:1982;R465-R470.
48. Moyer J.D., Oliver J.T., Handschumacher R.E. Salvage of circulating pyrimidine nucleosides in the rat. Cancer Res. 41:1981;3010-3017.
49. Niedzwicki J.G., el Kouni M.H., Chu S.H., Cha S. Structure-activity relationship of ligands of the pyrimidine nucleoside phosphorylases. Biochem Pharmacol. 32:1983;399-415.
50. el Kouni M.H., Naguib F.N.M., Chu S.H., Cha S., Ueda T., Gosselin G., Imbach J.-L., Shealy F., Otter B.A. Effect of the N-glycosidic bond conformation and modifications in the pentose moiety on the binding of nucleoside ligands to uridine phosphorylase. Mol Pharmacol. 34:1988;104-110.
51. Orr G.F., Musso D.L., Boswell G.E., Keeley J.L., Joyner S.S., Davis S.T., Baccanari D.P. Inhibition of uridine phosphorylase Synthesis and structure-activity relationships of aryl-substituted 5-benzyluracils and 1-[(2-hydroxyethoxy)methyl]-5-benzyluracils . J Med Chem. 38:1995;3850-3856.
52. Guerin D.J., Mazeas D., Musale M.S., Naguib F.N.M., Al Safarjalani O.N., el Kouni M.H., Panzica R.P. Uridine phosphorylase inhibitors. Chemical modification of benzyloxybenzylbarbituric acid and its effect on UrdPase inhibition. Bioorg Med Chem Lett. 9:1999;1477-1480.