Deoxy sugar analogues of triciribine: Correlation of antiviral and antiproliferative activity with intracellular phosphorylation

Journal of Medicinal Chemistry

Volumn 43, Issue 12, 2000, Pages 2438-2448

  Porcari, Anthony R ^c   Ptak, Roger G ^c   Borysko, Katherine Z ^c   Breitenbach, Julie M ^c   Vittori, Sauro ^a,c   Wotring, Linda L ^b,c   Drach, John C ^c   Townsend, Leroy B ^c  

^a UNIVERSITY OF CAMERINO   (Italy)

^b MICHIGAN DEPARTMENT OF COMMUNITY HEALTH   (United States)

^c UNIVERSITY OF MICHIGAN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

TRICIRIBINE; TRICIRIBINE MONOPHOSPHATE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ANTIVIRAL ACTIVITY; ARTICLE; CYTOMEGALOVIRUS; DRUG SYNTHESIS; HERPES SIMPLEX VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; STRUCTURE ACTIVITY RELATION;

ANTI-HIV AGENTS; ANTINEOPLASTIC AGENTS; ANTIVIRAL AGENTS; CELL LINE; CYTOMEGALOVIRUS; DRUG SCREENING ASSAYS, ANTITUMOR; ENZYME-LINKED IMMUNOSORBENT ASSAY; HERPESVIRUS 1, HUMAN; HIV-1; HUMANS; INHIBITORY CONCENTRATION 50; PHOSPHORYLATION; PLAQUE ASSAY; RIBONUCLEOSIDES; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR CELLS, CULTURED;

EID: 0033919842     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990205m     Document Type: Article

References (57)

1. Schram, K. H.; Townsend, L. B. The synthesis of 6-amino-4-methyl-8-(beta-D-ribofuranosyl)(4-H, 8-H)pyrrolo[4,3,2-de]pyrimido[4,5-c]pyridazine, A new tricyclic nucleoside. Tetrahedron Lett. 1971, 4757-4760.
2. Townsend, L. B.; Lewis, A. F.; Roti Roti, L. W. Synthesis of 6-amino-4-methyl-8-(beta-D-ribofuranosyl)pyrrolo[4,3,2-de]pyrimido[4,5-c] pyridazine-5′-phosphate as a novel compound and its utility against L-1210 mouse leukemia. U.S. Patent No. 4, 123, 524, Oct 31, 1978.
3. Plagemann, P. G. W. Transport, phosphorylation, and toxicity of a tricyclic nucleoside in cultured Novikoff rat hepatoma cells and other cell lines and release of its monophosphate by the cells. J. Natl. Cancer Inst. 1976, 57, 1283-1295.
4. Roti Roti, L. W.; Roti Roti, J. L.; Townsend, L. B. Studies on the mechanism of cytotoxicity of the tricyclic nucleoside NSC#154020 in L1210 cells. Proc. Am. Assoc. Cancer Res. 1978, 19, 40.
5. Bennett, L. L., Jr.; Smithers, D.; Hill, D. L.; Rose, L. M.; Alexander, J. A. Biochemical properties of the nucleoside of 3-amino-1,5-dihydro-5-methyl-1,4,5,6,8-pentaazaacenaphthylene (NSC-154020). Biochem. Pharmacol. 1978, 27, 233-241.
6. Schweinsberg, P. D.; Smith, R. G.; Loo, T. L. Identification of the metabolites of an antitumor tricyclic nucleoside (NSC-154020). Biochem. Pharmacol. 1981, 30, 2521-2526.
7. Wotring, L. L.; Townsend, L. B.; Crabtree, G. W.; Parks, R. E., Jr. A possible role for ecto-5′-nucleotidase in cytotoxicity and intracellular nucleotide formation from the tricyclic nucleoside-5′-phosphate (TCN-P). Proc. Am. Assoc. Cancer Res. 1981, 22, 257.
8. Bennett, L. L., Jr.; Allan, P. W.; Chang, C. H. Phosphorylation of "tricyclic nucleoside" by adenosine kinases from L1210 cells and HEp-2 cells. Biochem. Pharmacol. 1983, 32, 2601-2602.
9. Wotring, L. L.; Passiatore, J. E.; Roti Roti, J. L.; Hudson, J. L.; Townsend, L. B. Effects of the tricyclic nucleoside 6-amino-4-methyl-8-(beta-D-ribofuranosyl)pyrrolo[4,3,2-de]pyrimido[4,5-c] pyridazine on the viability and cell cycle distribution of L1210 cells in vitro. Cancer Res. 1985, 45, 6355-6361.
10. Moore, E. C.; Hurlbert, R. B.; Ravel, J. M.; Massia, S. Mechanisms of inhibition of protein and purine biosynthesis by tricyclic nucleoside phosphate (TCN-P, triciribine phosphate, NSC 280594). Proc. Am. Assoc. Cancer Res. 1986, 27, 303.
11. Behrens, B. C.; Hamilton, T. C.; Louie, K. G.; Grotzinger, K. R.; McKoy, W. M.; Tsuruo, T.; Young, R. C.; Ozols, R. F. Activity of tricyclic nucleoside 5′-phosphate in model systems of human ovarian cancer. Invest. New Drugs 1986, 4, 295-304.
12. Wotring, L. L.; Crabtree, G. W.; Edwards, N. L.; Parks, R. E., Jr.; Townsend, L. B. Mechanism of activation of triciribine phosphate (TCN-P) as a prodrug form of TCN. Cancer Treat. Rep. 1986, 70, 491-497.
13. Wotring, L. L.; Roti Roti, J. L.; Hudson, J. L.; Passiatore, J. E.; Borysko, K. Z.; Newcomb, R. D.; Townsend, L. B. Triciribine (TCN), A novel tricyclic adenosine analogue with anticancer activity. Nucleosides Nucleotides 1987, 6, 95-109.
14. Wotring, L. L.; Townsend, L. B.; Mandell, K. L.; Borysko, K. Z. Metabolism of triciribine in L1210 cells. Proc. Am. Assoc. Cancer Res. 1989, 30, 590.
15. Moore, E. C.; Hurlbert, R. B.; Boss, G. R.; Massia, S. P. Inhibition of two enzymes in de novo purine nucleotide synthesis by triciribine phosphate (TCN-P). Biochem. Pharmacol. 1989, 38, 4045-4051.
16. Wotring, L. L.; Townsend, L. B.; Jones, L. M.; Borysko, K. Z.; Gildersleeve, D. L.; Parker, W. B. Dual mechanisms of inhibition of DNA synthesis by triciribine. Cancer Res. 1990, 50, 4891-4899.
17. Moore, E. C.; Hurlbert, R. B.; Massia, S. P. Inhibition of CCRF-CEM human leukemic lymphoblasts by triciribine (tricyclic nucleoside, TCN, NSC-154020). Accumulation of drug in cells and comparison of effects on viability, protein synthesis and purine synthesis. Biochem. Pharmacol. 1989, 38, 4037-4044.
18. Basseches, P. J.; Durski, A.; Powis, G. High-performance liquid chromatographic assay of the antineoplastic agent tricyclic nucleoside 5′-phosphate and its disposition in rabbit. J. Chromatogr. 1982, 233, 227-234.
19. Basseches, P. J.; Powis, G. Metabolism and disposition of 3-amino-1,5-dihydro-5-methyl-1-beta-D-ribofuranosyl-1,4,5,6,8- pentaazaacenaphthylene in the rat. Cancer Res. 1984, 44, 3672-3678.
20. Liu, C.; Kimler, B. F.; Evans, R. G.; Morantz, R. A. Intracerebral chemotherapy in the 9L rat brain tumor model. Proc. Ann. Meet. Am. Assoc. Cancer Res. 1992, 33, 444.
21. Schilcher, R. B.; Young, J. D.; Baker, L. H. Reversed-phase high-performance liquid chromatographic determination of tricyclic nucleoside and tricyclic nucleoside 5′-phosphate in biological specimens. J. Chromatogr. 1985, 337, 55-62.
22. Townsend, L. B.; Milne, G. H. Synthesis, chemical reactivity, and chemotherapeutic activity of certain selenonucleosides and nucleosides related to the pyrrolo[2,3-d]pyrimidine nucleoside antibiotics. Ann. N. Y. Acad. Sci. 1975, 255, 91-103.
23. Mittelman, A.; Casper, E. S.; Godwin, T. A.; Cassidy, C.; Young, C. W. Phase I study of tricyclic nucleoside phosphate. Cancer Treat. Rep. 1983, 67, 159-162.
24. Cobb, W. R.; Bogden, A. E.; Reich, S. D.; Griffin, T. W.; Kelton, D. E.; LePage, D. J. Activity of two phase I drugs, homoharringtonine and tricyclic nucleotide, against surgical explants of human tumors in the 6-day subrenal capsule assay. Cancer Treat. Rep. 1983, 67, 173-178.
25. Crabtree, G. W.; Spremulli, E. N.; Weiman, M. C.; Smith, D. E.; Salvatore, J. R.; Cummings, F. J.; Calabresi, P. Phase I clinical and pharmacokinetic study of tricyclic nucleoside-5′-monophosphate (TCN-P; NSC 280594). Proc. Am. Soc. Clin. Oncol. 1983, 2, 33.
26. Feun, L. G.; Savaraj, N.; Bodey, G. P.; Lu, K.; Yap, B. S.; Ajani, J. A.; Burgess, M. A.; Benjamin, R. S.; McKelvey, E.; Krakoff, I. Phase I study of tricyclic nucleoside phosphate using a five-day continuous infusion schedule. Cancer Res. 1984, 44, 3608-3612.
27. Powis, G.; Basseches, P. J.; Kroschel, D. M.; Richardson, R. L.; O'Connell, M. J.; Kvols, L. K. Disposition of tricyclic nucleoside-5′-monophosphate in blood and plasma of patients during phase I and II clinical trials. Cancer Treat. Rep. 1986, 70, 359-362.
28. Schilcher, R. B.; Haas, C. D.; Samson, M. K.; Young, J. D.; Baker, L. H. Phase I evaluation and clinical pharmacology of tricyclic nucleoside 5′-phosphate using a weekly intravenous regimen. Cancer Rex. 1986, 46, 3147-3151.
29. Hoffman, K.; Holmes, F. A.; Fraschini, G.; Esparza, L.; Frye, D.; Raber, M. N.; Newman, R. A.; Hortobagyi, G. N. Phase I-II study: triciribine (tricyclic nucleoside phosphate) for metastatic breast cancer. Cancer Chemother. Pharmacol. 1996, 37, 254-258.
30. O'Connell, M. J.; Rubin, J.; Hahn, R. G.; Kvols, L. K.; Moertel, C. G. Phase II clinical trial of tricyclic nucleoside phosphate for advanced colorectal cancer. Cancer Treat. Rep. 1987, 77, 333-334.
31. Lyss, A. P.; Morrell, L. E.; Perry, M. C. Triciribine phosphate (TCN-P) in advanced non-small cell lung cancer (NSCLC): Interim analysis of toxicity. Proc. Am. Soc. Clin. Oncol. 1991, 10, 120.
32. Feun, L. G.; Blessing, J. A.; Barrett, R. J.; Hanjani, P. A phase II trial of tricyclic nucleoside phosphate in patients with advanced squamous cell carcinoma of the cervix. A Gynecologic Oncology Group Study. Am. J. Clin. Oncol. 1993, 16, 506-508.
33. Kucera, L. S.; Iyer, N. P.; Puckett, S. H.; Buckheit, R. W., Jr.; Westbrook, L.; Toyer, B. R.; White, E. L.; Germany-Decker, J. M.; Shannon, W. M.; Chen, R. S.; Nassiri, M. R.; Shipman, C., Jr.; Townsend, L. B.; Drach, J. C. Activity of triciribine and triciribine-5′-monophosphate against human immunodeficiency virus types 1 and 2. AIDS Res. Hum. Retroviruses 1993, 9, 307-314.
34. Ptak, R. G.; Borysko, K. Z.; Porcari, A. R.; Buthod, J. L.; Holland, L. E.; Shipman, C., Jr.; Townsend, L. B.; Drach, J. C. Phosphorylation of triciribine is necessary for activity against HIV-1. AIDS Res. Human Retroviruses 1998, 14, 1315-1322.
35. Ptak, R. G.; Drach, J. C.; Jacobson, J. G.; Townsend, L. B.; Stup, T. L.; Russell, J.; Buckheit, R. W. HIV-1 Regulatory Proteins: Targets of Triciribine? 6th Conference on Retroviruses & Opportunistic Infections, Chicago, IL, February 1999; Abstr. 622.
36. Townsend, L. B.; Kawasaki, A. M.; VanSickle, A. P.; Wotring, L. L. The synthesis and biological activity of certain pentaazaacenaphthylenes, hexaazaacenaphthylenes and their corresponding nucleosides. Nucleic Acids Symp. Ser. 1986, 17, 41-44.
37. Kawasaki, A. M.; Townsend, L. B. An unusual reductive ring-opening of the 1,2,3,5,6,7-hexaazaacenaphthylene ring system. Tetrahedron Lett. 1989, 30, 3287-3290.
38. Van Sickle, A.; Kawasaki, A. M.; Townsend, L. B. The Synthesis of 8-amino-6-N-methyl-1,2,3,5,6,7-hexaazaacenaphthylene. Heterocycles 1990, 30, 963-969.
39. Kawasaki, A. M.; Wotring, L. L.; Townsend, L. B. Synthesis and cytotoxicity studies of 8-amino-6-methyl-2-beta-D-ribofuranosyl-1,2,3,5,6,7-hexaazaacenaphthylene (7-aza-TCN) and the corresponding 2′-deoxy- and arabinonucleoside analogues. J. Med. Chem. 1990, 33, 3170-3176.
40. Kawasaki, A. M.; Townsend, L. B. Synthesis of 8-amino-4-methylthio-6-methyl-2-(beta-D-ribofuranosyl)-2,6-dihydro-1,2,3,5,6,7- hexaazaacenaphthylene and an unusual reductive ring-opening of the 1,2,3,5,6,7-hexaazaacenaphthylene ring system. J. Heterocycl. Chem. 1991, 28, 1-5.
41. Porcari, A. R.; Borysko, K. Z.; Ptak, R. G.; Breitenbach, J. M.; Wotring, L. L.; Drach, J. C.; Townsend, L. B. Acyclic sugar analogues of triciribine: Lack of antiviral and antiproliferative activity correlates with low intracellular phosphorylation. Nucleosides Nucleotides 1999, accepted for publication.
42. Porcari, A. R.; Townsend, L. B. An improved synthesis of the versatile heterocycle, 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]pyrimidine. Synth. Commun. 1998, 28, 3835-3843.
43. Bhat, C. C. 2-Deoxy-3,5-di-O-p-toluoyl-D-erythro-pentosyl chloride. Preparation of a crystaline O-acyl-2-deoxypentofuranosyl halide. In Synthetic Procedures in Nucleic Acid Chemistry, Zorbach, W. W., Tipson, R. S., Eds.; Interscience Publishers: New York, 1968; Vol. 1, pp 521-522.
44. Gupta, P. K.; Vittori, S.; Townsend, L. B. An unexpected nucleophilic displacement involving 6-bromo-4-chloro-5-cyanopyrrolo[2,3-d]pyrimidine with methanolic ammonia. Nucleosides Nucleotides 1990, 9, 35-41.
45. Russel, A. F.; Greenberg, S.; Moffatt, J. G. Reactions of 2-acyl-oxyisobutyryl halides with nucleosides. II. Reactions of adenosine. J. Am. Chem. Soc. 1973, 95, 4025-4030.
46. Krawczyk, S. H.; Townsend, L. B. 2′,3′-Dideoxyadenosine analogues of the nucleoside antibiotics tubercidin, toyocamycin and sangivamycin. Nucleosides Nucleotides 1989, 8, 97-115.
47. Wang, Y.; Hogenkamp, H. P. C.; Long, R. A.; Revankar, G. R.; Robins, R. K. A convenient synthesis of 5′-deoxyribonucleosides. Carbohydr. Res. 1977, 59, 449-457.
48. Tolman, R. L.; Robins, R. K.; Townsend, L. B. Pyrrolopyrimidine nucleosides. 3. The total synthesis of toyocamycin, sangivamycin, tubercidin, and related derivatives. J. Am. Chem. Soc. 1969, 91, 2102-2108.
49. Porcari, A. R.; Townsend, L. B. Total synthesis of the naturally occurring antibiotic toyocamycin using new and improved synthetic procedures. Nucleosides Nucleotides 1999, 18, 153-159.
50. Wotring, L. L.; Townsend, L. B. Study of the cytotoxicity and metabolism of 4-amino-3-carboxamido-1-(beta-D-ribofuranosyl)-pyrazolo[3,4-d]pyrimidine using inhibitors of adenosine kinase and adenosine deaminase. Cancer Res. 1979, 39, 3018-3023.
51. Turk, S. R.; Shipman, C., Jr.; Nassiri, R.; Genzlinger, G.; Krawczyk, S. H.; Townsend, L. B.; Drach, J. C. Pyrrolo[2,3-d]-pyrimidine nucleosides as inhibitors of human cytomegalovirus. Antimicrob. Agents Chemother. 1987, 31, 544-550.
52. Kucera, L. S.; Iyer, N.; Leake, E.; Raben, A.; Modest, E. J.; Daniel, L. W.; Piantadosi, C. Novel membrane-interactive ether lipid analogues that inhibit infectious HTV-1 production and induce defective virus formation. AIDS Res. Hum. Retroviruses 1990, 6, 491-501.
53. White, E. L.; Buckheit, R. W., Jr.; Ross, L. J.; Germany, J. M.; Andries, K.; Pauwels, R.; Janssen, P. A. J.; Shannon, W. M.; Chirigos, M. A. A TIBO derivative, R82913, is a potent inhibitor of HIV-1 reverse transcriptase with heteropolymer templates. Antiviral Res. 1991, 16, 257-266.
54. Prichard, M. N.; Shipman, C., Jr. A three-dimensional model to analyze drug-drug interactions. Antiviral Res. 1990, 14, 181-206.
55. Prichard, M. N.; Prichard, L. E.; Baguley, W. A.; Nassiri, M. R.; Shipman, C., Jr. Three-dimensional analysis of the synergistic cytotoxicity of ganciclovir and zidovudine. Antimicrob. Agents Chemother. 1991, 35, 1060-1065.
56. Pogolotti, A. L., Jr.; Santi, D. V. High-pressure liquid chromatography-Ultraviolet analysis of intracellular nucleotides. Anal. Biochem. 1982, 126, 335-345.
57. Walseth, T. F.; Graff, G.; Moos, M. C., Jr.; Goldberg, N. D. Separation of 5′-ribonucleoside monophosphates by ion-pair reverse-phase high-performance liquid chromatography. Anal. Biochem. 1980, 107, 240-245.