Triapine (3-aminopyridine-2-carboxaldehyde-thiosemicarbazone): A potent inhibitor of ribonucleotide reductase activity with broad spectrum antitumor activity

Biochemical Pharmacology

Volumn 59, Issue 8, 2000, Pages 983-991

  Finch, Rick A ^a   Liu, Mao Chin ^a   Grill, Susan P ^a   Rose, William C ^b   Loomis, Regina ^a   Vasquez, Karen M ^c   Cheng, Yung Chi ^a   Sartorelli, Alan C ^a  

^a YALE CANCER CENTER   (United States)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c BRISTOL MYERS SQUIBB   (United States)

Author keywords

(N) heterocyclic carboxaldehyde thiosemicarbazone; Antineoplastic agents, combined; Inhibition of DNA synthesis; L1210 leukemia cells; Ribonucleotide reductase, antagonists and inhibitors; Triapine, 3 AP

Indexed keywords

3 AMINOPICOLINALDEHYDE THIOSEMICARBAZONE; ANTINEOPLASTIC AGENT; CISPLATIN; DOXORUBICIN; ETOPOSIDE; HYDROXYUREA; OXIDOREDUCTASE INHIBITOR; RIBONUCLEOTIDE REDUCTASE; RIBONUCLEOTIDE REDUCTASE INHIBITOR; SEMICARBAZONE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER INHIBITION; CONTROLLED STUDY; DNA REPAIR; DNA SYNTHESIS INHIBITION; DRUG EFFICACY; ENZYME INHIBITION; FEMALE; HUMAN; HUMAN CELL; LEUKEMIA; LUNG CARCINOMA; MOUSE; NONHUMAN; OVARY CARCINOMA; PRIORITY JOURNAL;

ANIMALS; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BLOOD-BRAIN BARRIER; CELL DIVISION; DNA; DRUG RESISTANCE, NEOPLASM; ENZYME INHIBITORS; HUMANS; HYDROXYUREA; KB CELLS; LEUKEMIA L1210; MICE; NEOPLASM TRANSPLANTATION; NEOPLASMS, EXPERIMENTAL; PYRIDINES; RIBONUCLEOTIDE REDUCTASES; THIOSEMICARBAZONES; TUMOR CELLS, CULTURED;

EID: 0033975268     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0006-2952(99)00419-0     Document Type: Article

References (34)

1. Thelander L., Reichard P. Reduction of ribonucleotides. Annu Rev Biochem. 48:1979;133-158.
2. Cory J.G., Sato A. Regulation of ribonucleotide reductase activity in mammalian cells. Mol Cell Biochem. 53:1983;257-266.
3. Thelander M., Gräslund A., Thelander L. Subunit M2 of mammalian ribonucleotide reductase. Characterization of a homogeneous protein isolated from M2-overproducing mouse cells. J Biol Chem. 260:1985;2737-2741.
4. Elford H.L., Freese M., Passamani E., Morris H.P. Ribonucleotide reductase and cell proliferation. 1. Variations of ribonucleotide reductase activity with tumor growth in a series of rat hepatomas. J Biol Chem. 245:1970;5228-5233.
5. Weber G. Biochemical strategy of cancer cells and the design of chemotherapy. Cancer Res. 43:1983;3466-3492.
6. Moore E.C., Hurlbert R.B. The inhibition of ribonucleoside diphosphate reductase by hydroxyurea, guanazole and pyrazoloimidazole (IMPY). Cory J.G., Cory A.H. Inhibitors of Ribonucleoside Diphosphate Reductase Activity. 1989;165-201 Pergamon Press, Oxford.
7. Cory J.G., Carter G.L. Drug action on ribonucleotide reductase. Adv Enzyme Regul. 24:1985;385-401.
8. Kwon N.S., Stuehr D.J., Nathan C.F. Inhibition of tumor cell ribonucleotide reductase by macrophage-derived nitric oxide. J Exp Med. 174:1991;761-767.
9. Beckloff G.L., Lerner H.J., Frost D., Russo-Alesi F.M., Gitomer S. Hydroxyurea (NSC-32065) in biologic fluids Dose-concentration relationship . Cancer Chemother Rep. 48:1965;57-58.
10. Gwilt P.R., Tracewell W.G. Pharmacokinetics and pharmacodynamics of hydroxyurea. Clin Pharmacokinet. 34:1998;347-358.
11. Donehower R.C. Hydroxyurea. Chabner B.A., Longo C.L. Cancer Chemotherapy and Biotherapy. 1996;253-260 Lippincott-Raven, Philadelphia.
12. Moore E.C., Sartorelli A.C. The inhibition of ribonucleotide reductase by α-(N)-heterocyclic carboxaldehyde thiosemicarbazones. Cory J.G., Cory A.H. Inhibitors of Ribonucleoside Diphosphate Reductase Activity. 1989;203-215 Pergamon Press, Oxford.
13. Antholine W., Knight J., Whelan H., Petering D.H. Studies of the reaction of 2-formylpyridine thiosemicarbazone and its iron and copper complexes with biological systems. Mol Pharmacol. 13:1977;89-98.
14. Sartorelli A.C., Agrawal K.C., Tsiftsoglou A.S., Moore E.C. Characterization of the biochemical mechanism of action of α-(N)-heterocyclic carboxaldehyde thiosemicarbazones. Adv Enzyme Regul. 15:1977;117-139.
15. Thelander L., Gräslund A. Mechanism of inhibition of mammalian ribonucleotide reductase by the iron chelate of 1-formylisoquinoline thiosemicarbazone. Destruction of the tyrosine free radical of the enzyme in an oxygen-requiring reaction. J Biol Chem. 258:1983;4063-4066.
16. Saryan L.A., Ankel E., Krishnamurti C., Petering D.H. Comparative cytotoxic and biochemical effects of ligands and metal complexes of α-(N)-heterocyclic carboxaldehyde thiosemicarbazones. J Med Chem. 22:1979;1218-1221.
17. Preidecker P.J., Agrawal K.C., Sartorelli A.C., Moore E.C. Effects of the ferrous chelate of 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone (MAIQ-1) on the kinetics of reduction of CDP by ribonucleotide reductase of the Novikoff tumor. Mol Pharmacol. 18:1980;507-512.
18. Finch R.A., Liu M.C., Cory A.H., Cory J.G., Sartorelli A.C. Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone; 3-AP) An inhibitor of ribonucleotide reductase with antineoplastic activity . Adv Enzyme Regul. 39:1999;3-12.
19. DeConti R.C., Toftness B.R., Agrawal K.C., Tomchik R., Mead J.A., Bertino J.R., Sartorelli A.C., Creasey W.A. Clinical and pharmacological studies with 5-hydroxy-2-formylpyridine thiosemicarbazone. Cancer Res. 32:1972;1455-1462.
20. Krakoff I.H., Etcubanas E., Tan C., Mayer K., Bethune V., Burchenal J.H. Clinical trial of 5-hydroxypicolinaldehyde thiosemicarbazone (5-HP; NSC-107392), with special reference to its iron-chelating properties. Cancer Chemother Rep. 58:1974;207-212.
21. Creasey W.A., Agrawal K.C., Capizzi R.L., Stinson K.K., Sartorelli A.C. Studies of the antineoplastic activity and metabolism of α-(N)-heterocyclic carboxaldehyde thiosemicarbazones in dogs and mice. Cancer Res. 32:1972;565-572.
22. Liu M.C., Lin T.S., Sartorelli A.C. Synthesis and antitumor evaluation of amino derivatives of pyridine-2-carboxaldehyde thiosemicarbazone. J Med Chem. 35:1992;3672-3677.
23. Shyam K., Penketh P.G., Divo A.A., Loomis R.H., Rose W.C., Sartorelli A.C. Synthesis and evaluation of 1-acyl-1,2-bis(methylsulfonyl)-2-(2-chloroethyl)hydrazines as antineoplastic agents. J Med Chem. 36:1993;3496-3502.
24. Skipper H.E., Schabel F.M., Trader M.W., Thompson S.A. Experimental evaluation of potential anticancer agents. XVIII. Effects of therapy on viability and rate of proliferation of leukemic cells in various anatomic sites. Cancer Chemother Rep. 47:1965;41-64.
25. Rose W.C. Taxol A review of its preclinical in vivo antitumor activity . Anticancer Drugs. 3:1992;311-321.
26. Gehan E.A. A generalized Wilcoxon test for comparing arbitrarily singly censored samples. Biometrika. 52:1965;203-223.
27. Yen Y., Grill S.P., Dutschman G.E., Chang C.N., Zhou B.S., Cheng Y.C. Characterization of a hydroxyurea-resistant human KB cell line with supersensitivity to 6-thioguanosine. Cancer Res. 54:1994;3686-3691.
28. Finlay G.J., Baguley B.C., Wilson W.R. A semiautomated microculture method for investigating growth inhibitory effects of cytotoxic compounds on exponentially growing carcinoma cells. Anal Biochem. 139:1984;272-277.
29. Steeper J.R., Steuart C.D. A rapid assay for CDP reductase activity in mammalian cell extracts. Anal Biochem. 34:1970;123-130.
30. Cory J.G., Cory A.H., Rappa G., Lorico A., Liu M.C., Lin T.S., Sartorelli A.C. Inhibitors of ribonucleotide reductase. Comparative effects of amino- and hydroxy-substituted pyridine-2-carboxaldehyde thiosemicarbazones. Biochem Pharmacol. 48:1994;335-344.
31. Rappa G., Lorico A., Liu M.C., Kruh G.D., Cory A.H., Cory J.G., Sartorelli A.C. Overexpression of the multidrug resistance genes mdr1, mdr3, and mrp in L1210 cells resistant to inhibitors of ribonucleotide reductase. Biochem Pharmacol. 54:1997;649-655.
32. Cory J.G., Cory A.H., Rappa G., Lorico A., Liu M.C., Lin T.S., Sartorelli A.C. Structure-function relationships for a new series of pyridine-2-carboxaldehyde thiosemicarbazones on ribonucleotide reductase activity and tumor cell growth in culture and in vivo. Adv Enzyme Regul. 35:1995;55-68.
33. Cory J.G., Lasater L., Sato A. Effect of iron-chelating agents on inhibitors of ribonucleotide reductase. Biochem Pharmacol. 30:1981;979-984.
34. Avery T.L., Finch R.A., Vasquez K.M., Radparvar S., Hanna N.B., Revankar G.R., Robins R.K. Chemotherapeutic characterization in mice of 2-amino-9-β-D-ribofuranosylpurine-6-sulfinamide (sulfinosine), a novel purine nucleoside with unique antitumor properties. Cancer Res. 50:1990;2625-2630.