1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl] hydrazine (VNP40101M): II. Role of O6-alkylguanine-DNA alkyltransferase in cytotoxicity

Cancer Chemotherapy and Pharmacology

Volumn 53, Issue 4, 2004, Pages 288-295

  Baumann, R P ^a   Shyam, K ^a   Penketh, P G ^a   Remack, J S ^b   Brent, T P ^b   Sartorelli, A C ^a  

^a YALE CANCER CENTER   (United States)

^b ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

Author keywords

AGT; Cancer therapeutics; Sulfonylhydrazine prodrugs; VNP40101M

Indexed keywords

1,2 BIS(METHYLSULFONYL) 1 (2 CHLOROETHYL) 2 [(METHYLAMINO)CARBONYL]HYDRAZINE; 6 O ALKYLGUANINE DNA ALKYLTRANSFERASE; 6 O ALKYLGUANINE DNA ALKYLTRANSFERASE INHIBITOR; ANTINEOPLASTIC AGENT; DNA; ENZYME INHIBITOR; GUANINE DERIVATIVE; HYDRAZINE DERIVATIVE; METHYL ISOCYANATE; PRODRUG; SULFONYLHYDRAZINE DERIVATIVE; UNCLASSIFIED DRUG; VNP40101M;

AGT GENE; ALKYLATION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CARBAMOYLATION; CATALYSIS; CELL KILLING; CHO CELL; COMBINATION CHEMOTHERAPY; CONTROLLED STUDY; CYTOTOXICITY; DNA CROSS LINKING; DNA REPAIR; DRUG MECHANISM; ENZYME ANALYSIS; EXPRESSION VECTOR; GENE; GENE OVEREXPRESSION; MOUSE; NONHUMAN; PRIORITY JOURNAL; RESIDUE ANALYSIS; SENSITIVITY ANALYSIS;

ANIMALS; ANTINEOPLASTIC AGENTS, ALKYLATING; CELL SURVIVAL; CHO CELLS; CRICETINAE; CRICETULUS; DRUG RESISTANCE, NEOPLASM; DRUG SYNERGISM; HUMANS; HYDRAZINES; ISOCYANATES; O(6)-METHYLGUANINE-DNA METHYLTRANSFERASE; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSFECTION;

EID: 1642291215     PISSN: 03445704     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00280-003-0739-0     Document Type: Article

References (28)

1. Teicher BA (1997) Antitumor alkylating agents. In: DeVita VT Jr, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology, 5th edn, Lippincott-Raven, Philadelphia, p 405
2. Shyam K, Penketh PG, Divo AA, Loomis RH, Rose WC, Sartorelli AC (1990) Synthesis and evaluation of 1,2,2-tris(sulfonyl)hydrazines as antineoplastic and trypanocidal agents. J Med Chem 33:2259
3. Shyam K, Penketh PG, Divo AA, Loomis RH, Rose WC, Sartorelli AC (1993) Synthesis and evaluation of 1-acyl-1,2-bis(methylsulfonyl)-2-(2-chloroethyl) hydrazines as antineoplastic agents. J Med Chem 36:3496
4. Shyam K, Penketh PG, Loomis RH, Rose WC, Sartorelli AC (1996) Antitumor 2-(aminocarbonyl)-1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazines. J Med Chem 39:796
5. Shyam K, Penketh PG, Shapiro M, Belcourt MF, Loomis RH, Rockwell S, Sartorelli AC (1999) Hypoxia-selective nitrobenzyloxycarbonyl derivatives of 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazines. J Med Chem 42:941
6. Finch RA, Shyam K, Penketh PG, Sartorelli AC (2001) 1,2- Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (101M): a novel sulfonylhydrazine prodrug with broad-spectrum antineoplastic activity. Cancer Res 61:3033
7. 6-alkylguanine-DNA alkyltransferase. In: Cohen WE, Moldave K (eds) Progress in nucleic acid research and molecular biology, vol. 51. Academic Press, New York, p 167
8. Gerson S (2002) Clinical relevance of MGMT in the treatment of cancer. J Clin Oncol 20:2388
9. Pelfrene A, Mirvish SS, Gold B (1976) Induction of malignant bone tumors in rats by 1-(2-hydroxyethyl)-1-nitrosourea. J Natl Cancer Inst 56:445
10. Swenson DH, Frei JV, Lawley PD (1979) Synthesis of 1-(2-hydroxyethyl)-1- nitrosourea and comparison of its toxicity to that of 1-ethyl-1-nitrosourea. J Natl Cancer Inst 63:1469
11. Colvin M, Brundrett RB, Cowens JW, Jardine I, Ludlum DB (1976) A chemical basis for the antitumor activity of the chloroethylnitrosoureas. Biochem Pharmacol 25:695
12. Wheeler GP, Bowdon BJ, Grimsley J, Lloyd HH (1974) Interrelationships of some chemical, physicochemical and biological activities of several 1-(2-haloethyl)-1-nitrosoureas. Cancer Res 34:194
13. Panasci LC, Green D, Nagourney R, Fox P, Schein PS (1977) A structure-activity analysis of chemical and biological parameters of chloroethylnitrosoureas in mice. Cancer Res 37:2615
14. Gibson NW, Hickman JA (1982) The role of isocyanates in the toxicity of antitumor haloalkylnitrosoureas. Biochem Pharmacol 31:2795
15. Colvin OM (1997) Alkylating agents and platinum antitumor compounds. In: Holland JF, Bast RC Jr, Morton DL, Frei E III, Kufe DW, Weichselbaum RR (eds) Cancer medicine. Williams and Wilkins, Baltimore, p 983
16. Penketh PG, Shyam K, Sartorelli AC (2000) Comparison of DNA lesions produced by tumor inhibitory 1,2-bis(sulfonyl)hydrazines and chloroethylnitrosoureas. Biochem Pharmacol 59:283
17. 6-alkylguanine DNA alkyltransferase (AGT) by electrophilic species generated by decomposition. Cancer Chemother Pharmacol 53, DOI 10.1007/s00280-003-0740-7
18. Baril BB, Baril EF, Lazlo J, Wheeler GP (1975) Inhibition of rat liver DNA polymerase by nitrosoureas and isocyanates. Cancer Res 35:1
19. Petak I, Mihalik R, Bauer PI, Suli-Vargha H, Sebestyen A, Kopper L (1998) BCNU is a caspase-mediated inhibitor of drug-induced apoptosis. Cancer Res 58:614
20. Schallreuter KU, Gleason FK, Wood JM (1990) The mechanism of action of the nitrosourea antitumor drugs on thioredoxin reductase, glutathione reductase and ribonucleotide reductase. Biochim Biophys Acta 1054:14
21. Kann HH, Kohn KW, Lyles JM (1974) Inhibition of DNA repair by 1,3-bis(2-chloroethyl)-1-nitrosourea breakdown product, 2-chloroethyl isocyanate. Cancer Res 34:398
22. 6-alkylguanine. Proc Natl Acad Sci U S A 87:686
23. 6-alkylguanine-DNA alkyltransferase activity in human cells and tumor tissues by restriction endonuclease inhibition. Cancer Res 47:6227
24. 6-benzylguanine plus 1,3-bis(2-chloroethyl)-1- nitrosourea cytotoxicity. Clin Cancer Res 3:301
25. Baumann RP, Hodnick WF, Seow HA, Belcourt MF, Rockwell S, Sherman DH, Sartorelli AC (2001) Reversal of mitomycin C resistance by overexpression of bioreductive enzymes in Chinese hamster ovary cells. Cancer Res 61:7770
26. 6-alkylguanine-DNA alkyltransferase in protecting against cyclophosphamide-induced toxicity and mutagenicity. Cancer Res 59:3059
27. Mitra S, Kaina B (1993) Regulation of repair of alkylation damage in mammalian genomes. Prog Nucleic Acids Res Mol Biol 44:109
28. 6-alkylguanine-DNA alkyltransferase: regulation and importance in response to alkylating carcinogenic and therapeutic agents. Cancer Res 50:6119