Inhibition of human O6-alkylguanine-DNA alkyltransferase and potentiation of the cytotoxicity of chloroethylnitrosourea by 4(6)- (benzyloxy)-2,6(4)-diamino-5-(nitro or nitroso)pyrimidine derivatives and analogues

Journal of Medicinal Chemistry

Volumn 41, Issue 4, 1998, Pages 503-508

  Terashima, Isamu ^a   Kohda, Kohfuku ^a  

^a NAGOYA CITY UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

2,4 DIAMINO 6 [(4 FLUOROBENZYL)OXY] 5 NITROSOPYRIMIDINE; 6 O ALKYLGUANINE DNA ALKYLTRANSFERASE; 6 O BENZYLGUANINE; CHLOROETHYLNITROSOUREA; NIMUSTINE; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG; 1-(2-CHLOROETHYL)-1-NITROSOUREA; 4 (BENZYLOXY) 2,6 DIAMINO 5 NITROPYRIMIDINE; 4-(BENZYLOXY)-2,6-DIAMINO-5-NITROPYRIMIDINE; DRUG DERIVATIVE; DYES, REAGENTS, INDICATORS, MARKERS AND BUFFERS; ENZYME INHIBITOR; ETHYLNITROSOUREA; METHYLATED DNA PROTEIN CYSTEINE METHYLTRANSFERASE; RECOMBINANT PROTEIN;

ARTICLE; CYTOTOXICITY; CYTOTOXICITY TEST; DOSE RESPONSE; DRUG EFFECT; DRUG POTENTIATION; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME INHIBITION; HELA CELL; HUMAN; HUMAN CELL; CELL SURVIVAL; CHEMISTRY; DRUG ANTAGONISM; KINETICS; MOLECULAR CLONING; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

CELL SURVIVAL; CLONING, MOLECULAR; DRUG SYNERGISM; ENZYME INHIBITORS; ETHYLNITROSOUREA; HELA CELLS; HUMANS; INDICATORS AND REAGENTS; KINETICS; O(6)-METHYLGUANINE-DNA METHYLTRANSFERASE; PYRIMIDINES; RECOMBINANT PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0032509860     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970363i     Document Type: Article

References (27)

1. Singer, B. The chemical effects of nucleic acid alkylation and their relation to mutagenesis and carcinogenesis. Prog. Nucleic Acid Res. Mol. Biol. 1975, 16, 219-284.
2. Loveless, A. Possible relevance of O-6 alkylation of deoxyguanosine to the mutagenicity and carcinogenicity of nitrosamines and nitrosamides. Nature 1969, 223, 206-207.
3. Lindahl, T.; Sedgwick, B.; Sekiguchi, M.; Nakabeppu, Y. Regulation and expression of the adaptive response to alkylating agents. Annu. Rev. Biochem. 1988, 57, 133-157.
4. Scudiero, D. A.; Meyer, S. A.; Clatterbuck, B. E.; Mattern, M. R.; Ziolkowski, C. H. J.; Day, R. S., III. Sensitivity of human cell strains having different abilities to repair O6-methylguanine in DNA to inactivation by alkylating agents including chloroethylnitrosoureas. Cancer Res. 1984, 44, 2467-2474.
5. Belanich, M.; Pastor, M.; Randall, T.; Guerra, D.; Kibitel, J.; Alas, L.; Li, B.; Citron, M.; Wasserman, P.; White, A.; Eyre, H.; Jaeckle, K.; Schulman, S.; Rector, D.; Prados, M.; Coons, S.; Shapiro, W.; Yarosh, D. Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine. Cancer Res. 1996, 50, 783-788.
6. 6-benzylguanine provides a means to evaluate the role of this protein in protection against carcinogenic and therapeutic alkylating agents. Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 5368-5372.
7. 6-benzylguanine analogues on sensitivity of human tumor cells to the cytotoxic effects of alkylating agents. Cancer Res. 1991, 51, 3367-3372.
8. 6-benzylguanine. Biol. Pharm. Bull. 1996, 19, 956-961.
9. 6-alkylguanine-DNA alkyl-transferase. J. Med. Chem. 1992, 35, 4486-4491.
10. 6-alkylguanine-DNA alkyl-transferase. J. Med. Chem. 1994, 37, 342-347.
11. 6-alkylguanine-DNA alkyltransferase. J. Med. Chem. 1995, 38, 359-365.
12. 6-arylmethylguanines. Biol. Pharm. Bull. 1995, 18, 424-430.
13. 6alkylguanine derivatives on chloroethylnitrosourea cytotoxicity toward tumor cells. Int. J. Cancer 1994, 58, 706-712.
14. 4-alkylthymidine and related compounds in an alkyl-transfer system. Chem. Biol. Interact. 1991, 78, 23-32.
15. Eyer, P. Reactions of oxidatively activated arylamines with thiols: Mechanisms and biologic implications. An overview. Environ. Health Perspect. 1994, 102 (Suppl. 6), 123-132.
16. 4-methylthymine in DNA. Carcinogenesis 1995, 16, 1595-1602.
17. 6-methylguanine-DNA methyltransferase. J. Biol. Chem. 1985, 260, 7281-7288.
18. 4methylthymine. J. Biol. Chem. 1991, 266, 2767-2771.
19. 6-arylmethylguanines. Int. J. Cancer 1995, 63, 148-151.
20. Ludlum, D. B. DNA alkylation by the haloethylnitrosoureas: Nature of modifications produced and their enzymatic repair or removal. Mutat. Res. 1990, 233, 117-126.
21. 8-alkylguanine-DNA alkyltransferase and N,N'-bis(2-chloroethyl)-N-nitrosourea. Biochem. Pharmacol. 1995, 50, 1141-1148.
22. Balsiger, R. W.; Montgomery, J. A. Synthesis of potential anticancer agents. XXV. Preparation of 6-alkoxy-2-aminopurines. J. Org. Chem. 1960, 25, 1573-1575.
23. Kosary, J.; Diesler, E.; Matyus, P.; Kasztreiner, E. Preparation of pyrimidine derivatives with potential cardiotonic activity. Acta Pharm. Hung. 1989, 49, 241-247.
24. Pfleiderer, W.; Lohrmann, R. Synthesis of 2-amino-4-alkoxypteridine. Chem. Ber. 1961, 94, 12-18.
25. O'Brien, D. E.; Cheng, C. C.; Pfleiderer, W. Pyrimidines. XVIII. 2,4-Diamino-5-nitro-6-arylaminopyrimidines. Nitration study of 2,4-diamino-6-chloropyrimidine and a literature correction. J. Med. Chem. 1966, 9, 573-575.
26. 6-methylguanine-DNA methyltransferase. J. Biol. Chem. 1990, 265, 14754-14762.
27. 6-methylguanine-DNA methyltransferase activity: Analyses of three residues at or near the methyl acceptor site. Carcinogenesis 1992, 13, 837-843.