Mustard prodrugs for activation by Escherichia coli nitroreductase in gene-directed enzyme prodrug therapy

Journal of Medicinal Chemistry

Volumn 40, Issue 8, 1997, Pages 1270-1275

  Friedlos, Frank ^a   Denny, William A ^b   Palmer, Brian D ^b   Springer, Caroline J ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b UNIVERSITY OF AUCKLAND   (New Zealand)

Author keywords

[No Author keywords available]

Indexed keywords

2 [N,N BIS(2 BROMOETHYL)AMINO] 3,5 DINITROBENZAMIDE; 2 [N,N BIS(2 IODOETHYL)AMINO] 3,5 DINITROBENZAMIDE; 5 (1 AZIRIDINYL) 2,4 DINITROBENZAMIDE; 5 [N,N BIS(2 BROMOETHYL)AMINO] 2,4 DINITROBENZAMIDE; 5 [N,N BIS(2 IODOETHYL)AMINO] 2,4 DINITROBENZAMIDE; ANTINEOPLASTIC AGENT; MUSTARD GAS DERIVATIVE; NITROREDUCTASE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CANCER INHIBITION; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG POTENCY; ENZYME ACTIVATION; ENZYME THERAPY; ESCHERICHIA COLI; GENE THERAPY; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

ANIMALS; CELL LINE; CRICETINAE; CRICETULUS; DRUG DESIGN; ENZYME ACTIVATION; ESCHERICHIA COLI; GENETIC ENGINEERING; MECHLORETHAMINE; NITROREDUCTASES; PRODRUGS;

EID: 0030907756     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960794l     Document Type: Article

References (11)

1. Deonarain, M. P.; Spooner, R. A.; Epenetos, A. A. Genetic delivery of enzymes for cancer therapy. Gene Ther. 1995, 2, 235-244.
2. Cobb, L. M.; Connors, T. A.; Elson, L. A.; Khan, A. H.; Mitchley, B. V. C.; Ross, W. J. C.; Whisson, M. E. 2,4-Dinitro-5-ethylene-iminobenzamide (CB1954): a potent and selective inhibitor of the growth of the Walker carcinoma 256. Biochem. Pharmacol. 1969, 18, 1519-1527.
3. Knox, R. J.; Friedlos, F.; Jarman, M.; Roberts, J. J. A new cytotoxic, DNA interstrand crosslinking agent, 5-aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide, is formed from 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954) by a nitroreductase enzyme in Walker carcinoma cells. Biochem. Pharmacol. 1988, 37, 4661-4669.
4. Knox, R. J.; Friedlos, F.; Marchbank, T.; Roberts, J. J. Bioactivation of CB 1954: Reaction of the Active 4-Hydroxylamino Derivative with Thioesters to Form the Ultimate DNA-DNA interstrand Crosslinking Species. Biochem. Pharmacol. 1991, 42, 1691-1697.
5. Boland, M. P.; Knox, R. J.; Roberts, J. J. The differences in kinetics of rat and human DT diaphorase result in a differential sensitivity of derived cells lines to CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide). Biochem. Pharmacol. 1991, 41, 867-875.
6. Anlezark, G. M.; Melton, R. G.; Sherwood, R. F.; Coles, B.; Friedlos, F.; Knox, R. J. The Bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954) I. Purification and properties of a nitroreductase enzyme from Escherischia coli - a potential enzyme for antibody-directed enzyme prodrug therapy (ADEPT). Biochem. Pharmacol. 1992, 44, 2289-2295.
7. Anlezark, G. M.; Melton, R. G.; Sherwood, R. F.; Wilson, W. R.; Denny, W. A.; Palmer, B. D.; Knox, R. J.; Friedlos, F.; Williams, A. Bioactivation of dinitrobenzamide mustards by an E. Coli B nitroreductase. Biochem. Pharmacol. 1995, 50, 609-618.
8. Palmer, B. D.; Wilson, W. R.; Cliffe, S.; Denny, W. A. Hypoxiaselective antitumour agents. 5. Synthesis of water-soluble nitroaniline mustards with selective cytotoxicity for hypoxic mammalian cells. J. Med. Chem. 1992, 35, 3214-3222.
9. Huber, B. E.; Austin, E. A.; Richards, C. A.; Davis, S. T.; Good, S. S. Metabolism of 5-fluorocytosine to 5-fluorouracil in human colorectal tumor cells transduced with the cytosine deaminase gene: significant antitumour effects when only a small percentage of tumour cells express cytosine deaminase. Proc. Natl. Acad. Sci. 1994, 91, 8302-8306.
10. Palmer, B. D.; Wilson, W. R.; Anderson, R. F.; Boyd, M.; Denny, W. A. Hypoxia-selective antitumor agents. 14. Synthesis and hypoxic cell cytotoxicity of regioisomers of the hy poxia-selective cytotoxin 5-[N,N-bis(2-chloroethyl)amino]-2,4-dinitro-benzamide. J. Med. Chem. 1996, 39, 2518-2528.
11. Atwell, G. J.; Boyd, M.; Palmer, B. D.; Anderson, R. F.; Pullen, S. M.; Wilson, W. R.; Denny, W. A. Synthesis and evaluation of 4-substituted analogues of 5-[N,N,-bis(2-chloroethyl)amino]-2-nitrobenzamide as bioreductively-activated prodrugs using an E. coli nitroreductase. Anti-Cancer Drug Des. 1996, 11, 553-557.