The bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954)-II. A comparison of an Escherichia coli nitroreductase and Walker DT diaphorase

Biochemical Pharmacology

Volumn 44, Issue 12, 1992, Pages 2297-2301

  Knox, Richard J ^a   Friedlos, Frank ^a   Sherwood, Roger F ^b   Melton, Roger G ^b   Anlezark, Gillian M ^b  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b PUBLIC HEALTH ENGLAND   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

5 (1 AZIRIDINYL) 2,4 DINITROBENZAMIDE; BACTERIAL ENZYME; NITROREDUCTASE; RADIOISOTOPE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE);

ARTICLE; CELL STRAIN V 79; CYTOTOXICITY; ESCHERICHIA COLI; METABOLIC ACTIVATION; PRIORITY JOURNAL; REDUCTION; WALKER CARCINOMA;

ANTIBODIES; AZIRIDINES; BIOTRANSFORMATION; COMPARATIVE STUDY; DRUG THERAPY; ESCHERICHIA COLI; KINETICS; NAD(P)H DEHYDROGENASE (QUINONE); NITROREDUCTASES; PRODRUGS; SUPPORT, NON-U.S. GOV'T;

EID: 0026677838     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/0006-2952(92)90672-6     Document Type: Article

References (14)

1. 2,4-Dinitro-5-ethyleneiminobenzamide (CB1954): a potent and selective inhibitor of the growth of the Walker carcinoma 256
2. Cell hybridization study of resistance to alkylating agents
3. CB1954 (2,4-dinitro-5-aziridinyl benzamide) becomes a DNA interstrand crosslinking agent in Walker tumour cells
4. 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
5. The nitroreductase enzyme in Walker cell that activates 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954) to 5-(aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide is a form of NAD(P)H dehydrogenase (quinone) (EC 1.6.99.2)
6. DT-diaphorase and cancer chemotherapy
7. The differences in kinetics of rat and human DT diaphorase result in a differential sensitivity of derived cell lines to CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide)
8. Bioactivation of CB1954: reaction of the active 4-hydroxylamino derivative with thioesters to form the ultimate DNA-DNA interstrand crosslinking species
9. The properties of total adducts and interstrand crosslinks in the DNA of cells treated with CB1954. Exceptional frequency and stability of the crosslink
10. Cytotoxicity and activation of CB1954 in a human tumour cell line
11. Antibody directed enzymes revive anticancer prodrugs concept
12. Towards generating cytotoxic agents at cancer sites
13. The bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide CB1954—I. Purification and properties of a nitroreductase enzyme from Escherichia coli—a potential enzyme for antibody-directed enzyme prodrug therapy (ADEPT)
14. Identification of novel reduced pyridinium derivatives as synthetic co-factors for the enzyme DT diaphorase (NAD(P)H dehydrogenase (quinone), EC 1.6.99.2)