Effect of Nitroreduction on the Alkylating Reactivity and Cytotoxicity of the 2,4-Dinitrobenzamide-5-aziridine CB 1954 and the Corresponding Nitrogen Mustard SN 23862: Distinct Mechanisms of Bioreductive Activation
Author:
Affiliation:
1. Auckland Cancer Society Research Centre, The University of Auckland, Private Bag 92019, Auckland, New Zealand
Publisher
American Chemical Society (ACS)
Subject
Toxicology,General Medicine
Link
https://pubs.acs.org/doi/pdf/10.1021/tx025662b
Reference41 articles.
1. Knox, R. J., Boland, M. P., Friedlos, F., Coles, B., Southan, C., and Roberts, J. J. (1988) The nitroreductase enzyme in Walker cells that activates 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) to 5-(aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide is a form of NAD(P)H dehydrogenase (quinone) (EC 1.6.99.2).Biochem. Pharmacol.37, 4671−4677.
2. Boland, M. P., Knox, R. J., and Roberts, J. J. (1991) The differences in kinetics of rat and human DT diaphorase result in a differential sensitivity of derived cell lines to CB 1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide).Biochem. Pharmacol.41, 867−875.
3. Anlezark, G. M., Melton, R. G., Sherwood, R. F., Coles, B., Friedlos, F., and Knox, R. J. (1992) The bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954)−I. Purification and properties of a nitroreductase enzyme fromEscherichia coli- -a potential enzyme for antibody-directed enzyme prodrug therapy (ADEPT).Biochem. Pharmacol.44, 2289−2295.
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