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Nitroaryl phosphoramides as novel prodrugs for E. coli nitroreductase activation in enzyme prodrug therapy.

Abstract：

:Cyclic and acyclic nitroaryl phosphoramide mustard analogues were activated by E. coli nitroreductase, an enzyme explored in GDEPT. The more active acyclic 4-nitrobenzyl phosphoramide mustard (7) showed 167 500x selective cytotoxicity toward nitroreductase-expressing V79 cells with an IC(50) as low as 0.4 nM. This is about 100x more active and 27x more selective than CB1954 (1). The superior activity was attributed to its better substrate activity (k(cat)/K(m) 19x better than 1) and/or excellent cytotoxicity of phosphoramide mustard released.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Hu L,Yu C,Jiang Y,Han J,Li Z,Browne P,Race PR,Knox RJ,Searle PF,Hyde EI

doi

10.1021/jm034133h

keywords:

subject

Has Abstract

pub_date

2003-11-06 00:00:00

pages

4818-21

issue

23

eissn

0022-2623

issn

1520-4804

journal_volume

46

pub_type

杂志文章

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