Synthesis and cytotoxic activity of a glucuronylated prodrug of nornitrogen mustard

Authors
Papot, S Combaud, D Bosslet, K Gerken, M Czech, J Gesson, JP
Citation
S. Papot et al., Synthesis and cytotoxic activity of a glucuronylated prodrug of nornitrogen mustard, BIOORG MED, 10(16), 2000, pp. 1835-1837
Citations number
19
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
10
Issue
16
Year of publication
2000
Pages
1835 - 1837
Database
ISI
SICI code
0960-894X(20000821)10:16<1835:SACAOA>2.0.ZU;2-G
Abstract
A new glucuronlylated prodrug of nornitrogen mustard, incorporating the sam e spacer group as the doxorubicin prodrug HMR 1826, has been prepared. Upon exposure to E. coli beta-glucuronidase, fast hydrolysis occurs but a lower cytotoxicity against LoVo cancer cells is observed compared to the nornitr ogen mustard alone. This is explained by cyclization of the intermediate ca rbamic acid to the inactive chloroethyl oxazolidinone. (C) 2000 Elsevier Sc ience Ltd. All rights reserved.