SYNTHESIS OF AN AMINOPROPYL, ANALOG OF THE EXPERIMENTAL ANTICANCER DRUG TALLIMUSTINE, AND ACTIVATION OF ITS 4-NITROBENZYLCARBAMOYL PRODRUG BY NITROREDUCTASE AND NADH

Authors
LEE M SIMPSON JE WOO S KAENZIG C ANLEZARK GM ENOAMOOQUAYE E BURKE PJ
Citation
M. Lee et al., SYNTHESIS OF AN AMINOPROPYL, ANALOG OF THE EXPERIMENTAL ANTICANCER DRUG TALLIMUSTINE, AND ACTIVATION OF ITS 4-NITROBENZYLCARBAMOYL PRODRUG BY NITROREDUCTASE AND NADH, Bioorganic & medicinal chemistry letters, 7(8), 1997, pp. 1065-1070
Citations number
33
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
7
Issue
8
Year of publication
1997
Pages
1065 - 1070
Database
ISI
SICI code
0960-894X(1997)7:8<1065:SOAAAO>2.0.ZU;2-6
Abstract
Compound I, an analog of tallimustine that contains an aminopropyl gro up at the C-terminus, and its 4-nitrobenzylcarbamoyl prodrug 2 have be en prepared. Analog 1 binds preferentially to the minor groove of poly (dA-dT) over poly(dG-dC), and is cytotoxic against the growth of LS174 7 and SW1116 human colon cancer cells, with IC50 values of 0.02 mu M a nd 10.0 mu M, respectively. The prodrug 2 is significantly less cytoto xic (2.3 and 22.9 mu M, respectively) than the parent drug 1. However, in the presence of nitroreductase and NADH prodrug 2 is as active as compound 1. (C) 1997 Elsevier Science Ltd.