Synthesis of an aminopropyl, analog of the experimental anticancer drug tallimustine, and activation of its 4-nitrobenzylcarbamoyl prodrug by nitroreductase and NADH

被引：19

作者：

Lee, M

Simpson, JE

Woo, S

Kaenzig, C

Anlezark, GM

EnoAmooquaye, E

Burke, PJ

机构：

[1] CHARING CROSS HOSP,DEPT MED ONCOL,CANC RES CAMPAIGN LABS,LONDON W6 8RF,ENGLAND

[2] PUBL HLTH LAB SERV,CTR APPL MICROBIOL & RES,SALISBURY SP4 0JG,WILTS,ENGLAND

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1997年 / 7卷 / 08期

关键词：

D O I：

10.1016/S0960-894X(97)00162-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Compound I, an analog of tallimustine that contains an aminopropyl group at the C-terminus, and its 4-nitrobenzylcarbamoyl prodrug 2 have been prepared. Analog 1 binds preferentially to the minor groove of poly(dA-dT) over poly(dG-dC), and is cytotoxic against the growth of LS1747 and SW1116 human colon cancer cells, with IC50 values of 0.02 mu M and 10.0 mu M, respectively. The prodrug 2 is significantly less cytotoxic (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.

引用

页码：1065 / 1070

页数：6

共 33 条

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