Nitrobenzyl carbamate prodrugs of enediynes for nitroreductase gene-directed enzyme prodrug therapy (GDEPT)

被引：32

作者：

Hay, MP ^{[1
]}

Wilson, WR ^{[1
]}

Denny, WA ^{[1
]}

机构：

[1] Univ Auckland, Fac Med & Hlth Sci, Auckland Canc Soc Res Ctr, Auckland 1, New Zealand

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1999年 / 9卷 / 24期

关键词：

D O I：

10.1016/S0960-894X(99)00627-7

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and evaluation of the 4-nitrobenzylcarbamate enediyne 6 and related compounds as prodrugs activated by a nitroreductase enzyme (NTR) from E. coli B is described. Expression of NTR in three different cell lines gives increases in cytotoxicity of 21- to 135-fold for 6 (IC50 values 13-24 nM in the NTR expressing lines), indicating its potential as a prodrug for NTR-mediated Gene-Directed Enzyme Prodrug Therapy. The cytotoxicity of 6 and related enediynes is shown to be oxygen-dependent, especially in nucleotide excision repair-proficient cells, which might limit activity in hypoxic regions of tumours. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：3417 / 3422

页数：6

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