Self-immolative anthracycline prodrugs for suicide gene therapy

被引：36

作者：

Niculescu-Duvaz, I ^{[1
]}

Niculescu-Duvaz, D ^{[1
]}

Friedlos, F ^{[1
]}

Spooner, R ^{[1
]}

Martin, J ^{[1
]}

Marais, R ^{[1
]}

Springer, CJ ^{[1
]}

机构：

[1] Inst Canc Res, CRC, Ctr Canc Therapeut, Sutton SM2 5NG, Surrey, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1999年 / 42卷 / 13期

关键词：

D O I：

10.1021/jm980696v

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Four novel potential prodrugs derived from daunorubicin (8, 10) and doxorubicin (12, 14) were designed and synthesized. They are self-immolative prodrugs for suicide gene therapy activation by the enzyme carboxypeptidase G2 (CPG2) subsequently releasing the corresponding anthracyclines, by a 1,6-elimination mechanism. A mammary carcinoma cell line (MDA MB 361) was engineered to express CPG2 intracellularly (CPG2*) or extracellularly, tethered to the outer cell membrane (stCPG2(Q)3). The prodrugs derived from doxorubicin showed prodrug/drug cytotoxicity differentials of 21-fold (compound 12) and 23-fold (compound 14). Prodrug 12 underwent an 11-fold activation when assayed in the cell line expressing externally surface-tethered CPG2.

引用

页码：2485 / 2489

页数：5

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