Dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines

被引：29

作者：

Xiao, XS

Miao, ZH

Antony, S

Pommier, Y

Cushman, M ^{[1
]}

机构：

[1] Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA

[2] Purdue Univ, Sch Pharm & Pharmaceut Sci, Purdue Canc Ctr, W Lafayette, IN 47907 USA

[3] NCI, Canc Res Ctr, Mol Pharmacol Lab, Bethesda, MD 20892 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 11期

关键词：

indenoisoquinoline; dihydroindenoisoquinoline; antitumor; topoisomerase; 1; prodrug;

D O I：

10.1016/j.bmcl.2005.03.101

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Dihydroindenoisoquinolines are analogs of cytotoxic indenoisoquinoline topoisomerase 1 (Top1) inhibitors, exhibiting potent cytotoxicity but weak inhibitory activity toward Top 1. Through COMPARE analysis, cytotoxicity studies in Top 1-deficient cells, chemical synthesis and biological evaluation of methylated dihydroindenoisoquinoline 5, we demonstrated that dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines in cancer cells. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：2795 / 2798

页数：4

共 23 条

[1] Cellular topoisomerase I inhibition and antiproliferative activity by MJ-III-65 (NSC 706744), an indenoisoquinoline topoisomerase I poison [J].