Synthesis of nitrated indenoisoquinolines as topoisomerase I inhibitors

被引：54

作者：

Morrell, A

Antony, S

Kohlhagen, G

Pommier, Y

Cushman, M ^{[1
]}

机构：

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

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 14期

关键词：

indenoisoquinoline; topoisomerase I inhibitor; anticancer; cytotoxicity;

D O I：

10.1016/j.bmcl.2004.05.022

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Indenoisoquinolines and dihydroindenoisoquinolines have been synthesized possessing a nitro-substituted isoquinoline ring in an effort to explore the effects of electron-withdrawing substituents on biological activity. The in vitro anticancer activities of these molecules have been tested in the National Cancer Institute's screen of 55 cell lines. The compounds have also been tested for topoisomerase I (topI) inhibition. The results indicate that these substances are a potent class of topI inhibitors with sub-micromolar cytotoxicity mean graph midpoints (MGM) and topI inhibition equal to camptothecin. (C) 2004 Elsevier Ltd. All rights reserved.

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收藏

页码：3659 / 3663

页数：5

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