Inhibition of DNA topoisomerase II by azaelliptitoxins functionalized in the variable substituent domain

被引：41

作者：

Tepe, JJ ^{[1
]}

Madalengoitia, JS ^{[1
]}

Slunt, KM ^{[1
]}

Werbovetz, KW ^{[1
]}

Spoors, PG ^{[1
]}

Macdonald, TL ^{[1
]}

机构：

[1] UNIV VIRGINIA,DEPT CHEM,CHARLOTTESVILLE,VA 22901

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1996年 / 39卷 / 11期

关键词：

D O I：

10.1021/jm9508806

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel C-11-substituted derivatives of azaelliptitoxin (azatoxin) have been synthesized and tested for their inhibitory activity against human DNA topoisomerase II. Incorporation of a C-11 polyamine pr amine resulted in an increase in the intercalation properties of the drug and a decrease of topoisomerase II activity. The structure-activity relationship (SAR) profile of the nonintercalating C-11 anilino azatoxin class follows the SAR of the (anilino)acridine family. 11-(4-Cyanoanilino)azatoxin (14) was found to be the most active analog in this series, exhibiting similar to 10-fold higher activity than azatoxin 12 and etoposide.

引用

页码：2188 / 2196

页数：9

共 19 条

[1] POTENTIAL ANTI-TUMOR AGENTS .34. QUANTITATIVE RELATIONSHIPS BETWEEN DNA-BINDING AND MOLECULAR-STRUCTURE FOR 9-ANILINOACRIDINES SUBSTITUTED IN THE ANILINO RING [J].