Inhibition of DNA topoisomerase II by azaelliptitoxins functionalized in the variable substituent domain.
Inhibition of DNA topoisomerase II by azaelliptitoxins functionalized in the variable substituent domain.
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在可变取代域中功能化的氮杂环毒素对 DNA 拓扑异构酶 II 的抑制。
DOI：
10.1021/jm9508806
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Macdonald,TL
中科院分区：
文献类型：
--
作者：
Tepe,JJ;Madalengoitia,JS;Slunt,KM;Werbovetz,KW;Spoors,PG;Macdonald,TL
合成了一系列新的氮杂椭圆形毒素（azatoxin）的C11取代衍生物，并测试了它们对人DNA拓扑异构酶II的抑制活性。C11多胺或胺的掺入导致药物的插层性质增加和拓扑异构酶II活性降低。非嵌入C11苯胺基氮杂毒素类的构效关系（SAR）与（苯胺基）吖啶家族的SAR相似。11-（4-Cyanoanilino）azatoxin（14）是这一系列化合物中活性最高的类似物，其活性比azatoxin（12）和依托泊苷高10倍。
A series of novel C11-substituted derivatives of azaelliptitoxin (azatoxin) have been synthesized and tested for their inhibitory activity against human DNA topoisomerase II. Incorporation of a C11polyamine or 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 C11anilino 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 ∼10-fold higher activity than azatoxin12and etoposide.