A series of 8,9-substituted Luotonin A analogs were designed, synthesized, and evaluated for antiproliferative activity against four cancer cell lines. The structure–activity relationship study revealed that the in vitro anticancer activity of Luotonin A was significantly improved by the introduction of 8-piperazine group and the 5-deaza modification. Two promising compounds 6a and 7a displayed potent topoisomerase I inhibitory activity. And a rational binding mode of 7a with topoisomerase I–DNA complex was proposed based on the molecular docking study.

中文翻译：

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作为新型拓扑异构酶 I 抑制剂的 8,9-取代罗托宁 A 类似物的设计、合成和抗癌活性

设计、合成了一系列 8,9-取代的洛托宁 A 类似物，并评估了它们对四种癌细胞系的抗增殖活性。构效关系研究表明，引入8-哌嗪基团和5-去氮杂修饰后，罗托宁A的体外抗癌活性显着提高。两种有前景的化合物6a和7a显示出有效的拓扑异构酶 I 抑制活性。并基于分子对接研究提出了7a与拓扑异构酶I-DNA复合物的合理结合模式。