Unlike other DNA topoisomerase II (topo II) inhibitors, our recently identified acridone derivative E17 exerted strong cytotoxic activity by inhibiting topo II without causing topo II degradation and DNA damage, which promoted us to explore more analogues of E17 by expanding its chemical diversification and enrich the structure-activity relationship (SAR) outcomes of acridone-oriented chemotypes. To achieve this goal, 42 novel acridone derivatives were synthesized and evaluated for their antiproliferative efficacies. SAR investigations revealed that orientation and spatial topology of R³ substituents make greater contributions to the bioactivity, exemplified by compounds E24, E25 and E27, which has provided valuable information for guiding further development of acridone derivatives as promising drug candidates.

与其他 DNA 拓扑异构酶 II (topo II) 抑制剂不同，我们最近发现的吖啶酮衍生物E17通过抑制拓扑 II 而不引起拓扑 II 降解和 DNA 损伤发挥了强大的细胞毒活性，这促使我们通过扩大其化学多样化和富集来探索更多的E17类似物。吖啶酮导向化学型的构效关系（SAR）结果。为了实现这一目标，合成了 42 种新型吖啶酮衍生物并评估了它们的抗增殖功效。SAR 研究表明，R ³取代基的取向和空间拓扑结构对生物活性的贡献更大，例如化合物E24、E25和E27，这为指导吖啶酮衍生物作为有前途的候选药物的进一步开发提供了宝贵的信息。