Background: Targeting the DNA topoisomerase II enzyme (topo II) is a promising anticancer treatment approach. TopoII controls and modifies the topological states of DNA and plays key roles in DNA replication, transcription, and chromosome segregation. The DNA binding and cleavage domain is one of the active sites of this enzyme. It is known that topoisomerase inhibitors, also known as topoisomerase poisons, bind to the transient enzyme-DNA complex and inhibit the religation of DNA, generating single- and double-stranded breaks that harm the integrity of the genome. This ultimately leads to the accumulation of DNA strand breaks and cell death.

Methods: Our previously synthesized benzazole derivatives were tested for their eukaryotic DNA topoisomerase II inhibitory activity in a cell-free system. Their interactions with the enzyme were studied by carrying out molecular docking studies using and comparing two different docking programs.

Results: The results of the docking studies clarified binding modes of these compounds to the topoisomerase II enzyme.

Conclusion: This study also provides guidelines to design novel and more potent antitumor agents functioning as human topoisomerase II enzyme inhibitors.

背景：靶向DNA拓扑异构酶II酶（拓扑II）是一种有前途的抗癌治疗方法。TopoII控制和修改DNA的拓扑状态，并在DNA复制，转录和染色体分离中起关键作用。DNA结合和切割结构域是该酶的活性位点之一。已知拓扑异构酶抑制剂（也称为拓扑异构酶毒物）会与瞬时酶-DNA复合体结合并抑制DNA的重新连接，从而产生损害基因组完整性的单链和双链断裂。最终导致DNA链断裂的积累和细胞死亡。

方法：我们在无细胞系统中测试了我们先前合成的苯并唑衍生物的真核DNA拓扑异构酶II抑制活性。通过使用和比较两种不同的对接程序进行分子对接研究，研究了它们与酶的相互作用。

结果：对接研究的结果阐明了这些化合物与拓扑异构酶II酶的结合方式。

结论：这项研究还提供了设计新型和更有效的抗肿瘤剂作为人类拓扑异构酶II酶抑制剂的指南。